Marcelino de Souza Durão

Successful prevention of ventilator-associated pneumonia in an intensive care setting

BACKGROUND Ventilator-associated pneumonia (VAP) is one of the most common health care-associated infections (HAIs) in critical care settings. OBJECTIVE Our objective was to examine the effect of a series of interventions, implemented in 3 different periods to reduce the incidence of VAP in an intensive care unit (ICU). METHODS A quasiexperimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize VAP prevention were performed during different phases. From March 2001 to December 2002 (phase 1: P1), some Centers for Disease Control and Prevention (CDC) evidence-based practices were implemented. From January 2003 to December 2006 (P2), we intervened in these processes at the same time that performance monitoring was occurring at the bedside, and, from January 2007 to September 2008 (P3), we continued P2 interventions and implemented the Institute for Healthcare Improvements ventilator bundle plus oral decontamination with chlorhexidine and continuous aspiration of subglottic secretions. RESULTS The incidence density of VAP in the ICU per 1000 patient-days was 16.4 in phase 1, 15.0 in phase 2, and 10.4 in phase 3, P=.05. Getting to zero VAP was possible only in P3 when compliance with all interventions exceeded 95%. CONCLUSION These results suggest that reducing VAP rates to zero is a complex process that involves multiple performance measures and interventions.

Impact of a program to prevent central line-associated bloodstream infection in the zero tolerance era

BACKGROUND Central line-associated bloodstream infection (CLABSI) is one of the most important health care-associated infections in the critical care setting. METHODS A quasiexperimental study involving multiple interventions to reduce the incidence of CLABSI was conducted in a medical-surgical intensive care unit (ICU) and in 2 step-down units (SDUs). From March 2005 to March 2007 (phase 1 [P1]), some Centers for Disease Control and Prevention evidence-based practices were implemented. From April 2007 to April 2009 (P2), we intervened in these processes at the same time that performance monitoring was occurring at the bedside, and we implemented the Institute for Healthcare Improvement central line bundle for all ICU and SDU patients requiring central venous lines. RESULTS The mean incidence density of CLABSI per 1000 catheter-days in the ICU was 6.4 in phase 1 and 3.2 in phase 2, P < .001. The mean incidence density of CLABSI per 1000 catheter-days in the SDUs was 4.1 in phase 1 and 1.6 in phase 2, P = .005. CONCLUSION These results suggest that reducing CLABSI rates in an ICU setting is a complex process that involves multiple performance measures and interventions that can also be applied to SDU settings.

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

BackgroundVentilator-associated pneumonia (VAP) is a common infection in the intensive care unit (ICU) and associated with a high mortality.MethodsA 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.ResultsWe 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%.ConclusionThese 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.

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.

Nec-1 Protects against Nonapoptotic Cell Death in Cisplatin-Induced Kidney Injury

Background/aims: Necrostatin-1 (Nec-1) inhibits necroptosis, a nonapoptotic cell death pathway. Acute kidney injury (AKI) is a clinical problem of high incidence and mortality. It involves several mechanisms of cell death. We aim to evaluate the effect of Nec-1 in the toxic kidney injury model by cisplatin. Methods: We analyzed the effect of Nec-1 in AKI by cisplatin in human proximal tubule cells by flow cytometry. Results: Our results show that Nec-1 has no effect on apoptosis in renal tubular epithelial cells (Nec-1 + Cis group 13.4 ± 1.7% vs. Cis group 14.6 ± 1.4%) (p > 0.05). But, in conditions in which apoptosis was blocked by benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk) the use of Nec-1 completely reversed cell viability (Nec-1 + Cis + z-VAD group 72.9 ± 6.3% vs. Cis group 35.5 ± 2.2%) (p < 0.05) suggesting that Nec-1 has effect on nonapoptotic cell death (necroptosis). Conclusion: Our findings suggest that the combined use of apoptosis and necroptosis inhibitors can provide additional cytoprotection in AKI. Furthermore, this is the first study to demonstrate that Nec-1 inhibits tubular kidney cell death and restores cell viability via a nonapoptotic mechanism.

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.

The role of growth factors on renal tubular cells submitted to hypoxia and deprived of glucose.

Background. In acute renal failure (ARF) renal tubular cell death and detachment can be induced by necrotic and apoptotic mechanisms. Several studies have demonstrated some benefits of the use of growth factors in experimental models of ARF. Methods. MDCK cells were cultured in a glucose-free medium for 24 h and were submitted to hypoxia (pO2 around 35 mmHg) for additional 24 h. To evaluate the possible protective role of growth factors, EGF, IGF-I or HGF were added to the medium (20 ng mL). LDH release, viability (acridine orange and ethidium bromide dyes) and quantification of apoptotic cells (Hoechst 33342 dye fluorescence) were determined. Results. In the injury group, an increase on LDH release (60% vs. 3%) and on number of apoptotic cells (22% vs. 0.2%) which was associated with a reduced cell viability (61% vs. 94%) when compared with controls. Only HGF, not EGF or IGF-I, was able to protect cells from injury. HGF caused a significant reduction on LDH release (30%) and on number of apoptotic cells (5%), with an increase on viability cellular (79%). Conclusions. HGF decreases cell death on MDCK cells after hypoxic-induced injury, probably acting in both necrotic and apoptotic mechanisms.

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.

Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients

Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of −308 G < A tumour necrosis factor (TNF)‐α, −174 G > C interleukin (IL)‐6 and −1082 G > A IL‐10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case–control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF‐α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF‐α/IL‐10 combinations, it was observed that low TNF‐α plus low IL‐10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF‐α producer plus low IL‐10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16–4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19–12·23; P = 0·02). In this study, the combination of low TNF‐α plus low IL‐10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long‐term follow‐up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.