The timing of renal replacement therapy (RRT) for severe acute kidney injury is highly debated when no life-threatening complications are present. We assessed whether a strategy of delayed versus ...early RRT initiation affects 28-day survival in critically ill adults with severe acute kidney injury.
In this systematic review and individual patient data meta-analysis, we searched MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials for randomised trials published from April 1, 2008, to Dec 20, 2019, that compared delayed and early RRT initiation strategies in patients with severe acute kidney injury. Trials were eligible for inclusion if they included critically ill patients aged 18 years or older with acute kidney injury (defined as a Kidney Disease: Improving Global Outcomes KDIGO acute kidney injury stage 2 or 3, or, where KDIGO was unavailable, a renal Sequential Organ Failure Assessment score of 3 or higher). We contacted the principal investigator of each eligible trial to request individual patient data. From the included trials, any patients without acute kidney injury or who were not randomly allocated were not included in the individual patient data meta-analysis. The primary outcome was all-cause mortality at day 28 after randomisation. This study is registered with PROSPERO (CRD42019125025).
Among the 1031 studies identified, one study that met the eligibility criteria was excluded because the recruitment period was not recent enough, and ten (including 2143 patients) were included in the analysis. Individual patient data were available for nine studies (2083 patients), from which 1879 patients had severe acute kidney injury and were randomly allocated: 946 (50%) to the delayed RRT group and 933 (50%) to the early RRT group. 390 (42%) of 929 patients allocated to the delayed RRT group and who had available data did not receive RRT. The proportion of patients who died by day 28 did not significantly differ between the delayed RRT group (366 44% of 837) and the early RRT group (355 43% of 827; risk ratio 1·01 95% CI 0·91 to 1·13, p=0·80), corresponding to an overall risk difference of 0·01 (95% CI −0·04 to 0·06). There was no heterogeneity across studies (I2=0%; τ2=0), and most studies had a low risk of bias.
The timing of RRT initiation does not affect survival in critically ill patients with severe acute kidney injury in the absence of urgent indications for RRT. Delaying RRT initiation, with close patient monitoring, might lead to a reduced use of RRT, thereby saving health resources.
None.
One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal ...time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients.
This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015.
This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances.
ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012.
Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical ...devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.
This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.
Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0–25) in the delayed strategy and 10 days (IQR 0–24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09–2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups.
In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.
Programme Hospitalier de Recherche Clinique.
Purpose
The effect of the routine use of a stylet during tracheal intubation on first-attempt intubation success is unclear. We hypothesised that the first-attempt intubation success rate would be ...higher with tracheal tube + stylet than with tracheal tube alone.
Methods
In this multicentre randomised controlled trial, conducted in 32 intensive care units, we randomly assigned patients to tracheal tube + stylet or tracheal tube alone (i.e. without stylet). The primary outcome was the proportion of patients with first-attempt intubation success. The secondary outcome was the proportion of patients with complications related to tracheal intubation. Serious adverse events, i.e., traumatic injuries related to tracheal intubation, were evaluated.
Results
A total of 999 patients were included in the modified intention-to-treat analysis: 501 (50%) to tracheal tube + stylet and 498 (50%) to tracheal tube alone. First-attempt intubation success occurred in 392 patients (78.2%) in the tracheal tube + stylet group and in 356 (71.5%) in the tracheal tube alone group (absolute risk difference, 6.7; 95%CI 1.4–12.1; relative risk, 1.10; 95%CI 1.02–1.18;
P
= 0.01). A total of 194 patients (38.7%) in the tracheal tube + stylet group had complications related to tracheal intubation, as compared with 200 patients (40.2%) in the tracheal tube alone group (absolute risk difference, − 1.5; 95%CI − 7.5 to 4.6; relative risk, 0.96; 95%CI 0.83–1.12;
P
= 0.64). The incidence of serious adverse events was 4.0% and 3.6%, respectively (absolute risk difference, 0.4; 95%CI, − 2.0 to 2.8; relative risk, 1.10; 95%CI 0.59–2.06.
P
= 0.76).
Conclusions
Among critically ill adults undergoing tracheal intubation, using a stylet improves first-attempt intubation success.
A 47-year-old man presented to our intensive care unit in May 2018 with a 2-day history of abdominal pain, fever, vomiting and diarrhoea. The patient has been known to be human immunodeficiency virus ...(HIV)-positive since 1998 and reported his risk for HIV as men having sex with men (MSM).
Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than ...10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI.
This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting.
A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients.
Compared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.
Purpose
We compared hemodynamic and biological effects of the Cascade system, which uses very high volume hemofiltration (HVHF) (120 mL kg
−1
h
−1
), with those of usual care in patients with septic ...shock.
Methods
Multicenter, prospective, randomized, open-label trial in three intensive care units (ICU). Adults with septic shock with administration of epinephrine/norepinephrine were eligible. Patients were randomized to usual care plus HVHF (Cascade group), or usual care alone (control group). Primary end point was the number of catecholamine-free days up to 28 days after randomization. Secondary end points were number of days free of mechanical ventilation, renal replacement therapy (RRT) or ICU up to 90 days, and 7-, 28-, and 90-day mortality.
Results
We included 60 patients (29 Cascade, 31 usual care). Baseline characteristics were comparable. Median number of catecholamine-free days was 22 IQR 11–23 vs 20 0–25 for Cascade vs control; there was no significant difference even after adjustment. There was no significant difference in number of mechanical ventilation-free days or ICU requirement. Median number of RRT-free days was 85 46–90 vs 74 0–90 for Cascade vs control groups,
p
= 0.42. By multivariate analysis, the number of RRT-free days was significantly higher in the Cascade group (up to 25 days higher after adjustment). There was no difference in mortality at 7, 28, or 90 days.
Conclusion
Very HVHF using the Cascade system can safely be used in patients presenting with septic shock, but it was not associated with a reduction in the need for catecholamines during the first 28 days.
Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients ...at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy.
We used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation.
We analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects (P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, - 14%; 95% confidence interval, - 27% to - 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, - 5% to 21% in patients at intermediate-low risk).
We have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch.
Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia ...development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid alone tended to reduce pulmonary MRSA load in both SB and MV rabbits, but failed to prevent bacteremia (59%) in the latter. Linezolid alone dampened TNF-α lung production in both SB and MV rabbits (e.g., 2226 789 vs. 11478 10251 pg/g; p = 0.022). Statins alone did the same in both SB and MV animals (e.g., 2040 133; p = 0.016), and dampened systemic inflammation in the latter, possibly through TLR2 down-regulation within the lung. However, the combination of LNZ and statin led to an increased rate of bacteremia in MV animals up to 75%. Statins provide an anti-inflammatory effect in rabbits with MRSA pneumonia, especially in MV ones. However, dampening the systemic inflammatory response with statins could impede blood defenses against MRSA.
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