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.
To determine whether temporal bone computed tomography (CT) features are linked to the presence and type of hearing loss in osteogenesis imperfecta (OI) when considering hearing-impaired OI patients ...and normally hearing (NH) OI ones. A secondary objective was to assess whether other factors influence CT features in a large sample: age, type of mutation, or bone mineral density (BMD).
A total of 41 adults with OI underwent CTs and pure-tone audiometry in 82 ears. Hearing thresholds were normal in 64 out of 82 ears, and most had not been operated on for stapedectomy or stapedotomy. Ossicle density, footplates, oval and round windows, retrofenestral peri- and endolabyrinths, and temporal pneumatization were analyzed twice by an experienced radiologist. CT features were compared to hearing, age, collagen mutations, and bone mineral density.
Unexpectedly a high prevalence of footplate, ossicle, and otic capsule anomalies was observed, even in NH ears. Footplate hypodensity or thickening was mostly found in ears without conductive hearing loss. There were significantly more retrofenestral anomalies or window obstruction in ears with a sensorineural hearing loss component than in ears without. Age was significantly higher in ears with middle layer hypodensity than in ears without. Patients with mutations were expected to have reduced collagen quantity and had significantly more footplate or retrofenestral anomalies than those with qualitative mutations. BMD was significantly higher in ears without temporal hyperpneumatization.
Temporal bone CT features in OI are present in a large proportion of patients, had they hearing loss or not, and might be determined more by collagen mutation type than by age or BMD.
Background
The extent of the consequences of an episode of severe acute kidney injury (AKI) on long-term outcome of critically ill patients remain debated. We conducted a prospective follow-up of ...patients included in a large multicenter clinical trial of renal replacement therapy (RRT) initiation strategy during severe AKI (the Artificial Kidney Initiation in Kidney Injury, AKIKI) to investigate long-term survival, renal outcome and health related quality of life (HRQOL). We also assessed the influence of RRT initiation strategy on these outcomes.
Results
Follow-up of patients extended from 60 days to a median of 3.35 years interquartile range (IQR), 1.89 to 4.09 after the end of initial study. Of the 619 patients included in the AKIKI trial, 316 survived after 60 days. The overall survival rate at 3 years from inclusion was 39.4% (95% CI 35.4 to 43.4). A total of 46 patients (on the 175 with available data on long-term kidney function) experienced worsening of renal function (WRF) at the time of follow-up overall incidence of 26%, cumulative incidence at 4 years: 20.6% (CI 95% 13.0 to 28.3). Fifteen patients required chronic dialysis (5% of patients who survived after day 90). Among the 226 long-term survivors, 80 (35%) answered the EQ-5D questionnaire. The median index value reported was 0.67 (IQR 0.40 to 1.00) indicating a noticeable alteration of quality of life. Initiation strategy for RRT had no effect on any long-term outcome.
Conclusion
Severe AKI in critically ill patients was associated with a high proportion of death within the first 2 months but less so during long-term follow-up. A quarter of long-term survivors experienced a WRF and suffered from a noticeable impairment of quality of life. Renal replacement therapy initiation strategy was not associated with mortality outcome.
Graphical Abstract
Background. Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, ...adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy. Methods. In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF). Results. Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r = 0.6; P = .025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r = 0.66; P = .01). Conclusions. Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).
This review summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of development, maintenance, function, and regeneration of skeletal ...muscle fibers. Increasing evidence suggests that this family of neurotrophic factors not only modulates survival and function of innervating motoneurons and proprioceptive neurons but also development and differentiation of myoblasts and muscle fibers. Neurotrophins and neurotrophin receptors play a role in the coordination of muscle innervation and functional differentiation of neuromuscular junctions. However, neurotrophin receptors are also expressed in differentiating muscle cells, in particular at early developmental stages in myoblasts before they fuse. In adults with pathological conditions such as human degenerative and inflammatory muscle disorders, variations of neurotrophin expression are found, but the role of neurotrophins under such conditions is still not clear. The goal of this review is to provide a basis for a better understanding and future studies on the role of these factors under such pathological conditions and for treatment of human muscle diseases. Muscle Nerve, 2005
Abstract Purpose A preliminary observational study was undertaken to evaluate the risk of failure of ultrasound-guided peripheral intravenous catheterization of a deep arm vein for a maximum of 7 ...days, after peripheral intravenous (PIV) cannulation failure. Methods This prospective study included patients referred to the intensive care unit for placement of a central line, a polyurethane cannula commercialized for arterial catheterization was used for peripheral venous cannulation. Catheter length and diameter were chosen based on preliminary ultrasound measurements of vein diameter and skin-vein distance. Results Catheterization was successful for all 29 patients. Mean vein diameter was 0.42 ± 0.39 cm; mean vein depth was 0.94 ± 0.52 cm. Mean catheter duration was 6 (median 7) days. Two occluded catheters were removed prematurely. No thrombophlebitis, catheter infection, or extravasation was observed. Conclusion Our results suggest that catheters inserted with the Seldinger method are adapted to prolonged peripheral deep-vein infusion. Ultrasound can play a role in catheter monitoring by identifying early thrombosis formation.
The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of ...debate.
In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes KDIGO classification, stage 3 stages range from 1 to 3, with higher stages indicating more severe kidney injury) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60.
A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval CI, 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001).
In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).
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 renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in ...comatose patients with severe AKI.
Methods
We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale RASS < − 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < − 3), incomplete awakening (RASS − 3; − 2), awakening (RASS − 1; + 1 two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization.
Results
A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio HR = 0.36 0.17–0.78;
p
= 0.010). Time spent awake was 10.11 days 8.11–12.15 and 7.63 days 5.57–9.64 in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results.
Conclusion
In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.
Escherichia coli infections are frequent in ICU patients. The increased resistance to fluoroquinolones and amoxicillin/clavulanate of this pathogen mandates the prescription of broad-spectrum ...antibiotics such as piperacillin/tazobactam (PIP-TAZ) or third generation cephalosporins (3GC).
To assess incidence and impact on clinical outcome of infections with PIP-TAZ resistant E. coli in ICU patients, we conducted a retrospective cohort study with infections due to PIP-TAZ resistant (PIP-TAZ R) or to PIP-TAZ susceptible strains (PIP-TAZ S) between 1 January 2002 and 30 June 2004.
Of 83 strains, 13 were PIP-TAZ R: 2 strains produced an extended-spectrum beta-lactamase (2%), 11 produced a high level penicillinase (13%). Prior amoxicillin or amoxicillin/clavulanate prescription was reported in 7 cases (54%) of infections with PIP-TAZ R isolates and in 15 cases (21%) of infections with PIP-TAZ S isolates (p = 0.03). Time of onset of the infection from hospital admission was longer in case of infections with PIP-TAZ R than with PIP-TAZ S isolates (22 +/- 32 vs 10 +/- 21 days, p = 0.01). The overall ICU mortality rate was 38%. Mortality and length of stay in ICU were similar in case of infections with PIP-TAZ R isolates and with PIP-TAZ S isolates.
Infections with PIP-TAZ R E. coli are frequent in ICU patients. No prognostic impact of this pattern of resistance was found. Prescription of PIP-TAZ for empirical treatment of E. coli infections in ICU however exposes to inappropriate therapy.
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