G Baltopoulos

Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients.

Abstract Background: Neutrophil gelatinase-associated lipocalin (NGAL), an iron-transporting protein rapidly accumulating in the kidney tubules and urine after nephrotoxic and ischemic insults, has been put forward as an early, sensitive, non-invasive biomarker for acute kidney injury (AKI). The aim of this study was to evaluate urinary NGAL levels as a predictor of early AKI (first 5 days after injury) in multi-trauma patients. Methods: We studied multi-trauma adult patients admitted to the intensive care unit of a trauma hospital. Exclusion criteria were a) known cardiac or chronic kidney disease, and b) initial evaluation after more than 24 h had elapsed from injury. Urinary NGAL was measured using an ELISA technique upon admission and at 24 and 48 h. Presence of AKI was defined by the risk injury failure loss and end-stage kidney classification (RIFLE) criteria. Data are reported as median and interquartile range. Results: A total of 31 patients (25 male, 6 female) were studied. NGAL levels at admission were significantly higher among patients who subsequently developed AKI [155.5 (50.5–205.9) ng/mL vs. 8.0 (5.7–17.7) ng/mL, p=0.0000] and these higher levels persisted over the following 2 days. On the basis of receiver-operating characteristic analysis both NGAL and serum creatinine baseline measurements could predict AKI [area under the curve (95% confidence interval) 0.977 (0.823–0.980) and 0.789 (0.556–0.906), respectively], but the area under the curve for NGAL was significantly larger (p=0.024). A cut-off point >25 ng/mL for NGAL had a sensitivity of 0.91 and specificity of 0.95 in predicting AKI. Conclusions: Urinary NGAL can be used from the 1st day of injury as a reliable predictor of early AKI in multi-trauma patients. Clin Chem Lab Med 2009;47:79–82.

Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.

BACKGROUND The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients. OBJECTIVE The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function. METHODS This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day. RESULTS Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients. CONCLUSION CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

Central Venous and Mixed Venous Oxygen Saturation in Critically Ill Patients

Background: Although mixed venous O₂ saturation (SvO₂) accurately indicates the balance of O₂ supply/demand and provides an index of tissue oxygenation, the use of a pulmonary artery (PA) catheter is associated with significant costs, risks and complications. Central venous O₂ saturation (ScvO₂), obtained in a less risky and costly manner, can be an attractive alternative to SvO₂. Objectives: To investigate whether the values of ScvO₂ and SvO₂ are well correlated and interchangeable in the evaluation of critically ill ICU patients and to create an equation that could estimate SvO₂ from ScvO₂. Methods: Sixty-one mechanically ventilated patients were catheterized upon admission and ScvO₂ and SvO₂ values were simultaneously measured in the lower part of the superior vena cava and PA respectively. Results: SvO₂ was 68.6 ± 1.2% (mean ± SEM) and ScvO₂ was 69.4 ± 1.1%. The difference is statistically significant (p < 0.03). The correlation coefficient r is 0.945 for the total population, 0.937 and 0.950 in surgical and medical patients, respectively. In 90.2% of patients the difference was <5%. When regression analysis was performed, among 11 models tested, power model [SvO₂ = b0(ScvO₂)^b1] best described the relationship between the two parameters (R² = 0.917). Conclusions: ScvO₂ and SvO₂ are closely related and are interchangeable for the initial evaluation of critically ill patients even if cardiac indices are different. SvO₂ can be estimated with great accuracy by ScvO₂ in 92% of the patients using a power model.

Leptin serum levels in cachectic heart failure patients: Relationship with tumor necrosis factor-α system

Cachexia is a strong predictor for mortality in patients with congestive heart failure. To investigate the role of leptin and regulators of apoptosis in cardiac cachexia we compared leptin concentrations and their relation to the TNF system, interleukin 1-beta (IL-1b), and soluble Fas in patients with heart failure with and without cachexia. Patients with cardiac cachexia have increased levels of interleukin-1b compared to non-cachectic heart failure patients [mean(S.E.)=1.11(0.62) vs. 0.02(0.02), P=0.01] and decreased concentrations of leptin [10.79(3.93) vs. 23.24 (8.35), P=0.1]. Leptin levels correlate with TNF-RI in cachectic heart failure patients (r=0.58, P=0.018). The TNF-RI levels were also correlated with Fas, both in all the patients taken together (r=0.5, P=0.006) and in those with cachexia (r=0.52, P=0.036). Our data indicate that more prospective studies are needed to clarify the role of leptin in the pathophysiology of heart failure cachexia.

Efficacy of CPR in a general, adult ICU

AIM To investigate the initial cardiopulmonary resuscitation (CPR) success rate and long term survival in an Intensive care unit (ICU) population. PATIENTS All patients with cardiac arrest over a 2-year-period (1999-2000) in a general, adult ICU of a general hospital of Athens. METHODS Retrospective collection of clinical data concerning patients, CPR characteristics and survival rates. RESULTS We examined 111 ICU patients, aged 56.4+/-1.9 years (72 males). SAPS II score was 43.9+/-3.8. CPR was performed in 98.2% of the patients within 30 s. Initial restoration of cardiac function (RCF) and successful CPR rate was 100% while 24 h survival was 9.2%. Survivors at 24 h were younger, mainly males, with lower SAPS II score, mainly with pulmonary disease, ventricular fibrillation or ventricular tachycardia (8/10) and initial pupil reactivity (5/10). Four patients required more than one cycle of CPR. Survival to discharge was zero. CONCLUSION Although the initial successful CPR rate in ICU patients may be high, long term survival and hospital discharge is disappointing. Although ICU patients are better monitored and treated in a timely fashion, they are disadvantaged by chronic underlying diseases, severe current medical illnesses and multi organ dysfunction syndrome (MODS) leads to worst outcome after CPR compared with in-ward patients.

Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study

OBJECTIVES Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure. PATIENTS AND METHODS Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated. RESULTS Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations. CONCLUSIONS In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.

Procalcitonin in acute myocardial infarction

Objective: Procalcitonin (PCT) is released in severe bacterial infections, sepsis and in infection independent cases such as major surgery, multiple trauma, cardiogenic shock, burns, resuscitation, and after cardiac surgery. The aim of this study was to determine the levels and the kinetics of PCT in AMI and to investigate their possible correlation with the release of IL‐6 and CRP. Design‐Patients: The study included 60 patients (47 men, 63.2±14.8 years) with the diagnosis of AMI at admission. In all patients, serum levels of PCT, IL‐6, CK‐MB, TnI and CRP were measured at admission, at 3, 6, 12, 24, 48 and 72 h and at the seventh day. Results: PCT was elevated in all patients with AMI. It was initially detected in serum approximately 2–3 h after the onset of the symptoms. The median value at admission was 1.3 ng/ml (95% CI: 0.89 to 1.80). The value of PCT showed an increase and reached a plateau after 12–24 h. The median value at 24 h was 3.57 ng/ml (95% CI: 2.89 to 4.55). PCT values fell to baseline (<0.5 ng/ml) by the seventh day. PCT was detected in serum earlier than CK‐MB or TnI in 56 of the 60 patients (93.3%). The kinetics of PCT was similar to those of CK‐MB and TnI. The maximal values of PCT were positively correlated with the maximal values of IL‐6 (r = 0.59, P = 0.00) and of CRP (r = 0.65, P = 0.001). The maximal values of IL‐6 were positively correlated with max CRP (r = 0.35, P = 0.045). Conclusions: PCT could be considered as a novel sensitive myocardial index. Its release in AMI is probably due to the inflammatory process that occurs during AMI.

Monitoring plasma voriconazole levels following intravenous administration in critically ill patients: an observational study

Data relating to the pharmacokinetics of voriconazole in critically ill patients are lacking. A prospective observational study was conducted on 18 non-consecutive critically ill patients aged 24-97 years, comprising 12 patients with normal renal function (NRF) [creatinine clearance (CL(Cr)) > or = 60 mL/min] and 6 patients with moderate renal impairment (MRI) (CL(Cr) 40-55 mL/min), administered voriconazole intravenously (6 mg/kg loading dose and 3-4 mg/kg twice daily thereafter) in order to determine the suitability of these doses in this patient population. Steady-state blood levels were monitored and liver and renal function were recorded throughout treatment. Large variability in patient plasma levels was observed, ranging from 37% at < or = 1 mg/L (minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) to 19% at >5.5mg/L. Moreover, maintaining trough concentrations above clinical breakpoints was not consistently achieved because 16/30 (53%) were < or = 1 mg/L. In a few MRI patients, average concentrations were found to be significantly different compared with those of NRF patients administered the same dose, however this difference was not noted in pharmacokinetic parameters following dose normalisation. None of the patients experienced deterioration in renal or liver function. Recommended voriconazole doses are inadequate to achieve drug concentrations >1 microg/mL over the entire dosing interval in some critically ill patients.

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis: another point of view

We read with interest the paper by Tugrul et al. [1] regarding the effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis managed in their intensive care unit. Apart from the global interest of reading a paper in the field of the treatment of severe sepsis and septic shock, we have an almost similar project in progress. It is well known that the immunotherapy in sepsis is still a gray zone, and it will remain so as long as the relevant literature presents conflicting results [2]. From our understanding and the interim analysis of our data, it seems that we could expect some definitive immunotherapy informationin the near future. In our study, we have presently included 34 patients in the treatment group (IgM + IgG + IgA) and 34 in the control group. Analyzing our data in a manner comparable with that of Tugrul et al. [1], we reach a different conclusion regarding the results. The only difference that exists between our protocol and that of Tugrul et al. regarding the study design and the inclusion criteria is that we include only adults older than 18 years old (the lower age limit of Tugrul et al.s study is 10 years, and adolescents are probably included). The number of patients needed per arm of the study in order to achieve a safe conclusion (statistical power analysis, 80%; P < 0.05 for a mortality decrease of 17%, which was the mortality decrease in our preliminary analysis) is 120 patients in each arm. In a study with a smaller number of patients, therefore, such as those of Tugrul et al. (21 patients in each arm) or ourselves (34 patients in each arm to the present time), any conclusion may be unsafe. Although the data in both studies (in our opinion) are so far not sufficient, a significant difference trend is recorded. The mean age in Tugrul et al.s study is 42.0 ± 18 years in the IgM + IgG + IgA group and 49.3 ± 20.6 years in the control group. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score in that same study is 10.5 ± 4.6 in the IgM + IgG + IgA group and 14.0 ± 8.5 in the control group. Although there is no statistically significant difference, there is a strong tendency for the two means to become different (P = 0.10). In our preliminary data analysis, the mean age is 50.5 ± 3.33 years in the IgM + IgG + IgA group and 50.7 ± 7.36 years in the control group. The APACHE II score in our study is 21.27 ± 7.23 in the IgM + IgG + IgA group and 23.5 ± 7.91 in the control group. The 28-day mortality rate in Tugrul et al.s study is 23.8% in the IgM + IgG + IgA group versus 33.3% in the control group. In our preliminary data analysis, the mortality rate is 22.35% and 40.0% in the IgM + IgG + IgA group and the control group, respectively. Although this difference is a statistically significant one, the analysis of the mortality rate of the subgroups according to the APACHE II scoring of inclusion to the study day is more interesting. The mortality rate in our preliminary data for the IgM + IgG + IgA group with an APACHE II score ranging between 20 and 29 was 22.22%, and that of the control group with the same APACHE II score range was 55%. As we pointed out earlier, in order to demonstrate the clinical effectiveness of immunotherapy in severe sepsis and septic shock, a number of 120 patients is necessary to be included in each arm of our study. Using our preliminary results in the same manner as those in Tugrul et al.s paper [1], we could conclude that it is sometimes possible to present the data in such a way resulting in delusive conclusions. Analyzing the data by means of definitions of sepsis and septic shock, and assuming the patients to be a uniform group, we cannot demonstrate the special subgroups of patients in whom the administration of IgM-enriched immunoglobulin preparations may have highly beneficial effects. By grouping the patients according to some characteristics (such as APACHE II score or Simplified Acute Physiology Score IIscore), the beneficial effect of immunoglobulins could be shown. Using such an approach, a beneficial effect of IgG immunotherapy in a special subgroup of septic patients has already been shown in the study by Dominioni et al. [3]. In conclusion, it seems that there is a subgroup of patients with severe sepsis or septic shock in which the delivery of IgM-enriched immunoglobulin preparations may have a beneficial effect. Further study with more patients, either in our study or that of Tugrul et al., is necessary before we decide whether to use this type of immunotherapy in the treatment of severe sepsis.

Respiratory failure: an overview.

Respiratory failure is defined as a failure in gas exchange due to an impaired respiratory system--either pump or lung failure, or both. The hallmark of respiratory failure is impairment in arterial blood gases. This review describes the mechanisms leading to respiratory failure, the indices that can be used to better describe gas exchange abnormalities and the physiologic and clinical consequences of these abnormalities. The possible causes of respiratory failure are then briefly mentioned and a quick reference to the clinical evaluation of such patients is made. Finally treatment options are briefly outlined for both acute and chronic respiratory failure.