Background
Multi-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal ...replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO).
Methods
A consensus conference on the spectrum of lung–kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function.
Conclusion
The ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung–kidney interactions to improve care processes and outcomes in critical illness.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on ...severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19.
Methods
Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN).
Results
72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO
2
/FiO
2:
82 (58–114) vs. 117 (83–155);
p
< 0.05). Thus, required more frequently mechanical ventilation (95% vs. 64%;
p
< 0.01), rescue therapies (ECMO) (27% vs. 12%;
p
= 0.106), vasopressor (95% vs. 72%;
p
< 0.05) and renal replacement therapy (86% vs. 30%;
p
< 0.001). Severity of illness was significantly higher (SAPS II: 48 (39–52) vs. 40 (32–45);
p
< 0.01). Patients with SLD and without presented viremic during ICU stay in 68% and 34%, respectively (
p
= 0.002). Occurrence of SLD was independently associated with presence of viremia OR 6.359; 95% CI 1.336–30.253;
p
< 0.05 and severity of illness (SAPS II) OR 1.078; 95% CI 1.004–1.157;
p
< 0.05. Mortality was high in patients with SLD compared to other patients (68% vs. 16%,
p
< 0.001). After adjustment for confounders, SLD was independently associated with mortality HR3.347; 95% CI 1.401–7.999;
p
< 0.01.
Conclusion
One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.
Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet ...pass undetected by standard laboratory tests.
In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid CDCA and taurodeoxycholic acid TDCA) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87).
Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these concepts into clinical practice. Please see later in the article for the Editors' Summary.
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Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Adequate dosing of antimicrobial therapy is of central importance to improve outcome. Liver failure may ...alter antibiotic drug concentrations via changes of drug distribution and elimination. We studied the pharmacokinetics of meropenem in critically ill patients with ACLF during continuous veno-venous hemodialysis (CVVHD) and compared it to critically ill patients without concomitant liver failure (NLF).
Methods
In this prospective cohort study, patients received meropenem 1 g tid short-term infusion (SI). Meropenem serum samples were analyzed by high-performance liquid chromatography. A population pharmacokinetic analysis was performed followed by Monte Carlo simulations of (A) meropenem 1 g tid SI, (B) 2 g loading plus 1 g prolonged infusion tid (C) 2 g tid SI, and (D) 2 g loading and continuous infusion of 3 g/day on days 1 and 7. Probability of target attainment (PTA) was assessed for 4× the epidemiological cut-off values for
Enterobacterales
(4 × 0.25 mg/L) and
Pseudomonas
spp. (4 × 2 mg/L).
Results
Nineteen patients were included in this study. Of these, 8 patients suffered from ACLF. A two-compartment model with linear clearance from the central compartment described meropenem pharmacokinetics. The peripheral volume of distribution (
V
2
) was significantly higher in ACLF compared to NLF (38.6L versus 19.7L,
p
= .05). PTA for
Enterobacterales
was achieved in 100% for all dosing regimens. PTA for
Pseudomonas
spp. in ACLF on day 1/7 was: A: 18%/80%, B: 94%/88%, C: 85%/98% D: 100%/100% and NLF: A: 48%/65%, B: 91%/83%, C: 91%/93%, D: 100%/100%.
Conclusion
ALCF patients receiving CVVHD had a higher
V
2
and may require a higher loading dose of meropenem. For
Pseudomonas
, high doses or continuous infusion are required to reach PTA in ACLF patients.
Phosphate imbalances or disorders have a high risk of morbidity and mortality in patients with chronic kidney disease. It is unknown if this finding extends to mortality in patients presenting at an ...emergency room with or without normal kidney function.
This cross sectional analysis included all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland. A multivariable cox regression model was applied to assess the association between phosphate levels and in-hospital mortality up to 28 days.
22,239 subjects were screened for the study. Plasma phosphate concentrations were measured in 2,390 patients on hospital admission and were included in the analysis. 3.5% of the 480 patients with hypophosphatemia and 10.7% of the 215 patients with hyperphosphatemia died. In univariate analysis, phosphate levels were associated with mortality, age, diuretic therapy and kidney function (all p<0.001). In a multivariate Cox regression model, hyperphosphatemia (OR 3.29, p<0.001) was a strong independent risk factor for mortality. Hypophosphatemia was not associated with mortality (p>0.05).
Hyperphosphatemia is associated with 28-day in-hospital mortality in an unselected cohort of patients presenting in an emergency room.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Critically ill patients in the intensive care unit (ICU) are at high risk for developing Clostridioides difficile infections (CDI). Risk factors predicting their mortality or standardized treatment ...recommendations have not been defined for this cohort. Our goal is to determine outcome and mortality associated risk factors for patients at the ICU with CDI by evaluating clinical characteristics and therapy regimens.
A retrospective single-centre cohort study. One hundred forty-four patients (0.4%) with CDI-associated diarrhoea were included (total 36.477 patients admitted to 12 ICUs from January 2010 to September 2015). Eight patients without specific antibiotic therapy were excluded, so 132 patients were analysed regarding mortality, associated risk factors and therapy regimens using univariate and multivariate regression.
Twenty-eight-day mortality was high in patients diagnosed with CDI (27.3%) compared to non-infected ICU patients (9%). Patients with non CDI-related sepsis (n = 40/132; 30.3%) showed further increase in 28-day mortality (45%; p = 0.003). Initially, most patients were treated with a single CDI-specific agent (n = 120/132; 90.9%), either metronidazole (orally, 35.6%; or IV, 37.1%) or vancomycin (18.2%), or with a combination of antibiotics (n = 12/132; 9.1%). Patients treated with metronidazole IV showed significantly longer duration of diarrhoea > 5 days (p = 0.006). In a multivariate regression model, metronidazole IV as initial therapy was an independent risk factor for delayed clinical cure. Immunosuppressants (p = 0.007) during ICU stay lead to increased 28-day mortality.
Treatment of CDI with solely metronidazole IV leads to a prolonged disease course in critically ill patients.
Purpose
Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage at the intensive care unit. Although mortality is reported to be high, risk factors for mortality in this population ...are unknown.
Methods
One-hundred and seventeen consecutive patients with HH were studied prospectively at three medical intensive care units of a university hospital.
Results
The main causes of hypoxic hepatitis were low cardiac output and septic shock, and most patients (74%) had more than one underlying factor. Peak aspartate transaminase (
P
= 0.02), lactate dehydrogenase (
P
= 0.03), INR (
P
< 0.001) and lactate (
P
< 0.01) were higher in non-survivors. Prolonged duration of HH caused higher overall mortality rate (
P
= 0.03). INR > 2 (
P
= 0.02), septic shock (
P
= 0.01) and SOFA score >10 (
P
= 0.04) were risk factors of mortality in the regression model.
Conclusions
Hypoxic hepatitis is the consequence of multiorgan injury. Outcome is influenced by the severity of liver impairment and the etiology and severity of the basic disease.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Prevalence of multiple organ failure (MOF) in critically ill patients is increasing and associated mortality remains high. Extracorporeal organ support is a cornerstone in the management ...of MOF. We report data of an advanced hemodialysis system based on albumin dialysis (ADVOS multi device) that can regulate acid–base balance in addition to the established properties of renal replacement therapy and albumin dialysis systems in critically ill patients with MOF.
Methods
34 critically ill patients with MOF received 102 ADVOS treatment sessions in the Department of Intensive Care Medicine of the University Medical Center Hamburg-Eppendorf. Markers of metabolic detoxification and acid–base regulation were collected and blood gas analyses were performed. A subgroup analyses were performed in patients with severe acidemia (pH < 7.2).
Results
Median number of treatment sessions was 2 (range 1–9) per patient. Median duration of treatment was 17.5 (IQR 11–23) hours per session. Treatment with the ADVOS multi-albumin dialysis device caused a significant decrease in bilirubin levels, serum creatinine, BUN and ammonia levels. The relative elimination rate of bilirubin was concentration dependent. Furthermore, a significant improvement in blood pH, HCO
3
−
and PaCO
2
, was achieved during ADVOS treatment including six patients that suffered from severe metabolic acidosis refractory to continuous renal replacement therapy. Delta pH, HCO
3
−
and PaCO
2
were significantly affected by the ADVOS blood flow rate and pH settings. This improvement in the clinical course during ADVOS treatments allowed a reduction in norepinephrine during ADVOS therapy. Treatments were well tolerated. Mortality rates were 50% and 62% for 28 and 90 days, respectively.
Conclusions
In this case series in patients with MOF, ADVOS was able to eliminate water-soluble and albumin-bound substances. Furthermore, the device corrected severe metabolic and respiratory acid–base disequilibrium. No major adverse events associated with the ADVOS treatments were observed.
Background
Since the overall prognosis of very elderly patients is generally limited, admissions to intensive care in these patients are often restricted. Therefore, only very few information is ...available on the prognosis of nonagenarians after intensive care treatment. The aim of this study was to analyze the clinical characteristics and outcomes of very elderly patients (≥90 years) admitted to an intensive care unit (ICU).
Methods
Monocentric, retrospective observational study of all patients aged ≥90 years admitted to the Department of Intensive Care Medicine with a total capacity of 132 ICU beds at the University Medical Center Hamburg in Germany between January 2008 and June 2013. A multivariate Cox regression analysis was used to identify risk factors for 28-day outcome.
Results
A total of 372 patients ≥90 years of age were admitted to one of the departments ICUs. The majority of patients (66.7 %) were admitted as an emergency admission, of which half underwent unscheduled surgery. 39.8 % of patients required support by mechanical ventilation and vasoactive drugs, and 1.9 % of patients received renal replacement. ICU and hospital mortality rates were 18.3 and 30.9 %, respectively. Overall survival at 1 year after hospital discharge was 34.9 %. Multivariate Cox regression analysis revealed creatinine, bilirubin, age, and necessity of catecholamines as independent risk factors and scheduled surgery as protective factor for 28-day outcome.
Conclusion
Nearly 70 % of patients aged ≥90 years were discharged alive from hospital following treatment at the ICU, and more than half of them were still alive 1 year after their discharge. The results suggest that 1-year survival prognosis of very old ICU patients is not as poor as often perceived and that age per se should not be an exclusion criterion for ICU admission.
Trial registration: WF-0561/13
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