Summary Objective To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated ...pneumonia (VAP). Methods A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8 h) or COL (3 MIU every 8 h) intravenously. Dosage was adjusted according to creatinine clearance. Results A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively ( p < 0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group ( p = NS). Conclusion Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.
Ischemia and reperfusion (I/R) - induced injury has been described as one of the main factors that contribute to the observed morbidity and mortality in a variety of clinical entities, including ...myocardial infarction, ischemic stroke, cardiac arrest and trauma. An imbalance between oxygen demand and supply, within the organ beds during ischemia, results in profound tissue hypoxia. The subsequent abrupt oxygen re-entry upon reperfusion, may lead to a burst of oxidative aggression through production of reactive oxygen species by the primed cells. The predominant role of oxidative stress in the pathophysiology of I/R mediated injury, has been well established. A number of strategies that target the attenuation of the oxidative burst have been tested both in the experimental and the clinical setting. Despite these advances, I/R injury continues to be a major problem in everyday medical practice. The aim of this paper is to review the existing literature regarding an alternative approach, termed hypoxemic reperfusion, that has exhibited promising results in the attenuation of I/R injury, both in the experimental and the clinical setting. Further research to clarify its underlying mechanisms and to assess its efficacy in the clinical setting is warranted.
Acute renal dysfunction in liver diseases Betrosian, Alex-P; Agarwal, Banwari; Douzinas, Emmanuel E
World journal of gastroenterology,
11/2007, Letnik:
13, Številka:
42
Journal Article
Odprti dostop
Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a ...poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.
Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury.
...Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO(2) = 95-105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO(2) = 35-40 mmHg) followed, modifying the FiO(2). Animals not subjected to shock constituted the sham group (n = 11, PaO(2) = 95-105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed.
Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor--alpha, interleukin (IL) -1β and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals.
Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.
The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24
h of septic onset, ...Interleukins (IL)-8, -1β, -6, -10, and -12p70, tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (
p
<
0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (
p
<
0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (
p
<
0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR
=
1.3,
p
=
0.01 for CD64 and OR
=
1.26,
p
=
0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.
Background
A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of ...clarithromycin was tested in a larger population with sepsis.
Methods
Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes.
Results
The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502).
Conclusions
Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.
Adenoid cystic carcinoma (ACC) is a rare epithelial tumor with a distinct natural history characterized by an indolent but persistent growth, late onset of distant metastases and eventual death of ...patients. Between 1991 and 2003, 23 patients with ACC were treated in our Department. Surgery with a curative intent followed by radiotherapy (RT) was applied in 22 patients. Complete resection was achieved in 72.73% of patients. Local recurrence occurred in 26% of patients. Positive margins emerged as the only statistically significant parameter (p < 0.0001) influencing the development of local recurrence. Distant metastasis (DM) occurred in 47.8% of patients. In 54.5% of the patients developing DM, this occurred between 5 and 10 years after the initial treatment. DM was influenced by perineural invasion (p = 0.04) and was disassociated from local control of the tumor. The mean overall survival of our patients was 70.58 months and the mean disease free survival 61.85 months. Perineural invasion (p = 0.048) and DM (p = 0.001) had a statistically significant impact on final patients' outcome. The most important factor influencing survival was DM. Its late onset, irrespectively of local control, supports the hypothesis that ACC has a potential to develop DM in the very early phases of tumor growth.
Objective
We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the ...standard strategy.
Design and setting
Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit.
Subjects
Thirty-one New Zealand white rabbits weighting 3.1–3.4 kg
Interventions
Anesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for 60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under normoxemia (PaO
2
95–105 mmHg, control group,
n
= 10) or hypoxemia (PaO
2
35–40 mmHg, hypox-res group,
n
= 10); Ringer's lactate was given from 30 to 60 min to restore arterial pressure within baseline values. A sham group was assigned (
n
= 11). Animals were recorded for 120 min postresuscitation and for further 360 min to assess the early mortality rate.
Measurements and results
Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1β, TNF-α, and IL-6; and (d) no difference in mortality rate.
Conclusions
Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.
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