High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial

Purpose

Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI.

Methods

This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period.

Results

Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups.

Conclusions

In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.     

Continuous venovenous hemofiltration versus extended daily hemofiltration in patients with septic acute kidney injury: a retrospective cohort study

Introduction

Whether continuous venovenous hemofiltration (CVVHF) is superior to extended daily hemofiltration (EDHF) for the treatment of septic AKI is unknown. We compared the effect of CVVHF (greater than 72 hours) with EDHF (8 to 12 hours daily) on renal recovery and mortality in patients with severe sepsis or septic shock and concurrent acute kidney injury (AKI).

Methods

A retrospective analysis of 145 septic AKI patients who underwent renal replacement therapy (RRT) between July 2009 and May 2013 was performed. These patients were treated by CVVHF or EDHF with the same polyacrylonitrile membrane and bicarbonate-based buffer. The primary outcomes measured were occurrence of renal recovery and all-cause mortality by 60 days.

Results

Sixty-five and eighty patients were treated with CVVHF and EDHF, respectively. Patients in the CVVHF group had significantly higher recovery of renal function (50.77% of CVVHF group versus 32.50% in the EDHF group, P = 0.026). Median time to renal recovery was 17.26 days for CVVHF patients and 25.46 days for EDHF patients (P = 0.039). Sixty-day all-cause mortality was similar between CVVHF and EDHF groups (44.62%, and 46.25%, respectively; P = 0.844). 55.38% of patients on CVVHF and 28.75% on EDHF developed hypophosphatemia (P = 0.001). The other adverse events related to RRT did not differ between groups. On multivariate analysis, including physiologically clinical relevant variables, CVVHF therapy was significantly associated with recovery of renal function (HR 3.74; 95% CI 1.82 to 7.68; P < 0.001), but not with mortality (HR 0.69; 95% CI 0.34 to 1.41; P = 0.312).

Conclusions

Patients undergoing CVVHF therapy had significantly improved renal recovery independent of clinically relevant variables. The patients with septic AKI had similar 60-day all-cause mortality rates, regardless of type of RRT.     

The benefit of specialized team approaches in patients with acute kidney injury undergoing continuous renal replacement therapy: propensity score matched analysis

Introduction

Continuous renal replacement therapy (CRRT) has been widely used in critically ill acute kidney injury (AKI) patients. Moreover, some centers operate a specialized CRRT team (SCT) composed of physicians and nurses, but few studies have yet determined the superiority of SCT control.

Methods

A total of 334 among 534 patients in the original cohort, who started CRRT for severe AKI between August 2007 and September 2009 in Yonsei University Health System and were matched with a propensity score (PS), were divided into two groups based on SCT application. Moreover, we compared CRRT-related outcomes including down-time per day and lost time per filter-exchange between the two groups. The primary outcomes were 28- and 90-day all-cause mortality, and the secondary outcomes were the rates of renal function recovery at 28- and 90-day.

Results

The down-time per day, lost time per filter-exchange, and red blood cell-transfused numbers during CRRT treatment were significantly lower after SCT approach compared with the group before SCT, while net ultrafiltration rate in the after SCT group was significantly higher compared to the before SCT group. During the study period, the 28- and 90-day all-cause mortality rates were significantly decreased after SCT application. Cox regression analysis revealed that 28- and 90-day all-cause mortality rates were significantly lower under SCT control, after adjusting for primary diagnosis, emergent surgical cases, Charlson Comorbidity Index and biochemical parameters. However, there were no significant differences in the rate of renal function recovery before and after SCT approach in CRRT.

Conclusions

A well-organized CRRT team could be beneficial for clinical outcomes through improving quality of care in AKI patients requiring CRRT treatment in the ICU.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0454-8) contains supplementary material, which is available to authorized users.     

Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin,matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study

Introduction

The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED).

Methods

In total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients.

Results

The median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days’ follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group.

Conclusions

NGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.     

Invasive mechanical ventilation as a risk factor for acute kidney injury in the critically ill: a systematic review and meta-analysis

Introduction

Mechanical ventilation (MV) is commonly regarded as a risk factor for acute kidney injury (AKI) in the critically ill. We investigated the strength of this association and whether settings of tidal volume (Vt) and positive end-expiratory pressure (PEEP) affect the risk for AKI.

Methods

We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included studies reporting on a relation between the use of invasive MV and subsequent onset of AKI, or comparing higher with lower Vt or PEEP and subsequent onset of AKI. All studies clearly stating that MV was initiated after onset of AKI were excluded. We extracted the proportion with and without MV and AKI. We included 31 studies on invasive MV.

Results

The pooled odds ratio (OR) for the overall effect of MV on AKI was 3.16 (95% CI 2.32 to 4.28, P <0.001). Nearly all subgroups showed that MV increases the risk for AKI. The pooled OR for studies with a multivariate analysis including MV as a risk factor for AKI was 3.58 (95% CI 1.85 to 6.92; P <0.001). Different settings of Vt and PEEP showed no effect.

Conclusions

Invasive MV is associated with a threefold increase in the odds of developing AKI and various Vt or PEEP settings do not modify this risk. The latter argues in favour of a haemodynamic origin of AKI during MV.     

Hypophosphatemia during continuous veno-venous hemofiltration is associated with mortality in critically ill patients with acute kidney injury

Introduction

The primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI).

Methods

760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia.

Results

The Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103–1.910, p = 0.008).

Conclusions

Hypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate.     

Procalcitonin-guided antibiotics in severe sepsis

Citation

Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008, 177: 498–505 [1].

Background

The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. Procalcitonin (PCT)-guided antibiotic use reduces antibiotic exposure in community-acquired pneumonia. Whether it might also reduce antibiotic exposure in severe sepsis is unknown.

Methods

Objective

To test the hypothesis that an algorithm based on serial measurements of PCT allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.

Design

Single-center, non-blinded randomized controlled trial.

Setting

Mixed medical and surgical ICU at a university teaching hospital.

Subjects

79 adult patients with suspected severe sepsis or septic shock.

Intervention

All patients had circulating PCT levels drawn daily. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 mg/L) or Day 5 (if baseline PCT levels were >1 mg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.

Outcome

Systemic antibiotic exposure, measured using three variables: 1) duration of antibiotic treatment, 2) antibiotic exposure days per 1000 inpatient days, and 3) days alive without antibiotics within the 28-day follow-up period.

Results

Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).

Conclusion

Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.     

Inter-hospital transfers and outcomes of critically ill patients with severe acute kidney injury: a multicenter cohort study

Introduction

Patients with severe acute kidney injury (AKI) who are hospitalized at centers that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared with the receipt of initial care in a center that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.

Methods

We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome), by using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices, and severity of illness.

Results

Of 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared with non-transferred patients who started RRT, transferred patients were younger (61 ± 15 versus 65 ± 15 years, P = 0.03) and had a higher serum creatinine concentration at RRT initiation (474 ± 295 versus 365 ± 169 μmol/L, P = 0.002). Inter-hospital transfer was not associated with mortality (adjusted odds ratio 0.61, 95% confidence interval 0.33 to 1.12) or RRT-dependence (adjusted odds ratio 1.64, 95% confidence interval 0.70 to 3.81) at 30 days.

Conclusions

Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0513-1) contains supplementary material, which is available to authorized users.     

Age of red blood cells and outcome in acute kidney injury

Introduction

Transfusion of red blood cells (RBCs) and, in particular, older RBCs has been associated with increased short-term mortality in critically ill patients. We evaluated the association between age of transfused RBCs and acute kidney injury (AKI), hospital, and 90-day mortality in critically ill patients.

Methods

We conducted a prospective, observational, predefined sub-study within the FINNish Acute Kidney Injury (FINNAKI) study. This study included all elective ICU admissions with expected ICU stay of more than 24 hours and all emergency admissions from September to November 2011. To study the age of RBCs, we classified transfused patients into quartiles according to the age of oldest transfused RBC unit in the ICU. AKI was defined according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria.

Results

Out of 1798 patients, 652 received at least one RBC unit. The median [interquartile range] age of the oldest RBC unit transfused was 12 [11-13] days in the freshest quartile and 21 [17-27] days in the quartiles 2 to 4. On logistic regression, RBC age was not associated with the development of KDIGO stage 3 AKI. Patients in the quartile of freshest RBCs had lower crude hospital and 90-day mortality rates compared to those in the quartiles of older blood. After adjustments, older RBC age was associated with significantly increased risk for hospital mortality. Age, Simplified Acute Physiology Score II (SAPS II)-score without age points, maximum Sequental Organ Failure Assessment (SOFA) score and the total number of transfused RBC units were independently associated with 90-day mortality.

Conclusions

The age of transfused RBC units was independently associated with hospital mortality but not with 90-day mortality or KDIGO stage 3 AKI. The number of transfused RBC units was an independent risk factor for 90-day mortality.     

Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study

Introduction

The role of systemic hemodynamics in the pathogenesis of septic acute kidney injury (AKI) has received little attention. The purpose of this study was to investigate the association between systemic hemodynamics and new or persistent of AKI in severe sepsis.

Methods

A retrospective study between 2006 and 2010 was performed in a surgical ICU in a teaching hospital. AKI was defined as development (new AKI) or persistent AKI during the five days following admission based on the Acute Kidney Injury Network (AKIN) criteria. We studied the association between the following hemodynamic targets within 24 hours of admission and AKI: central venous pressure (CVP), cardiac output (CO), mean arterial pressure (MAP), diastolic arterial pressure (DAP), central venous oxygen saturation (ScvO₂) or mixed venous oxygen saturation (SvO₂).

Results

This study included 137 ICU septic patients. Of these, 69 had new or persistent AKI. AKI patients had a higher Simplified Acute Physiology Score (SAPS II) (57 (46 to 67) vs. 45 (33 to 52), P < 0.001) and higher mortality (38% vs. 15%, P = 0.003) than those with no AKI or improving AKI. MAP, ScvO₂ and CO were not significantly different between groups. Patients with AKI had lower DAP and higher CVP (P = 0.0003). The CVP value was associated with the risk of developing new or persistent AKI even after adjustment for fluid balance and positive end-expiratory pressure (PEEP) level (OR = 1.22 (1.08 to 1.39), P = 0.002). A linear relationship between CVP and the risk of new or persistent AKI was observed.

Conclusions

We observed no association between most systemic hemodynamic parameters and AKI in septic patients. Association between elevated CVP and AKI suggests a role of venous congestion in the development of AKI. The paradigm that targeting high CVP may reduce occurrence of AKI should probably be revised. Furthermore, DAP should be considered as a potential important hemodynamic target for the kidney.     

Steroids in early ARDS?

Citation

Annane D, Sebille V, Bellissant E: Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med 2006, 34:22–30 [1].

Background

Experimental evidence suggests that corticosteroids may be beneficial in early acute respiratory distress syndrome (ARDS).

Methods

Objective

To investigate the efficacy of low doses of corticosteroids in septic shock patients with or without early ARDS by post hoc analysis of a previously completed clinical trial.

Design

Retrospective analysis of a placebo-controlled, randomized, double-blind trial of low doses of corticosteroids in septic shock.

Setting

Nineteen intensive care units in France.

Subjects

Among the 300 septic shock patients enrolled, we selected those meeting standard criteria for ARDS at inclusion.

Intervention

Seven-day treatment with 50 mg of hydrocortisone every 6 hrs and 50 μg of 9-alpha-fludrocortisone once a day.

Measurements and main results

There were 177 patients with ARDS (placebo, n = 92; corticosteroids, n = 85) including 129 (placebo, n = 67; corticosteroids, n = 62) nonresponders and 48 (placebo, n = 25; corticosteroids, n = 23) responders. In nonresponders, there were 50 deaths (75%) in the placebo group and 33 deaths (53%) in the steroid group (hazard ratio 0.57, 95% confidence interval 0.36–0.89, p = .013; relative risk 0.71, 95% confidence interval 0.54–0.94, p = .011). The number of days alive and off the ventilator was 2.6 +/- 6.6 in the placebo group and 5.7 +/- 8.6 in the steroid group (p = .006). There was no significant difference between groups in responders. There was no significant difference between groups in the two subsets of patients without ARDS. Adverse events rates were similar in the two groups.

Conclusion

This post hoc analysis shows that a 7-day treatment with low doses of corticosteroids was associated with better outcomes in septic shock-associated early ARDS nonresponders, but not in responders and not in septic shock patients without ARDS.     

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

Introduction

Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis.

Methods

We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis.

Results

Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI.

Conclusions

The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis.     

NGAL: an emerging tool for predicting severity of AKI is easily detected by a clinical assay

Citation

Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008, 3:665-673 [1].

Background

The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). The availability of a standardized clinical platform for NGAL measurements could revolutionize renal diagnostics, especially in intensive care situations.

Methods

Objective

The first objective of the present study was to determine whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT^® analyzer, Abbott Diagnostics) correlates with the research-based assay. The second objective was to determine the utility of the standardized NGAL immunoassay as a predictive biomarker of AKI after CPB in a large prospective cohort.

Design

Prospective cohort study

Setting

Children''s hospital at a large US academic medical center.

Subjects

196 children undergoing elective CPB for surgical correction or palliation of congenital heart lesions between January 2004 and June 2006.

Intervention

None.

Outcomes

The primary outcome variable was the development of AKI, defined as a 50% or greater increase in serum creatinine from baseline. Other outcomes included percent change in serum creatinine, days in AKI, dialysis requirement, length of hospital stay, and mortality.

Results

In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, serial urine NGAL measurements were obtained by ARCHITECT assay. Of the 196 children undergoing CPB, AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.

Conclusions

Accurate measurements of urine NGAL are obtained using the ARCHITECT^® platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.     

Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

Introduction

The pathophysiology of acute kidney injury (AKI) in sepsis is ill defined. We investigated parameters associated with low glomerular filtration, and their predictive value to discriminate transient from intrinsic septic AKI.

Methods

In 107 sepsis patients, AKI was defined by the Risk, Injury, Failure, Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was defined as RIFLE R, I, or F on the first day evolving to no AKI or not, respectively, over the following 5 days. Fractional excretion of sodium (FENa), urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1) was determined.

Results

Including versus not including the urinary-output criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and FENGAL were lower in no AKI versus transient AKI when AKI was defined based on creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in those with high versus low fractional sodium excretion, but this was only in patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in patients without AKI. The negative predictive value for either intrinsic AKI or not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92% and 94.5% respectively.

Conclusions

A low FENa and FEUrea is highly prevalent in the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending AKI than increase in serum creatinine. A combination of a high FENa and a low FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea is strongly predictive of transient AKI.     

Optimal Mode of clearance in critically ill patients with Acute Kidney Injury (OMAKI) - a pilot randomized controlled trial of hemofiltration versus hemodialysis: a Canadian Critical Care Trials Group project

Introduction

Among critically ill patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT), the effect of convective (via continuous venovenous hemofiltration [CVVH]) versus diffusive (via continuous venovenous hemodialysis [CVVHD]) solute clearance on clinical outcomes is unclear. Our objective was to evaluate the feasibility of comparing these two modes in a randomized trial.

Methods

This was a multicenter open-label parallel-group pilot randomized trial of CVVH versus CVVHD. Using concealed allocation, we randomized critically ill adults with AKI and hemodynamic instability to CVVH or CVVHD, with a prescribed small solute clearance of 35 mL/kg/hour in both arms. The primary outcome was trial feasibility, defined by randomization of >25% of eligible patients, delivery of >75% of the prescribed CRRT dose, and follow-up of >95% of patients to 60 days. A secondary analysis using a mixed-effects model examined the impact of therapy on illness severity, defined by sequential organ failure assessment (SOFA) score, over the first week.

Results

We randomized 78 patients (mean age 61.5 years; 39% women; 23% with chronic kidney disease; 82% with sepsis). Baseline SOFA scores (mean 15.9, SD 3.2) were similar between groups. We recruited 55% of eligible patients, delivered >80% of the prescribed dose in each arm, and achieved 100% follow-up. SOFA tended to decline more over the first week in CVVH recipients (-0.8, 95% CI -2.1, +0.5) driven by a reduction in vasopressor requirements. Mortality (54% CVVH; 55% CVVHD) and dialysis dependence in survivors (24% CVVH; 19% CVVHD) at 60 days were similar.

Conclusions

Our results suggest that a large trial comparing CVVH to CVVHD would be feasible. There is a trend toward improved vasopressor requirements among CVVH-treated patients over the first week of treatment.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00675818","term_id":"NCT00675818"}}NCT00675818     

Sustained Low-Efficiency Daily Diafiltration for Diabetic Nephropathy Patients with Acute Kidney Injury

Objective

To investigate the efficacy, safety and cost of treating patients with acute kidney injury (AKI) and diabetic nephropathy (DN) with continuous renal replacement therapy (CRRT) or sustained low-efficiency daily diafiltration with hemofiltration (SLEDD-f).

Subjects and Methods

Medical records of patients with AKI/DN from January 2006 to December 2012 were reviewed. Fifty-five patients who received CRRT and 52 who received SLEDD-f were included in the study. CRRT and SLEDD-f were performed for 20-72 h per session and 8-10 h per session, respectively. Mortality and renal function recovery rates were evaluated 30 days after the initiation of renal replacement therapy (RRT) and APACHE-II and SOFA scores, anticoagulant dose, inflammatory indices and cost were calculated at baseline and at the end of RRT.

Results

Of the 55 patients treated with CRRT, 49 (89.1%) had a 30-day survival rate and 30 (54.5%) had a 30-day renal recovery rate. Of the 52 patients with SLEDD-f, these rates were 92.3% (n = 48) and 61.5% (n = 32), respectively. The dosage of low-molecular-weight heparin in the CRRT and SLEDD-f groups was 15,230 ± 1,460 and 6,320 ± 490 U/day, respectively. The cost of hemopurification and the total cost for patients treated with CRRT was CNY 28,628 ± 5,576 (USD 4,210 ± 820) and CNY 38,828 ± 6,324 (USD 5,710 ± 930), respectively. These were higher than those for patients treated with SLEDD-f at CNY 13,260 ± 1,564 (USD 1,950 ± 230) and CNY 19,720 ± 2,652 (USD 2,900 ± 390), respectively.

Conclusions

SLEDD-f offered a similar chance of renal recovery and also had further advantages such as a lower heparin dosage, a shorter therapy time and lower hospitalization costs for patients than CRRT. Studies with larger, randomized sample sizes are needed to confirm these findings.Key Words: Acute kidney injury, Diabetic nephropathy, Continuous renal replacement treatment, Sustained low-efficiency daily diafiltration     

CORTICUS: The end of unconditional love for steroid use?

Citation

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358: 111–124 [1].

Background

Hydrocortisone is widely used in patients with septic shock, even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.

Methods

Objective

To evaluate the efficacy and safety of low-dose hydrocortisone therapy in a broad population of patients with septic shock – in particular, patients who had had a response to a corticotropin test, in whom a benefit was unproven.

Design

Multi-center, prospective randomized, double-blind, placebo-controlled trial.

Setting

International study involving 52 intensive care units.

Subjects

499 patients 18 years or older with the diagnosis of septic shock.

Intervention

251 patients received 50 mg of intravenous hydrocortisone and 248 patients received placebo every 6 hours for 5 days; the dose was then tapered over a 6-day period. A short corticotropin test was performed from blood samples taken immediately before and 60 minutes after an intravenous administration of 250 mcg of cosyntropin prior to administration of hydrocortisone.

Outcomes

Primary outcome was the mortality rate at 28 days in patients who did not have a response to corticotropin. Secondary outcomes included 28-day mortality in corticotropin responders and in all patients; length of stay; reversal of organ failure; and rates of new infection, hypernatremia and hyperglycemia.

Results

Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P = 0.69) or in patients who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P = 1.00). Mortality at 28 days included 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) (P = 0.51). Shock reversal was quicker in the hydrocortisone group compared to the placebo group. However, there were more episodes of super infection, including new sepsis and septic shock in the hydrocortisone group.

Conclusion

Hydrocortisone did not improve survival in patients with septic shock, either overall or in patients who did not have a response to corticotropin. However, hydrocortisone hastened reversal of shock in all study patients.

Trial Registration

(ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00147004","term_id":"NCT00147004"}}NCT00147004.)     

Time from admission to initiation of surgery for source control is a critical determinant of survival in patients with gastrointestinal perforation with associated septic shock

Introduction

We developed a protocol to initiate surgical source control immediately after admission (early source control) and perform initial resuscitation using early goal-directed therapy (EGDT) for gastrointestinal (GI) perforation with associated septic shock. This study evaluated the relationship between the time from admission to initiation of surgery and the outcome of the protocol.

Methods

This examination is a prospective observational study and involved 154 patients of GI perforation with associated septic shock. We statistically analyzed the relationship between time to initiation of surgery and 60-day outcome, examined the change in 60-day outcome associated with each 2 hour delay in surgery initiation and determined a target time for 60-day survival.

Results

Logistic regression analysis demonstrated that time to initiation of surgery (hours) was significantly associated with 60-day outcome (Odds ratio (OR), 0.31; 95% Confidence intervals (CI)), 0.19-0.45; P <0.0001). Time to initiation of surgery (hours) was selected as an independent factor for 60-day outcome in multiple logistic regression analysis (OR), 0.29; 95% CI, 0.16-0.47; P <0.0001). The survival rate fell as surgery initiation was delayed and was 0% for times greater than 6 hours.

Conclusions

For patients of GI perforation with associated septic shock, time from admission to initiation of surgery for source control is a critical determinant, under the condition of being supported by hemodynamic stabilization. The target time for a favorable outcome may be within 6 hours from admission. We should not delay in initiating EGDT-assisted surgery if patients are complicated with septic shock.     

Risk of developing severe sepsis after acute kidney injury: a population-based cohort study

Introduction

Sepsis has been a factor of acute kidney injury (AKI); however, little is known about dialysis-requiring AKI and the risk of severe sepsis after survival to discharge.

Methods

We conducted a population-based cohort study based on the Taiwan National Health Insurance Research Database from 1999 to 2009. We identified patients with AKI requiring dialysis during hospitalization and survived for at least 90 days after discharge, and matched them with those without AKI according to age, sex, and concurrent diabetes. The primary outcome was severe sepsis, defined as sepsis with a diagnosis of acute organ dysfunction. Individuals who recovered enough to survive without acute dialysis were further analyzed.

Results

We identified 2983 individuals (mean age, 62 years; median follow-up, 3.96 years) with dialysis-requiring AKI and 11,932 matched controls. The incidence rate of severe sepsis was 6.84 and 2.32 per 100 person-years among individuals with dialysis-requiring AKI and without AKI in the index hospitalization, respectively. Dialysis-requiring AKI patients had a higher risk of developing de novo severe sepsis than the non-AKI group. In subgroup analysis, even individuals with recovery from dialysis-requiring AKI were at high risk of developing severe sepsis.

Conclusions

AKI is an independent risk factor for severe sepsis. Even patients who recovered from AKI had a high risk of long-term severe sepsis.     

Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis

Introduction

Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.

Method

Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org.Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.

Results

Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis.Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups.Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.

Conclusion

Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care.Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.