scholarly journals Soluble neprilysin and survival in critically ill patients

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
M Lenz ◽  
KA Krychtiuk ◽  
M Brekalo ◽  
C Hengstenberg ◽  
K Huber ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): -) Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) -) Ludwig Boltzmann Cluster for Cardiovascular Research BACKGROUND Critically ill patients admitted to an intensive care unit (ICU) exhibit a high mortality rate irrespective of the initial cause of hospitalization. Neprilysin is a neutral endopeptidase degrading an array of vasoactive peptides, including bradykinin, adrenomedullin and natriuretic peptides and became a drug target within the treatment of heart failure with reduced ejection fraction. The aim of this study was to analyze whether circulating levels of neprilysin at ICU admission are associated with 30-day mortality, due to its physiologic effects. METHODS In this single-center prospective observational study, 222 consecutive patients admitted to a tertiary ICU at a university hospital were included. Blood was drawn at admission and soluble neprilysin levels were measured using ELISA. RESULTS Median simplified acute physiology score was 44 and 30-day mortality was 35.1% in medical patients (n = 151) and 7.1% in patients after surgery and heart valve interventions (n = 71). Neprilysin levels did not differ according to survival status after 30 days and admission type. When assessing neprilysin and survival according to admission type, no association was found in medical patients, while in patients after surgery or heart valve intervention, 30-day survivors exhibited significantly lower neprilysin levels as compared to those that died within 30 days (660.2, IQR: 156.4 – 2512.5 pg/ml versus 6532.6, IQR: 1840.1 – 10000.0 pg/ml; p = 0.02). Neprilysin predicted mortality independently from age, gender, NT-proBNP, and SAPS II score (OR per 1-SD increase of neprilysin: 2.52, 95%CI 1.01–6.32; p = 0.049). Additionally, neprilysin was markedly elevated in patients with sepsis and septic shock (p < 0.05). CONCLUSION At the time of ICU-admission, circulating levels of neprilysin independently predicted 30-day mortality in patients following cardiac surgery or heart valve intervention, but not in critically ill medical patients.

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 990
Author(s):  
Theresa H. Wirtz ◽  
Lukas Buendgens ◽  
Ralf Weiskirchen ◽  
Sven H. Loosen ◽  
Nina Haehnsen ◽  
...  

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO2; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome.


2009 ◽  
Vol 160 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Philipp Schuetz ◽  
Beat Müller ◽  
Charly Nusbaumer ◽  
Melanie Wieland ◽  
Mirjam Christ-Crain

BackgroundCirculating levels of GH are increased during critical illness and correlate with outcome in children with meningococcal sepsis. We assessed the prognostic implications of GH on admission and during follow-up in critically ill adult patients admitted to a medical intensive care unit.Materials and methodsWe measured GH, IGF1 and IGF-binding protein3 (IGFBP-3) plasma concentrations in 103 consecutive critically ill patients and compared it with two clinical severity scores (APACHE II, SAPS II).ResultsMedian GH levels on admission were similar in septic (n=53) and non-septic (n=50) patients and about 7-fold increased in the 24 non-survivors as compared with survivors (9.50 (interquartile ranges (IQR) 3.53–18.40) vs 1.4 (IQR 0.63–5.04), P<0.0001). GH levels increased with increasing severity of sepsis (sepsis, severe sepsis, and septic shock, P=0.019). By contrast, IGF1 and IGFBP-3 did not correlate with severity of disease or mortality. Logistic regression models showed that GH and both clinical scores were independent predictors of mortality with a similar prognostic accuracy (GH: area under the curve (AUC) 0.81 (95% confidence interval (CI), 0.71–0.92), APACHE II: AUC 0.71 (95% CI, 0.58–0.83), P=0.16, SAPS II: AUC 0.75 (95% CI, 0.63–0.86, P=0.36)). GH improved the prognostic accuracy of the APACHE II score to an AUC of 0.78 (95% CI, 0.66–090, P=0.04) and tended to improve the SAPS II score to an AUC of 0.79 (95% CI, 0.67–0.90, P=0.09).ConclusionGH plasma concentrations on admission are independent predictors for mortality in adult critically ill patients and may complement existing risk prediction scores, namely the APACHE II and the SAPS II score.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Eleni Papoutsi ◽  
Vassilis G. Giannakoulis ◽  
Eleni Xourgia ◽  
Christina Routsi ◽  
Anastasia Kotanidou ◽  
...  

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rene A. Posma ◽  
Trine Frøslev ◽  
Bente Jespersen ◽  
Iwan C. C. van der Horst ◽  
Daan J. Touw ◽  
...  

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sofia Dahlberg ◽  
Ulf Schött ◽  
Thomas Kander

Abstract Background Previous studies have indicated that vitamin K deficiency is common in non-bleeding critically ill patients with slightly prolonged prothrombin time-international normalized ratio (PT-INR). It has never been investigated thoroughly whether the administration of vitamin K to these patients could affect their PT-INR. Therefore, the aim of this registry study was to evaluate changes in PT-INR in response to vitamin K in critically ill patients with PT-INR in the range of 1.3–1.9. Methods Patients admitted to a mixed 9-bed general intensive care unit at a University Hospital, between 2013 and 2019 (n = 4541) with a PT-INR between 1.3 and 1.9 at any time during the stay were identified. Patients who received vitamin K with appropriate sampling times for PT-INR and without exclusion criteria were matched with propensity score to patients from the same cohort who did not receive vitamin K (controls). PT-INR was measured at admission, within 12 h before vitamin K administration and 12–36 h following vitamin K administration. Exclusion criteria included pre-existing liver cirrhosis, any plasma or platelet transfusion, or > 1 unit red blood cell transfusion between PT-INR samplings. Results Propensity score matching resulted in two groups of patients with 129 patients in each group. PT-INR decreased in both groups (1.4 [1.3–1.4] in the vitamin K group and 1.4 [1.3–1.6] in the controls, p < 0.001 and p = 0.004, respectively). The decrease in PT-INR was slightly more pronounced in patients who received vitamin K (delta PT-INR − 0.10 [− 0.30 to − 0.10] in the vitamin K group and − 0.10 [− 0.20 to 0.10] in the controls, p = 0.01). Conclusion In critically ill patients with a PT-INR of 1.3–1.9, the administration of vitamin K resulted in a slightly larger decrease of PT-INR 12–36 h after administration compared to controls. Future studies should focus on identifying which patient populations may benefit most from vitamin K administration as well as whether vitamin K could be a better alternative than plasma or prothrombin complex concentrate to improve PT-INR before non-emergent invasive procedures.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin Roedl ◽  
Dominik Jarczak ◽  
Andreas Drolz ◽  
Dominic Wichmann ◽  
Olaf Boenisch ◽  
...  

Abstract 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 (paO2/FiO2: 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.


2020 ◽  
Vol 10 (4) ◽  
pp. 72
Author(s):  
Mohamed E. Abdelgawad ◽  
Nadia T. Ahmed ◽  
Ahmed M. Elmenshawy

Background and objective: Electrolyte disturbances remain a common lifesaving issue in the intensive care units. They are associated with increased morbidity and mortality. They are mostly resulted secondary to critical illness itself or associated treatment modalities. Therefore, electrolytes repletion should be done effectively and timely. This could be ensured using nurse driven protocols rather than traditional methods of repletion. These protocols are nurse initiated and collaboratively developed. They have been shown to improve patient care outcomes through the provision of high quality care. They are increasingly being used in the critical care setting. Objective: Determine the effect of applying nurses driven electrolytes repletion protocol on electrolytes disturbance control among critically ill patients.Methods: Quasi experimental research design was used. Sixty two critically ill patients with electrolytes loss were enrolled in the study at Alexandria Main University Hospital intensive care units, Egypt. All episodes of electrolyte loss were evaluated. Repletion of electrolyte loss was done according to unit routine for the control group and nurses driven electrolytes repletion protocol for the study group. Episodes of electrolyte disturbances, adverse events and timing of repletion were evaluated.Results: Neurological disorders represent the most encountered diagnosis. The most common cause of electrolyte loss in was the use of diuretics. Furthermore, there was a highly statistical difference between the two groups as regard electrolytes levels, effectiveness and timing of replacement.Conclusions: Application of nurses driven electrolyte repletion protocol resulted in improvements in the effectiveness and timeliness of electrolyte replacement.


2012 ◽  
Vol 33 (3) ◽  
pp. 619-629 ◽  
Author(s):  
Catherine Ingels ◽  
Holger J. Møller ◽  
Troels K. Hansen ◽  
Pieter J. Wouters ◽  
Ilse Vanhorebeek ◽  
...  

2010 ◽  
Vol 44 (4) ◽  
pp. 1039-1045 ◽  
Author(s):  
Aretha Pereira de Oliveira ◽  
Dalmo Valério Machado de Lima

This is a participant study, quasi-experimental, of a before and after type. A quantitative approach of biophysiological measures was used, represented by the saturation of oxygen measured by pulse oximeter (SpO2), and recorded on three occasions: before, during and after the bedbath in critically ill patients hospitalized at the ICU of a University Hospital in Brazil. Objective: to compare the SpO2 in various stages of the bath, with and without control of water temperature. Data collection was performed between December 2007 and April 2008 on a convenience sample consisting of 30 patients aged over 18 who had classification in TISS-28 from level II. Results show that water temperature control means a lower variation of SpO2 (p<0.05). No marked differences in variation of saturation between men and women or between age groups were established. In conclusion, heated and constant water temperature during the bedbath is able to minimize the fall of SpO2 that occurs while handling patients during procedures.


2021 ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Alaa Alhubaishi ◽  
Ohoud Al Juhani ◽  
Khalid Eljaaly ◽  
Omar Al Harbi ◽  
...  

Abstract Background: Corticosteroids, especially dexamethasone, showed a survival benefit in critically ill COVID 19 patients. However, it is unclear whether the timing of dexamethasone initiation is associated with positive outcomes. The aim of this study is to evaluate the timing of dexamethasone initiation and 30-day ICU mortality in critically ill patients with COVID19. Methods: A multicenter, non-interventional, prospective study for all adult COVID19 admitted to intensive care units (ICUs) who received systemic dexamethasone between March 01 to December 31, 2020. Patients were divided into two groups based on the timing for dexamethasone initiation (early vs. late). Early use defined as the initiation of dexamethasone within three days of ICU admission. Multivariate logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: A total of 475 patients were included in the study; dexamethasone was initiated early within three days of ICU admission in 433 patients. Early initiation of dexamethasone was associated with lower 30-day ICU mortality (OR [95%CI]: 0.43 [0.23, 0.81], p-value = 0.01), and acute kidney injury during ICU stay, (OR [95%CI]: 0.45 [0.21, 0.94], p-value = 0.03). Additionally, among survivors, early initiation was associated with shorter MV duration (beta coefficient [95% CI]: -0.94 [-1.477, -0.395], p-value = 0.0001), ICU length of stay (LOS) (beta coefficient [95%CI]: -0.73 [-0.9971, -0.469], p-value = 0.0001), and hospital LOS (beta coefficient [95%CI]: -0.68 [-0.913, -0.452], p-value = 0.0001). Conclusion: Early initiation of dexamethasone within three days of ICU admission in COVID-19 critically ill patients was associated with a mortality benefit. Additionally, it was associated with shorter MV duration, hospital, and ICU LOS.


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