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, and 14. RESULTS: One hundred and fifty patients were included [75% male; median age 64 years (IQR 54-70)]. BMI upon admission was 28 kg/m2 (IQR 25-33), of which 43% obese (BMI > 30 kg/m2). 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% D0; 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.

Energy expenditure and feeding practices and tolerance during the acute and late phase of critically ill COVID-19 patients.

BACKGROUND & AIMS: Different metabolic phases can be distinguished in critical illness, which influences nutritional treatment. Achieving optimal nutritional treatment during these phases in critically ill patients is challenging. COVID-19 patients seem particularly difficult to feed due to gastrointestinal problems. Our aim was to describe measured resting energy expenditure (mREE) and feeding practices and tolerance during the acute and late phases of critical illness in COVID-19 patients. METHODS: Observational study including critically ill mechanically ventilated adult COVID-19 patients. Indirect calorimetry (Q-NRG+, Cosmed) was used to determine mREE during the acute (day 0-7) and late phase (>day 7) of critical illness. Data on nutritional intake, feeding tolerance and urinary nitrogen loss were collected simultaneously. A paired sample t-test was performed for mREE in both phases. RESULTS: We enrolled 21 patients with a median age of 59 years [44-66], 67% male and median BMI of 31.5 kg/m2 [25.7-37.8]. Patients were predominantly fed with EN in both phases. No significant difference in mREE was observed between phases (p = 0.529). Sixty-five percent of the patients were hypermetabolic in both phases. Median delivery of energy as percentage of mREE was higher in the late phase (94%) compared to the acute phase (70%) (p = 0.001). Urinary nitrogen losses were significant higher in the late phase (p = 0.003). CONCLUSION: In both the acute and late phase, the majority of the patients were hypermetabolic and fed enterally. In the acute phase patients were fed hypocaloric whereas in the late phase this was almost normocaloric, conform ESPEN guidelines. No significant difference in mREE was observed between phases. Hypermetabolism in both phases in conjunction with an increasing loss of urinary nitrogen may indicate that COVID-19 patients remain in a prolonged acute, catabolic phase.

In-hospital cardiovascular events after liver transplantation: predictors and long-term outcome.

INTRODUCTION: Liver transplantation has emerged as a successful therapy for end-stage liver disease. However, cardiovascular mortality is the leading cause of fatality in the postoperative period. The aim of this study was to reveal the prevalence and identify risk factors of early cardiovascular events (CVEs). METHODS: We performed a retrospective study of all consecutive patients who underwent a primary liver transplantation from 1986 to 2017 (n = 916). We investigated the occurrence of in-hospital CVEs, their predictors, and short- and long-term outcome. RESULTS: The prevalence of CVEs was 11%. The adjusted analysis showed that higher age (OR 1.06, 95% CI 1.03-1.09), higher MELD score (OR 1.04, 95% CI 1.01-1.07 CI) and sinus tachycardia at time of screening (OR 3.12, 95% CI 1.45-6.72) were positive predictors for a CVE. Preoperative propranolol use showed a trend towards a higher risk of CVE (OR 1.66, 95% CI 1.00-2.77, p = 0.051). In a sub-analysis of patients where echocardiography data were available (n = 597), a larger left atrial diameter and a higher E/E' ratio were related to early CVEs. Ten-year survival in 30-day survivors was favourable (68.6%; 56.0% vs. 69.8% in the CVE+ vs. the CVE-group, respectively, p = 0.056). DISCUSSION: In conclusion, besides known risk factors (age and MELD score), sinus tachycardia (related to the presence of acute liver failure and cirrhosis) was an independent predictor for CVE after liver transplantation.

Severe group A streptococcal toxic shock syndrome presenting as primary peritonitis: a case report and brief review of the literature.

Streptococcal toxic shock syndrome (STSS) can be defined as a septic shock syndrome resulting from infection with toxin-producing group A streptococci (GAS). STSS can sporadically present as primary peritonitis in previously healthy persons. Signs of STSS are non-specific and patients generally present with flu-like symptoms and can develop a life-threatening toxic shock syndrome in just a few hours. Diagnosis is mainly by a combination of physical examination, laboratory/culture results, and exclusion of surgical causes by means of imaging modalities and/or surgical exploration. GAS remain penicillin-sensitive and most are clindamycin-sensitive. Prompt supportive treatment, possibly together with high-dose intravenous immunoglobulins, is crucial.

The effect of rosiglitazone on asymmetric dimethylarginine (ADMA) in critically ill patients.

Asymmetric dimethylarginine (ADMA) plays a crucial role in the arginine-nitric oxide pathway. Critically ill patients have elevated levels of ADMA which proved to be a strong and independent risk factor for ICU mortality. The aim of this study was to investigate the effect of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone on ADMA plasma levels in critically ill patients. In a randomized controlled pilot study, ADMA, arginine and symmetric dimethylarginine (SDMA) were measured in 21 critically ill patients on the intensive care unit (ICU). Twelve patients received 4mg rosiglitazone once a day for a maximum of 6 weeks or until discharge or death. Nine patients served as control patients. In addition, total sequential organ failure assessment (SOFA score), kidney function and liver function were determined. Compared to the ADMA levels of healthy individuals as specified in earlier studies, ADMA plasma levels of critically ill patients were significantly higher (0.42+/-0.06 versus 0.73+/-0.2micromol/L, respectively; p<0.001). Both ADMA (B=3.5; 95% CI: 0.5-6.5; p=0.023) and SDMA (B=1.7; 95% CI: 0.7-2.7; p=0.001) were independently related to SOFA scores. Overall, rosiglitazone treatment had no effect on ADMA levels, which only significantly differed between the rosiglitazone and control groups at day 7 (p=0.028). The SOFA score in the rosiglitazone group was lower compared to the control group but the difference was only statistically significant at day 10 (p=0.01). In conclusion, in critically ill patients plasma ADMA levels were elevated and associated with the extent of multiple organ failure, but no significant ADMA-lowering effect of the PPAR-gamma agonist rosiglitazone was observed.

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 distressing symptoms that can occur after withdrawal of mechanical ventilation and extubation. We recommend a two-phase process. Six hours before extubation, enteral feeding should be stopped and parenteral fluids reduced, overhydrated patients should be dehydrated with furosemide, administration of sedatives (for distress) and opioids (for pain and/or dyspnea) should be continued or started and methylprednisolone should be given in anticipation of stridor after extubation. Thirty minutes before extubation, Butylscopolamine should be given and methylprednisolone repeated. After this the patient should be extubated to secure a dying process as natural as possible with the lowest burden due to distress.

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.

Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality.

BACKGROUND AND AIMS: Accumulation of asymmetrical dimethylarginine (ADMA) has been linked to endothelial dysfunction, and is an important risk factor for cardiovascular disease. Its elimination from the body is dependent on urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase. This enzyme is highly expressed in the liver, and in rat studies a high net hepatic uptake of asymmetrical dimethylarginine was found. In critically ill patients, we investigated the relation between indicators of renal and hepatic dysfunction and plasma ADMA concentration, and tested the association between ADMA concentration and outcome. METHODS: We prospectively collected blood samples from a cross-section of critically ill patients (n=52) with clinical evidence of dysfunction of more than two organs. We identified correlates of plasma ADMA concentration with laboratory values, organ failures score and outcome by univariate and multiple regression analyses. RESULTS: In critically ill patients, plasma ADMA concentration was independently related to the presence of hepatic failure (b=0.334, 95% CI: 0.207-0.461; P<0.001), and to lactic acid (b=0.395, 95% CI: 0.230-0.560; P<0.001) and bilirubin (b=0.121, 95% CI: 0.031-0.212; P=0.009) concentration as markers of hepatic function. Twenty-one (40%) patients deceased during their ICU stay. In a logistic regression model, plasma ADMA ranked as the first and strongest predictor for outcome, with a 17-fold (95% CI: 3-100) increased risk for ICU death in patients who were in the highest quartile for ADMA. CONCLUSIONS: In critically ill patients, plasma ADMA concentration is a strong and independent risk factor for ICU mortality, and hepatic dysfunction is the most prominent determinant of ADMA concentration in this population.

Gut luminal endotoxin reduces ischemia-reperfusion injury of the small gut in germ-free pigs.

Translocation of luminal bacteria and their products through the intestinal mucosa during ischemia-reperfusion (I/R) may modify I/R injury. To test this hypothesis, 16 germ-free pigs were studied prior to and after clamping the superior mesenteric artery (SMA) and 12 pigs served as controls. Nine pigs in the I/R and 5 in the control group received endotoxin intragastrically, 60 min before baseline. Gut absorption of an inert indicator (polyethyleneglycol [PEG] 3350), gut intraluminal PCO2 (tonometry), and systemic and regional hemodynamic variables were measured up to 4 h after baseline. Gut blood flow was stopped during clamping, some reactive hyperemia occurred up to 30 min after declamping in the I/R groups, independently of prior endotoxin administration. Gut intraluminal-arterial PCO2 gradients were elevated in I/R versus control groups during I and for some time during R, prior endotoxin had no effect. However, in controls without and with luminal endotoxin, PEG urinary excretion, as percentage of the dose administered, was 0.12 +/- 0.12 and 0.17 +/- 0.07, respectively, while it measured 1.82 +/- 0.70 in the I/R group and 0.55 +/- 0.37% in the I/R and endotoxin groups, respectively (P< 0.001). The data suggest that gut luminal endotoxin ameliorates I/R injury of the gut wall in germ-free pigs, without altering changes in gut perfusion adequacy and systemic hemodynamics.

Intraoperative continuous hemofiltration for metabolic management in acute aortoiliac occlusion.

Acute aortoiliac occlusion, or Leriche's syndrome, carries a risk of the development of severe ischemia-reperfusion injury, characterized by electrolyte and acid-base balance disturbances. These injuries are often fatal, because of the rapid deterioration of multiple organ systems. We present a case in which we intraoperatively and postoperatively treated hyperkalemia and metabolic acidosis by high-volume, continuous, veno-venous hemofiltration, which is a recently developed form of continuous renal replacement therapy.

Lipoid pneumonitis complicating treatment of Hodgkin's disease.

The development of lipoid pneumonitis (LP) is associated with exposure to mineral, animal or vegetable oils through inhalation or local application. We report here on a 34-year-old patient with lipoid pneumonitis complicating the treatment of Hodgkin's disease. A review of the relevant literature on the pathophysiology and diagnosis of LP is provided with emphasis on possible mechanisms of development of LP in Hodgkin's disease.

Tumour lysis syndrome in haematological malignancies.

The tumour lysis syndrome, a combination of metabolic derangements, is a complication of intensive cytotoxic chemotherapy, especially in rapidly proliferating lymphoid malignancies. During the last three years we have encountered four cases with different forms of haematological neoplasms, all of whom developed tumour lysis, i.e. some degree of hyperuricaemia, hyperkalaemia, hyperphosphataemia or hypocalcaemia, resulting in renal, circulatory and/or respiratory failure. Relevant literature is reviewed.

High volume hemofiltration improves right ventricular function in endotoxin-induced shock in the pig.

This study assessed the influence of continuous high volume hemofiltration on right ventricular function of pigs with endotoxin induced shock. Eighteen anesthetized and ventilated pigs were studied for 240 min after the start of infusion of 0.5 mg/kg endotoxin over 30 min. Right ventricular ejection fraction (RVEF) was measured by rapid response thermodilution technique. After endotoxin infusion, the pigs were randomly divided into 3 groups: group 1 as a control group, receiving endotoxin only, group 2 to observe the effects of zero balance high volume veno-venous hemofiltration with removal of ultrafiltrate at a rate of 6000 ml/h, and group 3 to evaluate the effect of the extracorporeal circuit itself on RVEF. The decline of RVEF in group 2 was less than in group 1 (0.04 +/- 0.02 vs 0.21 +/- 0.03 (mean +/- SEM); p less than 0.001). The decline of RVEF in group 3 (0.24 +/- 0.02) was more pronounced than that in group 1 (p less than 0.05). The differences in the course of RVEF between group 1 and group 2 could not be explained by differences in heart rate, preload or afterload. Cardiac output and mean arterial pressure were significantly higher in group 2 than in group 1 (p less than 0.01). It is concluded that in this model, high volume hemofiltration improves RVEF and cardiac performance by removal of vasoactive mediators, responsible for myocardial depression.

Retroperitoneal fibrosis: report of 12 cases and a review of the literature.

Twelve patients with retroperitoneal fibrosis (RPF) over a 10-yr period (1980-1990) are reviewed. The clinical manifestations, radiographic findings as well as treatment and follow-up are discussed and a review of the literature is presented. Nowadays the diagnosis can be established with near-certainty by means of computed tomographic scan (CT). In case of diagnostic problems, CT- or ultrasound guided percutaneous needle biopsy can aid the diagnosis. There is now considerable evidence that RPF can be treated effectively with corticosteroids and should be considered the treatment of choice, surgery being confined to medical failures or those who do not tolerate steroids. Early and frequent CT follow-up may demonstrate the beneficial response to steroids, thereby obviating the need for exploratory or therapeutic surgery. In steroid-resistant cases, when there is no doubt about the initial diagnosis, azathioprine or cyclophosphamide may be used. Long-term follow-up is recommended in all patients.

Albumin abuse in intensive care medicine.

Albumin is a much abused and expensive drug in intensive care units. One of the motivations for its use is the prevention of pulmonary edema by enhancing the colloid osmotic pressure (COP). Fear of pulmonary edema has led to the formation of a magic (arbitrary) albumin value varying from one intensive care unit to another. Many intensive care units start substituting albumin when it is below 25 g/l. The objective of this paper is to look at the rationale of this policy. Our results show that in intensive care patients, with a variety of primary diagnoses, a poor correlation exists between COP and serum albumin concentration (r = 0.56; p less than 0.001). To get an index of the colloid osmotic status of the I. C.-patient measuring albumin concentration is useless and COP should be measured instead. From 19 patients with a COP in the 15.0-20.0 mmHg range (corresponding albumin range: 12.0-25.0 g/l) and from 10 patients with a COP in the 11.6-15.0 mmHg range (corresponding albumin range 10.5-19.2 g/l) none developed pulmonary edema. It is questionable if expensive, scarce albumin is the drug of choice with which to increase COP, for the mean increase (+/- SD) in COP after infusion of 100 grams albumin is 2.2 (+/- 1.5) mmHg (p less than 0.001). Adopting a COP action level of 15 mmHg can lead to considerable savings.