Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Results: Timing of RRT was stratified into ""early"" and ""late"" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea <= 24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 mu mol/L vs 71.4% for creatinine <= 309 mu mol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001).However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence. Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. (C) 2009 Elsevier Inc. All rights reserved.

Arterial pulse pressure variation predicting fluid responsiveness in critically ill patients (Retracted article. See vol. 31, pg. 542, 2009)

In critically ill patients, it is important to predict which patients will have their systemic blood flow increased in response to volume expansion to avoid undesired hypovolemia and fluid overloading. Static parameters such as the central venous pressure, the pulmonary arterial occlusion pressure, and the left ventricular end-diastolic dimension cannot accurately discriminate between responders and nonresponders to a fluid challenge. In this regard, respiratory-induced changes in arterial pulse pressure have been demonstrated to accurately predict preload responsiveness in mechanically ventilated patients. Some experimental and clinical studies confirm the usefulness of arterial pulse pressure as a useful tool to guide fluid therapy in critically ill patients.

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose: The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients. Methods: This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement +/- 150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment-subcutaneous insulin if glucose > 150 mg/dL. The main efficacy outcome was the mean of patients` median BG, and the safety outcome was the incidence of hypoglycemia (<= 40 mg/dL). Results: The mean of patients` median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional). Conclusions: The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols. (C) 2009 Elsevier Inc. All rights reserved.

Dual candidemia detected by nested polymerase chain reaction in two critically ill children

The use of improved microbiological procedures associated with molecular techniques has increased the identification of Candida bloodstream infections, even if the isolation of more than one species by culture methods remains uncommon. We report the cases of two children presenting with severe gastrointestinal disorders and other risk factors that contribute to Candida infections. In the first patient, C. albicans DNA was initially detected by a nested-amplification and C. tropicalis was found later during hospitalization, while blood cultures were persistently negative. In the second child, there was amplification of C. albicans and C. glabrata DNA in the same samples, but blood cultures yielded only C. albicans. Both patients received antifungal therapy but had unfavorable outcomes. These two cases illustrate that PCR was more successful than culture methods in detecting Candida in the bloodstream of high risk children, and was also able to detect the presence of more than one species in the same patient that might impact therapy when the fungi are resistant to azole compounds.

The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients

Purpose: Inorganic apparent strong ion difference (SIDai) improves chloride-associated acidosis recognition in dysnatremic patients. We investigated whether the difference between sodium and chloride (Na+-C1-) or the ratio between chloride and sodium (Cl-/Na+) could be used as SIDai surrogates in mixed and dysnatremic patients. Patients and Methods: Two arterial blood samples were collected from 128 patients. Physicochemical analytical approach was used. Correlation, agreement, accuracy, sensitivity, and specificity were measured to examine whether Na(+)-C1(-) and CI(-)/Na(+) could be used instead of SIDai in the diagnosis of acidosis. Results: Na(+)-C1(-) and CF/Na+ were well correlated with SIDai (R = 0.987, P < 0.001 and R = 0.959, P < 0.001, respectively). Bias between Na(+)-C1(-) and SIDai was high (6.384 with a limit of agreement of 4.4638.305 mEq/L). Accuracy values for the identification of SIDai acidosis (<38.9 mEq/L) were 0.989 (95% confidence interval [CI], 0.980-0.998) for Na+-C1- and 0.974 (95% CI, 0.959-0.989) for Cr/Na+. Receiver operator characteristic curve showed that values revealing SIDai acidosis were less than 32.5 mEq/L for Nata- and more than 0.764 for C17Na+ with sensitivities of 94.0% and 92.0% and specificities of 97.0% and 90.0%, respectively. Nata- was a reliable S IDai surrogate in dysnatremic patients. Conclusions: Nata- and CI-/Na+ are good tools to disclose S IDai acidosis. In patients with dysnatremia, Nata- is an accurate tool to diagnose SIDai acidosis. (C) 2010 Elsevier Inc. All rights reserved.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.

Can an adequate energy intake be able to reverse the negative nitrogen balance in mechanically ventilated critically ill patients?

Purpose: Adequate energy provision and nitrogen losses prevention of critically ill patients are essentials for treatment and recovery. The aims of this study were to evaluate energy expenditure (EE) and nitrogen balance (NB) of critically ill patients, to classify adequacy of energy intake (El), and to verify adequacy of El capacity to reverse the negative NB. Methods: Seventeen patients from an intensive care unit were evaluated within a 24-hour period. Indirect calorimetry was performed to calculate patient`s EE and Kjeldhal for urinary nitrogen analysis. The total El and protein intake were calculated from the standard parenteral and enteral nutrition infused. Underfeeding was characterized as El 90% or less and overfeeding as 110% or greater of EE. The adequacy of the El (El EE(-1) x 100) and the NB were estimated and associated with each other by Spearman coefficient. Results: The mean EE was 1515 +/- 268 kcal d(-1) and most of the patients (11/14) presented a negative NB (-8.2 +/- 4.7 g.d(-1)). A high rate (53%) of inadequate energy intake was found, and a positive correlation between El EE(-1) and NB was observed (r = 0.670; P = .007). Conclusion: The results show a high rate of inadequate El and negative NB, and equilibrium between El and EE may improve NB. Indirect calorimetry can be used to adjust the energy requirements in the critically ill patients. (C) 2010 Elsevier Inc. All rights reserved.

Harris-Benedict equation for critically ill patients: Are there differences with indirect calorimetry?

Purpose: The aim of this study was to compare the measured energy expenditure (EE) and the estimated basal EE (BEE) in critically ill patients. Materials and Methods: Seventeen patients from an intensive care unit were randomly evaluated. Indirect calorimetry was performed to calculate patient`s EE, and BEE was estimated by the Harris-Benedict formula. The metabolic state (EE/BEE x 100) was determined according to the following criteria: hypermetabolism, more than 130%; normal metabolism, between 90% and 130%; and hypometabolism, less than 90%. To determine the limits of agreement between EE and BEE, we performed a Bland-Altman analysis. Results: The average EE of patients was 6339 +/- 1119 kJ/d. Two patients were hypermetabolic (11.8%), 4 were hypometabolic (23.5%), and 11 normometabolic (64.7%). Bland-Altman analysis showed a mean of -126 +/- 2135 kJ/d for EE and BEE. Only one patient was outside the limits of agreement between the 2 methods (indirect calorimetry and Harris-Benedict). Conclusions: The calculation of energy needs can be done with the equation of Harris-Benedict associated with lower values of correction factors (approximately 10%) to avoid overfeeding, with constant monitoring of anthropometric and biochemical parameters to assess the nutritional changing and adjust the infusion of energy. (C) 2009 Elsevier Inc. All rights reserved.

Predicting Hospital Mortality in Critically Ill Cancer Patients according to Acute Kidney Injury Severity

Background: Acute kidney injury (AKI) is a frequent complication in hospitalized patients, especially in those in intensive care units (ICU). The RIFLE classification might be a valid prognostic factor for critically ill cancer patients. The present study aims to evaluate the discriminatory capacity of RIFLE versus other general prognostic scores in predicting hospital mortality in critically ill cancer patients. Methods: This is a single-center study conducted in a cancer-specialized ICU in Brazil. All of the 288 patients hospitalized from May 2006 to June 2008 were included. RIFLE classification, APACHE II, SOFA, and SAPS II scores were calculated and the area under receiver operating characteristic (AROC) curves and logistic multiple regression were performed using hospital mortality as the outcome. Results: AKI, defined by RIFLE criteria, was observed in 156 (54.2%) patients. The distribution of patients with any degree of AKI was: risk, n = 96 (33.3%); injury, n = 30 (10.4%), and failure, n = 30 (10.4%). Mortality was 13.6% for non-AKI patients, 49% for RIFLE `R` patients, 62.3% for RIFLE `I` patients, and 86.8% for RIFLE `F` patients (p = 0.0006). Logistic regression analysis showed that RIFLE criteria, APACHE II, SOFA, and SAPS II were independent factors for mortality in this population. The discrimination of RIFLE was good (AROC 0.801, 95% CI 0.748-0.854) but inferior compared to those of APACHE II (AROC 0.940, 95% CI 0.915-0.966), SOFA (AROC 0.910, 95% CI 0.876-0.943), and SAPS II (AROC 0.869, 95% CI 0.827-0.912). Conclusion: AKI is a frequent complication in ICU patients with cancer. RIFLE was inferior to commonly used prognostic scores for predicting mortality in this cohort of patients. Copyright (C) 2011 S. Karger AG, Basel

Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

Background: Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. Methods: We studied nineteen neonates (27.3 +/- 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO(2) and VCO(2) measured by gas chromatography. Results: REE significantly increased from 49.4 +/- 13.1 kcal/kg/day during the acute to 68.3 +/- 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO(2) (7.4 +/- 1.9 vs 10 +/- 1.5 ml/kg/min) and VCO(2) (5.1 +/- 1.7 vs 7.4 +/- 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01). Conclusion: REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities.

Adverse drug events in an intensive care unit of a university hospital

Purpose Adverse drug events (ADEs) are harmful and occur with alarming frequency in critically ill patients. Complex pharmacotherapy with multiple medications increases the probability of a drug interaction (DI) and ADEs in patients in intensive care units (ICUs). The objective of the study is to determine the frequency of ADEs among patients in the ICU of a university hospital and the drugs implicated. Also, factors associated with ADEs are investigated. Methods This cross-sectional study investigated 299 medical records of patients hospitalized for 5 or more days in an ICU. ADEs were identified through intensive monitoring adopted in hospital pharmacovigilance and also ADE triggers. Adverse drug reactions (ADR) causality was classified using the Naranjo algorithm. Data were analyzed through descriptive analysis, and through univariate and multiple logistic regression. Results The most frequent ADEs were ADRs type A, of possible causality and moderate severity. The most frequent ADR was drug-induced acute kidney injury. Patients with ADEs related to DIs corresponded to 7% of the sample. The multiple logistic regression showed that length of hospitalization (OR = 1.06) and administration of cardiovascular drugs (OR = 2.2) were associated with the occurrence of ADEs. Conclusion Adverse drug reactions of clinical significance were the most frequent ADEs in the ICU studied, which reduces patient safety. The number of ADEs related to drug interactions was small, suggesting that clinical manifestations of drug interactions that harm patients are not frequent in ICUs.

Effects of glutamine on the nuclear factor-kappaB signaling pathway of murine peritoneal macrophages

The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappaB (NF-kappa B) signaling pathway of murine peritoneal macrophages. Since glutamine is essential for the normal functioning of macrophages, it was hypothesized that in vitro glutamine supplementation would increase NF-kappa B activation. Peritoneal macrophages were pretreated with glutamine (0, 0.6, 2 and 10 mM) before incubation with lipopolysaccharide (LPS), and the effects of glutamine on the production of tumor necrosis factor-alpha and on the expression and activity of proteins involved in the NF-kappa B signaling pathway were studied by an enzyme linked immuno-sorbent assay, Western blotting, and an electrophoretic mobility shift assay. Glutamine treatment (2 and 10 mM) increased the activation of NF-kappa B in LPS-stimulated peritoneal macrophages (P < 0.05). In non-stimulated cells, glutamine treatment (2 and 10 mM) significantly reduced I kappa B-alpha protein expression (P < 0.05). Glutamine modulates NF-kappa B signaling pathway by reducing the level of I kappa B-alpha, leading to an increase in NF-kappa B within the nucleus in peritoneal macrophages.

BLOCKING CENTRAL LEUKOTRIENES SYNTHESIS AFFECTS VASOPRESSIN RELEASE DURING SEPSIS

Recent studies revealed that vasopressinergic neurons have a high content of cys-leukotriene C(4) (LTC(4)) synthase, a critical enzyme in cys-leukotriene synthesis that may play a role in regulating vasopressin secretion. This study investigates the role of this enzyme in arginine vasopressin (AVP) release during experimentally induced sepsis. Male Wistar rats received an i.c.v. injection of 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2, 2-dimethylpropanoic acid (MK-886) (1.0 mu g/kg), a leukotrienes (LTs) synthesis inhibitor, or vehicle, 1 h before cecal ligation and puncture (CLP) or sham operation. In one group of animals the survival rate was monitored for 3 days. In another group, the animals were decapitated at 0, 4, 6, 18 and 24 h after CLP or sham operation, and blood was collected for hematocrit, serum sodium and nitrate, plasma osmolality, protein and AVP determination. A third group was used for blood pressure measurements. The neurohypophysis was removed for quantification of AVP content, and the hypothalamus was dissected for LTC4 synthase analysis by Western blot. Mortality after CLP was reduced by the central administration of MK-886. The increase in plasma AVP levels and hypothalamus LTC4 synthase content in the initial phase of sepsis was blocked, whereas the decrease in neurohypophyseal AVP content was partially reversed. Also the blood pressure drop was abolished in this phase. The increase of serum nitric oxide and hematocrit was reduced, and the decrease in plasma protein and osmolality was not affected by the LTs blocker. In the final phase of sepsis, the plasma AVID level and the hypothalamic LTC4 synthase content were at basal levels. The central administration of MK-886 increased the hypothalamic LTC4 synthase content but did not alter the plasma and neurohypophysis AVID levels observed, or the blood pressure during this phase. These results suggest that the central LTs are involved in the vasopressin release observed during sepsis. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Constipation in intensive care unit: Incidence and risk factors

Purpose: Although gastrointestinal motility disorders are common in critically ill patients, constipation and its implications have received very little attention. We aimed to determine the incidence of constipation to find risk factors and its implications in critically ill patients Materials and Methods: During a 6-month period, we enrolled all patients admitted to an intensive care unit from an universitary hospital who stayed 3 or more days. Patients submitted to bowel surgery were excluded. Results: Constipation occurred in 69.9% of the patients. There was no difference between constipated and not constipated in terms of sex, age, Acute Physiology and Chronic Health Evaluation II, type of admission (surgical, clinical, or trauma), opiate use, antibiotic therapy, and mechanical ventilation. Early (<24 hours) enteral nutrition was associated with less constipation, a finding that persisted at multivariable analysis (P < .01). Constipation was not associated with greater intensive care unit or mortality, length of stay, or days free from mechanical ventilation. Conclusions: Constipation is very common among critically ill patients. Early enteral nutrition is associated with earlier return of bowel function. (C) 2009 Elsevier Inc. All rights reserved.