Elevated asymmetric dimethylarginine levels predict short- and long-term mortality risk in critically ill patients

Objective

Serum concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may contribute to endothelial dysfunction and organ failure in sepsis. We aimed at investigating ADMA levels as a potential diagnostic or prognostic biomarker in critically ill patients.

Methods

Two hundred fifty-five patients (164 with sepsis, 91 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 78 healthy controls. ADMA serum concentrations were correlated with clinical data and extensive laboratory parameters. Patients’ survival was followed up for up to 3 years.

Results

ADMA serum levels were significantly elevated in critically ill patients at admission compared to controls. ADMA levels did not differ between patients with or without sepsis, but were closely related to hepatic and renal dysfunction, metabolism and clinical scores of disease severity. ADMA levels further increased during the first week of ICU treatment. ADMA serum levels at admission were an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU, but also for unfavorable long-term survival.

Conclusion

Serum ADMA concentrations are significantly elevated in critically ill patients, associated with organ failure and related to short- and long-term mortality risk.     

Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients

Introduction  

Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis.     

Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients

Introduction  

The endothelial specific angiopoietin (Ang)-Tie2 ligand-receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis. Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage, whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function. Here, we examine whether circulating Ang-1 and/or Ang-2 independently predict mortality in a cohort of critically ill medical patients.     

Prognostic importance of neutrophil-lymphocyte ratio in critically ill patients: short- and long-term outcomes

Study objectiveThe number of critically ill patients admitted to the emergency department increases daily. To decrease mortality, interventions and treatments should be conducted in a timely manner. It has been found that the neutrophil-lymphocyte ratio (NLR) is related to mortality in some disease groups, such as acute coronary syndrome and pulmonary emboli. The effect of the NLR on mortality is unknown in critically ill patients who are admitted to the emergency department. Our aim in this study is to evaluate the effect of the NLR on mortality in critically ill patients.MethodsThis study was planned as a prospective, observational cohort study. Patients who were admitted to the emergency department because they were critically ill and required the intensive care unit were included in the study. Demographic characteristics, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sepsis-related Organ Failure Assessment, Glasgow Coma Score, and NLR values were recorded upon emergency department admission. The patients were followed up for sepsis, ventilator-associated pneumonia, multiorgan failure, in-hospital mortality, and 6-month mortality.ResultsThe median (interquartile range) age of the 373 patients was 74 (190) years, and 54.4% were men. Neutrophil-lymphocyte ratio values were divided into quartiles, as follows: less than 3.48, 3.48 to 6.73, 6.74-13.6, and more than 13.6. There was no difference among these 4 groups regarding demographic characteristics, APACHE II score, Sepsis-related Organ Failure Assessment score, Glasgow Coma Score, and length of hospital stay (P > .05). In the multivariable Cox regression model, in-hospital mortality and 6-month mortality NLR were hazard ratio (HR), 1.63 (1.110-2.415; P = .01) and HR, 1.58 (1.136-2.213; P = .007), respectively, and APACHE II scores were detected as independent indicators.ConclusionThe NLR is a simple, cheap, rapidly available, and independent indicator of short- and long-term mortalities. We suggest that the NLR can provide direction to emergency department physicians for interventions, particularly within a few hours after admission, in the critically ill patient group.     

Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients

OBJECTIVE: To evaluate the prognostic value of lactate clearance and lactate production in severely ill septic patients with normal or mildly elevated blood lactate concentration.DESIGN Prospective, observational study. SETTING: Nineteen-bed mixed medicosurgical intensive care unit. PATIENTS: Fifty-six patients with severe sepsis and blood lactate concentration <3 mmol/L. MEASUREMENTS AND MAIN RESULTS: Lactate metabolism was evaluated in all patients. Lactate clearance was measured by modeling the change in arterial blood lactate over time induced by an infusion of 1 mmol/kg sodium lactate for 15 mins. Lactate production was calculated as the product of lactate clearance times the blood lactate concentration before the infusion. Outcome was taken to be mortality at 28 days after the beginning of the septic episode. A logistic regression model taking into account different risk factors was constructed. Among the 56 patients, 17 (30.3%) died before the 28th day. Basal blood lactate concentration was not different between survivors and nonsurvivors, whereas lactate clearance and production were higher in survivors (0.86 +/- 0.32 vs. 0.58 +/- 0.18 L/hr/kg, p < .005, and 1.19 +/- 0.63 vs. 0.89 +/- 0.24 mmol/hr/kg, p = .055, respectively). An increase in blood lactate 45 mins after the end of the lactate infusion (Deltalact-T60) > or = 0.6 mmol/L was predictive of 28-day mortality with 53% sensitivity and 90% specificity. Multivariate analysis showed that only three factors were independently and significantly correlated with 28-day mortality: presence of more than two organ failures (odds ratio, 27; p = .04), age >70 yrs (odds ratio, 5.7; p = .032), and Deltalact-T60 > or =0.6 mmol/L (odds ratio, 14.2; p = .042). CONCLUSION: Low lactate clearance in severely ill septic patients with normal or mildly elevated blood lactate is predictive of poor outcome independently of other known risk factors such as age and number of organ failures.     

Hyperglycaemia and mortality in critically ill patients

Objective To describe hyperglycaemia as a possible marker of morbidity and mortality in critically ill medical and surgical patients admitted to a multidisciplinary ICU.Design Prospective cohort study.Setting A 13-bed non-cardiac multidisciplinary ICU in a university hospital.Patients and participants Adult patients consecutively admitted to the ICU in a 6-month period. Patients with fewer than 2 days stay in the ICU and patients with known diabetes were excluded.Measurements and results At admission a registration form was filled in including demographic data, first and second day APACHE II scores, infections and daily maximum blood glucose level. In surgical patients, high maximum blood glucose level during the stay in ICU was correlated with increased mortality, morbidity and frequency of infection. In medical patients, we found a non-significant trend towards a correlation between hyperglycaemia and morbidity and mortality, respectively.Conclusions High blood glucose level during the stay in ICU was a marker of increased morbidity and mortality in critically ill surgical patients. In medical patients the same trend was found, but non-significant. The population of patients in the present study are heterogeneous and the results from surgical critically ill patients should not be generalised to medical patients.     

Favorable short- and long-term outcomes of prolonged translaryngeal intubation in critically ill children

In those children who require protracted mechanical ventilation, we use long-term intubation in order to avoid the consequences of tracheostomy in young children. A retrospective 9-year review was performed to document the efficacy and safety of this practice. A retrospective review of children admitted from January 1, 1991, to December 31, 1998, who required mechanical ventilatory support for at least 7 consecutive days was performed. Data are presented as mean +/- standard deviation. There were 98 children, ventilated for a total of 1967 days, who satisfied review criteria. They had an average age of 6.1 +/- 5.3 years (range, 3 months to 17 years) a total body surface area burn of 53 +/- 25% (range, 0-100%), and 71 of 98 (72%) had suffered an inhalation injury. They were ventilated for 19.7 +/- 16.8 days (range, 7-92 days) and were hospitalized for 67.8 +/- 48.9 days (range, 9-211 days). Ninety-three percent (91 of 98) of the patients were maintained on morphine infusions at a mean hourly rate of 0.35 +/- 0.33 mg/kg/hr (range, 0.01-4.38) and 78% (76 of 98) on midazolam infusions at a mean hourly rate of 0.14 +/- 0.17 mg/kg/hr (range, 0.01-1.82). Neuromuscular blocking agents were administered in 39% (38 of 98) of patients during all or part of 355 (18%) of the 1967 ventilator days. Patients were ventilated with an oral endotracheal (ET) tube in 82% of ventilator days and nasal ET tube in 18% of ventilator days. Two patients (2%) required tracheostomies for long-term management, and five patients (5.1%) died during the study period unrelated to airway issues. There were five unplanned extubation events, for an incidence rate of 2.54 per 1000 ventilator days. All patients were reintubated successfully. Thirteen ET tubes needed to be changed for issues such as leaking cuffs. Patients were followed up for a mean of 2.99 +/- 2.24 years (range, 1 month to 8 years). Possible sequelae related to prolonged intubation were noted in follow-up visits in 8 patients, including sinusitis (one; resolved without treatment), subglottic stenosis (one; required reconstructive surgery), persistent cough (three; all resolved spontaneously), occipital breakdown because of ET ties (one; healed after 1 month), soft voice (two; resolved spontaneously), and decreased pharyngeal sensation (one; resolved without treatment). Translaryngeal intubation is a safe and effective method to provide long-term ventilatory support in children.     

Eosinopenia,an early marker of increased mortality in critically ill medical patients

Purpose  

Inflammatory markers may have a role in predicting severity of illness of intensive care unit (ICU) patients. The aim of this study is to determine whether low eosinophil count can predict 28-day mortality in medical ICU.     

Urinary creatinine excretion is related to short-term and long-term mortality in critically ill patients

Purpose

Patients with reduced muscle mass have a worse outcome, but muscle mass is difficult to quantify in the ICU. Urinary creatinine excretion (UCE) reflects muscle mass, but has not been studied in critically ill patients. We evaluated the relation of baseline UCE with short-term and long-term mortality in patients admitted to our ICU.

Methods

Patients who stayed ≥?24 h in the ICU with UCE measured within 3 days of admission were included. We excluded patients who developed acute kidney injury stage 3 during the first week of ICU stay. As muscle mass is considerably higher in men than women, we used sex-stratified UCE quintiles. We assessed the relation of UCE with both in-hospital mortality and long-term mortality.

Results

From 37,283 patients, 6151 patients with 11,198 UCE measurements were included. Mean UCE was 54% higher in males compared to females. In-hospital mortality was 17%, while at 5-year follow-up, 1299 (25%) patients had died. After adjustment for age, sex, estimated glomerular filtration rate, body mass index, reason for admission and disease severity, patients in the lowest UCE quintile had an increased in-hospital mortality compared to the patients in the highest UCE quintile (OR 2.56, 95% CI 1.96–3.34). For long-term mortality, the highest risk was also observed for patients in the lowest UCE quintile (HR 2.32, 95% CI 1.89–2.85), independent of confounders.

Conclusions

In ICU patients without severe renal dysfunction, low urinary creatinine excretion is associated with short-term and long-term mortality, independent of age, sex, renal function and disease characteristics, underscoring the role of muscle mass as risk factor for mortality and UCE as relevant biomarker.

     

Frailty in the critically ill: a novel concept

The concept of frailty has been defined as a multidimensional syndrome characterized by the loss of physical and cognitive reserve that predisposes to the accumulation of deficits and increased vulnerability to adverse events. Frailty is strongly correlated with age, and overlaps with and extends aspects of a patient's disability status (that is, functional limitation) and/or burden of comorbid disease. The frail phenotype has more specifically been characterized by adverse changes to a patient's mobility, muscle mass, nutritional status, strength and endurance. We contend that, in selected circumstances, the critically ill patient may be analogous to the frail geriatric patient. The prevalence of frailty amongst critically ill patients is currently unknown; however, it is probably increasing, based on data showing that the utilization of intensive care unit (ICU) resources by older people is rising. Owing to the theoretical similarities in frailty between geriatric and critically ill patients, this concept may have clinical relevance and may be predictive of outcomes, along with showing important interaction with several factors including illness severity, comorbid disease, and the social and structural environment. We believe studies of frailty in critically ill patients are needed to evaluate how it correlates with outcomes such as survival and quality of life, and how it relates to resource utilization, such as length of mechanical ventilation, ICU stay and duration of hospitalization. We hypothesize that the objective measurement of frailty may provide additional support and reinforcement to clinicians confronted with end-of-life decisions on the appropriateness of ICU support and/or withholding of life-sustaining therapies.     

Gastric mucosal pH as a prognostic index of mortality in critically ill patients.

OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU.     

Frailty as a mortality predictor in older adults with COVID-19: A systematic review and meta-analysis of cohort studies

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the coronavirus diseases 2019 (COVID-19) pandemic, continues to spread rapidly worldwide and is associated with high rates of mortality among older adults, those with comorbidities, and those in poor physiological states. This paper aimed to systematically identify the impact of frailty on overall mortality among older adults with COVID-19. We conducted a systematic review of the literature indexed in 4 databases. A random-effects model with inverse variance-weighted meta-analysis using the odds ratio was used to study the association of frailty levels with clinical outcomes among older adults with COVID-19. Heterogeneity was measured using the I² statistic and Egger's test. We identified 22 studies that met our inclusion criteria, including 924,520 total patients. Overall, frailty among older adults was associated with high rates of COVID-19-related mortality compared with non-frail older adults (OR [odds ratio]:5.76; 95% confidence interval [95% CI]: 3.85–8.61, I²: 40.5%). Our results show that physical limitations, such as those associated with frailty among older adults, are associated with higher rates of COVID-19-related mortality.     

Hypermagnesemia and hypocalcemia as predictors of high mortality in critically ill pediatric patients

Ca and Mg are biologically important minerals that are involved in maintaining the stability of membranes, muscle contractions, and enzyme activity in nearly all cells. Derangements of Ca and Mg homeostasis can precipitate serious and life-threatening problems in the critically ill patients. We examined serum ionized Ca and Mg levels in pediatric patients consecutively admitted to a pediatric ICU. Abnormal Mg and ionized Ca levels on admission were found in 43.3% and 17% of the patients, respectively. Hypocalcemia and hyper-magnesemia were both associated with poor outcome as measured by either survival or length of ICU stay. In addition, ionized Ca levels could not be predicted from total Ca measurement either alone or in combination with serum albumin and pH.     

Intensive insulin therapy and mortality in critically ill patients

Introduction  

Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.     

Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically ill non-cirrhotic patients at a medical ICU

Introduction  

Hepatic dysfunction is a common finding in critically ill patients on the ICU and directly influences survival. Liver stiffness can be measured by the novel method of transient elastography (fibroscan) and is closely associated with hepatic fibrosis in patients with chronic liver disease, but also is increased in patients with acute hepatitis, acute liver failure and cholestasis. We investigated liver stiffness as a potentially useful tool for early detection of patients with hepatic deterioration and risk stratification with respect to short- and long-term mortality.     

Rapid decrease in plasma D-lactate as an early potential predictor of diminished 28-day mortality in critically ill septic shock patients.

BACKGROUND: Splanchnic ischemia plays a major role in the development of organ failure during septic shock. Plasma D-lactate has been proposed as a better marker of splanchnic hypoperfusion than L-lactate. We studied the prognostic ability of plasma D- and L-lactate levels. METHODS: A prospective study was performed in an intensive care unit and included patients with septic shock. Two samples for plasma D- and L-lactate determination were collected: the first within 6 h after the patient met the criteria for septic shock (day 1) and the second 24 h later (day 2). RESULTS: In univariate analysis, day 1 plasma D- and L-lactate values were associated with 28-day mortality. For plasma D- and L- lactate, the area under the receiver operating characteristic curve was 0.68+/-0.09 and 0.84+/-0.07 on day 1 (p=0.09), and 0.74+/-0.10 and 0.90+/-0.07 on day 2 (p=0.06), respectively. In survivors, D-lactate levels decreased between day 1 and day 2 (p=0.03), but L-lactate did not (p=0.29). In septic shock patients, plasma D- and L-lactate levels reliably discriminate between survivors and non-survivors. The prognostic ability of plasma L-lactate was better than that of plasma D-lactate. CONCLUSION: A rapid decrease in plasma D-lactate during the course of septic shock could indicate reduced 28-day mortality.