Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).

Esophageal versus surface recording of diaphragm compound muscle action potential.

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.

Early changes of muscle membrane properties in porcine faecal peritonitis.

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 anesthetized 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 <0.01) and a decrease of ESN by 31% from 9.64 ± 2.82% to 6.50 ± 2.64% (P <0.01). ESN reduction was already apparent 6 hours after induction of peritonitis. Values in controls did not show any significant alterations. CONCLUSIONS: Muscle membrane abnormalities consistent with membrane depolarization and/or sodium channel inactivation occurred within 6 hours of peritonitis induction. This indicates that changes that have been described in established sepsis-induced myopathy and/or CIM start early in the course of sepsis. Muscle excitability testing facilitates evaluation of the time course of these changes.

[What is the spleen needed for?]. / Wozu braucht es die Milz?

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.

A new high protein-to-energy enteral formula with a whey protein hydrolysate to achieve protein targets in critically ill patients: a prospective observational tolerability study.

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.

Bite by a juvenile Bothrops venezuelensis (Venezuelan lancehead) resulting in severe envenomation: A case report.

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.

Prolonged respiratory failure due to pulmonary embolism in a young woman: a case report.

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.

ESBL-colonization at ICU admission: impact on subsequent infection, carbapenem-consumption, and outcome.

OBJECTIVE: To determine whether colonization with extended-spectrum ß-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.

Neurally adjusted ventilatory assist in patients with critical illness-associated polyneuromyopathy.

PURPOSE: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Physiologic response to changing positive end-expiratory pressure during neurally adjusted ventilatory assist in sedated, critically ill adults.

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 (Vt) 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 Vt were recorded. RESULTS: Median NAVAal was 2.7 (interquartile range, 2.3-3.5) cm H(2)O/muV and was similar to NAVAal identified post hoc by 17 independent physicians (2.5 [2.0-3.4] cm H(2)O/muV; 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 Vt and respiratory rate remained unchanged. The response pattern in Vt/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 Vt/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.