A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension

The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtained at FRC and at TLC with a positive airway pressure of 30 cm H2O. In patients, lung volumes were quantified by the analysis of the frequency distribution of CT numbers on the entire lung at zero end-expiratory pressure (ZEEP) and PEEP. In healthy volunteers at FRC, the distribution of the density histograms was monophasic with a peak at -791 ± 12 Hounsfield units (HU). The lowest CT number observed was -912 HU. At TLC, lung volume increased by 79 ± 35% and the peak CT number decreased to -886 ± 26 HU. More than 70% of the increase in lung volume was located below -900 HU, suggesting that this value can be considered as the threshold separating normal aeration from overdistension. In patients with ALI, at ZEEP the distribution of density histograms was either monophasic (n = 3) or biphasic (n = 3). The mean CT number was -319 ± 34 HU. At PEEP 13 ± 3 cm H2O, lung volume increased by 47 ± 19% whereas mean CT number decreased to -538 ± 171 HU. PEEP induced a mean alveolar recruitment of 320 ± 160 ml and a mean lung overdistension of 238 ± 320 ml. In conclusion, overdistended lung parenchyma of healthy volunteers is characterized by a CT number below -900 HU. This threshold can be used in patients with ALI for differentiating PEEP-induced alveolar recruitment from lung overdistension.

Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: Activation of CD8+ cells, interferon-γ recovery and reduction of lung injury

A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis. In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65. We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice. After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated. Our results show that the most significant effect of pHSP65 was the stimulation of CD8+ lung cell activation, interferon-γ recovery and reduction of lung injury. There was also partial restoration of the production of tumour necrosis factor-α. Treatment with pcDNA3 vector also induced an immune stimulatory effect. However, only infected pHSP65-treated mice were able to produce significant levels of interferon-γ and to restrict the growth of bacilli.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Different prescribed doses of high-volume peritoneal dialysis and outcome of patients with acute kidney injury.

The optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. No studies have directly examined the effects of peritoneal dialysis (PD) dose on outcomes in AKI. From January 2005 to January 2007, we randomly assigned critically ill patients with AKI to receive higher- or lower-intensity PD therapy (prescribed Kt/Vof 0.8 and 0.5 per session respectively). The main outcome measure was death within 30 days. Of the 61 enrolled patients, 30 were randomly assigned to higher-intensity therapy, and 31, to a lower-intensity PD dose. The two study groups had similar baseline characteristics and received treatment for 6.1 days and 5.7 days respectively (p = 0.42). At 30 days after randomization, 17 deaths had occurred in the higher-intensity group (55%), and 16 deaths, in the lower-intensity group (53%, p = 0.83). There was a significant difference between the groups in the PD dose prescribed compared with the dose delivered (higher-intensity group: 0.8 vs. 0.59, p = 0.04; lower-intensity group: 0.5 vs. 0.49, p = 0.89). The groups had similar metabolic control after 4 PD sessions (blood urea nitrogen: 69.3 +/- 14.4 mg/dL and 60.3 +/- 11.1 mg/dL respectively, p = 0. 71). In critically ill patients with AKI, an intensive PD dose did not lower the mortality or improve the recovery of kidney function or metabolic control. The PD dose is limited by dialysate flow and membrane permeability, and clearance per exchange can decrease if a shorter dwell time is applied.

Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

Background: Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. Results: The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. Conclusion: Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion. © 2013 Guido et al.; licensee BioMed Central Ltd.

A randomized clinical trial of high volume peritoneal dialysis versus extended daily hemodialysis for acute kidney injury patients

Background: Acute kidney injury (AKI) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50-80 %. Extended daily hemodialysis (EHD) and high volume peritoneal dialysis (HVPD) have emerged as alternative modalities. Methods: A double-center, randomized, controlled trial was conducted comparing EHD versus HVPD for the treatment for AKI in the intensive care unit (ICU). Four hundred and seven patients were randomized and 143 patients were analyzed. Principal outcome measure was hospital mortality, and secondary end points were recovery of renal function and metabolic and fluid control. Results: There was no difference between the two groups in relation to median ICU stay [11 (5.7-20) vs. 9 (5.7-19)], recovery of kidney function (26.9 vs. 29.6 %, p = 0.11), need for chronic dialysis (9.7 vs. 6.5 %, p = 0.23), and hospital mortality (63.4 vs. 63.9 %, p = 0.94). The groups were different in metabolic and fluid control. Blood urea nitrogen (BUN), creatinine, and bicarbonate levels were stabilized faster in EHD group than in HVPD group. Delivered Kt/V and ultrafiltration were higher in EHD group. Despite randomization, there were significant differences between the groups in some covariates, including age, pre-dialysis BUN, and creatinine levels, biased in favor of the EHD. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with HVPD was 1.4 (95 % CI 0.7-2.4, p = 0.19). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment. Conclusions: Despite faster metabolic control and higher dialysis dose and ultrafiltration with EHD, this study provides no evidence of a survival benefit of EHD compared with HVPD. The limitations of this study were that the results were not presented according to the intention to treat and it did not control other supportive management strategies as nutrition support and timing of dialysis initiation that might influence outcomes in AKI. © 2012 Springer Science+Business Media Dordrecht.

Hypothyroidism and acute kidney injury: An unusual association

Association between severe hypothyroidism and acute kidney injury (AKI) is rare. A 40-year-old woman presented with 15 days history of generalised muscle pain, weakness, weight gain and oedema. Medical history: hypertension and hypothyroidism. Physical examination: dry skin, peripheral/periorbital oedema, slow thought and speaking, thyroid increased. Laboratory examinations: high levels of creatine kinase , creatinine, uric acid and lactate dehydrogenase. Free T4 was very low (<0.3 ng/dL) and thyroid-stimulating hormone was high (21.7 mIU/mL). Urinalysis showed haem pigment without haematuria. We performed the diagnosis of AKI secondary to hypothyroidism-induced rhabdomyolysis. Intravenous fluids were started, urinary alkalisation and increased l-thyroxine dose replacement. On the day after admission, forced diuresis with furosemide was introduced leading to a progressive improvement of symptoms. Although hypothyroidism and AKI is unusual, it should be suspected in patients presenting decrease of renal function and high creatine kinase in the absence of other causes of rhabdomyolysis.

Extended Daily Dialysis in Acute Kidney Injury Patients: Metabolic and Fluid Control and Risk Factors for Death

Intermittent hemodialysis (IHD) and continuous renal replacement therapies (CRRT) are used as Acute Kidney Injury (AKI) therapy and have certain advantages and disadvantages. Extended daily dialysis (EDD) has emerged as an alternative to CRRT in the management of hemodynamically unstable AKI patients, mainly in developed countries.Objectives: We hypothesized that EDD is a safe option for AKI treatment and aimed to describe metabolic and fluid control of AKI patients undergoing EDD and identify complications and risk factors associated with death.Study Selection: This is an observational and retrospective study describing introduction of EDD at our institution. A total of 231 hemodynamically unstable AKI patients (noradrenalin dose between 0.3 and 1.0 ucg/kg/min) were assigned to 1367 EDD session. EDD consisted of 6-8 h of HD 6 days a week, with blood flow of 200 ml/min, dialysate flows of 300 ml/min.Data Synthesis: Mean age was 60.6 +/- 15.8 years, 97.4% of patients were in the intensive care unit, and sepsis was the main etiology of AKI (76.2). BUN and creatinine levels stabilized after four sessions at around 38 and 2.4 mg/dl, respectively. Fluid balance decreased progressively and stabilized around zero after five sessions. Weekly delivered Kt/V was 5.94 +/- 0.7. Hypotension and filter clotting occurred in 47.5 and 12.4% of treatment session, respectively. Regarding AKI outcome, 22.5% of patients presented renal function recovery, 5.6% of patients remained on dialysis after 30 days, and 71.9% of patients died. Age and focus abdominal sepsis were identified as risk factors for death. Urine output and negative fluid balance were identified as protective factors.Conclusions: EDD is effective for AKI patients, allowing adequate metabolic and fluid control. Age, focus abdominal sepsis, and lower urine output as well as positive fluid balance after two EDD sessions were associated significantly with death.

METABOLIC IMPLICATIONS OF PERITONEAL DIALYSIS IN PATIENTS WITH ACUTE KIDNEY INJURY

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Intra-abdominal pressure as a predictor of acute kidney injury in postoperative abdominal surgery

Objectives: The purpose of this study was to determine if intra-abdominal pressure (IAP) could predict acute renal injury (AKI) in the postoperative period of abdominal surgeries, and which would be its cutoff value. Patients and methods: A prospective observational study was conducted in the period from January 2010 to March 2011 in the Intensive Care Units (ICUs) of the University Hospital of Botucatu Medical School, UNESP. Consecutive patients undergoing abdominal surgery were included in the study. Initial evaluation, at admission in ICU, was performed in order to obtain demographic, clinical surgical and therapeutic data. Evaluation of IAP was obtained by the intravesical method, four times per day, and renal function was evaluated during the patient's stay in the ICU until discharge, death or occurrence of AKI. Results: A total of 60 patients were evaluated, 16 patients developed intra-abdominal hypertension (IAH), 45 developed an abnormal IAP (>7 mmHg) and 26 developed AKI. The first IAP at the time of admission to the ICU was able to predict the occurrence of AKI (area under the receiver-operating characteristic curve was 0.669; p=0.029) with the best cutoff point (by Youden index method) >= 7.68 mmHg, sensitivity of 87%, specificity of 46% at this point. The serial assessment of this parameter did not added prognostic value to initial evaluation. Conclusion: IAH was frequent in patients undergoing abdominal surgeries during ICU stay, and it predicted the occurrence of AKI. Serial assessments of IAP did not provided better discriminatory power than initial evaluation.

Nutritional parameters are associated with mortality in acute kidney injury

OBJECTIVE: The objective of this study was to perform a nutritional assessment of acute kidney injury patients and to identify the relationship between nutritional markers and outcomes.METHOD: This was a prospective and observational study. Patients who were hospitalized at the Hospital of Botucatu School of Medicine were evaluated between January 2009 and December 2011. We evaluated a total of 133 patients with a clinical diagnosis of acute kidney injury and a clinical presentation suggestive of acute tubular necrosis. We explored the associations between clinical, laboratory and nutritional markers and in hospital mortality. Multivariable logistic regression was used to adjust for confounding and selection bias.RESULTS: Non-survivor patients were older (67 +/- 14 vs. 59 +/- 16 years) and exhibited a higher prevalence of sepsis (57.1 vs. 21.4%) and higher Acute Tubular Necrosis-Individual Severity Scores (0.60 +/- 0.22 vs. 0.41 +/- 0.21) than did survivor patients. Based on the multivariable analysis, laboratorial parameters such as blood urea nitrogen and C-reactive protein were associated with a higher risk of death (OR: 1.013, p = 0.0052; OR: 1.050, p = 0.01, respectively), and nutritional parameters such as low calorie intake, higher levels of edema, lower resistance based on bioelectrical impedance analysis and a more negative nitrogen balance were significantly associated with a higher risk of death (OR: 0.950, p = 0.01; OR: 1.138, p = 0.03; OR: 0.995, p = 0.03; OR: 0.934, p = 0.04, respectively).CONCLUSIONS: In acute kidney injury patients, a nutritional assessment seems to identify nutritional markers that are associated with outcome. In this study, a low caloric intake, higher C-reactive protein levels, the presence of edema, a lower resistance measured during a bioelectrical impedance analysis and a lower nitrogen balance were significantly associated with risk of death in acute kidney injury patients.

The long-term outcome after acute kidney injury: a narrative review

This review will focus on long-term outcomes after acute kidney injury (AKI). Surviving AKI patients have a higher late mortality compared with those admitted without AKI. Recent studies have claimed that long-term mortality in patients after AKI varied from 15% to 74% and older age, presence of previous co-morbidities, and the incomplete recovery of renal function have been identified as risk factors for reduced survival. AKI is also associated with progression to chronic kidney (CKD) disease and the decline of renal function at hospital discharge and the number and severity of AKI episodes have been associated with progression to CKD. IN the most studies, recovery of renal function is defined as non-dependence on renal replacement therapy which is probably too simplistic and it is expected in 60-70% of survivors by 90 days. Further studies are needed to explore the long-term prognosis of AKI patients.

Peritoneal dialysis in acute kidney injury: trends in the outcome across time periods

Peritoneal dialysis (PD) should be considered a suitable method of renal replacement therapy in acute kidney injury (AKI) patients. This study is the largest cohort providing patient characteristics, clinical practice, patterns and their relationship to outcomes in a developing country. Its objective was to describe the main determinants of patient and technique survival, including trends over time of PD treatment in AKI patients. This was a Brazilian prospective cohort study in which all adult AKI patients on PD were studied from January/2004 to January/2014. For comparison purposes, patients were divided into 2 groups according to the year of treatment: 2004-2008 and 2009-2014. Patient survival and technique failure (TF) were analyzed using the competing risk model of Fine and Gray. A total of 301 patients were included, 51 were transferred to hemodialysis (16.9%) during the study period. The main cause of TF was mechanical complication (47%) followed by peritonitis (41.2%). There was change in TF during the study period: compared to 2004-2008, patients treated at 2009-2014 had relative risk (RR) reduction of 0.86 (95% CI 0.77-0.96) and three independent risk factors were identified: period of treatment at 2009 and 2014, sepsis and age>65 years. There were 180 deaths (59.8%) during the study. Death was the leading cause of dropout (77.9% of all cases) mainly by sepsis (58.3%), followed cardiovascular disease (36.1%). The overall patient survival was 41% at 30 days. Patient survival improved along study periods: compared to 2004-2008, patients treated at 2009-2014 had a RR reduction of 0.87 (95% CI 0.79-0.98). The independent risk factors for mortality were sepsis, age>70 years, ATN-ISS > 0.65 and positive fluid balance. As conclusion, we observed an improvement in patient survival and TF along the years even after correction for several confounders and using a competing risk approach.