Characterization of critically ill patients with septic shock and sepsis-associated cardiomyopathy using cardiovascular MRI.

AIMS: Sepsis-induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR). METHODS AND RESULTS: Fifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady-state free precession imaging was performed for evaluation of cardiac anatomy and function in long-axis and short-axis views. Native T1 maps (modified Look-Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid-ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high-sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF) < 50% (39.8 ± 5.7%), and three individuals had preserved LVEF (66.9 ± 6.7%). Global longitudinal strain was impaired in both subgroups (LVEF impaired: 11.0 ± 1.8%; LVEF preserved: 16.0 ± 5.8%; P = 0.1). All patients with initially preserved LVEF died during hospital stay; in-hospital mortality with initially impaired LVEF was 11%. Upon echocardiographic follow-up, LVEF improved in all previously impaired patients at 48 (52.3 ± 9.0%, P = 0.06) and 96 h (54.9 ± 7.0%, P = 0.02). Patients with impaired systolic function had increased T2 times as compared with patients with preserved LVEF (60.8 ± 5.6 ms vs. 52.2 ± 2.8 ms; P = 0.02). Left ventricular GLS was decreased in all study individuals with impaired LVEF (11.0 ± 1.8%) and less impaired with preserved LVEF (16.0 ± 5.8%; P = 0.01). T1 mapping showed increased T1 times in patients with LVEF impairment as compared with patients with preserved LVEF (1093.9 ± 86.6 ms vs. 987.7 ± 69.3 ms; P = 0.03). Extracellular volume values were elevated in patients with LVEF impairment (27.9 ± 2.1%) as compared with patients with preserved LVEF (22.7 ± 1.9%; P < 0.01). CONCLUSIONS: Septic cardiomyopathy with impaired LVEF reflects inflammatory cardiomyopathy. Takotsubo-like contractility patterns occur in some cases. Cardiac MR is safely feasible in critically ill, sedated, and ventilated patients using extensive monitoring and experienced staff. TRIAL REGISTRATION: retrospectively registered (ISRCTN85297773).

Clinical course and factors associated with outcomes among 1904 patients hospitalized with COVID-19 in Germany: an observational study.

OBJECTIVES: In Germany the coronavirus disease 2019 (COVID-19) pandemic situation is unique among large European countries in that incidence and case fatality rate are distinctly lower. We describe the clinical course and examine factors associated with outcomes among patients hospitalized with COVID-19 in Germany. METHODS: In this retrospective cohort study we included patients with COVID-19 admitted to a national network of German hospitals between February 12 and June 12, 2020. We examined demographic characteristics, comorbidities and clinical outcomes. RESULTS: We included 1904 patients with a median age of 73 years, 48.5% (924/1904) of whom were female. The mortality rate was 17% (317/1835; 95% confidence interval (95%CI) 16-19), the rate of admission to the intensive care unit (ICU) was 21% (399/1860; 95%CI 20-23), and the rate of invasive mechanical ventilation was 14% (250/1850: 95%CI 12-15). The most prominent risk factors for death were male sex (hazard ratio (HR) 1.45; 95%CI 1.15-1.83), pre-existing lung disease (HR 1.61; 95%CI 1.20-2.16), and increased patient age (HR 4.11 (95%CI 2.57-6.58) for age >79 years versus <60 years). Among patients admitted to the ICU, the mortality rate was 29% (109/374; 95%CI 25-34) and higher in ventilated (33% [77/235; 95%CI 27-39]) than in non-ventilated ICU patients (23%, 32/139; 95%CI 16-30; p < 0.05). CONCLUSIONS: In this nationwide series of patients hospitalized with COVID-19 in Germany, in-hospital and ICU mortality rates were substantial. The most prominent risk factors for death were male sex, pre-existing lung disease, and greater patient age.

High-frequency oscillatory ventilation with and without arteriovenous extracorporeal lung assist in patients with severe respiratory failure.

PURPOSE: Elimination of carbon dioxide by an arteriovenous extracorporeal lung assist (av-ECLA) can facilitate the lung protective capabilities of high-frequency oscillatory ventilation (HFOV). This case series describes patients treated with HFOV because of severe respiratory failure with and without additional av-ECLA. METHODS: A retrospective analysis of 31 patients regarding patient characteristics, gas exchange, respirator settings, hemodynamics, and outcome. In 18 patients, av-ECLA was started before, together with, or during HFOV. RESULTS: The initial arterial carbon dioxide tension before HFOV and av-ECLA was higher in patients who received av-ECLA compared with patients without (P = .043): 65 (48-84) mm Hg and 50 (44-60) mmHg (median and interquartile range). The initial arterial oxygen tension (Pao(2))/inspiratory oxygen fraction (Fio(2)) index in patients who received av-ECLA was 79 (63-133) mm Hg. The Pao(2)/Fio(2) index immediately before HFOV was 84 (65-124) mm Hg (av-ECLA) and 121 (68-150) mmHg (no av-ECLA) and improved to 149 (89-231) mm Hg and 200 (117-233) mmHg during HFOV. Similarly, the oxygenation index improved. No statistically significant differences among groups were detected for Pao(2)/Fio(2) index, oxygenation index, and arterial carbon dioxide tension immediately before and during HFOV. The hospital mortality was 39% (av-ECLA) and 69% (no av-ECLA). CONCLUSIONS: High-frequency oscillatory ventilation improved the oxygenation in patients with severe respiratory failure. Additional av-ECLA may facilitate using lung protective HFOV settings in more severe lung injury and hypercapnia.

Hepatic effects of lung-protective pressure-controlled ventilation and a combination of high-frequency oscillatory ventilation and extracorporeal lung assist in experimental lung injury.

BACKGROUND: Ventilation with high positive end-expiratory pressure (PEEP) can lead to hepatic dysfunction. The aim of this study was to investigate the hepatic effects of strategies using high airway pressures either in pressure-controlled ventilation (PCV) or in high-frequency oscillatory ventilation (HFOV) combined with an arteriovenous extracorporeal lung assist (ECLA). MATERIAL/METHODS: Pietrain pigs underwent induction of lung injury by saline lavage. Ventilation was continued for 24 hours either as PCV with tidal volumes of 6 ml/kg and PEEP 3 cmH2O above the lower inflection point of the pressure-volume curve or as HFOV (≥ 12 Hz) with a mean tracheal airway pressure 3 cmH2O above the lower inflection point combined with arteriovenous ECLA (HFOV+ECLA). Fluids and norepinephrine stabilized the circulation. The indocyanine green plasma disappearance rate, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, glutamate dehydrogenase, lactate dehydrogenase and creatine kinase were determined repeatedly. Finally, liver neutrophils were counted and liver cell apoptosis was assessed by terminal deoxynucleotidyl transferase nick end labeling (TUNEL). RESULTS: Aspartate aminotransferase increased in the PCV group about three-fold and in the HFOV+ECLA group five-fold (p<0.001). Correspondingly, creatine kinase increased about two-fold and four-fold, respectively (p<0.001). Lactate dehydrogenase was increased in the HFOV+ECLA group (p<0.028). The number of neutrophils infiltrating the liver tissue and the apoptotic index were low. CONCLUSIONS: High airway pressure PCV and HFOV with ECLA in the treatment of lavage-induced lung injury in pigs did not cause liver dysfunction or damage. The detected elevation of enzymes might be of extrahepatic origin.

Ultrasound use in non-cardiac surgery.

Ultrasound is used in anaesthesia for diagnostic and interventional reasons. This article gives the anaesthesiolgoist an overview about the relevant indications for ultrasound in non-cardiac surgical patients. Other chapters will focus in more detail on different aspects of ultrasound use in non-cardiac anaesthesia. Echocardiography is a monitoring tool for cardiac structures and function. In the anaesthetized patient the transoesophageal approach is preferred due to the unrestricted ultrasound view to the heart. Its use for non-cardiac surgery is discussed. The use of transcutaneous ultrasound in anaesthesia is mainly interventional: The puncture rate for vascular access e.g. central venous catheterization is higher and the procedure can be performed safer under continuous sonographic guidance. Nerve blockade under direct visualisation of target and accompanying structures has amplified the regional anaesthetic methods. The major nerve blocks are described and discussed.

Comparison of arterial and central venous cannulations using ultrasound guidance in pigs.

OBJECTIVE: To evaluate the feasibility of ultrasound guided vascular access in pigs by comparing central venous and arterial cannulation techniques. ANIMALS: Twenty-two healthy female Pietrain pigs, 14-18 weeks old and weighing 51.1 +/- 4.3 kg (mean +/- SD). STUDY DESIGN: Comparative animal trial. MATERIALS AND METHODS: After induction of general anaesthesia, cannulation of the external jugular vein and internal carotid artery was attempted using real-time ultrasound guidance. The quality of the ultrasound picture was assessed on an analogue scale from 1 (excellent) to 5 (insufficient). Vessel size, cannulation success rate, number of puncture attempts and time from first puncture attempt until insertion of the Seldinger wire were recorded. RESULTS: Cannulation was successful in all but one animal in which a cut-down technique was performed. The arteries were significantly smaller than the veins (p < 0.001) resulting in a significantly prolonged cannulation time (p = 0.032) for insertion of arterial catheters without differences in success rate. In 89% of attempted cannulations, the Seldinger wire was inserted within 5 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: In anaesthetized pigs undergoing instrumentation for biomedical research, ultrasound-guided vascular access is a simple and rapid alternative to surgical cut-down. In veterinary anaesthesia, the technique might be useful in sedated or anesthetized pigs in which arterial or central venous access is required.

Combination of arteriovenous extracorporeal lung assist and high-frequency oscillatory ventilation in a porcine model of lavage-induced acute lung injury: a randomized controlled trial.

BACKGROUND: To compare the combined effects of arteriovenous extracorporeal lung assist (AV-ECLA) and high-frequency oscillatory ventilation (HFOV) on pulmonary gas exchange, hemodynamics, and respiratory parameters in a lavage-induced porcine lung injury model. METHODS: A prospective, randomized animal study. Saline lung lavage was performed in 33 healthy female pigs, weighing 52 +/- 4.1 kg (mean +/- SD), until the Pao2 decreased to 53 +/- 8 mm Hg. After a stabilization period of 60 minutes, the animals were randomly assigned to four groups: group 1, pressure-controlled ventilation (PCV) with a tidal volume of 6 mL/kg; group 2, PCV with a tidal volume of 6 mL/kg and AV-ECLA; group 3, HFOV; group 4, HFOV and AV-ECLA. In groups 2 and 4, the femoral artery and vein were cannulated and a low-resistance membrane lung was interposed. After isolated evaluation of AV-ECLA, the mean airway pressure was increased by 3 cm H2O from 16 to 34 cm H2O every 20 minutes, accompanied by blood gas analyses and measurements of respiratory and hemodynamic variables. RESULTS: Only in AV-ECLA-treated animals was normocapnia achieved. No significant increase of Pao2 attributable to AV-ECLA alone was detected. Mean airway pressure augmentation resulted in a significant increase in Pao2 in all groups. Peak inspiratory pressure was significantly lower in HFOV-treated animals. CONCLUSIONS: The combination of AV-ECLA and HFOV resulted in normocapnia and comparable Pao2, although a smaller ventilator pressure amplitude was applied. Long-term animal studies are needed to assess whether this approach results in further lung protection.

Liver dysfunction after lung recruitment manoeuvres during pressure-controlled ventilation in experimental acute respiratory distress.

INTRODUCTION: Consequences of lung recruitment with prolonged high positive end-expiratory pressure (PEEP) ventilation for liver function are unclear. We therefore investigated liver dysfunction during two different ventilation treatment regimens of experimental acute respiratory distress syndrome. METHODS: Sixteen anaesthetised juvenile pietrain pigs were ventilated in the pressure-controlled mode (PCV) with an inspiratory fraction of oxygen (FiO2) of 1.0, a respiratory frequency of 30 per minute, a tidal volume of 6 ml/kg, and a PEEP of 5 cm H2O. After lung injury was induced by repeated pulmonary lavage with normal saline, animals were randomly assigned into two groups (n = 8 each) for a 24-hour trial: PCV (unchanged ventilation) and PCV with recruitment (PCV+R) (starting with a sustained inflation of 50 cm H2O for 1 minute, the ventilation was continued while increasing PEEP in increments of 3 cm H2O every 15 minutes as long as arterial oxygen tension [PaO2] improved). After recruitment, FiO2 was reduced to 0.4 and the PEEP was lowered every 15 minutes until PaO2 decreased to 12.0 to 14.7 kPa (90 to 110 torr). Serum levels of hyaluronic acid (HA), routine liver serum markers, and plasma disappearance rate of indocyanine green (ICG) were tested before and after lung injury, and 6 and 18 hours after randomisation. Liver serum markers were also tested at 24 hours. Paraffin sections of liver tissue stained by haematoxylin and eosin were made after euthanisation. RESULTS: The PCV+R group exhibited more polymorphonuclear neutrophils and lymphocytes in the liver sinusoids: median score (interquartile range) of 1.5 (1.4 to 1.5) compared to 0.9 (0.7 to 1.1) (p = 0.01). Elevation of bilirubin, aspartate aminotransferase, and lactate dehydrogenase was more prominent in the PCV+R group. Plasma disappearance rate of ICG indicated no liver dysfunction. HA levels in the PCV+R group gradually increased and were significantly higher (p < 0.001) at 6 and 18 hours with 59 (57 to 64) and 75 (66 to 84) ng/ml, respectively, than in the PCV group with 34 (32 to 48) and 41 (38 to 42) ng/ml, respectively. CONCLUSION: The PCV+R group showed a more prominent inflammatory reaction in their liver sinusoids accompanied by increased serum levels of liver enzymes and HA. Therefore, recruitment with higher PEEP levels for treatment of respiratory failure might lead to liver dysfunction.

Sustained inflation and incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation in a large porcine model of acute respiratory distress syndrome.

BACKGROUND: To compare the effect of a sustained inflation followed by an incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation on oxygenation and hemodynamics in a large porcine model of early acute respiratory distress syndrome. METHODS: Severe lung injury (Ali) was induced in 18 healthy pigs (55.3 +/- 3.9 kg, mean +/- SD) by repeated saline lung lavage until PaO2 decreased to less than 60 mmHg. After a stabilisation period of 60 minutes, the animals were randomly assigned to two groups: Group 1 (Pressure controlled ventilation; PCV): FIO2 = 1.0, PEEP = 5 cmH2O, V(T) = 6 ml/kg, respiratory rate = 30/min, I:E = 1:1; group 2 (High-frequency oscillatory ventilation; HFOV): FIO2 = 1.0, Bias flow = 30 l/min, Amplitude = 60 cmH2O, Frequency = 6 Hz, I:E = 1:1. A sustained inflation (SI; 50 cmH2O for 60s) followed by an incremental mean airway pressure (mPaw) trial (steps of 3 cmH2O every 15 minutes) were performed in both groups until PaO2 no longer increased. This was regarded as full lung inflation. The mPaw was decreased by 3 cmH2O and the animals reached the end of the study protocol. Gas exchange and hemodynamic data were collected at each step. RESULTS: The SI led to a significant improvement of the PaO2/FiO2-Index (HFOV: 200 +/- 100 vs. PCV: 58 +/- 15 and T(Ali): 57 +/- 12; p < 0.001) and PaCO2-reduction (HFOV: 42 +/- 5 vs. PCV: 62 +/- 13 and T(Ali): 55 +/- 9; p < 0.001) during HFOV compared to lung injury and PCV. Augmentation of mPaw improved gas exchange and pulmonary shunt fraction in both groups, but at a significant lower mPaw in the HFOV treated animals. Cardiac output was continuously deteriorating during the recruitment manoeuvre in both study groups (HFOV: T(Ali): 6.1 +/- 1 vs. T(75): 3.4 +/- 0.4; PCV: T(Ali): 6.7 +/- 2.4 vs. T(75): 4 +/- 0.5; p < 0.001). CONCLUSION: A sustained inflation followed by an incremental mean airway pressure trial in HFOV improved oxygenation at a lower mPaw than during conventional lung protective ventilation. HFOV but not PCV resulted in normocapnia, suggesting that during HFOV there are alternatives to tidal ventilation to achieve CO2-elimination in an "open lung" approach.

High frequency oscillatory ventilation and prone positioning in a porcine model of lavage-induced acute lung injury.

BACKGROUND: This animal study was conducted to assess the combined effects of high frequency oscillatory ventilation (HFOV) and prone positioning on pulmonary gas exchange and hemodynamics. METHODS: Saline lung lavage was performed in 14 healthy pigs (54 +/- 3.1 kg, mean +/- SD) until the arterial oxygen partial pressure (PaO2) decreased to 55 +/- 7 mmHg. The animals were ventilated in the pressure controlled mode (PCV) with a positive endexpiratory pressure (PEEP) of 5 cmH2O and a tidal volume (VT) of 6 ml/kg body weight. After a stabilisation period of 60 minutes, the animals were randomly assigned to 2 groups. Group 1: HFOV in supine position; group 2: HFOV in prone position. After evaluation of prone positioning in group 2, the mean airway pressure (Pmean) was increased by 3 cmH2O from 16 to 34 cmH2O every 20 minutes in both groups accompanied by measurements of respiratory and hemodynamic variables. Finally all animals were ventilated supine with PCV, PEEP = 5 cm H2O, VT = 6 ml/kg. RESULTS: Combination of HFOV with prone positioning improves oxygenation and results in normalisation of cardiac output and considerable reduction of pulmonary shunt fraction at a significant (p < 0.05) lower Pmean than HFOV and supine positioning. CONCLUSION: If ventilator induced lung injury is ameliorated by a lower Pmean, a combined treatment approach using HFOV and prone positioning might result in further lung protection.