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

Gastric intramucosal pH is stable during titration of positive end-expiratory pressure to improve oxygenation in acute respiratory distress syndrome

BACKGROUND: Optimal positive end-expiratory pressure (PEEP) is an important component of adequate mechanical ventilation in acute lung injury and acute respiratory distress syndrome (ARDS). In the present study we tested the effect on gastric intramucosal pH of incremental increases in PEEP level (i.e. PEEP titration) to improve oxygenation in ARDS. Seventeen consecutive patients with ARDS, as defined by consensus criteria, were included in this clinical, prospective study. All patients were haemodynamically stable, and were not receiving vasopressors. From an initial level of 5 cmH(2)O, PEEP was titrated at 2 cmH(2)O increments until the partial arterial oxygen tension was 300 mmHg or greater, peak airway pressure was 45 cmH(2)O or greater, or mean arterial blood pressure decreased by 20% or more of the baseline value. Optimal PEEP was defined as the level of PEEP that achieved the best oxygenation. The maximum PEEP was the highest PEEP level reached during titration in each patient. RESULTS: Gastric mucosal pH was measured using gastric tonometry at all levels of PEEP. The thermodilution technique was used for measurement of cardiac index. Gastric mucosal pH was similar at baseline and at optimal PEEP levels, but it was slightly reduced at maximum PEEP. Cardiac index and oxygen delivery remained stable at all PEEP levels. CONCLUSION: Incremental titration of PEEP based on improvement in oxygenation does not decrease gastric intramucosal perfusion when cardiac output is preserved in patients with ARDS

Brain Death and Deceased Organ Donation in a Hospital in Istanbul, Turkey: The Effect of Early Identification of Brain Dead on Organ Donation Rates: A Retrospective Study

Introduction: The possibility of brain death (BD) among patients with a Glasgow Coma scale <7 must be considered by physicians who work in intensive care units. Deceased organ transplantation can be lifesaving so every BD patient should be seen as a potential donor. The aim of this study was to describe the causes of BD, rate of organ donation and to investigate the effect of diagnosis time on donation rates in our hospital over a 9-year period

Effect of Heart Rate Control on Oxygenation and Vasopressor Need in Sepsis and Septic Shock-A Pilot Randomised Controlled Study

Objective: The goal of this study was to examine the effect of keeping resting heart rate below 95 bpm on oxygenation, organ function, vasopressor need and mortality in sepsis and septic shock

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-kappa B and Bax expressions, thereby, inhibiting major inflammation and apoptosis cascades. Future animal model experiments performed with specific C5aR and NF-kappa B agonists/antagonists or C5aR-deficient mice might more robustly disclose the significance of these pathways. C5a, C5aR, and NF-kappa B, 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

A Different Approach to Toxic Epidermal Necrolysis: Cytokine Filter

Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder that erythema and exfoliation of the skin involve more than 30% of the body surface and usually drug related. A 68-year-old male patient who was admitted to the emergency department with the complaint of extensive bullous lesions on his skin was followed up in the intensive care unit (ICU) with the diagnosis of TEN. He had been on multiple anti-inflammatory, antibiotic and analgesic treatment for approximately 20 days due to respiratory tract infection and gout. Methyl-prednisolone 1 g day(-1) was started after the patient's previous treatments were discontinued. The patient was connected to the mechanical ventilator on 11th day due to sepsis and respiratory mucosal involvement. Regression and epithelialisation of skin lesions started after starting cytokine filter treatment on 14th day. The cytokine filter was applied with a renal replacement therapy machine in our patient. Withdrawal of suspected drugs, maintaining an optimal electrolyte balance, sterile care of skin lesions and management in the ICU of specialised centres are essential. Although agents, such as corticosteroids, intravenous immunoglobulins and cyclosporine, are used in the treatment, we think that the use of cytokine filters will contribute to recovery by stopping the cytokine storm in these cases

Is There a Relationship Between Rectal Colonization and Nosocomial Infection of Patients in Intensive Care Unit?

Nosocomial infections caused by multidrug-resistant (MDR) microorganisms are a major problem in intensive care units (ICUs) with high mortality and morbidity rates and the prior colonization is an important risk factor for these infections. The aim of this study was to investigate the prevalence of rectal colonization of MDR microorganisms and the association between the microorganisms that caused colonization and infection in the patients with nosocomial infections in ICUs. Rectal swabs were obtained on the day of 0, 3, 7, 14, 21 and weekly thereafter from 80 patients over 18 years of age hospitalized in ICU for more than 48 hours, and cultured for vancomycin-resistant enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)- producing gram-negative bacilli (GNB) and carbapenem-resistant enteric and nonenteric bacilli. Patients whose rectal swabs were not obtained on admission (on the day of 0), were excluded even they were hospitalized more than 48 hours. Bile esculin agar containing 64 mu g/mL ceftazidime and 6 mu g/mL vancomycin, chromogenic MRSA agar and blood agar media, MacConkey agar containing 1 mg/L cefitazidime and ceftriaxone, and 5 mL tryptic soy broth media containing 10 mu g imipenem and meropenem discs were used for identification. Identification of GNB was determined by conventional methods and ESBL production was determined by double-disc synergy test. Patients have been followed up for nosocomial infections. Bacterial identification and antibiotic susceptibility tests were performed with standard microbiological methods. In 37 (46%) of the 80 patients, at least one MDR microorganism was isolated in rectal swab cultures on the day of 0. The most common microorganisms were ESBL-positive E.coli (19%), followed by ESBL-positive K.pneumoniae (13%), carbapenem-resistant P.aeruginosa (10%), ESBL-positive K.oxytoca (3%), MRSA (1%), VRE (1%), carbapenem-resistant Acinetobacter sp. (1%) and carbapenem-resistant K.pneumoniae (1%), respectively. The number of microorganisms isolated from rectal swab cultures on the following days have increased, and on the 7th day, the rate of the patients with rectal colonization ascended to 72%. Out of 80 patients, 52 (65%) had nosocomial infections in the follow-up and the mean duration of infection development was 11.8 +/- 9.9 days in these patients. Patients with and without rectal colonization were compared in terms of subsequent nosocomial infection rates. While no statistically significant difference has been detected between two groups on the day of 0, patients with rectal colonization detected on the day of 3 and 7, had a significantly higher incidence of nosocomial infections (p= 0.02, p= 0.01). Among the patients with ESBL-positive GNB, carbapenem-resistant K.pneumoniae, carbapenem-resistant P.aeruginosa and VRE infections, the same microorganisms have been isolated in the rectal swab cultures taken before the development of infection. This result was statistically significant for each of these microorganisms (p= 0.00 - 0.03). However, such a correlation was not observed for Acinetobacter infections. Since MRSA infections developed in only two patients, no istatistical analysis has been done for this microorganism. In conclusion, our data suggest that MDR microorganisms that cause nosocomial infections, initially colonize the gastrointestinal tract, and early detection of colonized patients in ICUs may help an effective infection control by preventing the spread. of these resistant microorganisms