Does Whole-Blood Neutrophil Gelatinase-Associated Lipocalin Stratify Acute Kidney Injury in Critically Ill Patients?

PURPOSE: To analyse the capacity of whole-blood NGAL (wbNGAL) to stratify AKI in critically ill patients with and without sepsis. METHODS: Whole-blood NGAL was measured with a point-of-care device at admission and 48 hours later in patients admitted to a general ICU. Patients were classified by the AKIN and KDIGO classifications at admission and 24 and 48 hours. We performed an ROC curve analysis. wbNGAL values at admission were compared in patients with sepsis and septic shock. RESULTS: The study included 100 consecutively admitted patients (40 female) with mean age 59.1 ± 17.8 years. Thirty-three patients presented AKI at admission, and 10 more developed it in the next 48 h. Eighteen patients had AKI stage 3, 14 of them at admission. Nine patients required renal replacement therapy. According to KDIGO at admission, wbNGAL values were 78 µg/L (60-187) in stage 0 (n = 67), 263 µg/L (89-314) in stage 1 (n = 8), 484 µg/L (333-708) in stage 2 (n = 11), and 623 µg/L (231-911) in stage 3 (n = 14), p = 0.0001 for trend. Ten patients did not complete 48 hours of study: 6 of 10 were discharged (initial wbNGAL 130 µg/L (60-514)) and 4 died (773 µg/L (311-1010)). The AUROC curve of wbNGAL to predict AKI was 0.838 (95% confidence interval 0.76-0.92, p = 0.0001), with optimal cut-off value of 178 µg/L (sensitivity 76.7%, specificity 78.9%, p < 0.0001). At admission, twenty-nine patients had sepsis, of whom 20 were in septic shock. wbNGAL concentrations were 81 µg/L (60-187) in patients without sepsis, 481 (247-687) in those with sepsis, and 623.5 µg/L (361-798) in the subgroup of septic shock (p < 0.0001). CONCLUSIONS: Whole-blood NGAL concentration at ICU admission was a good stratifier of AKI in critically ill patients. However, wbNGAL concentrations were higher in septic patients irrespective of AKI occurrence.

Cell-cycle arrest biomarkers in urine to predict acute kidney injury in septic and non-septic critically ill patients.

PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1.73 m2 and hospitalisation 2 months prior to current admission. The [TIMP-2]·[IGFBP7] index was analysed twice, within the first 12 h of ICU admission. RESULTS: The sample included 98 patients. AKI incidence during ICU stay was 50%. Sepsis was diagnosed in 40.8%. Baseline renal variables were comparable between subgroups except for a higher baseline eGFR in non-septic patients. Patients were stratified based on the presence of AKI and their highest level of [TIMP-2]·[IGFBP7] within the first 12 h of stay. [TIMP-2]·[IGFBP7] index values were dependent on the incidence of AKI but not of sepsis. [TIMP-2]·[IGFBP7] values were significantly related to AKI severity according to AKIN criteria (p < 0.0001). The AUROC curve to predict AKI of the worst [TIMP-2]·[IGFBP7] index value was 0.798 (sensitivity 73.5%, specificity 71.4%, p < 0.0001). Index values below 0.8 ruled out any need for renal replacement (NPV 100%), whereas an index >0.8 predicted a rate of AKI of 71% and AKIN ≥ 2 of 62.9%. CONCLUSIONS: In our study, urinary [TIMP-2]·[IGFBP7] was an early predictor of AKI in ICU patients regardless of sepsis. Besides, index values <0.8(ng/mL)2/1000 ruled out the need for renal replacement.

Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes.

BACKGROUND: Surgical site infection (SSI) remains a significant problem in the postoperative period that can negatively affect clinical outcomes. Microbiology findings are typically similar to other nosocomial infections, with differences dependent on microbiology selection due to antibiotic pressure or the resident flora. However, this is poorly understood in the critical care setting. We therefore aimed to assess the incidence, epidemiology and microbiology of SSI and its association with outcomes in patients with severe peritonitis in the intensive care unit (ICU). METHODS: We prospectively studied 305 consecutive patients admitted to our surgical ICU from 2010 to 2014 with a diagnosis of secondary or tertiary peritonitis. We collected the following data: SSI diagnosis, demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II score, type of surgery, microbiology, antibiotic treatment and outcomes. Microbiological sampling was done by means of swabs. RESULTS: We identified 269 episodes of SSI in 162 patients (53.1%) aged 64.4 ± 14.3 years, of which 200 episodes occurred in men (64.6%). The mean APACHE II and SAPS II scores were 19.7 ± 7.8 and 36.5 ± 16.1 respectively. The mean ICU and hospital stays were 19.8 ± 24.8 and 21.7 ± 30 days respectively. Pseudomonas spp. (n = 52, 19.3%), Escherichia coli (n = 55, 20.4%) and Candida spp. (n = 46, 17.1%) were the most frequently isolated microorganisms, but gram-positive cocci (n = 80, 29.7%) were also frequent. Microorganisms isolated from SSIs were associated with a higher incidence of antibiotic resistance (64.9%) in ICU patients, but not with higher in-hospital mortality. However, patients who suffered from SSI had longer ICU admissions (odds ratio = 1.024, 95% confidence interval 1.010-1.039, P = 0.001). CONCLUSIONS: The incidence of SSI in secondary or tertiary peritonitis requiring ICU admission is very high. Physicians may consider antibiotic-resistant pathogens, gram-positive cocci and fungi when choosing empiric antibiotic treatment for SSI, although more studies are needed to confirm our results due to the inherent limitations of the microbiological sampling with swabs performed in our research. The presence of SSI may be associated with prolonged ICU stays, but without any influence on overall mortality.

Use of B-type natriuretic peptides to detect the existence and severity of diastolic dysfunction in non-cardiac critically ill patients: a pilot study.

BACKGROUND: This observational study was designed to evaluate and compare the usefulness of BNP and NT-proBNP concentrations to detect the existence and severity of left ventricular diastolic dysfunction (LVDD) in critically ill patients. METHODS: A prospective, observational study in a university hospital. The sample included 86 consecutive adult patients. Based on echocardiography data, LVDD were classified into normal, impaired relaxation, pseudonormal or restrictive patterns. Patients were classified according to whether filling pressures were elevated or non-elevated in the echocardiography. Sampling for natriuretic peptides was performed immediately before echocardiography. RESULTS: Fifty patients showed LVDD. The most frequently observed pattern was impaired relaxation (N.=35), followed by the restrictive (N.=9) and the pseudonormal (N.=6) patterns. BNP concentrations in restrictive and pseudonormal patterns were higher than in normal and impaired relaxation patterns, while NT-proBNP only showed differences between normal and pseudonormal or restrictive patterns. Cut-off values using ROC curve analyses to detect LVDD were 125 ng/L for BNP and 390 ng/L NT-proBNP. BNP and NT-proBNP concentrations were higher in the 15 patients with restrictive and pseudonormal patterns, suggesting elevated filling pressures. Cut-off values using ROC curve analyses to detect echocardiography signs of elevated filling pressures were 254 ng/L for BNP and 968 for NT-proBNP. Both natriopeptides performed in a similar way to detect LVDD and elevated filling pressures. CONCLUSION: Both BNP and NT-proBNP are useful screening tools to detect the presence of advanced degrees of LVDD, and especially to rule out elevated filling pressures.

[Hemodynamic and antipyretic effects of paracetamol, metamizol and dexketoprofen in critical patients]. / Efectos hemodinámicos y antipiréticos del paracetamol, metamizol y dexketoprofeno en pacientes críticos.

BACKGROUND: The objective was to study the antipyretic and hemodynamic effects of three different drugs used to treat fever in critically ill patients. DESIGN AND SETTING: Prospective, observational study in a 16-bed, general ICU of a university hospital. PATIENT POPULATION: We studied 150 patients who had a febrile episode (temperature>38°C): 50 received paracetamol, 50 metamizol and 50 dexketoprofen. INTERVENTIONS: None. Body temperature, systolic, diastolic and mean arterial pressure, heart rate, central venous pressure and oxygen saturation were determined at baseline and at 30, 60 and 120minutes after infusion of the drug. Additionally, we recorded temperature 180minutes after starting drug infusion. Diuresis and the need for or change of dose of vasodilator or vasoconstrictor drugs were also recorded. RESULTS: Patient characteristics, baseline temperature and hemodynamics were similar in all groups. We observed a significant decrease of at least 1°C in temperature after 180minutes in 38 patients treated with dexketoprofen (76%), in 36 with metamizol (72%), and in 20 with paracetamol (40%) (p<0.001). After 120minutes, the mean decrease in mean arterial pressure was 8.5±13.6mmHg with paracetamol, 14.9±11.8mmHg with metamizol, and 16.8±13.7mmHg with dexketoprofen (p=0.005). CONCLUSIONS: Dexketoprofen was the most effective antipyretic agent at the doses tested. Although all three drugs reduced mean arterial pressure, the reduction with paracetamol was less pronounced.

Short-term effects of inhaled nitric oxide and prone position in pulmonary and extrapulmonary acute respiratory distress syndrome.

Inhaled nitric oxide (NO) and prone position (PP) are frequently used in the treatment of acute respiratory distress syndrome (ARDS). We compared the gas exchange and hemodynamic effects induced by the combination of NO inhalation and PP in patients with ARDS and analyzed whether or not pulmonary (Pu) and extrapulmonary (Epu) ARDS patients behave differently. Eight Pu and seven Epu ARDS patients were studied in four situations: supine position (SP); SP with NO inhalation at 5 ppm (SP + NO); PP; and PP with NO inhalation (PP + NO). In comparison with SP, NO inhalation and PP induced significant increases in Pa(O(2))/FI(O(2)) (from 106 +/- 58 in SP to 131 +/- 69 mm Hg in SP + NO, p = 0.01, and to 184 +/- 67 mm Hg in PP, p < 0.001). Pu and Epu ARDS showed a similar improvement in Pa(O(2))/FI(O2) with PP. Only Pu ARDS patients showed a significant increase (p < 0.001) in oxygenation induced by NO inhalation from 81 +/- 45 to 100 +/- 50 mm Hg in SP, and from 146 +/- 53 to 197 +/- 98 mm Hg in PP. In conclusion, PP is associated with a marked improvement in oxygenation, irrespective of the causes of ARDS, and additive effects of NO inhalation are mainly seen in patients with Pu ARDS.

Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial.

BACKGROUND: Non-invasive pressure support ventilation (NIPSV) is an effective treatment for acute respiratory failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy of this therapy in acute cardiogenic pulmonary oedema in a randomised comparison with conventional oxygen therapy. METHODS: 40 patients were randomly assigned conventional oxygen therapy or NIPSV supplied by a standard ventilator through a face mask, with adjustment of tidal volume and pressure support in addition to a positive end-expiratory pressure of 5 cm water. Physiological measurements were obtained in the first 2 h and at 3 h, 4 h, and 10 h. The main endpoints were intubation rate and resolution time. Analyses were by intention to treat. FINDINGS: Three patients were withdrawn on the basis of clinical and chest radiography results. Endotracheal intubation was required in one (5%) of 19 patients assigned NIPSV and in six (33%) of 18 assigned conventional oxygen therapy (p=0.037). Resolution time (defined as a clinical improvement with oxygen saturation of 96% or more and respiratory rate less than 30 breaths/min) was significantly shorter in the NIPSV group (median 30 [IQR 15-53] vs 105 [50-230] min, p=0.002). NIPSV led to a rapid improvement in oxygenation in the first 2 h. There were no differences in hospital length of stay or mortality. INTERPRETATION: In this study of acute cardiogenic pulmonary oedema, NIPSV was superior to conventional oxygen therapy. Further studies should compare NIPSV with continuous positive airway pressure.

A prospective study of unplanned endotracheal extubation in intensive care unit patients.

OBJECTIVE: To evaluate incidence, factors associated with unplanned endotracheal extubation (UEE), and prognostic factors for reintubation. DESIGN: A prospective study over a 32-mo period. SETTING: A 16-bed general intensive care unit of a tertiary university hospital. PATIENTS: Adult subjects undergoing endotracheal intubation for >48 hrs. INTERVENTIONS: Observation of patients who presented unplanned extubation. MEASUREMENTS AND MAIN RESULTS: Over the 32-mo period, there were 59 episodes of UEE in 55 patients (frequency 7.3%). Deliberate self-extubation occurred in 46 episodes (77.9%), while there were 13 episodes (22.1%) of accidental extubation. Twenty-seven (45.8%) episodes occurred in patients who were receiving full mechanical ventilatory support and 32 (54.2%) episodes occurred during the weaning period from mechanical ventilation. Reintubation was required in 27 (45.8%) episodes of UEE. The need for reintubation after UEE was 36.9% in deliberate self-extubation patients and 76.9% in accidental extubation patients (p = .01). Only 15.6% (5/32) of patients who presented UEE during weaning required reintubation, while reintubation was mandatory in 81.5% (22/27) of patients who presented UEE during full mechanical ventilatory support (p < .001). A multiple logistic regression analysis was performed to determine the variables independently associated with the need for reintubation: days of mechanical ventilation were significantly associated with the need for reintubation, and weaning was associated with no need for reintubation. The model correctly classified the need for reintubation in 84.7% (50/59) of cases. CONCLUSIONS: Reintubation in UEE patients strongly depends on the type of mechanical ventilatory support. The probability of requiring reintubation if UEE occurs during full ventilatory support is higher than if UEE occurs during weaning. These data suggest that some patients are under mechanical ventilation longer than necessary.

Short-term effects of prone position in critically ill patients with acute respiratory distress syndrome.

OBJECTIVE: Changing the position from supine to prone is an emerging strategy to improve gas exchange in patients with the acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the acute effects on gas exchange, hemodynamics, and respiratory system mechanics of turning critically ill patients with ARDS from supine to prone. DESIGN: Open, prospective study. SETTING: General intensive care units. PATIENTS: 23 patients [mean age 56 +/- 17 (SD) years] who met ARDS criteria and had a Lung Injury Score > 2.5 (mean 3.25 +/- 0.3). INTERVENTIONS: The decision to turn a patient was made using a protocol based on impaired oxygenation despite the use of positive end-expiratory pressure and a fractional inspired oxygen (FIO2) of 1. MEASUREMENTS AND RESULTS: We measured gas exchange and hemodynamic variables in all patients and in 16 patients calculated respiratory system compliance when they were supine and 60 to 90 min after turning them to a prone position. This latter position was remarkably well tolerated and no clinically relevant complications or events were detected either during turning or while prone. The partial pressure of oxygen in arterial blood (PaO2)/FIO2 ratio improved from 78 +/- 37 mm Hg supine to 115 +/- 31 mm Hg prone (p < 0.001), and intrapulmonary shunt decreased from 43 +/- 11 to 34 +/- 8% (p < 0.001). Cardiac output and other hemodynamic parameters were not affected. Respiratory system compliance slightly improved from 24.7 +/- 10.2 ml/cmH20 supine to 27.8 +/- 13.2 ml/cmH20 prone (p < 0.05). An improvement in PaO2/FIO2 of more than 15% from changing from supine to prone was found in 16 patients (responders). Responders had more hypoxemia (PaO2/FIO2 70 +/- 23 vs 99 +/- 53 mm Hg in non-responders, p < 0.01), more hypercapnia (partial pressure of carbon dioxide in arterial blood (70 +/- 27 vs 64 +/- 9 mm Hg, p < 0.01) and a shorter elapsed time to the onset of ARDS and turning to the prone position (11.8 +/- 16 vs 32.8 +/- 42 days, p < 0.01). CONCLUSIONS: Turning critically ill, severely hypoxemic patients from the supine to the prone position is a safe and useful therapeutic intervention. Our data suggest that prone positioning should be carried out early in the course of ARDS.

[Cranioencephalic trauma in adults: clinical and radiologic features]. / Traumatismo craneoencefálico del adulto: aspectos clínicos y radiológicos.

BACKGROUND: To analyse extracranial complications and basic variables in head-injury patients, such as Glasgow coma score (GCS), intracranial pressure (ICP) and cranial computerized tomography (CT), in relation to the outcome of these patients. PATIENTS AND METHODS: 64 consecutive patients (47 males and 17 females) with head injury, admitted from January 1992 to May 1994, were studied in this prospective study. Mean age was 37 +/- 18 years. Overall mortality was 23% (15/64). Student-t and Chi-square tests were used for statistical analysis, and p < 0.05 was considered statistical significant. RESULTS: Overall GCS was 7 +/- 3, survivors presenting GCS of 7.7 +/- 2.9 and non-survivors 4.7 +/- 1.5 (p = 0.04). CT were classified as follows: diffuse injury, 4 patients (7%); focal injury, 32 (53%), and mixed injury 24 (40%). Depending on the presence or absence of mesencephalic cisterns in the CT, GSC was 7.6 +/- 2.8 and 4.3 +/- 1.4, respectively (p = 0.04). Subarachnoid hemorrhage (SAH) was associated to a GCS of 6.3 +/- 2.5 and its absence to 8 +/- 3.3 (p = 0.03). The absence of mesencephalic cisterns and SAH were more frequent in the non-survivors, 72% and 32% (p = 0.01 and 0.04), respectively. ICP was recorded in 42 patients. Regarding to ICP, mortality was: 6.7% with ICP < or = 20 mmHg, 37% with ICP 21-30, 44% with ICP 31-40 and 67% with ICP > 50 mmHg (p = 0.03). Diabetes insipidus, cardiorespiratory arrest, shock, prolonged mechanical ventilation, SDRA and sepsis were the most frequent extracranial complications in non-survivors. CONCLUSIONS: There is an association between the outcome of head-injury patients with the GCS and ICP values. Absence of mesencephalic cisterns and SAH were radiologic signs of poor prognosis. Patients who died had more extracranial complications.

Prognostic indexes and mortality in critically ill patients with acute renal failure treated with different dialytic techniques.

The objective of this study was to compare the evolution of patients with acute renal failure (ARF) treated conservatively or with different dialytic techniques in an intensive care unit (ICU). From June 1992 to November 1994, 1087 consecutive patients were admitted in our ICU. Two hundred and twenty of these presented with ARF, and were divided into three groups; group I (control group): 156 patients with ARF who did not receive substitutive techniques; group II: 21 patients under intermittent hemodialysis (IHD) or peritoneal dialysis (PD); group III: 43 patients under continuous hemodiafiltration (CHDF). The studied variables were age, etiology of renal failure, requirement of dialysis, type of dialysis, length of ICU and hospital stay, and renal function outcome. APACHE II and SAPS scores were recorded on admission and analyzed for hospital mortality. Chi-square test and the analysis of variance were used for the statistical analysis. Results are presented as mean +/- SD. A p value below 0.05 was considered statistically significant. Although etiology of ARF was multifactorial, we found a high frequency of ARF due to sepsis (56.8%), hypoperfusion (58.7%), and acute tubular necrosis (62.5%). Sepsis and heart failure were clinical conditions associated to a greater mortality. We did not find any statistical difference between the two dialyzed groups for all the studied variables, nor between the three groups regarding APACHE II and hospital stay. Significant differences were found between dialyzed and non-dialyzed patients respect to age, group I: 64.1 +/- 13.6, group II: 56.4 +/- 19.7, and group III: 56.0 +/- 14.1 (p < 0.001), creatinine peak serum levels, group I: 260 +/- 130, group II: 494 +/- 209, and group III: 441 +/- 170 mumol/L (p < 0.0001), and mortality, group I: 46.9%, group II: 66.7%, and group III: 76.2% (p < 0.002). SAPS score showed differences between the control group and the CHDF group 13.9 +/- 4.8 and 16.4 +/- 5.4 (p < 0.007), respectively. The use of dialytic techniques in critically ill ARF patients is associated with greater mortality. Prognostic indexes on admission did not correctly classify our patients with ARF. Continuous hemodiafiltration does not involve greater mortality or length of stay as compared to conventional dialysis.

[Gas exchange and hemodynamic effects of nitric oxide inhalation in patients with acute respiratory distress syndrome]. / Efectos gasométricos y hemodinámicos de la inhalación de óxido nítrico en pacientes con síndrome de distrés respiratorio agudo.

BACKGROUND: To analyze the effects on gas exchange and hemodynamics of nitric oxide inhalation in patients with acute respiratory distress syndrome. PATIENTS AND METHODS: Prospective study including 16 acute respiratory distress syndrome patients. We analyzed the acute and short-term (5 days) effects of inhaling 5 parts per million (ppm) nitric oxide on gas exchange and hemodynamics. RESULTS: After nitric oxide inhalation, PaO2/FiO2 ratio changed from 81 +/- 25 to 126 +/- 57 mmHg (p = 0.0001), mean pulmonary artery pressure decreased from 30.1 +/- 8.2 to 27.3 +/- 6.6 mmHg (p = 0.002), intrapulmonary shunt decreased from 44.6 +/- 11% to 34.1 +/- 7.9% (p = 0.002) and cardiac index did not change. Thirteen out of 16 patients (81.2%) presented at least a 20% improvement in PaO2/FiO2 ratio. In the 10 patients treated over 5 consecutive days, we observed that those who improved (increase in PaO2/FiO2 ratio higher than 20% after inhaling 5 ppm nitric oxide) showed a lower cardiac index, a higher mean pulmonary artery pressure and a higher pulmonary vascular resistance index than those who did not: Cl 3.9 +/- 0.81 vs 4.9 +/- 0.81 l/min/m2 (p < 0.001), mean pulmonary artery pressure 32.4 +/- 7 vs 25.3 +/- 4.2 mmHg (p = 0.001), and pulmonary vascular resistance index 421 +/- 199 vs 241 +/- 106 dyn.s.cm5/m2 (p = 0.003). Mean levels of methemoglobin were 1.1 +/- 0.24% (range: 0.4-1.6%), and NO2 concentration was always lower than 100 parts per billion. CONCLUSIONS: Low doses of inhaled nitric oxide induce a selective pulmonary vasodilatation and significant improvement of oxygenation in the majority of acute respiratory distress syndrome patients, although those with a hyperkinetic hemodynamic status are less likely to improve the oxygenation. These effects are maintained for at least 5 days. We did not observe rebound effects.