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Objectives Current guidelines and expert recommendations stress the need to implement enteral feeds with a higher protein-to-energy ratio to meet protein requirements as recommended while avoiding gastrointestinal side effects and energy overfeeding in ICU patients. Materials and methods Prospective tolerability study in 18 critically ill patients with a high protein formula (high protein-to-energy (HP:E) formula = Fresubin® Intensive; HPG) compared to a contemporary matched conventional therapy group (CTG). The primary outcome was GI intolerance defined as ≥300 ml daily gastric residual volume (GRV), vomiting, or diarrhea on days 1 and 2. Secondary outcomes were the percentage of patients reaching their protein target on day 4 and overall protein intake. Results Groups were comparable regarding demographic characteristics, disease severity, organ failures, mechanical ventilation, and NUTRIC score at baseline. Eighteen patients completed the 4-day feeding period. The number of events of GRV of ≥300 ml/day was equal in both groups (33.3%). The incidence of diarrhea and vomiting was low in the HPG (two patients concerned). EN did not need to be discontinued due to intolerance in any group. Seventy-two percent of patients reached protein targets ≥1.3 g/kgBW/d within 4 days after initiation of enteral feeding, which was superior to the CTG (33%). Post-hoc testing showed group differences of protein intake between HPG and CTG were significant at t = 72 h and t = 96 h. Energy targets were met in both groups. Conclusion The HP:E formula containing 33% whey protein hydrolysate is well tolerated in this tolerability study. Due to the HP:E ratio protein targets can be reached faster. Larger randomized trials are needed to confirm preliminary results. Trial registration ClinicalTrials.gov Identifier: NCT02678325. Registered 2 May 2016.

Bothrops venezuelensis is a venomous snake of the Viperidae family. It is associated with a high snakebite-related morbidity and mortality in Venezuela, although clinical case descriptions are scarce. Bites by other Bothrops sp. can result in coagulopathy and acute kidney injury. We describe a bite by a captive juvenile B. venezuelensis that caused local swelling, severe pain, endothelial damage, excessive fibrinolysis (INR >12, aPTT 136s, fibrinogen 0.3g/l) and incoagulable blood within 1.5 hours after the bite. The patient was treated with prothrombin complex factors concentrate, fibrinogen and antivenom (Antivipmyn®, Instituto Bioclon, Mexico) 4.5 h after the bite, which improved coagulation parameters progressively. Subsequently signs of compensated disseminated intravascular coagulation manifested and the patient received fresh frozen plasma and erythrocyte concentrate. The patient developed acute kidney injury with macroscopic hematuria. Fluid overload resulted in pulmonary edema requiring intermittent ventilation and diuretic treatment with furosemide. He was discharged with moderately elevated creatinine 16 days after hospitalization. Creatinine level normalized within another week. This case displays the life-threatening toxicity even after juvenile B. venezuelensis bites and the comparability to bites by other Bothrops sp.

Objective:To determine whether colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) predicts the risk for subsequent infection and impacts carbapenem-consumption and outcome in intensive care unit (ICU) patients.Design:Prospective cohort study.Setting:The 2 ICUs in the University Hospital Basel in Switzerland.Patients:All patients admitted to the 2 ICUs providing mechanical ventilation and an expected ICU stay >48 hours.Methods:Patients were routinely screened for ESBL-PE carriage by rectal swab on admission. Competing risk regression analyses were applied to calculate hazard ratios (HRs) for infection with ESBL-PE and mortality. Length of hospital stay, length of ICU stay, and duration of carbapenem exposure were compared using the Mann-Whitney U test.Results:Among 302 patients, 24 (8.0%) were colonized with ESBL-PE on ICU admission. Infections with ESBL-PE occurred in 4 patients, of whom 3 (75%) were identified as ESBL-PE colonized on admission. ESBL-PE colonization on admission was associated with subsequent ESBL-PE infection (hazard ratio [HR], 25.52; 95% confidence interval [CI], 2.40–271.41; P = .007) and exposure to carbapenems (HR, 2.42; 95% CI, 1.01–5.79; P = .047), whereas duration of carbapenem exposure did not differ in relation to ESBL-PE colonization (median, 7 days [IQR, 3–8 days] vs median, 6 days [IQR 3–9 days]; P = 0.983). Patients colonized with ESBL-PE were not at increased risk for death overall (HR, 1.00; 95% CI, 0.44–2.30; P = .993) or death attributable to infection (HR, 1.20; 95% CI, 0.28–5.11; P = .808).Conclusions:Screening strategies for detection of ESBL-PE colonization on ICU admission may allow the identification of patients at highest risk for ESBL-PE infection and the correct allocation of empiric carbapenem treatment.

Background The pathophysiology of pulmonary edema is generally considered to result from elevated pulmonary capillary hydrostatic pressure due to increased left atrial pressure in consequence of a failing left ventricle. Case presentation We present a case of pulmonary edema secondary to severe hypalbuminemia under excessive respiratory drive in a 29-year-old Caucasian woman in respiratory distress with detected bilateral central pulmonary embolism. Conclusion In conjunction with severe hypalbuminemia, even the negative intrathoracic pressure swings of respiratory distress may cause pulmonary edema. Detrimental consequences of non-invasive ventilation due to uncontrolled tidal volume and pressure swings need to be considered when treating patients in hypoxemic respiratory failure with low serum albumin.

Introduction: Repeated diaphragm compound muscle action potential (CMAP) recordings may help to understand the pathophysiology of respiratory muscle weakness. Neurally adjusted ventilator assist (NAVA) uses esophageal EMG electrodes to drive the ventilator. We evaluated the feasibility of CMAP recordings using these electrodes and established normal values. Methods: Bilateral cervical phrenic nerve electrical stimulation was performed in 15 healthy volunteers. CMAP recordings with esophageal NAVA electrodes were compared with surface electrode recordings during inspiratory and expiratory pause. Results: Compared with surface recordings, esophageal CMAP amplitudes were higher with increased latencies. Differences between the 2 techniques were most prominent in inspiration. For both recording techniques, amplitudes were higher, and latencies were longer during inspiration. Latencies were also longer when measured on the left side. Conclusions: Diaphragm CMAPs can be measured using the commercially available esophageal NAVA probe. This may facilitate repeated diaphragm CMAP studies in mechanically ventilated patients. Muscle Nerve 51: 598–600, 2015

Auch wenn die Milz nicht ein lebensnotwendiges Organ ist, hat sie wichtige Funktionen wie z. B. Immunabwehr, Blutfiltration, Speicherfunktion und bei Bedarf Blutbildung. Für die Immunabwehr ist die sogenannte weiße Pulpa mit T-Lymphozyten in periarteriolären Lymphozytenscheiden und B-Lymphozyten in Lymphfollikeln und der sogenannten Marginalzone verantwortlich, welche in einem komplexen Zusammenspiel Antigene und Erreger im Blutstrom aufspüren und eliminieren. Bei fehlender Milz besteht die Gefahr einer fulminanten Sepsis mit bekapselten Erregern. Die rote Pulpa ist der Bereich, in dem gealterte und defekte Erythrozyten herausfiltriert und durch Makrophagen phagozytiert werden, unter Wiederverwendung des Hämoglobin-Eisens. Deshalb ist die Milz nicht irgendein „Spleen“ der Natur, sondern ein hochentwickeltes Organ für die Instandhaltung der Blutzirkulation.

Repeated diaphragm compound muscle action potential (CMAP) recordings may help to understand the pathophysiology of respiratory muscle weakness. Neurally adjusted ventilator assist (NAVA) uses esophageal EMG electrodes to drive the ventilator. We evaluated the feasibility of CMAP recordings using these electrodes and established normal values.Bilateral cervical phrenic nerve electrical stimulation was performed in 15 healthy volunteers. CMAP recordings with esophageal NAVA electrodes were compared with surface electrode recordings during inspiratory and expiratory pause.Compared with surface recordings, esophageal CMAP amplitudes were higher with increased latencies. Differences between the 2 techniques were most prominent in inspiration. For both recording techniques, amplitudes were higher, and latencies were longer during inspiration. Latencies were also longer when measured on the left side.Diaphragm CMAPs can be measured using the commercially available esophageal NAVA probe. This may facilitate repeated diaphragm CMAP studies in mechanically ventilated patients.

Although the spleen is not essential for survival, it has important functions such as immune defence, blood filtration, retention and on demand extramedullary hematopoiesis. The white pulp with its T-lymphocytes in perarteriolar lymphoid sheaths and B-lymphocytes in lymphoid follicules is responsible for the detection and removal of circulating pathogens. After splenectomy, this immune defence is missing, which may lead to overwhelming post- splenectomy sepsis by encapsulated bacteria, which has a high mortality rate. In the red pulp, the blood is filtered through narrow slits in the sinusoidal endothelium, which abnormal and senescent erythrocytes can not pass and are eliminated by macrophages. The spleen is, therefore, not a "spleen" of nature, but a sophisticated organ.

Diaphragmatic electrical activity (EA(di)), reflecting respiratory drive, and its feedback control might be impaired in critical illness-associated polyneuromyopathy (CIPM). We aimed to evaluate whether titration and prolonged application of neurally adjusted ventilatory assist (NAVA), which delivers pressure (P (aw)) in proportion to EA(di), is feasible in CIPM patients.Peripheral and phrenic nerve electrophysiology studies were performed in 15 patients with clinically suspected CIPM and in 14 healthy volunteers. In patients, an adequate NAVA level (NAVAal) was titrated daily and was implemented for a maximum of 72 h. Changes in tidal volume (V (t)) generation per unit of EA(di) (V (t)/EA(di)) were assessed daily during standardized tests of neuro-ventilatory efficiency (NVET).In patients (median [range], 66 [44-80] years), peripheral electrophysiology studies confirmed CIPM. Phrenic nerve latency (PNL) was prolonged and diaphragm compound muscle action potential (CMAP) was reduced compared with healthy volunteers (p 0.05 for both). NAVAal could be titrated in all but two patients. During implementation of NAVAal for 61 (37-64) h, the EA(di) amplitude was 9.0 (4.4-15.2) μV, and the V (t) was 6.5 (3.7-14.3) ml/kg predicted body weight. V (t), respiratory rate, EA(di), PaCO(2), and hemodynamic parameters remained unchanged, while PaO(2)/FiO(2) increased from 238 (121-337) to 282 (150-440) mmHg (p = 0.007) during NAVAal. V (t)/EA(di) changed by -10 (-46; +31)% during the first NVET and by -0.1 (-26; +77)% during the last NVET (p = 0.048).In most patients with CIPM, EA(di) and its feedback control are sufficiently preserved to titrate and implement NAVA for up to 3 days. Whether monitoring neuro-ventilatory efficiency helps inform the weaning process warrants further evaluation.

To test the hypothesis that muscle fibers are depolarized in patients with critical illness myopathy by measuring velocity recovery cycles (VRCs) of muscle action potentials.VRCs were recorded from brachioradialis muscle by direct muscle stimulation in 10 patients in intensive care with evidence of critical illness myopathy (CIM). Two sets of recordings were made, mean 3.9 d apart, and compared with those from 10 age-matched controls.Muscle supernormality was reduced in the patients by 50% compared with controls (P0.002) and relative refractory period was increased by 59% (P0.01). Supernormality was correlated with plasma potassium levels (R=-0.753, P0.001), and the slope of this relationship was much steeper than previously reported for non-critically ill patients with renal failure (P0.01).The abnormal excitability properties indicate that the muscle fibers in CIM were depolarized, and/or that sodium channel inactivation was increased. The heightened sensitivity to potassium is consistent with the hypothesis that an endotoxin reduces sodium channel availability in depolarized muscle fibers.VRCs provide a practicable means to monitor muscle membrane changes in intensive care and to investigate the pathogenesis of CIM.

Background Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA. Methods In 20 adult patients, adequate assist (NAVAal) was first identified based on Paw and tidal volume (V t ) responses to systematic increases in NAVA level while using preset PEEP (PEEPbl). Thereafter, using NAVAal, PEEP was increased to 20 cm water (H 2 O) (PEEPhigh) and then lowered stepwise to 1 cm H 2 O (PEEP1). EAdi, Paw, and V t were recorded. Results Median NAVAal was 2.7 (interquartile range, 2.3–3.5) cm H 2 O/μV and was similar to NAVAal identified post hoc by 17 independent physicians (2.5 [2.0–3.4] cm H 2 O/μV; P = NS). Reducing PEEPhigh to PEEP1 increased inspiratory EAdi by 34% (2–67; P = .046) and was associated with an increase in mean Paw above PEEP from 8.5 (6.7–11.4) cm H 2 O to 12.2 (8.8–16.7) cm H 2 O ( P = .008), whereas V t and respiratory rate remained unchanged. The response pattern in V t /EAdi, indicating changes in neuroventilatory efficiency, differed among patients. Tidal breathing occurred at the lowest EAdi cost in seven patients with PEEP1 or half PEEPbl, in six patients with PEEPbl, and in seven patients with PEEPhigh. Conclusions During NAVAal, increasing PEEP reduces respiratory drive. Patients adapt their neuroventilatory efficiency such that the individual ventilatory pattern is preserved over a wide range of PEEP levels. Monitoring V t /EAdi during PEEP changes allows identification of a PEEP level at which tidal breathing occurs at minimal EAdi cost. Trial registration clinicaltrials.gov ; Identifier: NCT00529347

Introduction Sepsis-induced myopathy and critical illness myopathy (CIM) are possible causes of muscle weakness in intensive care patients. They have been attributed to muscle membrane dysfunction. The aim of this study was to investigate membrane properties in the early stage of experimental sepsis by evaluating muscle excitability. Methods In total, 20 anaesthetized and mechanically ventilated pigs were randomized to either faecal peritonitis (n = 10) or to non-septic controls (n = 10). Resuscitation with fluids and vasoactive drugs was started 3 hours after peritonitis induction. Muscle membrane properties were investigated by measuring muscle velocity recovery cycles before induction of peritonitis as well as 6, 18 and 27 hours thereafter. Muscle relative refractory period (MRRP) and early supernormality (ESN) were assessed. Results Peritonitis lasting 27 hours was associated with an increase of MRRP by 28% from 2.38 ± 0.18 ms (mean ± SD) to 3.47 ± 1.79 ms (P

Muscle weakness and atrophy due to critical illness polyneuromyopathy (CIPM) is common in long-stay intensive care patients. Recent nerve excitability studies suggest that the recovery cycle after a single supramaximal stimulus provides useful information about axonal membrane potential and ion channel function in neuropathies. We previously found that critical illness polyneuropathy is associated with nerve depolarization, and that this depolarization is strongly correlated with serum potassium in patients with renal failure [1]. We have adapted this method to human muscle fibres, by measuring the changes in conduction velocity of muscle fibres [2]. The muscle relative refractory period (RRP) increases and supernormality (SN) decreases in ischaemia, suggesting that these measures may be indicators of membrane potential also in the muscle [2]. The aim of this study was to evaluate muscle RRP and SN in patients with CIPM.

Neurally adjusted ventilatory assistance (NAVA) delivers pressure (Paw) in proportion to the electrical activity of the diaphragm (EAdi). It is not known whether EAdi adequately reflects the respiratory drive in patients with critical illness polyneuromyopathy (CIPM) and would be sufficient to deliver assistance using NAVA.