Maria Theodorakopoulou

Health-related quality of life and disability in survivors of multiple trauma one year after intensive care unit discharge.

Dimopoulou I, Anthi A, Mastora Z, Theodorakopoulou M, Konstandinidis A, Evangelou E, Mandragos K, Roussos C: Health-related quality of life and disability in survivors of multiple trauma one year after intensive care unit discharge. Am J Phys Med Rehabil 2004;83:171–176. ObjectiveTo evaluate health-related quality of life and disability in multiple-trauma patients requiring intensive care unit management. DesignA total of 87 survivors of multiple trauma, with a median age of 31 yrs and a median Injury Severity Score of 22, were enrolled in the present study. The Nottingham Health Profile, Glasgow Outcome Scale, and Rosser Disability Scale were used to assess the functional consequences of trauma 1 yr after intensive care unit discharge. ResultsA total of 64 of 87 patients had a problem in at least one of the six domains related to subjective health status. The most prevalent complaint was related to somatic subdimensions, but emotional functioning was also affected. Nottingham Health Profile part 2 showed that 63 of the survivors experienced problems in at least one of the daily activities. Of particular importance, inability to work was reported by 47% of the patients. Fifty-nine percent experienced moderate-to-severe disability as evaluated by Glasgow Outcome Scale and Rosser Disability Scale. High aggregate injury severity score along with severe head trauma were independent predictors of poor health-related quality of life and disability. ConclusionsThe majority of survivors of major trauma exhibit considerable levels of disability and impairment in health-related quality of life. Global injury severity score and degree of brain trauma determine functional limitations. This information may help in organizing long-term rehabilitation of multiple-trauma patients.

Prognostic importance of increased plasma amino-terminal pro-brain natriuretic peptide levels in a large noncardiac, general intensive care unit population.

The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. The study end point was ICU outcome. Blood samples were drawn on admission in the ICU and on postadmission days 1 and 2 to determine NT-pro-BNP levels. In a subgroup (n = 77), admission proinflammatory and anti-inflammatory cytokine levels, including TNF-&agr;, IL-6, and IL-10, were also measured. Nonsurvivors (n = 98) had significantly higher NT-pro-BNP levels than survivors (n = 135) on admission in the ICU (2,074 vs. 283 pg/mL; P < 0.001), on day 1 (2,197 vs. 221 pg/mL; P < 0.001), and on day 2 (2,726 vs. 139 pg/mL; P < 0.001). Median values for TNF-&agr;, IL-6, and IL-10 were 3.70, 131.57, and 111.88 pg/mL, respectively. Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve in predicting ICU mortality was 0.70 for APACHE II and 0.77 for admission NT-pro-BNP (P = 0.08). The cutoff in admission NT-pro-BNP that best predicted outcome was 941 pg/mL. Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P < 0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis

PURPOSE The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. METHODS A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. RESULTS Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). CONCLUSIONS Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.

Treatment of invasive candidiasis in the elderly: a review

Fungi are major causes of infections among immunocompromised or hospitalized patients with serious underlying diseases and comorbidities. Candida species remain the most important cause of opportunistic infections worldwide, affecting predominantly patients over 65 years old, while they are considered to be the fourth most common cause of nosocomial bloodstream infections. The rapidly growing elderly population has specific physiological characteristics, which makes it susceptible to colonization and subsequent infection due to Candida species. Comorbidities and multidrug use should be taken into account any time the therapeutic regimen is under consideration. Different classes of antifungal drugs are available for the treatment of invasive fungal infections but echinocandins, apart from their activity against resistant strains (Candida glabrata and Candida krusei), seem to be safe, with limited adverse events and minimal drug–drug interactions in comparison to the other regimens. Therefore, these agents are strongly recommended when dealing with elderly patients suffering from an invasive form of Candida infection.

Controversies in the management of the critically ill: the role of probiotics

Probiotics are commercially available, viable, non-pathogenic micro-organisms that, when ingested in sufficient quantities, exert a health benefit to the host derived through modification of the gut flora, local release of antimicrobial factors, maintenance of integrity of the gut barrier, competition for epithelial adherence, prevention of bacterial translocation, and modulation of the local immune response. In critically ill patients, probiotics appear to lead to decreased susceptibility to antibiotic-associated diarrhoea, Clostridium difficile infections, ventilator-associated pneumonia, necrotising enterocolitis, acute severe pancreatitis, sepsis and multiple organ dysfunction syndrome as well as a shortened duration of infections. Current scientific evidence supporting the use of probiotics is not conclusive and is mainly derived from single-centre, not very well designed trials that are limited by many factors including small sample sizes, heterogeneity in the probiotic strains used, effectiveness of the combined strains, optimum dose regimens, frequency and duration of administration, and certainly incomplete knowledge of the mechanism of action of each strain. Probiotics appear to be well tolerated, whilst adverse events are very rare. The most commonly reported adverse events include bacteraemia, fungaemia and sepsis. At present, based on the available evidence and although helpful and relatively safe for certain disease conditions, routine use of probiotics in the critically ill is not recommended.

Interstitial cortisol obtained by microdialysis in mechanically ventilated septic patients: Correlations with total and free serum cortisol

PURPOSE The aim of this study was to measure subcutaneous tissue cortisol obtained by microdialysis (MD) in 35 mechanically ventilated septic patients. MATERIALS AND METHODS Upon intensive care unit admission, an MD catheter was inserted into the subcutaneous tissue of the thigh. Cortisol (CORT) was determined in a 5:00 to 9:00 am microdialysate sample collected within 72 hours. Concurrently, serum total (T-CORT) and free CORT (F-CORT) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment scores were calculated. Both T-CORT less than 10 μg/dL and F-CORT less than 0.8 μg/dL were considered as indicating critical illness-related corticosteroid insufficiency. Adrenal adequacy was defined as T-CORT greater than 20 μg/dL or F-CORT greater than 2.0 μg/dL. RESULTS Total CORT correlated significantly with F-CORT (rs = +0.8, P < .0001). Microdialysis CORT had a lower correlation with T-CORT (rs = +0.6, P < .0001) and F-CORT (rs = +0.7, P < .0001) and a weak correlation with APACHE II score (rs = +0.4, P < .01). On the basis of MD-CORT, the patients were divided in quartiles. Although the median F-CORT and T-CORT levels were significantly different (P < .001) among the MD-CORT quartiles, there was a considerable overlap between the subgroups. All patients with T-CORT less than 10 μg/dL and all but 3 patients with F-CORT less than 0.8 μg/dL had tissue CORT in the lower quartile. However, only 50% and 58% of patients with adequate T-CORT and F-CORT levels, respectively, had concordant MD-CORT in the highest quartile. CONCLUSIONS Microdialysis CORT levels correlate moderately with circulating T-CORT and F-CORT. Of note, several patients presented with discrepant measurements between interstitial and circulating CORT concentrations. Thus, interstitial CORT measurements represent an additional tool to investigate the tissue CORT availability in critically ill patients.

KINETICS OF ADIPOSE TISSUE MICRODIALYSIS-DERIVED METABOLITES IN CRITICALLY ILL SEPTIC PATIENTS: ASSOCIATIONS WITH SEPSIS SEVERITY AND CLINICAL OUTCOME

Microdialysis (MD) provides the opportunity to monitor tissue metabolic changes. This study aimed to describe the kinetics of MD-derived metabolites during the course of critical sepsis, to assess whether these metabolites are useful in grading sepsis severity, and to investigate their prognostic use. To this end, 54 mechanically ventilated septic patients were prospectively studied, out of which 39 had shock. Upon sepsis onset, an MD catheter was inserted into the subcutaneous adipose tissue of the upper thigh. Dialysate samples were analyzed for glucose, pyruvate, lactate, and glycerol. Sampling was performed six times per day for a maximum of 6 days. The daily mean values of MD measurements were calculated for each patient. Arterial blood was analyzed for glucose, lactate, and glycerol concomitantly with dialysate sampling. Blood glucose and tissue glucose levels along with lactate levels were high during the entire study period. Tissue pyruvate and glycerol were also raised, whereas the lactate-pyruvate ratio was preserved. At study entry, patients with septic shock had higher tissue lactate (3.3 vs. 1.9 mmol/L, P = 0.01) and glycerol (340 vs. 169 &mgr;mol/L, P = 0.04) levels compared with those without shock. Nonsurvivors had higher tissue lactate (P = 0.008), glycerol (P = 0.004), and pyruvate (P = 0.002) levels than survivors during the whole observation period. Logistic regression analysis showed that age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.004-1.150; P = 0.03), Sequential Organ Failure Assessment score on day 1 (OR, 1.550; 95% CI, 1.043-2.312; P = 0.03), and tissue glycerol on day 1 (OR, 1.007; 95% CI, 1.001-1.012; P = 0.01) predicted mortality independently. In conclusion, critical sepsis is characterized by high tissue lactate and pyruvate levels and a preserved lactate-pyruvate ratio, suggesting a nonischemic mechanism for raised blood lactate levels. Septic shock is associated with higher tissue lactate and glycerol levels compared with sepsis without shock. Elevated tissue lactate, pyruvate, and glycerol levels are related to poor clinical outcome, with the latter constituting an independent predictor.

TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen

BackgroundCurrent knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis.MethodsPeripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients.ResultsWithin patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis.ConclusionsDecrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.

Interrelationship between blood and tissue lactate in a general intensive care unit: a subcutaneous adipose tissue microdialysis study on 162 critically ill patients.

PURPOSE The aim of the study was to study the interrelationship between blood and tissue lactate in critically ill patients with or without shock admitted in a general intensive care unit. MATERIALS AND METHODS We studied 162 mechanically ventilated patients: 106 with shock (septic shock, 97; cardiogenic shock, 9) and 56 without shock (severe sepsis, 38; systemic inflammatory response syndrome, 18). A microdialysis catheter was inserted in the subcutaneous adipose tissue of the upper thigh, and interstitial fluid was collected every 4 hours for a maximum of 6 days. We assessed the relationship between tissue and blood lactate using cross-approximate entropy and cross-correlation analysis. RESULTS Patients with shock had higher area under the curve for blood (261 vs 175 mmol/L*hours, P < .0001) and tissue lactate (386 vs 281 mmol/L*hours, P < .0001) compared with patients without shock. The interrelationship of tissue-blood lactate, as assessed with cross-approximate entropy, was more regular in patients with shock compared with patients without shock. Cross-correlation of tissue vs blood lactate yielded higher correlation coefficients in patients with shock compared with those without shock, being higher when tissue lactate preceded blood lactate by 4 hours compared with tissue vs blood lactate with no lag time. CONCLUSIONS In critical illness, the detailed dynamics between blood and tissue lactate are affected by the presence of shock. In patients with shock, microdialysis-assessed tissue lactate is higher compared with those without shock and may detect metabolic disturbances before these become evident in the systemic circulation.

Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: effects of shock and treatment.

PURPOSE The purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects. MATERIALS AND METHODS We studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute phase of critical illness (day 6). All subjects had a tissue microdialysis (MD) catheter placed in femoral adipose tissue upon admission to the intensive care unit (ICU). Plasma cholesterol, high-density lipoprotein, low-density lipoprotein, free fatty acids (FFAs), triglyceride, and MD glycerol (GLYC) were measured on days 1 and 6 in the ICU. RESULTS On admission, 56% of the patients had increased levels (>200 μmol/L) of MD GLYC. Patients with shock displayed more pronounced subcutaneous tissue lipolysis and more profound derangements of circulating lipids vs patients without shock (but no appreciable differences in FFA levels). Furthermore, in patients with shock during the acute period, there were positive, albeit weak, correlations of subcutaneous tissue lipolysis (MD GLYC), plasma FFAs (r=0.260; P=.01), and norepinephrines dose (r=0.230; P=.01), whereas during the subacute phase, MD GLY levels were higher in patients receiving glucocorticoids (344.7±276.0 μmol/L vs 252.2±158.4 μmol/L; P=.03). CONCLUSIONS Subcutaneous tissue lipolysis is only one of the many determinants of plasma FFAs. Routinely applied therapeutic modalities in the ICU interfere with adipose tissue metabolism.