Anticipation of distress after discontinuation of mechanical ventilation in the ICU at the end of life

Background: A considerable number of patients admitted to the intensive care unit (ICU) die following withdrawal of mechanical ventilation. After discontinuation of ventilation without proper preparation, excessive respiratory secretion is common, resulting in a 'death rattle'. Post-extubation stridor can give rise to the relatives' perception that the patient is choking and suffering. Existing protocols lack adequate anticipatory preparation to respond to all distressing symptoms. Methods: We analyzed existing treatment strategies in distressing symptoms after discontinuation of mechanical ventilation. Conclusion: The actual period of discontinuation of mechanical ventilation can be very short, but thoughtful anticipation of distressing symptoms takes time. There is an ethical responsibility to anticipate and treat (iatrogenic) symptoms such as pain, dyspnea-associated respiratory distress, anxiety, delirium, post-extubation stridor, and excessive broncho-pulmonary secretions. This makes withdrawal of mechanical ventilation in ICU patients a thoughtful process, taking palliative actions instead of fast terminal actions. We developed a flowchart covering all possible distressi

The usefulness of a new indirect calorimeter in critically ill adult patients

Background &amp; aims: The use of indirect calorimetry to determine energy requirements is highly recommended in critically ill patients. To facilitate this a new and easy to use calorimeter (Q-NRG+, Cosmed) was developed. The primary aim of our study was to describe the usefulness of this calorimeter and, secondarily, to investigate the agreement between measured and predicted energy needs in a large cohort of critically ill adult patients. Methods: A prospective observational study was conducted among adult mechanically ventilated patients with COVID-19. Indirect calorimetry (Q-NRG+) to measure resting energy expenditure (mREE) was performed in the first week after admission and, wherever possible, repeated weekly. Reasons for not performing indirect calorimetry were reported. Parameters of indirect calorimetry and patient's conditions during the measurements were collected. Measurements were defined as valid if less than 10% overall variation in VO2 and VCO2 and respiratory quotient ranges between 0.67 and 1.1 were observed. mREE was compared with predictive REE (pREE) using standard formulas to explore hypo (&lt;90%)-and hypermetabolism. (&gt;110%). Bland-Altman method and two-way mixed intraclass correlation coefficients (ICC) (single measures) were used to assess the agreement between mREE and pREE. Results: Indirect calorimetric measurements were performed in 180 of the 432 admitted patients (42%). Of the 276 performed measurements 85% were valid, and of these 90% were used to tailor nutritional therapy. Most patients were male (71%), median age was 62 years [IQR 52; 70]. Logistical issues (absence of measuring staff, no device, no stock of disposables, MRSA isolation) and clinical issues (e.g Fio2&gt;70%, detubated but still in ICU) were the main reasons for not performing indirect calorimetry. The majority of the REE-measurements indicated either hypo- or hypermetabolism (57% week 1 and 56% week 2). The correlation between mREE and pREE was very moderate (ICC = 0.527). Conclusions: Although indirect calorimetry was performed in less than half of the patients, it proved to be of value to guide nutritional therapy. We conclude that the technique is easily applicable and expect that its impact can be significantly increased with the resolution of logistical and organizational issues.</p

Nutritional intake and gastro-intestinal symptoms in critically ill COVID-19 patients

BACKGROUND & AIMS: Critically ill COVID-19 patients seem hypermetabolic and difficult to feed enterally, due to gastro-intestinal (GI) symptoms such as high gastric residual volumes (GRV) and diarrhea. Our aim was to describe the association of nutritional intake and GI symptoms during first 14 days of ICU admission. METHODS: Observational study including critically ill adult COVID-19 patients. Data on nutritional intake (enteral nutrition (EN) or parenteral nutrition) and GI symptoms were collected during 14 days after ICU admission. Target energy and protein feeding goals were calculated conform ESPEN guidelines. GI symptoms included GRV (ml/d), vomiting, abdominal distension and faeces (ml/d). High GRV’s were classified as ≥2 times ≥150 ml/d and diarrhea as Bristol stool chart ≥6. GI symptoms were defined as mild if at least one symptom occurred and as moderate when ≥2 symptoms occurred. Acute gastrointestinal injury (AGI) grades of III were classified as GI dysfunction and grades of IV were considered as GI failure with severe impact on distant organs. Linear mixed model analysis was performed to explore the development of nutritional intake and GI symptoms over time at day (D) 0,4,10 & 14. RESULTS: 150 patients were included (75% male; median age 64 years [IQR 54-70]). BMI upon admission was 28 kg/m(2) [IQR 25-33], of which 43% obese (BMI>30 kg/m(2)). Most patients received EN during admission (98% D4; 96% D10-14). Mean energy goals increased from 87% at D4 to 93% D10-14 and protein goals (g/kg) were increasingly achieved during admission (84% D4; 93% D10-14). Presence of moderate GI symptoms decreased (10% DO; 6% D4-10; 5% D14), reversely mild GI symptoms increased. Occurrence of GI dysfunction fluctuated (1% D0; 18% D4; 12% D10; 8% D14) and none of patients developed grade IV GI failure. Development of high GRV fluctuated (5% D0; 23% D4; 14% D10; 8% D14) and occurrence of diarrhea slightly increased during admission (5% D0; 22% D4; 25% D10; 27% D14). Linear mixed models showed only an association between AGI grades III and lower protein intake at day 10 (p=0.020). CONCLUSION: Occurrence of GI symptoms was limited and seems no major barrier for EN in our group of critically COVID-19 patients. Nutritional intake was just below requirements during the first 14 days of ICU admission. The effect on nutritional status remains to be studied

Association between fat-free mass and survival in critically ill patients with COVID-19:A prospective cohort study

Background: Most critically ill patients with COVID-19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. Methods: This prospective cohort study included adult critically ill patients with COVID-19. Body composition (fat-free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30–90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. Results: We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m 2, 54% had obesity (BMI &gt; 30 kg/m 2). Median weight change during ICU stay was −3 kg: +3 kg FM and −6 kg FFM (−4 kg SMM). Body composition changed significantly (P &lt; 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72–0.96; P = 0.015). Patients with optimal protein intake (&gt;80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received &lt;80%. Conclusion: FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility.</p

High plasma arginine concentrations in critically ill patients suffering from hepatic failure

Objective: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothesized high arginine plasma concentrations in critically ill patients suffering from hepatic failure. Design: We prospectively collected blood samples from a cross-section of intensive care unit patients. Setting: Surgical intensive care unit of a Dutch university medical center. Subjects: A total of 52 critically ill patients with clinical evidence of dysfunction of more than two organs were recruited. Measurements: Plasma arginine concentrations were determined by HPLC. We identified correlations of arginine concentrations with organ failure scores and laboratory variables by univariate and multiple regression analyses. Results: High plasma arginine concentrations were found in critically ill patients developing organ failure. Patients who were in the highest quartile of plasma arginine concentrations had significantly lower fibrinogen concentrations, higher lactic acid concentrations, and longer prothrombin time. Stepwise multiple regression analysis showed that concentrations of arginine were independently associated with the presence of hepatic failure (P = 0.03) and renal failure (P = 0.048). In addition, lactic acid proved to be an independent determinant of plasma arginine concentration (P = 0.014). Conclusions: Critically ill patients who suffer from hepatic failure have elevated plasma arginine concentrations. Additional arginine in the treatment of these patients can be harmful, and therefore should not be used as a standard nutritional regimen until further evaluation

Successful Reduction of Creatine Kinase and Myoglobin Levels in Severe Rhabdomyolysis Using Extracorporeal Blood Purification (CytoSorb®)

Rhabdomyolysis, if severe, can lead to acute kidney injury (AKI). Myoglobin is an iron and oxygen-binding protein that is freely filtered by the glomerulus. Precipitation of myoglobin in the nephrons' distal parts is responsible for tubular damage with AKI as a consequence. Extracorporeal clearance of myoglobin is conventionally attempted by the use of continuous renal replacement therapy (CRRT) with high cut-off dialysis membranes to limit the extent of the damage. We describe a case of a 56-year-old man with traumatic crush injury and a persistent source of muscle ischaemia unresponsive to high dose CRRT with EMiC-2 filter. Due to therapy failure, he was subsequently treated with the addition of a haemoadsorber (CytoSorb®) to the circuit. This reduced myoglobin and creatine kinase

Association between fat-free mass and survival in critically ill patients with COVID-19:A prospective cohort study

Background: Most critically ill patients with COVID-19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. Methods: This prospective cohort study included adult critically ill patients with COVID-19. Body composition (fat-free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30–90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. Results: We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m 2, 54% had obesity (BMI &gt; 30 kg/m 2). Median weight change during ICU stay was −3 kg: +3 kg FM and −6 kg FFM (−4 kg SMM). Body composition changed significantly (P &lt; 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72–0.96; P = 0.015). Patients with optimal protein intake (&gt;80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received &lt;80%. Conclusion: FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility.</p

Intestinal fatty acid binding protein as a marker for intra-abdominal pressure-related complications in patients admitted to the intensive care unit

Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have detrimental effects on all organ systems and are associated with increased morbidity and mortality in critically ill patients admitted to an intensive care unit. Intra-bladder measurement of the intra-abdominal pressure (IAP) is currently the gold standard. However, IAH is not always indicative of intestinal ischemia, which is an early and rapidly developing complication. Sensitive biomarkers for intestinal ischemia are needed to be able to intervene before damage becomes irreversible. Gut wall integrity loss, including epithelial cell disruption and tight junctions breakdown, is an early event in intestinal damage. Intestinal Fatty Acid Binding Protein (I-FABP) is excreted in urine and blood specifically from damaged intestinal epithelial cells. Claudin-3 is a specific protein which is excreted in urine following disruption of intercellular tight junctions. This study aims to investigate if I-FABP and Claudin-3 can be used as a diagnostic tool for identifying patients at risk for IAP-related complications. Methods/Design: In a multicenter, prospective cohort study 200 adult patients admitted to the intensive care unit with at least two risk factors for IAH as defined by the World Society of the Abdominal Compartment Syndrome (WSACS) will b

A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

Background. Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species. Methods. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10. Results. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P < .001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P < .001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P < .001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated. Conclusions. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasi

A jackass and a fish: A case of life-threatening intentional ingestion of a live pet catfish (Corydoras aeneus)

Inspired by Jackass (a tv-show about self-injuring stunts), some friends topped off a drinking party with live fishes from their aquarium. After the goldfishes had gone down smoothly, a bronze catfish was ingested. Unaware of the morphology and anti-predator behaviour of this species, a healthy but intoxicated 28-year-old man got a surprise. The catfish erected and locked the spines of its pectoral fins and got lodged in the hypopharynx. After several hours, he presented himself at the emergency department with dysphonia and dysphagia. The fish had to be removed endoscopically. Intubation and admittance to the intensive care unit was necessary due to laryngeal oedema. Two weeks postoperatively, the patient made a full recovery and donated the fish to the Natural History Museum Rotterdam. The publicity generated by public exhibition of the ‘do-not-swallow-fish’ emphasised the official Jackass warning: ‘.. do not attempt any of the stunts you’re about to see’