TNF-α depuration is a predictor of mortality in critically ill patients under continuous veno-venous hemodiafiltration treatment.

INTRODUCTION: Critically ill patients with acute kidney injury (AKI) present high mortality rates. The magnitude of inflammatory response could determine the prognosis of such patients. Continuous renal replacement therapy (CRRT) may play an important role in removing inflammatory mediators in patients with AKI. AIM: To investigate whether the magnitude of inflammatory mediator's removal is associated with mortality among critically ill patients on CVVHDF, a CRRT modality. METHODS: This study consisted of 64 critically ill patients requiring CVVHDF. Plasma levels of C3a, TNF-α, IL-10, IL-6, IL-1ß, sTNFRI and sTNFRII were determined by enzyme-linked immunosorbent assay (ELISA) at the beginning of CVVHDF and after 24h (outlet). Clearance of cytokines during the first 24h of CVVHDF was calculated. Clinical and laboratory data were acquired from patient's records data. RESULTS: Mean age of patients requiring CVVHDF was 63years, 67.2% were men and 87.3% were Caucasian. Thirty-five (35) patients (54.7%) died. Comparing non-survivors with the group of survivors we observed higher incidence of sepsis (68.6 versus 37.9%, p<0.05), higher APACHE II score (34.8±7.6 versus 29.2±7.1, p<0.05) and higher lactate levels (23.2±17.6 versus 16.4±6.6, p<0.05). According to the inter-tertile range of TNF-α clearance (ITR1 (<0.54); ITR2 (0.54-2.93); ITR3 (>2.93)) we found that those patients with higher TNF-α removal by RRT (ITR3) had a better survival. Multivariable analysis showed that lower clearance of TNF-α remained independently associated with high mortality after adjustment for sex, age, use of vasoactive drugs, APACHE II score sepsis, creatinine and lactate before CVVHDF (HR: 0.179, 95% IC: 0.049-0.661, p<0.01). CONCLUSION: The attenuation of inflammatory response may be related to the lower mortality observed on those patients with higher TNF-α removal by CVVHDF.

Impact of appropriate antimicrobial therapy for patients with severe sepsis and septic shock--a quality improvement study.

BACKGROUND: There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes. MATERIAL: This study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock. RESULTS: A total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023). CONCLUSIONS: The administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance.

Low estimated glomerular filtration rate and chronic kidney failure following liver transplant: a retrospective cohort study.

BACKGROUND: Patients undergoing orthotropic liver transplant (LTx) often present with chronic kidney disease (CKD). Identification of patients who will progress to end-stage renal disease (ESRD) might allow not only the implementation of kidney protective measures but also simultaneous kidney transplant. STUDY DESIGN: Retrospective cohort study in adults who underwent LTx at a single center. ESRD, death, and composite of ESRD or death were studied outcomes. RESULTS: 331 patients, who underwent LTx, were followed up for 2.6 ± 1.4 years; 31 (10%) developed ESRD, 6 (2%) underwent kidney transplant after LTx and 25 (8%) remained on chronic hemodialysis. Patients with preoperative eGFR lesser than 60 ml/min per 1.73 m2 had a 4-fold increased risk of developing ESRD after adjustment for sex, diabetes mellitus, APACHE II score, use of nephrotoxic drugs, and severe liver graft failure (HR = 3.95, 95% CI 1.73, 9.01; p = 0.001). Other independent risk factors for ESRD were preoperative diabetes mellitus and post-operative severe liver graft dysfunction. CONCLUSION: These findings emphasize low eGFR prior to LTx as a predictor for ESRD or death. The consideration for kidney after liver transplant as a treatment modality should be taken into account for those who develop chronic kidney failure after LTx.

A program for sustained improvement in preventing ventilator associated pneumonia in an intensive care setting.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common infection in the intensive care unit (ICU) and associated with a high mortality. METHODS: A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize VAP prevention were performed from October 2008 to December 2010. All of these processes, including the Institute for Healthcare Improvement's (IHI) ventilator bundle plus oral decontamination with chlorhexidine and continuous aspiration of subglottic secretions (CASS), were adopted for patients undergoing mechanical ventilation. RESULTS: We evaluated a total of 21,984 patient-days, and a total of 6,052 ventilator-days (ventilator utilization rate of 0.27). We found VAP rates of 1.3 and 2.0 per 1,000 ventilator days respectively in 2009 and 2010, achieving zero incidence of VAP several times during 12 months, whenever VAP bundle compliance was over 90%. CONCLUSION: These results suggest that it is possible to reduce VAP rates to near zero and sustain these rates, but it requires a complex process involving multiple performance measures and interventions that must be permanently monitored.

Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting.

BACKGROUND: The Surviving Sepsis Campaign (SSC) guidelines for the management of severe sepsis (SS) and septic shock (SSh) have been recommended to reduce morbidity and mortality. MATERIALS AND METHODS: A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize SS and SSh shock patients' clinical outcomes were performed by applying sepsis bundles (6- and 24-hour) in May 2006. We compared bundle compliance and patient outcomes before (July 2005-April 2006) and after (May 2006-December 2009) implementation of the interventions. RESULTS: A total of 564 SS and SSh patients were identified. Prior to the intervention, compliance with the 6 hour-sepsis resuscitation bundle was only 6%. After the intervention, compliance was as follows: 8.2% from May to December 2006, 9.3% in 2007, 21.1% in 2008 and 13.7% in 2009. For the 24 hour-management bundle, baseline compliance was 15.0%. After the intervention, compliance was 15.1% from May to December 2006, 21.4% in 2007, 27.8% in 2008 and 44.4% in 2009. The in-hospital mortality was 54.0% from July 2005 to April 2006, 41.1% from May to December 2006, 39.3% in 2007, 41.4% in 2008 and 16.2% in 2009. CONCLUSION: These results suggest reducing SS and SSh patient mortality is a complex process that involves multiple performance measures and interventions.

Salivary osmolality and hydration status in children with cerebral palsy.

BACKGROUND: Unstimulated whole salivary parameters have been identified as potential markers of hydration status. Reduced salivary flow rate and increased salivary osmolality have been shown to be useful to identify dehydration, even when minimal loss of body water occurs. This study aimed to evaluate whether unstimulated salivary flow rate and salivary osmolality from individuals with cerebral palsy correlate with plasma and urine osmolality. METHODS: Thirty-five male and female children, aged 9-13 years old, diagnosed with cerebral palsy were compared to 27 nondisabled children (10-12 years old). Unstimulated whole saliva was collected under slight suction and salivary flow rate (ml/min) was calculated. Plasma without venostasis and urine were also collected. Salivary, plasma and urine osmolality were measured using a freezing point depression osmometer. RESULTS: Cerebral palsy children presented a reduction in salivary flow rate (50%) compared to the control group (P < 0.01). Moreover, an increase in salivary (50%), plasma (3%), and urine osmolality (20%) was also observed in the cerebral palsy children compared to the control group (P < 0.01). Salivary flow rate was negatively correlated with the salivary, plasma and urine osmolality (P < 0.01). Salivary osmolality correlated positively with plasma and urine osmolality (P < 0.01). CONCLUSION: Cerebral palsy children seem to present impaired adequate hydration status. Since the possible hypohydration condition may be reflected in saliva fluid, which could compromise the protective function exerted by saliva, the earlier this condition is identified the greater the chances of administering preventive measures. Moreover, salivary osmolality is a reliable parameter that reflects changes in plasma and urine.

Salivary osmolality in individuals with cerebral palsy.

OBJECTIVE: To measure the salivary flow rate, osmolality, electrolyte and total protein concentrations in individuals with cerebral palsy (CP). DESIGN: Thirty-eight individuals with CP were divided according to the neuromotor abnormality type (total, spastic and dyskinectic) and compared to 22 nondisabled children (control group). Whole saliva was collected under slight suction. The salivary parameters studied were salivary flow rate, osmolality, sodium, potassium, chloride and total protein concentrations. RESULTS: CP individuals, with both neuromotor abnormality types (spastic and dyskinectic), presented an increase in salivary osmolality, total protein, potassium and chloride concentrations compared to the control group (p<0.05). Moreover, a reduction in salivary flow rate was verified in spastic individuals (p<0.05). CONCLUSION: The reduction in salivary flow rate and increase in osmolality, total protein and electrolyte concentrations of saliva from cerebral palsy individuals could be caused by hypohydration status.

The use of regional citrate anticoagulation for continuous venovenous hemodiafiltration in acute kidney injury.

OBJECTIVE: Continuous renal replacement therapy is commonly used in the treatment of acute kidney injury. Although the optimal anticoagulation system is not well defined, citrate has emerged as the most promising method. We evaluated the data of 143 patients with acute kidney injury subjected to citrate-based continuous venovenous hemodiafiltration. DESIGN: Retrospective cohort study. SETTING: Intensive care unit of tertiary care private hospital. PATIENTS: Patients with acute kidney injury treated from February 2004 to July 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cause of acute kidney injury was sepsis (58%). The mean dialysis dose was 36.6 mL/kg/hr allowing for excellent metabolic control (last tests: creatinine, 1.1 mg/dL; urea, 46 mg/dL). No significant bleeding, severe electrolyte, or calcium disorders were observed. Of the 418 filters used, almost 28,000 hrs of treatment, hemofilter patency was 68% at 72 hrs. Hospital mortality was 59%, and 22% of survivors were dialysis-dependent at the time of discharge. Within our sample, we identified 21 patients with liver failure (mean prothrombin time index, 21% vs. 67%, p < 0.001). This group presented with a lesser median systemic ionized calcium level (1.06 vs. 1.12 mmol/L, p < 0.001) and similar mean total calcium level (8.5 vs. 8.6 mg/dL, not significant), compared with patients without liver failure. These subjects also showed acidemia (median pH, 7.31 vs. 7.40, p < 0.001); however, they exhibited higher levels of lactate (median 29 vs. 16 mg/dL, p < 0.001), chloride (mean 109 vs. 107 mEq/L, p = 0.045) and had a trend to higher mortality rate (76% vs. 56%). CONCLUSIONS: Besides a trend toward higher mortality rate observed in the group with liver failure, we found that citrate-based continuous venovenous hemodiafiltration allowed an effective dialysis dose and reasonable filter patency.