Diagnosing acute brain dysfunction due to sepsis.

Developments in the management of critically ill patients suffering organ dysfunctions have demonstrated that brain is the prominent organ to be effected during critical illness. Acute brain dysfunction due to pathologic neuroinflammatory processes associated with sepsis is commonly seen and related to morbidity and mortality in the ICU treatment. Studies reported that survivors of sepsis may suffer long-term cognitive dysfunction that affects quality of life. However, there are no specific approaches to diagnose acute brain dysfunction in the early phase to target protective measures. In recent years, imaging methods and biomarkers are the most important issues of studies. This review will address the current diagnostic approaches to acute brain dysfunction related to sepsis.

Neuroimaging Findings in Sepsis-Induced Brain Dysfunction: Association with Clinical and Laboratory Findings.

BACKGROUND: Incidence and patterns of brain lesions of sepsis-induced brain dysfunction (SIBD) have been well defined. Our objective was to investigate the associations between neuroimaging features of SIBD patients and well-known neuroinflammation and neurodegeneration factors. METHODS: In this prospective observational study, 93 SIBD patients (45 men, 48 women; 50.6 ± 12.7 years old) were enrolled. Patients underwent a neurological examination and brain magnetic resonance imaging (MRI). Severity-of-disease scoring systems (APACHE II, SOFA, and SAPS II) and neurological outcome scoring system (GOSE) were used. Also, serum levels of a panel of mediators [IL-1ß, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-γ, TNF-α, complement factor Bb, C4d, C5a, iC3b, amyloid-ß peptides, total tau, phosphorylated tau (p-tau), S100b, neuron-specific enolase] were measured by ELISA. Voxel-based morphometry (VBM) was employed to available patients for assessment of neuronal loss pattern in SIBD. RESULTS: MRI of SIBD patients were normal (n = 27, 29%) or showed brain lesions (n = 51, 54.9%) or brain atrophy (n = 15, 16.1%). VBM analysis showed neuronal loss in the insula, cingulate cortex, frontal lobe, precuneus, and thalamus. Patients with abnormal MRI findings had worse APACHE II, SOFA, GOSE scores, increased prevalence of delirium and mortality. Presence of MRI lesions was associated with reduced C5a and iC3b levels and brain atrophy was associated with increased p-tau levels. Regression analysis identified an association between C5a levels and presence of lesion on MRI and p-tau levels and the presence of atrophy on MRI. CONCLUSIONS: Neuronal loss predominantly occurs in limbic and visceral pain perception regions of SIBD patients. Complement breakdown products and p-tau stand out as adverse neuroimaging outcome markers for SIBD.

Is SARS-CoV-2 viral load a predictor of mortality in COVID-19 acute respiratory distress syndrome patients?

OBJECTIVE: Viral load varies during infection and is higher during the initial stages of disease. Given the importance of the intensive care unit (ICU) in the late stages of COVID-19 infection, analyzing cycle threshold values to detect viral load upon ICU admission can be a clinically valuable tool for identifying patients with the highest mortality risk. METHODS: This was a retrospectively designed study. Patients older than 18 years who tested positive for SARS-CoV-2 PCR and had a PaO2/FiO2 ratio <200 were included in the study. The patient population was divided into two groups: survivors and non-survivors. RESULTS: Two hundred patients were included in the study. In non-survivors, age, relevant ICU admission scores, and procalcitonin levels were significantly higher whereas PaO2/FiO2 ratios and cycle threshold levels were significantly lower than in survivors. CONCLUSION: Viral load at ICU admission has significant prognostic value. In combination with age, comorbidities, and severity scores, viral load may assist clinicians in identifying individuals who need more intensive monitoring. Increased awareness may improve outcomes by allowing the more effective monitoring and treatment of patients. More prospective studies are needed to determine how a high viral load worsens disease and how to avoid irreversible results.

Complementary Roles of Cadaveric and Living Donor Liver Transplantation in Acute Liver Failure.

BACKGROUND: Living donor liver transplantation may complement cadaveric transplantation in acute liver failure (ALF) patients. METHODS: Between 2008 and 2017, 89 patients were treated for ALF; 15 patients (17%) recovered with intensive care treatment; 31 (35%) died without transplant. The records of the remaining 43 patients (median (range) age: 14 (1-62)) who underwent transplantation were evaluated. RESULTS: The etiologic factors were toxic agents (10; mushrooms: 8; herbs: 2), hepatitis viruses (7; A: 1; B: 6), Wilson's disease (7), autoimmune hepatitis (4), and Budd-Chiari syndrome (2); 13 cases were idiopathic. Cadaveric organs (whole, split, reduced) were transplanted to 32 patients; 11 patients underwent living donor transplantation. One patient (2%) died of septic shock on the second postoperative day. Bacterial infection was the most common early (< 3 months) complication in the remaining patients (31/42; 74%), followed by delirium (5/42; 12%) and acute rejection requiring steroid pulse (5/42; 12%). Seven other patients died during median (range) follow-up of 94 (14-142) months: various infections (5), leukemia (1), and acute myocardial infarction (1). The 1-, 5-, and 10-year survival rates were 100%, 96%, and 92% in children and 94%, 82%, and 65% in adults respectively. CONCLUSIONS: Cadaveric organ sharing and transplantation from living donors when appropriate yield a high survival rate, despite high early morbidity, in ALF patients whose conditions deteriorate despite intensive care treatment. Efforts to eliminate preventable causes of acute liver failure will lead to more efficient use of health care resources.

Association Between Inflammatory Markers and Cognitive Outcome in Patients with Acute Brain Dysfunction Due to Sepsis.

INTRODUCTION: Sepsis-induced brain dysfunction (SIBD) has been neglected until recently due to the absence of specific clinical or biological markers. There is increasing evidence that sepsis may pose substantial risks for long term cognitive impairment. METHODS: To find out clinical and inflammatory factors associated with acute SIBD serum levels of cytokines, complement breakdown products and neurodegeneration markers were measured by ELISA in sera of 86 SIBD patients and 33 healthy controls. Association between these biological markers and cognitive test results was investigated. RESULTS: SIBD patients showed significantly increased IL-6, IL-8, IL-10 and C4 d levels and decreased TNF-α, IL-12, C5a and iC3b levels than healthy controls. No significant alteration was observed in neuronal loss and neurodegeneration marker [neuron specific enolase (NSE), amyloid ß, tau] levels. Increased IL-1ß, IL-6, IL-8, IL-10, TNF-α and decreased C4 d, C5a and iC3b levels were associated with septic shock, coma and mortality. Transient mild cognitive impairment was observed in 7 of 21 patients who underwent neuropsychological assessment. Cognitive dysfunction and neuronal loss were associated with increased duration of septic shock and delirium but not baseline serum levels of inflammation and neurodegeneration markers. CONCLUSION: Increased cytokine levels, decreased complement activity and increased neuronal loss are indicators of poor prognosis and adverse events in SIBD. Cognitive dysfunction and neuronal destruction in SIBD do not seem to be associated with systemic inflammation factors and Alzheimer disease-type neurodegeneration but rather with increased duration of neuronal dysfunction and enhanced exposure of the brain to sepsis-inducing pathogens.

Mechanisms of action of intravenous immunoglobulin in septic encephalopathy.

Acute brain dysfunction associated with sepsis is a serious complication that results in morbidity and mortality. Intravenous immunoglobulin (IVIg) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Our results suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might suppress classical complement pathway by reducing C5a activity and proapoptotic NF-κB and Bax expressions, thereby, inhibiting major inflammation and apoptosis cascades. Future animal model experiments performed with specific C5aR and NF-κB agonists/antagonists or C5aR-deficient mice might more robustly disclose the significance of these pathways. C5a, C5aR, and NF-κB, which were shown to be the key molecules in brain injury pathogenesis in sepsis, might also be utilized as potential targets for future treatment trials of septic encephalopathy.

The frequency, risk factors, and complications of gastrointestinal dysfunction during enteral nutrition in critically ill patients.

BACKGROUND: Gastrointestinal (GI) motility disorders in intensive care patients remain relatively unexplored. Nowadays, the frequency, risk factors and complications of GI dysfunction during enteral nutrition (EN) become more questionable. AIM: To evaluate the frequency, risk factors and complications of GI dysfunction during EN in the first 2 weeks of the intensive care unit (ICU) stay and to identify precautions to prevent the development of GI dysfunction and avoid complications. METHODS: In this prospective observational study, we deliberately targeted at-risk patients. A total of 137 patients who received nasogastric tube feeding in an ICU of a tertiary hospital were enrolled. RESULTS: The incidence of GI dysfunction that was found to be 63% which was associated mainly between MDR bacteria positivity and negative fluid balance. Diarrhea was observed in 36 patients (26%) and on 147 patient-days (incidence rate, 5.5 per 100 patient-days). The median day of diarrhea onset was 6 days after the initiation of EN. Forty patients (29%) presented with constipation (85% during the first week). Fifty patients (36%) exhibited upper digestive intolerance on 212 patient-days (incidence rate, 7.9 per 100 patient-days), after a median EN duration of 6 days (range, 2-14 days). Logistic regression analysis revealed MDR bacteria growth in the culture (OR, 1.75; 95% CI, 1.15-2.67; P=0.008) and negative fluid balance (OR, 0.57; 95% CI, 0.34-0.94; P=0.03) as the risk factors for GI dysfunction. We also showed that GI dysfunction was associated with high SOFA score, hypoalbuminemia, catecholamine use, and prolonged length of stay (LOS). GI dysfunction, on the other hand, can cause some complications including inadequate nutrition, and newly developed decubitus ulcers. CONCLUSION: GI dysfunction should be considered a clinical predictor of inadequate nutrition and prolonged LOS. In addition, the most dramatic risk for GI dysfunction was observed in patients with MDR bacteria growth in the culture and patients in negative fluid balance. Intensivists provide appropriate nutrition for patients, as well as prompt intervention and the development of treatment strategies in the event of GI dysfunction.

The effects of airway pressure and inspiratory time on bacterial translocation.

BACKGROUND: Mechanical ventilation with high peak inspiratory pressure (PIP) induces lung injury and bacterial translocation from the lung into the systemic circulation. We investigated the effects of increased inspiratory time on translocation of intratracheally inoculated bacteria during mechanical ventilation with and without extrinsic positive end-expiratory pressure (PEEP). METHODS: Rats were ventilated in pressure-controlled mode with 14 cm H2O PIP, 0 cm H2O PEEP, I:E ratio 1/2, and Fio2 1.0. Subsequently, 0.5 mL of 10(5) cfu/mL Pseudomonas aeruginosa was inoculated through tracheostomy and rats were randomly assigned to six groups; two low-pressure groups (LP)1/2, 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and LP2/1 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two high-pressure groups (HP)1/2, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and HP2/1, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two HP PEEP groups (HPP)1/2, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 1/2, and HPP2/1, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 2/1. Blood cultures were obtained every 30 min. The rats were killed and their lungs were processed. RESULTS: When compared with baseline values, Pao2 decreased in the LP1/2, LP2/1, HP1/2, and HP2/1 groups at the last time point, but the decline in Pao2 reached statistical significance in only the HP1/2 group. The bacterial translocation rate was greater in group HPP2/1 than group HPP1/2 (P = 0.01). CONCLUSIONS: We found that high PIP, with or without prolonged inspiratory time, increased the rate of bacterial dissemination. PEEP prevented bacterial translocation in the high PIP group. However, the protective effect of PEEP was lost when inspiratory time was prolonged.

Neuroprotective effects of intravenous immunoglobulin are mediated through inhibition of complement activation and apoptosis in a rat model of sepsis.

BACKGROUND: Intravenous (IV) immunoglobulin (Ig) treatment is known to alleviate behavioral deficits and increase survival in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. METHODS: Sepsis was induced by cecal ligation perforation (CLP) in rats. The animals were divided into five groups: sham, control, CLP + saline, CLP + immunoglobulin G (IgG) (250 mg/kg, iv), and CLP + immunoglobulins enriched with immunoglobulin M (IgGAM) (250 mg/kg, iv). Blood and brain samples were taken in two sets of experiments to see the early (24 h) and late (10 days) effects of treatment. Total complement activity, complement 3 (C3), and soluble complement C5b-9 levels were measured in the sera of rats using ELISA-based methods. Cerebral complement, complement receptor, NF-κB, Bax, and Bcl-2 expressions were analyzed by western blot and/or RT-PCR methods. Immune cell infiltration and gliosis were examined by immunohistochemistry using CD3, CD4, CD8, CD11b, CD19, and glial fibrillary acidic protein antibodies. Apoptotic neuronal death was investigated by TUNEL staining. RESULTS: IVIgG and IgGAM administration significantly reduced systemic complement activity and cerebral C5a and C5a receptor expression. Likewise, both treatment methods reduced proapoptotic NF-κB and Bax expressions in the brain. IVIgG and IgGAM treatment induced considerable amelioration in glial cell proliferation and neuronal apoptosis which were increased in non-treated septic rats. CONCLUSIONS: We suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. In both treatment methods, these beneficial effects might be mediated through reduction of anaphylatoxic C5a activity and subsequent inhibition of inflammation and apoptosis pathways.

A Case of Biotinidase Deficiency in an Adult with Respiratory Failure in the Intensive Care Unit.

BACKGROUND: Biotinidase deficiency (BD) is a rare, inherited autosomal recessive disorder that is treatable within childhood. We present a patient with pneumonia and respiratory acidosis who was not diagnosed with any systemic disorders; the patient was finally diagnosed as BD. CASE REPORT: A thirty-year-old woman was admitted to the emergency department with respiratory failure that had persisted for a few days and progressively weakening over the previous six months. Then, the patient was admitted to the intensive care unit with marked respiratory acidosis, respiratory failure and alterations in consciousness. At the follow-up, the patient was not diagnosed with a systematic disorder. Rather, the patient's historical clinical findings suggested a metabolic disorder. Finally, the patient was diagnosed with biotinidase deficiency. CONCLUSION: Even though biotinidase deficiency is not frequently seen in the intensive care unit, metabolic syndromes such as biotinidase deficiency should be considered. Patients should be evaluated holistically with attention to medical history, family history and clinical findings.

Effects of intravenous immunoglobulin therapy on behavior deficits and functions in sepsis model.

BACKGROUND: We aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with IgA and IgM (IgGAM). METHODS: We divided 48 Wistar albino rats into five groups: control group, sham-operated group (only antibiotic treatment), cecal ligation and puncture (CLP) group (CLP plus antibiotic treatment), IgG group (250 mg/kg IV IgG) and IgGAM group (250 mg/kg IV IgGAM). Intravenous immunoglobulins were given 5 min after the CLP procedure. Experimental animals put into three behavioral tasks 10, 30 and 60 days after the surgery; to evaluate the locomotor activity, an open field test was performed, elevated plus maze test was used to measure anxiety levels, and depressive state was assessed by forced swimming test. The effects of therapy which were acquired from the results of these tests were used to estimate the behavioral changes after CLP. RESULTS: The mortality rate of 50% in the septic rats decreased to 30 and 20% with the administration of IgG and IgGAM, respectively. Significant changes on locomotor activity and depressive-like behavior were reported in the sepsis group; on the other hand, the treatment with immunoglobulins reduced the symptoms. Treatment with immunoglobulins attenuated the sepsis-related anxiogenic-like responses. Behavioral alterations returned to normal on day 60 in all groups. CONCLUSIONS: Sepsis caused deterioration on behavioral parameters. Immunoglobulin treatments alleviated the symptoms of functional disturbances and caused early reversal of behavioral deficits in septic animals.

[Iatrogenic hypernatremia during hydatid cyst operation]. / Karaciger Kist Hidatik Operasyonunda Iyatrojenik Hipernatremi.

Hypernatremia due to salt gain is generally iatrogenic. This case report presents a 55 year-old woman who was operated because of hepatic hydatid cyst. At the end of the operation, following extubation the patient was unconscious and serum sodium concentration was found to be 185 mEq/ L. The patient was entubated again and transferred to the intensive care unit. When the patient awaked and became conscious at 36th hour in intensive care unit, she was extubated and transferred to ward with serum sodium concentration of 142 mEq/L. The serum sodium concentration should be monitored carefully in hydatid cyst operation, during which hypertonic saline is used for scelosidal effects as general anesthesia can mask neurologic signs due to hypernatremia.

The Comparison of Automatic Tube Compensation (ATC) and T-piece During Weaning.

OBJECTIVE: Automatic Tube Compensation (ATC) is a newly developed mechanical ventilatory support method. The aim of this study was to compare the ATC and the T-piece as a weaning method. METHODS: Patients who were treated in ICU with mechanical ventilation for longer than 24 hours were included in this prospective clinical study. Fifty patients were divided into two groups for weaning, ATC or T-piece group. Patients tolerating 30 minutes spontaneous breathing trial underwent immediate extubation. The following parameters were recorded just before the spontaneous breathing trial and every 5 minutes during the 30 minute period; PEEP, Pplt, Pmean, FiO2, heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, SaO2, ETCO2. The primary outcome of the study was successful extubation defined as the ability to maintain spontaneous breathing for 48 hours after extubation. RESULTS: The mean duration of weaning were 4.96 days and 7.42 days in the ATC and T-piece groups, respectively (p value 0.022). There were no significant differences between the groups with respect to the hemodynamic parameters, mechanical ventilation and gas exchange parameters. CONCLUSION: In terms of success for weaning, there was no superiority between the ATC and the T-Piece methods for spontaneous breathing and it was concluded that each of the methods can be used for weaning. The ATC group were compared in terms of successful weaning period but have shown no significant periods of time were found to be lower.

The Comparison of Pressure (PSV) and Volume Support Ventilation (VSV) as a 'Weaning' Mode.

OBJECTIVE: The purpose of our study is to compare two different ventilation modes-pressure support ventilation (PSV) and volume support ventilation (VSV)-as the means of weaning. METHODS: Sixty patients were enrolled in our study. Patients were randomized in to two groups. For the PSV group, FiO2 and airway pressure values were adjusted in order to sustain PaCO2: 35-45 mm Hg, pH>7.32, 6-8 mL kg(-1) TV (tidal volume), and saturation >92%. For the VSV group, FiO2, TV, respiration frequency (f), and peak pressure were adjusted to obtain PaCO2: 35-45 mm Hg, pH>7.32, 6-8 mL kg(-1) TV, saturation >92%, and PO2>60 mm Hg. Every morning, spontaneous breathing was tried in those patients. The patients were extubated after 2 hours of T-piece breathing. The patients who failed spontaneous respiration with the T-piece were returned to mechanical ventilation. Assisted ventilation time (ART), mechanical ventilation time (MRT), total T-piece time (TTT), total weaning time (TWT), and sedation need (SN) values were recorded. "T-test" and "Chi-square" methods were used for statistical analysis. RESULTS: In our study, the mean ART was 82.60 hours for the PSV group and 56.03 hours for the VSV group (p<0.041). TWT was 93.30 hours for the PSV group and 56.03 hours for the VSV group (p<0.035). The mean TTT was 7.67 hours for the PSV group and 3.83 hours for the VSV group (p<0.007). Nineteen patients in the PSV group and 9 patients in the VSV group required sedation during the weaning process (p<0.01). CONCLUSION: In the weaning period, VSV seems to be more advantageous than PSV.

Recruitment Maneuver Does not Increase the Risk of Ventilator Induced Lung Injury.

BACKGROUND: Mechanical ventilation (MV) may induce lung injury. AIMS: To assess and evaluate the role of different mechanical ventilation strategies on ventilator-induced lung injury (VILI) in comparison to a strategy which includes recruitment manoeuvre (RM). STUDY DESIGN: Randomized animal experiment. METHODS: Thirty male Sprague-Dawley rats were anaesthetised, tracheostomised and divided into 5 groups randomly according to driving pressures; these were mechanically ventilated with following peak alveolar opening (Pao) and positive end-expiratory pressures (PEEP) for 1 hour: Group 15-0: 15 cmH2O Pao and 0 cmH2O PEEP; Group 30-10: 30 cmH2O Pao and 10 cmH2O PEEP; Group 30-5: 30 cmH2O Pao and 5 cmH2O PEEP; Group 30-5&RM: 30 cmH2O Pao and 5 cmH2O PEEP with additional 45 cmH2O CPAP for 30 seconds in every 15 minutes; Group 45-0: 45 cmH2O Pao and 0 cmH2O PEEP Before rats were sacrificed, blood samples were obtained for the evaluation of cytokine and chemokine levels; then, the lungs were subsequently processed for morphologic evaluation. RESULTS: Oxygenation results were similar in all groups; however, the groups were lined as follows according to the increasing severity of morphometric evaluation parameters: Group 15-0: (0±0.009) < Group 30-10: (0±0.14) < Group 30-5&RM: (1±0.12) < Group 30-5: (1±0.16) < Group 45-0: (2±0.16). Besides, inflammatory responses were the lowest in 30-5&RM group compared to all other groups. TNF-α, IL-1ß, IL-6, MCP-1 levels were significantly different between group 30-5&RM and group 15-0 vs. group 45-0 in each group. CONCLUSION: RM with low PEEP reduces the risk of ventilator-induced lung injury with a lower release of systemic inflammatory mediators in response to mechanical ventilation.

Role of magnesium sulfate in postoperative pain management for patients undergoing thoracotomy.

OBJECTIVE: The purpose of this study was to investigate the effect of magnesium sulfate on pain management for post-thoracotomy patients. DESIGN: A prospective, randomized, controlled clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four patients undergoing thoracotomy. INTERVENTIONS: After thoracotomy operations, patients were assigned to 2 groups. The control group received intravenous morphine (0.5 mg/h infusion, 0.3 mg patient-controlled anesthesia dose, 15-minute lockout time) via patient-controlled analgesia, and the magnesium group received magnesium sulfate (30-mg/kg bolus, 10 mg/kg/h infusion for 48 hours) plus the same patient-controlled analgesia protocol. MEASUREMENTS AND MAIN RESULTS: Visual analog scale for pain score, sedation score, mean arterial pressure, heart rate, and valid and invalid analgesic demand were recorded. Serum magnesium levels were determined at postanesthesia care unit admission, at 24 hours, and at 48 hours. Side effects were also recorded. There were no significant differences between groups with respect to demographics, sedation score, and pain score. Cumulative mean morphine consumption was found to be higher in the control group compared with the magnesium group at 4, 8, and 48 hours (5.6 +/- 1 mg v 3.2 +/- 0.6 mg [p < 0.0001], 10.2 +/- 1.8 mg v 7.2 +/- 1.6 mg [p = 0.0003), and 40.2 +/- 4.5 mg v 34.8 +/- 6.3 mg [p = 0.02], respectively). CONCLUSION: Postoperative use of magnesium sulfate reduced opioid consumption for pain after thoracotomy operations.

Risk factors for mortality of nosocomial bacteraemia in intensive care units.

OBJECTIVE: The aim of this study was to follow critically ill patients prospectively in intensive care units (ICUs) to determine risk factors for mortality and outcome associated with nosocomial bacteraemia (NB). SUBJECTS AND METHODS: A case-control study of 176 patients was conducted to identify the risk factors for mortality of NB in ICU patients. The study was performed in emergency, surgical and general surgical ICUs with 23 beds during a 15-month period. A total of 1,450 patients were admitted to the ICUs during the study period. The USA Center for Disease Control and Prevention definitions were used to diagnose nosocomial infections. Nosocomial bacteraemia was defined as the isolation of one or more organisms from blood cultures taken at least 48 h after admission, which were not related to a problem present on admission. An assessment of whether the isolated organisms represented true bacteraemia rather than contamination was made by clinical or laboratory evidence of infection. RESULTS: A total of 214 bacteraemia episodes were found in the 176 patients (64 female, 112 male; 51.3 +/- 21.3 years old), 90 of whom died and 86 survived. The bacteraemia rate was 12.1%. The most common etiological agents of bacteraemia were Klebsiella pneumoniae: 46 (21.5%), methicillin-resistant Staphylococcus aureus: 46 (21.5%), Pseudomonas aeruginosa: 32 (14.9%), and Escherichia coli: 20 (9.3%). Multivariate analysis showed that the requirement of mechanical ventilation for more than 7 days (p < 0.001), total parenteral nutrition (p = 0.034), inotropic drug (p < 0.001), and increased creatinine level (p = 0.034) were independent risk factors for mortality of NB in ICUs. CONCLUSIONS: Nosocomial infections caused by Gram-negative bacteria continue to be one of the major sources of morbidity and mortality.

Time required for equilibration of arterial oxygen pressure after setting optimal positive end-expiratory pressure in acute respiratory distress syndrome.

OBJECTIVE: To evaluate the time course of Pao2 change following the setting of optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty-five consecutive patients with ARDS. INTERVENTIONS: ARDS was diagnosed during pressure-regulated volume control ventilation with tidal volume of 7 mL/kg actual body weight, respiratory rate of 12 breaths/min, inspiratory/expiratory ratio of 1:2, Fio2 of 1, and PEEP of 5 cm H2O. A critical care attending physician obtained pressure volume curves and determined the lower inflection point. Following a rest period of 30 mins with initial ventilation variables, PEEP was set at 2 cm H2O above the lower inflection point, and serial blood samples were collected during 1-hr ventilation with optimal PEEP. Arterial blood gas analyses were performed at 1, 3, 5, 7, 9, 11, 15, 20, 30, 45, and 60 mins. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were found eligible for the study. Three patients were excluded due to deterioration of oxygen saturation and hemodynamic instability following the initiation of optimal PEEP. Eight cases (36%) were considered to be of pulmonary origin and 14 cases (64%) of extrapulmonary origin. Optimal PEEP levels were 14 +/- 3 cm H2O and 14 +/- 4 cm H2O in pulmonary and extrapulmonary ARDS, respectively. Pao2 demonstrated a 130 +/- 101% increase at the end of 1-hr period in total study population. This improvement did not differ significantly between pulmonary and extrapulmonary forms of ARDS (135 +/- 118% vs. 127 +/- 95%, p = .8). Mean 90% oxygenation time was found to be 20 +/- 19 mins. In the subset of patients with ARDS of pulmonary origin, 90% oxygenation time was 25 +/- 26 mins, whereas it was 17 +/- 15 mins in patients with ARDS of extrapulmonary origin (p = .8). CONCLUSIONS: Our data showed that 20 mins would be adequate for obtaining a blood gas sample in ARDS patients with pulmonary and extrapulmonary origin after application of optimal PEEP 2 cm H2O above the lower inflection point.

The effects of three different analgesia techniques on long-term postthoracotomy pain.

UNLABELLED: In this clinical, randomized, prospective study, we compared the effects of three different analgesia techniques (thoracic epidural analgesia [TEA] with and without preoperative initiation and IV patient-controlled analgesia [IV-PCA]) on postthoracotomy pain in 69 patients. In two groups, a thoracic epidural catheter was inserted preoperatively. Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively. Postoperative analgesia was maintained with epidural PCA with a similar solution. Group Post-TEA, with no intraoperative medication, had the same postoperative analgesia as Group Pre-TEA plus the bolus dose. Group IV-PCA received only IV-PCA with morphine for postoperative analgesia. Pain was evaluated every 4 h during the first 48 h at rest, cough, and movement. Pre-TEA was associated with decreased pain compared with the other groups. Six months later, the patients were asked about their pain. The incidence and the intensity of pain were most frequent in Group IV-PCA (78%) and were the least in Group Pre-TEA (45%) (Group Pre-TEA versus Group IV-PCA, P = 0.0233; Group Pre-TEA versus Group IV-PCA, P = 0.014). Patients having pain on the second postoperative day had 83% chronic pain. TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain. IMPLICATIONS: Preoperatively initiated thoracic epidural analgesia has the most satisfying results in controlling postthoracotomy pain in the acute and long-term period, and it is associated with a decreased incidence (and intensity) of chronic pain compared with postoperative (epidural or IV) analgesia. Chronic pain has an incidence of 62%.

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830].

INTRODUCTION: In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis. MATERIALS AND METHODS: Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. RESULTS AND DISCUSSION: Procalcitonin levels showed a statistically significant decrease in the Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin and control groups either. CONCLUSION: Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis.