Light affects heart rate's 24-h rhythmicity in intensive care unit patients: an observational study.

BACKGROUND: Intensive care unit (ICU) patients experience two affronts to normal 24-h rhythms: largely internal events such as medication and external factors such as light, noise and nursing interventions. AIMS AND OBJECTIVES: We investigated the impact of light variance within an ICU on 24-h rhythmicity of three key physiological parameters: heart rate (HR), mean arterial blood pressure (MAP) and body temperature (BT) in this patient population. DESIGN: Patients were assigned to beds either in the 'light' or 'dark' side within a single ICU. An actigraph continuously recorded light intensity for a 24-72-h period. METHODS: Measurements of HR, MAP and BT were recorded every 30 min. RESULTS: HR, MAP and BT did not follow 24-h rhythmicity in all patients. Higher light exposure in the Light Side of the ICU (122·3 versus 50·6 lx) was related to higher HR (89·4 versus 79·8 bpm), which may translate to clinically relevant outcomes in a larger sample. Duration of stay, the one clinical outcome measured in this study, showed no significant variation between the groups (p = 0·147). CONCLUSIONS: ICU patients are exposed to varying light intensities depending on bed positioning relative to natural sunlight, affecting the 24-h rhythm of HR. Larger, well-controlled studies also investigating the effect of relevant light intensity are indicated. RELEVANCE TO CLINICAL PRACTICE: Light is a variable that can be manipulated in the constrained environment of an ICU, thus offering an avenue for relatively unobtrusive interventions.

Variable cost of ICU care, a micro-costing analysis.

Intensive care unit (ICU) costs account for a great part of a hospital's expenses. The objective of the present study was to measure the patient-specific cost of ICU treatment, to identify the most important cost drivers in ICU and to examine the role of various contributing factors in cost configuration. A retrospective cost analysis of all ICU patients who were admitted during 2011 in a Greek General, seven-bed ICU and stayed for at least 24hours was performed, by applying bottom-up analysis. Data collected included demographics and the exact cost of every single material used for patients' care. Prices were yielded from the hospital's purchasing costs and from the national price list of the imaging and laboratory tests, which was provided by the Ministry of Health. A total of 138 patients were included. Variable cost per ICU day was €573.18. A substantial cost variation was found in the total costs obtained for individual patients (median: €3443, range: €243.70-€116,355). Medicines were responsible for more than half of the cost and antibiotics accounted for the largest part of it, followed by blood products and cardiovascular drugs. Medical cause of admission, severe illness and increased length of stay, mechanical ventilation and dialysis were the factors associated with cost escalation. ICU variable cost is patient-specific, varies according to each patient's needs and is influenced by several factors. The exact estimation of variable cost is a pre-requisite in order to control ICU expenses.

Role of new biomarkers: functional and structural damage.

Traditional diagnosis of acute kidney injury (AKI) depends on detection of oliguria and rise of serum creatinine level, which is an unreliable and delayed marker of kidney damage. Delayed diagnosis of AKI in the critically ill patient is related to increased morbidity and mortality, prolonged length of stay, and cost escalation. The discovery of a reliable biomarker for early diagnosis of AKI would be very helpful in facilitating early intervention, evaluating the effectiveness of therapy, and eventually reducing cost and improving outcome. Innovative technologies such as genomics and proteomics have contributed to the discovery of new biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys C), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP). The current status of the most promising of these novel AKI biomarkers, including NGAL, Cys C, KIM-1, L-FABP, and IL-18, is reviewed.

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.

Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients.

PURPOSE: The purpose of this study was to describe inhaled colistin pharmacokinetics in patients with ventilator-associated tracheobronchitis (VAT) due to polymyxin-only susceptible Gram-negative bacteria (GNB). METHODS: Inhaled colistimethate sodium (CMS) was administered at a dose of 80 mg every 8 h for 7 days. Mini bronchoalveolar lavage (BAL) was performed before and at 1, 4 and 8 h, while blood samples were collected before and at 0.16, 0.5, 1, 2, 4 and 8 h after the first dose. Colistin concentrations in BAL and serum were determined by high-performance liquid chromatography. RESULTS: Our study population included 20 patients. At the end of treatment, cure was achieved in 16 patients and favorable microbiological response in 12 patients. Median (25-75 % interquartile range) colistin concentrations in epithelial lining fluid (ELF) were 6.7 (4.8-10.1), 3.9 (2.5-6.0) and 2.0 (1.0-3.8) µg/ml at 1, 4 and 8 h, respectively, and fivefold higher than those achieved in serum. Median ELF concentrations at 1 and 4 h were above the minimum inhibitory concentrations of all isolated pathogens; however, the 4-h median was below the European Committee on Antimicrobial Susceptibility Guidelines (EUCAST) breakpoints for Pseudomonas aeruginosa and the 8-h median was low relative to EUCAST breakpoints for all GNB. Colistin pharmacokinetic/pharmacodynamic parameters in ELF were associated with favorable microbiological response at the end of treatment. CONCLUSION: Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 80 mg of inhaled CMS every 8 h may not be adequate for the treatment of lower respiratory tract infections due to multi-drug resistant GNB.

Combined nutritional support in patients with chronic obstructive pulmonary disease (COPD), under mechanical ventilation (MV).

BACKGROUND/AIMS: The importance of nutrition is clearly established in the management of the critically ill patient: malnutrition contributes to immune incompetence, poor wound healing, increased postoperative complication and prolonged hospital stay. The interaction between nutritional status, nutritional supply and respiratory function is important in the management of the Chronic Obstructive pulmonary Disease (COPD) patients under mechanical ventilation (MV). In the present study was analyzed the benefits of combined nutritional support in patients with COPD under MV. METHODOLOGY: One hundred ninety two (192) patients with COPD were admitted to our Intensive Care Unit (ICU), due to severe respiratory failure of whom 163 (84.9%) patients were under MV. In 18 (11.04%) patients after the 10th day under MV and due to severe malnutrition (serum albumin < 2.5 gm/dl, total lymphocyte count (TLC) < 900/mm3), added in the enteral nutrition (EN) of 1800 Kcals and parenteral nutrition (PN) of 2000 Kcals, at high concentration in lipids from central venous catheter. RESULTS: Seven (38.89%) patients on the 4th day, after combined nutrition, had a positive balance of nitrogen and normal level of the nutritional indices, 4 (22.22%) were on normal level on the 5th day, 3 (16.67%) on the 6th day, 1 (5.56%) on the 7th day after combined nutrition. We had no complications from the combination of EN and PN. Conclusively, of these 18 patients that were given both EN and PN, 15 (83.33%) were weaned from MV and continued the combined nutritional support for 3 days, while 3 (16.67%) died during the combination of EN and PN, without having achieved a normal level of the indices of nutrition and without a positive balance of nitrogen. CONCLUSIONS: In this study was found that: 1. patients with COPD under MV rapidly developed malnutrition, 2. the combination EN and PN without complications contribute to the weaning from MV, 3. positive nitrogen balance and normal increases of nutrition are achieved after the 4th day of combined nutrition and 4. Early addition of EN and PN in patients with COPD under MV, probably accelerates the weaning from MV, reduces hospitalization, changes the outcome and reduces the cost of hospitalization of patients with COPD under MV in ICU.

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).

Resolution of Page kidney-related hypertension with medical therapy: a case report.

A 24-year-old man developed systolic hypertension as a result of renal contusion, perinephric fluid collection, and renal compression (Page kidney) after blunt renal trauma. The patient was treated with an angiotensin-converting enzyme inhibitor for 30 days, after which his blood pressure normalized and the medications were discontinued. Follow-up clinical and laboratory examinations at 3, 6, and 12 months showed normal results. Transient hypertension may develop in patients after blunt renal injury as a result of Page phenomenon. Appropriate medical therapy is warranted and may be successful because spontaneous resolution may be delayed or not occur at all.

Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients.

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml, respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml, respectively, in CSF. The mean +/- SD areas under the concentration-time curves (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 microg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens.

Penetration of gentamicin into the alveolar lining fluid of critically ill patients with ventilator-associated pneumonia.

STUDY OBJECTIVES: To estimate the penetration of gentamicin into lung tissue by measuring its concentrations in alveolar lining fluid (ALF) and blood in critically ill patients with ventilator-associated pneumonia (VAP). PATIENTS AND INTERVENTIONS: The study population consisted of 24 patients who were admitted to an ICU for respiratory failure and developed VAP. Patients were scheduled to undergo bronchoscopy with BAL after IV administration of a once-daily, 240-mg schedule of gentamicin for the treatment of VAP. Patients were assigned at random to one of four groups of six patients each according to the scheduled time for bronchoscopy (1, 2, 4, or 6 h, respectively). A serum sample was obtained at 0.5 h (n = 24), and both serum and ALF samples (n = 6) were collected at each of the above specified times for measurement of antibiotic concentrations. MEASUREMENTS AND RESULTS: Mean +/- SEM gentamicin concentrations in the ALF were 2.95 +/- 0.37, 4.24 +/- 0.42, 3.10 +/- 0.39, and 2.65 +/- 0.35 microg/mL at 1, 2, 4, and 6 h, respectively, after the start of antibiotic infusion. Maximum gentamicin concentrations in serum (13.39 +/- 0.91 mug/mL, n = 24) and ALF (4.24 +/- 0.42 microg/mL, n = 6) were achieved at 0.5 h and 2 h, respectively, giving a penetration ratio of 0.32. The mean ratios of ALF/serum concentrations between 1 h and 6 h ranged from 0.30 to 1.14. After completion of the distribution phase, a significant positive correlation (p = 0.02) was found between gentamicin concentrations in the serum and ALF. CONCLUSIONS: Once-daily IV administration of 240-mg gentamicin achieved average peak antibiotic concentrations of 4.24 microg/mL in the ALF 2 h after administration, and an ALF/serum penetration ratio of 32%. Higher gentamicin doses to produce higher peak blood levels than those found with the study dose are necessary to obtain active alveolar concentrations against less sensitive microorganisms in the treatment of VAP in ICU patients.

Seasonal variation in whole blood cytokine production after LPS stimulation in normal individuals.

We examined seasonal differences in whole blood cytokine production after endotoxin (LPS) stimulation in 17 healthy individuals from an urban area having normal sleep/wakefulness pattern. We used 500 pg/ml of LPS for incubation period of 4 h to stimulate 100 microl of whole blood of the same subjects in June, September, February, and March. We found no differences in the circulating total WBCs and differentials including monocytes between different seasons. We found during September (autumn) a reduced pro-inflammatory cytokine production in terms of TNF-alpha and IL-6 production compared to the other seasons. We also found a reduced anti-inflammatory cytokine production in June (summer) and September (autumn) in terms of IL-10, TNF-RI and TNF-RII compared to February (winter) and March (spring). Our results suggest that in early summer there is a predominating pro-inflammatory cytokine response which is counterbalanced early in autumn. These results may have significant implications in the determination of reference values, in exploration of immune response and inflammatory disease prevalence between different seasons, in determining LPS tolerance (immunoparalysis) and planning clinical trials and immunomodulary therapies. However, the effect of dark/light exposure differences on the circadian periodicity in the responsiveness of immune cells during different seasons should be further investigated.

Safety and efficacy of molgramostim as an adjunctive therapy in critically ill patients with severe sepsis.

The aim of this uncontrolled, prospective, clinical study was to investigate the efficacy and safety of molgramostim administration in patients with severe sepsis. The subjects were 20 critically ill, mechanically ventilated patients with severe sepsis in a university intensive care unit (ICU). Molgramostim 300 microg s.c. was given every 12 h for 3 d. Treatment for severe sepsis was also administered as medically indicated. No adverse events (clinical or serum chemistry) were considered as drug related. Temperature (p = 0.334) and PaO2/FiO2 index (arterial oxygen tension/inspiratory oxygen fraction) (p = 0.178) were not significantly changed. Total leukocyte and neutrophil count increased significantly (p < 0.001) during drug administration. Simplified Acute Physiology Score II (SAPS II) was not significantly increased (p = 0.955), but there was a statistically significant decrease (p = 0.006) in Sepsis-related Organ Failure Assessment (SOFA) score. Death probability was not statistically different compared with mortality rate on day 28 and overall mortality (p = 0.238 and 0.700, respectively). There were statistically significant decreases (p < 0.01) in serum tumor necrosis factor-alpha (TNF-alpha), TNF-RII and interleukin-2 (IL-2), and an increase in TNF-RI levels between study entry and day 3. Mean ICU stay was 40.2 +/- 7.7 d. In conclusion, molgramostim administration may not affect serum chemistry and PaO2/FiO2 index, may decrease SOFA score but does not produce significant clinical benefit in terms of patients' outcome compared with death probability. It may also influence TNF-alpha, TNF-RI and TNF-RII serum complex levels. These changes may be attributed to the natural clinical course of sepsis or therapy applied.