Clinical factors affecting costs in patients receiving systemic antifungal therapy in intensive care units in Greece: Results from the ESTIMATOR study.

Invasive fungal infections are common in intensive care units (ICUs) but there is a great variability in factors affecting costs of different antifungal treatment strategies in clinical practice. To determine factors affecting treatment cost in adult ICU patients with or without documented invasive fungal infection receiving systemic antifungal therapy (SAT) we have performed a prospective, multicentre, observational study enrolling patients receiving SAT in participating ICUs in Greece. During the study period, 155 patients received SAT at 14 participating ICUs: 37 (23.9%) for proven fungal infection before treatment began, 10 (6.5%) prophylactically, 77 (49.7%) empirically and 31 (20.0%) pre-emptively; 66 patients receiving early SAT (55.9%) were subsequently confirmed to have proven infection with Candida spp. (eight while on treatment). The most frequently used antifungal drugs were echinocandins (89/155; 57.4%), fluconazole (31/155; 20%) and itraconazole (20/155; 12.9%). Mean total cost per patient by SAT strategy was €20 458 (proven), €15 054 (prophylaxis), €23 594 (empiric) and €22 184 (pre-emptive). Factors associated with significantly increased cost were initial treatment failure, length of stay (LOS) in ICU before starting SAT (i.e. from admission until treatment start), fever and proven candidaemia (all P≤.05). CONCLUSION: Early administration of antifungal drugs was not a substantial component of total hospital costs. However, there was a significant adverse impact on costs with increasing LOS in febrile patients in ICU for whom diagnosis of fungaemia was delayed before starting SAT, and with initial treatment failure. Awareness of potential candidaemia and initiation of pre-emptive or empirical strategy as early appropriate treatment may improve ICU patient outcomes while reducing direct medical costs.

Management of sudden hearing loss with hyperbaric oxygen therapy.

UNLABELLED: Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as the sensorineural hearing loss of a minimum of 30 dB in at least three frequencies for three days or more. This study aims to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBO2) in the management of idiopathic sudden sensorineural hearing loss. MATERIAL-METHODS: Patients with ISSHL received treatment including oral corticosteroids and HBO2. HBO2 protocol included five phases of five sessions each. ISSHL was assessed by measuring the tonal audiogram before and after each phase. Tinnitus was assessed using a questionnaire and a visual analogue scale at the beginning and the end of the study. Secondary assessment points included changes in the intensity and the improvement of tinnitus. RESULTS: 56 patients were included in the study. All patients completed Phases I and II of HBO2, 43 completed Phase III, 13 completed Phase IV, and six completed all five phases. Overall, a significant improvement was noted between the initial and final audiogram after HBO2 (p < 0.001). Tinnitus evaluation score, intensity and related problems were also significantly reduced (p < 0.001). CONCLUSION: This study affirms previous findings that the use of HBO2 and vasodilators are efficacious in the treatment of ISSHL. Our findings also suggest benefit for the treatment of tinnitus.

Immune responses during and after exercise of constant and alternating intensity above the lactate threshold.

AIM: Intense and prolonged exercise greatly affects circulating cytokine levels. The purpose of this study was to investigate the possible changes in tumour necrosis factor -a (TNF-a), interleukin 6 (IL-6) and cortisol concentrations during and after prolonged exercise of constant and alternating intensity of the same duration and total work performed. METHODS: Ten male subjects underwent two main cycling exercise trials lasting one hour each. On one occasion, exercise intensity was alternated between 46.5±1.9% of maximal oxygen uptake (VO2max ) for 40 s and 120% of VO2max for 20 s, so that the mean intensity corresponded to 105% of the lactate threshold. On the other occasion, exercise intensity was constant at 105% of the lactate threshold. Levels of TNF-a, IL-6 after lipo polysaccharide (LPS) stimulation as well as cortisol were measured at rest, 30 and 60 minutes of exercise and 1 hour after. RESULTS: No significant differences were observed in TNF-a concentrations between the two exercise protocols (P= 0.75), but there was a significant time effect (P<0.01). TNF-a was increased in both groups from a resting value of 436.1±102.5 to 649.5±187.7 pg/mL (P<0.05) at the end of exercise and was subsequently decreased 1 hour post exercise to 305.9±78.8 pg/mL (P<0.01). No significant difference in IL-6 and cortisol concentrations was observed between the two exercise protocols (P=0.13, P=0.10 accordingly). CONCLUSION: In conclusion, prolonged constant and alternating intensity exercise of the same mean intensity and duration seemed to provoke similar changes in aspects of immune response in healthy subjects.

Psychological distress and delusional memories after critical care: a literature review.

BACKGROUND: A considerable number of intensive care unit (ICU) survivors report delusional memories, which refer to dreams, nightmares, paranoid delusions and hallucinations experienced in the ICU. These memories often have a strong vividness, long duration and high emotional impact. AIM: The aim of this review was to investigate and synthesize published literature about psychological distress associated with delusional memories of adult ICU survivors. METHODS: Using key terms, a search was conducted in major health care electronic databases [Cumulative Index for Nursing and Allied Health Literature (CINAHL), PubMed, Web of Science and PsycInfo] focusing on articles published between 1990 and 2009 in English-language journals. FINDINGS: Ten articles met the inclusion criteria. Recall of delusional memories at various intervals after ICU discharge was associated with post-traumatic stress disorder (PTSD)-related symptoms in many studies, while associations with other aspects of psychological distress, mainly feelings of fear, anxiety and depression, were also reported. Recent studies did not seem to confirm the protective role of factual memories. CONCLUSIONS: The findings support the association between delusional memories and PTSD-related symptoms, but further research is needed to confirm their association with other psychological disorders. Development of a safety sense in the ICU can protect patients against the emotional impact of both delusional and stressful factual ICU memories. Appropriate follow-up of high-risk patients could improve their long-term psychological recovery.

Cardiopulmonary resuscitation in end-stage cancer patients.

Cardiopulmonary resuscitation (CPR) in patients with end-stage cancer is an issue of significant clinical and ethical importance. In general, the overall survival to discharge in cancer patients is referred to be 6.2% (localised - 9.5% vs. metastatic disease - 5.6%) compared to 15% of unselected in-hospital arrests. However, immediate survival, as well as survival to discharge after a successful CPR is affected by multiple factors. Type and extend of tumor, degree of clinical deterioration, functional status and many other factors do correlate with outcome in different degrees. Critical illness scoring systems are commonly used in order to assess performance status of patients and predict outcome. This article will review all the above mentioned factors, as well as patients' perception about "do-not-resuscitate" orders and palliative care.

Penetration of colistin into cerebrospinal fluid.

Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with the exception of one patient with an external ventriculostomy. CSF-to-serum ratios (0.051 to 0.057) for all study patients coincided at all sampling times. The low level (5%) of penetration suggests inadequate bactericidal colistin concentrations in the CSF.

Approach to patients with pulmonary embolism in a surgical intensive care unit.

BACKGROUND/AIMS: Pulmonary embolism (PE) is a potentially life threatening disease. Clinical signs and symptoms allow the clinician to determine the pretest probability of someone having pulmonary embolism but are insufficient to diagnose or rule out the condition. This paper aims to study the clinical presentation, identify the risk factors and evaluate the diagnostic strategies and management of patients with PE. METHODOLOGY: The medical files of 69 patients were searched, who were diagnosed with PE and who were admitted to the Surgical Care Unit. RESULTS: Dyspnea, pleuritic pain, haemoptysis, fever and cough were the most common presenting symptoms. Risk factors for PE were found in 90% of cases. D-dimers assay was elevated in all cases (100%) and the other diagnostic strategies used showed great accuracy in confirming the pretest probabilities of PE. It is of high importance that 75% of the patients had deep vein thrombosis as assessed by venous ultrasonography. Mortality due to PE was approximately 6.9%. CONCLUSIONS: PE can be often overlooked with hazardous consequences. Clinical evaluation in combination with spiral CT or lung scintigraphy and vein ultrasound and D-dimer level can establish the diagnosis in the majority of patients so that effective treatment to be started as soon as possible.

Effect of different ventilatory strategies on local and systemic cytokine production in intact swine lungs in vivo.

The purpose of the study was to investigate the effect of different ventilatory strategies on local and systemic cytokine production in swine with intact lungs in vivo after 4 h of mechanical ventilation. Twenty-five swine were anesthetized and then randomized into five groups (n = 5): (1) low tidal volume zero PEEP (LVZP); (2) medium tidal volume zero PEEP (MVZP); (3) high tidal volume zero PEEP (HVZP); (4) low tidal volume PEEP (LVP); (4) high tidal volume PEEP (HVP). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FiO2) was 1.0. TNF-alpha and IL-10 were measured in BALF and serum at baseline, 2 h, and 4 h of MV. One animal in LVZP (2 h) and two in HVP (3 h) group died before the end of the experiment. TNF-alpha level in BALF was significantly higher in LVZP and LVP at 4 h compared to baseline and the other groups. IL-10 level in BALF was significantly higher in LVP at 4h compared to baseline and the other groups. There was a statistically significant increase in serum TNF-alpha levels at 4 h in LVP group compared to baseline and the other groups at 4 h. There was statistically significant increase in serum IL-10 levels in HVZP and LVP groups at 2 and 4 h which was significantly higher compared to the other groups at 4 h. Our results show that a) low volume MV may induce local and systemic pro- and anti-inflammatory cytokine increase b) in the presence of pro-inflammatory cytokine response there is also an anti-inflammatory response in the same compartment (lungs, circulation). c) There maybe loss of alveolar-to-systemic cytokine compartmentalization.

The influence of varying blood and dialysate flow on haemodialysis adequacy.

The aim of this study was the exploration and correlation of the influence of variations in blood flow and dialysate flow on haemodialysis adequacy through the quantitative indexes Kt/V, TACurea and PCR. A prospective study of 48 patients subjected to haemodialysis was carried out. The collection of data included taking blood and urine samples according to the directives of DOQI, for a total of 8 months. Statistical analysis was based on the paired t-test and multiple regression analysis. The variations in blood flow and dialysate flow are positively related to the variation of the indexes Kt/V, TACurea and PCR and consequently to the haemodialysis adequacy both as isolated factors and when combined together.

Effects of furosemide on pulmonary shunts.

In 23 mechanically ventilated anuric (six) or oliguric (17) patients (less than 16 ml/h of urine output) with severe gas exchange abnormality, we investigated the effect of furosemide on intrapulmonary shunt (Qs/QT). Before and after 0.5, 1, and 2 h of IV administration of 200 mg of furosemide, we assessed the intrapulmonary shunt and PaO2 while patients' hemodynamic measurements were monitored. Ventilatory parameters remained constant throughout the study. While the urine output was minimal and no alteration in hemodynamic values was found, the Qs/QT decreased from 27.7 +/- 2.3 percent (mean +/- SEM) at control to 24.3 +/- 2.1 percent (p less than 0.01) at 0.5 h, 21.7 +/- 2.1 percent (p less than 0.001) at 1 h, and 18.1 +/- 1.8 percent (p less than 0.001) at 2 h. The PaO2 showed no significant difference at 0.5 h but rose significantly from 96 +/- 14 to 105 +/- 14 mm Hg (p less than 0.05) and 111 +/- 14 mm Hg (p less than 0.01) at 1 and 2 h, respectively. Since we observed no changes in hemodynamics, we speculate a direct effect of furosemide in the pulmonary vasculature affecting the ventilation-perfusion mismatch and, therefore, the Qs/QT and PaO2.

Ovarian hyperstimulation syndrome (OHSS): diagnosis and management.

OBJECTIVE: To present our experience and the current knowledge about pathophysiology, diagnosis, and management of the ovarian hyperstimulation syndrome (OHSS). DESIGN: Retrospective study concerning clinical and laboratory findings of severe OHSS. SETTING: General ICU at a maternity-surgical hospital. PATIENTS: Ten patients suffering from severe OHSS. INTERVENTIONS: Supportive and preventive therapeutic measures applied are described. MEASUREMENTS AND RESULTS: Admission and discharge data as well as worst values during disease course were recorded. Clinical and laboratory findings showed third space fluid shift leading to weight gain, generalized tissue edema, ascites, hydrothorax, abdominal distension and pain, chest discomfort, hypovolemia, dehydration, ovaries enlargement, electrolyte disturbances, hypoalbuminemia, high hematocrit, urea, and WBC. CONCLUSIONS: OHSS is an iatrogenic complication of assisted conception of unknown pathogenesis, with potentially life-threatening sequelae due to hemoconcentration such as circulatory shock, ARDS, hepato-renal failure, thromboembolic phenomena, and multi-organ dysfunction syndrome. Gynecologists and intensivists must be aware of the diagnosis and management of the syndrome because of the widely used reproductive techniques for assisted conception.

Paget's bone disease, anaemia and vitiligo: a case report.

The coexistence of Paget's bone disease, pernicious anaemia and vitiligo is very rare. The pathogenesis of Paget's bone disease remains still unknown. We report here a patient having these three entities simultaneously and we suggest that some cases of Paget's bone disease be due to autoimmunity.

Leptin serum levels in cachectic heart failure patients. Relationship with tumor necrosis factor-alpha 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.

Radiographic determination of total lung capacity in patients with pneumonectomy.

To determine whether total lung capacity (TLC) can be measured from plain chest radiographs in patients with pneumonectomy, we examined 20 such patients (17 male, 3 female) who had pneumonectomy for lung carcinoma. In 16 patients the right lung was preserved, and in 4 the left. The TLC was measured with the helium dilution method and by planimetry of the anterior and lateral projections of the lung on chest radiographs, summing the anterior and lateral projected areas of the lung to a single value, S. The correlation between S and TLC by helium gas dilution was r = 0.95. Linear fit of TLC to S explained 99.5% of the variance in TLC, with the equation. The side resected did not influence the predictive value (p < 0.001). The interquartile range of the residual error was +/-130 ml, and standard error was 64 ml. Therefore in patients with pneumonectomy, TLC of the preserved lung may be estimated within +/-130 ml by planimetry of the anterior and lateral chest radiographs.

Venous pressure measurements in the superior and inferior vena cava: the influence of intra-abdominal pressure.

BACKGROUND/AIMS: To investigate the relationship of pressure in the inferior vena cava (Pivc) with a) pressure in the superior vena cava (Psvc), b) intra-abdominal pressure as measured in the urinary bladder (Pcyst). METHODOLOGY: A prospective study of 38 mechanically ventilated patients. Simultaneous measurements of Psvc, Pivc and Pcyst (151 sets of measurements) were performed. Measurements were divided in: Group A (Pcyst < 10 mmHg), group B (10 mmHg < or = Pcyst < 15 mmHg), group C (Pcyst > or = 15 mmHg). Statistical analysis was performed with paired t-test, Pearson correlation. Results are expressed in mean +/- SEM. RESULTS: In Groups A and B, Psvc and Pivc were not significantly different and they were highly correlated (10.8+/-0.5 mmHg vs. 10.9+/-0.5 mmHg, r=0.93 for Group A and 14.4+/-0.7 mmHg vs. 14.7+/-0.6 mmHg, r=0.87 for Group B). Pcyst was significantly lower than Pivc in both groups. In Group C, Pivc was significantly higher than Psvc (18.9+/-0.7 mmHg vs. 16.4+/-0.7 mmHg). There was no significant difference between Pivc and Pcyst (19.2+/-0.6 mmHg). Pivc significantly correlated with Pcyst (r=0.78) and Psvc (r=0.7). A. When Pcyst > Psvc, Pivc was higher than Psvc (p<0.01). With Pcyst < 15 mmHg, no significant difference was found between Pcyst and Pivc and they were correlated (r=0.766, p<0.05). Pressures in the superior and inferior vena cava were also correlated (r=0.764, p<0.05). With Pcyst > or = 15 mmHg, Pivc was lower than Pcyst (p<0.01). It correlated highly with Pcyst (r=0.85, p<0.01) and less strongly with Psvc (r=0.701, p<0.01). B. When Pcyst < or = Psvc, no difference between Pivc and Psvc was observed. With Pcyst < 15 mmHg, Pivc was higher than Pcyst (p<0.01) and highly correlated with Psvc (r=0.932, p<0.01). Pivc also correlated with Pcyst (r=0.69, p<0.01). With Pcyst > or = 15 mmHg, Pivc was higher than Pcyst (p<0.01) and correlated with Psvc (r=0.74, p<0.01) and Pcyst (r=0.789, p<0.01). CONCLUSIONS: Although Psvc and Pivc are interchangeable in the absence of an increased Pcyst, when Pcyst is high, measurements of Pivc are misleading. A Pcyst > Psvc results in a "waterfall" effect, and Pivc does not accurately reflect Psvc any more.

Pain assessment in acute myocardial infarction patients.

UNLABELLED: The purpose of this study was to investigate the pain intensity and duration, and to assess the pain control intervention, in patients with acute myocardial infarction (AMI). METHODS: Ninety-seven patients (18 diabetics and 79 non-diabetics) admitted to the hospital with chest pain were included in this study. Pain was measured on the numerical rating scale (NRS) 0-10, where 0 means no pain and 10 unbearable pain. All patients were followed for 12 hours, after the last chest pain episode. The data were statistically evaluated with the Student's t-test and chi square (chi 2). RESULTS: The pain in AMI patients with diabetes mellitus was lower in intensity (P < 0.002) and shorter in duration (P < 0.000) respectively, compared with the non-diabetic AMI patients. The intensity of pain in patients with an anterior infarction tended to be higher (P < 0.03) than in those with an inferior infarction. Finally, the systolic blood pressure fell significantly (P < 0.000) 90 min after admission. No other significant differences were found.

The intensive care units in greater Athens: needs and resources.

UNLABELLED: The purpose of this study was to investigate the availability of intensive care unit (ICU) beds and the number of requests, the number and categories of nursing staff, the nursing care required, and the time spent in various nursing activities. METHODS: 19 district general hospitals were studied. The characteristics of the units and their nursing personnel were recorded. The availability of ICU beds, the frequency of bed requests, and the way of patient admission in the ICUs were studied retrospectively for 1 year and prospectively for 2 weeks. The staffing level of direct care for 36 patients was studied to determine the time required for direct nursing care. RESULTS: the distribution of intensive care beds was: GICU 108, CICU 114, PSICU 30. During 1991, 12363 patients were admitted and 12172 of them were discharged; 3 628 patients stayed less than 2 days while the average length of stay was 12.5 days. In 1992, during the 2-week period, there were 303 requests for an admission to ICUs and of these 150 requests could not be met because of lack of ICU beds. The mean staffing level was 2.3 nurses per bed (to cover the three shifts). The mean nursing time required for direct nursing care of each patient per shift was found to be 6 hours for GICU patients, 5.3 for CICU, and 6.0 for PSICU patients.

Intrahospital transportation: monitoring and risks.

Patients' intrahospital transport is considered as part of the mediconursing care continuum, since patients frequently need diagnostic or therapeutic procedures not performed at the bedside (Waddell 1975, Rutherford & Fisher 1986). Severe complications, such as airway obstruction, artificial airway or intravenous line removal, arterial blood gas and blood pressure changes, and arrhythmias or cardiac arrest, have been described during this transportation, especially in critically ill patients (Taylor et al 1970). Risks can be diminished if the patients are appropriately selected and carefully monitored during transportation (Venkataraman & Orr 1992).

Temperature multiscale entropy analysis: a promising marker for early prediction of mortality in septic patients.

A few studies estimating temperature complexity have found decreased Shannon entropy, during severe stress. In this study, we measured both Shannon and Tsallis entropy of temperature signals in a cohort of critically ill patients and compared these measures with the sequential organ failure assessment (SOFA) score, in terms of intensive care unit (ICU) mortality. Skin temperature was recorded in 21 mechanically ventilated patients, who developed sepsis and septic shock during the first 24 h of an ICU-acquired infection. Shannon and Tsallis entropies were calculated in wavelet-based decompositions of the temperature signal. Statistically significant differences of entropy features were tested between survivors and non-survivors and classification models were built, for predicting final outcome. Significantly reduced Tsallis and Shannon entropies were found in non-survivors (seven patients, 33%) as compared to survivors. Wavelet measurements of both entropy metrics were found to predict ICU mortality better than SOFA, according to a combination of area under the curve, sensitivity and specificity values. Both entropies exhibited similar prognostic accuracy. Combination of SOFA and entropy presented improved the outcome of univariate models. We suggest that reduced wavelet Shannon and Tsallis entropies of temperature signals may complement SOFA in mortality prediction, during the first 24 h of an ICU-acquired infection.

Measurement of tumour necrosis factor receptors for immune response in colon cancer patients.

Immune system is crucial to tumour's initiation, progress and establishment and is contributing to prevent upcoming damaging invasion. Tumour development and surgical resection are both immunosuppressive processes. Immune response could be evaluated by ex vivo lipopolysaccharide (LPS) test, measuring cytokines and receptors release. The aim of the study is to investigate the postoperative immune recovery of cancer patients upon discharge. Twenty-two patients with colon cancer, without pre-treatment, and 16 healthy volunteers (HV) were enrolled in the study. Ten ml of whole blood were collected from every patient on admission (PRE) and upon discharge (POD7) and every HV. Diluted whole blood samples were stimulated with 500 pg/ml LPS, at 37°C, for 4H. Cell culture supernatants (CCSP) were removed after centrifugation and stored at -70°C. Tumour necrosis factor-alpha (TNF-α), interleukin-6 and interleukin-10 (IL-6, IL-10), soluble TNF receptors (sTNFRs) were measured in serum and CCSP by enzymelinked immunosorbent assay. Serum cytokines and receptors, PRE and POD7, were significantly elevated compared to HV (P < 0.001) and significant correlations were found between POD7 IL-6 and sTNFRs (Spearman's ρ 0.47, P < 0.05). Ex vivo, TNF-α, IL-6 and TNFRI release were lower either PRE or POD7, while IL-10 and TNFRII were higher, than in HV. No significant differences (P > 0.05) were found between PRE and POD7 levels in serum or CCSP. Cancer patients are not postoperatively immune restored until discharge. The trend of anti-inflammatory TNFRs release could account for alternative marker for the control of cancer patients immune response and the schedule of their following therapeutic treatment.