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.).
Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the ...potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range IQR, 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.
•TTP patients who display persistent and severe ADAMTS13 deficiency after remission have a relapse rate of 74% during long-term follow-up.•Preemptive rituximab can decrease TTP relapses in 85% of patients with a favorable benefit-risk balance.
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Purpose
Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia ...management, by targeting the patient’s pre-admission usual glycaemia, could improve outcome.
Methods
In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days.
Results
Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI 64.2%; 70.3%; CC group: 69.6%, 95% CI 66.7%; 72.5%). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (
p
= 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI 1.05; 1.59,
p
= 0.018).
Conclusion
Targeting an ICU patient’s pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.
Proteinuria results from kidney damage and can be a predictor of illness severity and mortality in the intensive care unit (ICU). However, the optimal timing of proteinuria measurements and the ...reference values remain undetermined. Our objective was to identify the patterns of proteinuria change associated with mortality in ICU patients with sepsis or shock. This monocentric retrospective cohort study performed from April 2010 to April 2018 involved all ICU patients with sepsis or shock and at least two measurements of proteinuria from a 24h-urine collection during the first 10 days of ICU stay, the first of which was made within 48h after ICU admission. We identified proteinuria trajectories by a semi-parametric mixture model and analysed the association between the trajectories and the mortality at day 28 by Cox proportional-hazards model. A total of 3,344 measurements of proteinuria from 659 patients were analysed. Four proteinuria trajectories were identified. Trajectories 1, 2, 3 and 4 comprised 127, 421, 60 and 51 patients, and were characterized by a first proteinuria of 1.14 0.66-1.55, 0.52 0.26-0.91, 2.92 2.38-3.84 and 2.58 1.75-3.32 g/24h (p2g/24h). Only, the proteinuria of trajectory 4 increased within 3 days following the first measurement and was associated with increased mortality at day 28 (hazard ratio: 2.36 95%CI 1.07-5.19, p = 0.03), regardless of acute renal failure. The factors associated with trajectory 4 were cancer (relative risk: 8.91 95%CI 2.09-38.02, p = 0.003) and use of inotropic drugs (relative risk: 0.17 95%CI 0.04-0.69, p = 0.01). This exploratory study of ICU patients with sepsis or shock identified four proteinuria trajectories with distinct patterns of proteinuria change over time and mortality rates. These results provide novel insights into renal pathophysiology and may be helpful to investigate subphenotypes of kidney injury among ICU patients in future studies.
Around 10% of critically ill patients suffer acute kidney injury (AKI) requiring kidney replacement therapy (KRT), with a mortality rate approaching 50%. Although most survivors achieve sufficient ...renal recovery to be weaned from KRT, there are no recognized guidelines on the optimal period for weaning from KRT. A systematic review was conducted using a peer-reviewed strategy, combining themes of KRT (intermittent hemodialysis, CKRT: continuous veno-venous hemo/dialysis/filtration/diafiltration, sustained low-efficiency dialysis/filtration), factors predictive of successful weaning (defined as a prolonged period without new KRT) and patient outcomes. Our research resulted in studies, all observational, describing clinical and biological parameters predictive of successful weaning from KRT. Urine output prior to KRT cessation is the most studied variable and the most widely used in practice. Other predictive factors, such as urinary urea and creatinine and new urinary and serum renal biomarkers, including cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), were also analyzed in the light of recent studies. This review presents the rationale for early weaning from KRT, the parameters that can guide it, and its practical modalities. Once the patient's clinical condition has stabilized and volume status optimized, a diuresis greater than 500 mL/day should prompt the intensivist to consider weaning. Urinary parameters could be useful in predicting weaning success but have yet to be validated.
Background
Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index ...(ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure.
Results
In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (
n
= 150, 49.7%). Within 2 (1–3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (
n
= 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not 4.79 (3.69–7.01) vs. 6.10 (4.48–8.68),
p
< 0.001. The accuracy of the ROX index to predict intubation was poor AUC = 0.623 (0.557–0.689), with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 0.82–0.96,
p
= 0.04).
Conclusion
A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies.
Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features ...and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 9-57 vs 13 × 103/mm3 9-21, respectively P = .002; hemoglobin level, 9 g/dL 8-11 vs 8 g/dL 7-10, respectively P = .0007). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.
•iTTP in older patients has atypical clinical features delaying diagnosis; 1-month and 1-year mortality rates are higher.•A history of iTTP in older patients negatively impacts the life expectancy in survivors.
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There is a need for close communication with relatives of patients dying in the intensive care unit (ICU). We evaluated a format that included a proactive end-of-life conference and a brochure to see ...whether it could lessen the effects of bereavement.
Family members of 126 patients dying in 22 ICUs in France were randomly assigned to the intervention format or to the customary end-of-life conference. Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale (IES; scores range from 0, indicating no symptoms, to 75, indicating severe symptoms related to post-traumatic stress disorder PTSD) and the Hospital Anxiety and Depression Scale (HADS; subscale scores range from 0, indicating no distress, to 21, indicating maximum distress).
Participants in the intervention group had longer conferences than those in the control group (median, 30 minutes interquartile range, 19 to 45 vs. 20 minutes interquartile range, 15 to 30; P<0.001) and spent more of the time talking (median, 14 minutes interquartile range, 8 to 20 vs. 5 minutes interquartile range, 5 to 10). On day 90, the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group (27 vs. 39, P=0.02) and a lower prevalence of PTSD-related symptoms (45% vs. 69%, P=0.01). The median HADS score was also lower in the intervention group (11, vs. 17 in the control group; P=0.004), and symptoms of both anxiety and depression were less prevalent (anxiety, 45% vs. 67%; P=0.02; depression, 29% vs. 56%; P=0.003).
Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement. (ClinicalTrials.gov number, NCT00331877.)
Multiplex polymerase chain reaction (mPCR) for respiratory virus testing is increasingly used in community-acquired pneumonia (CAP), however data on one-year outcome in intensive care unit (ICU) ...patients with reference to the causative pathogen are scarce.
We performed a single-center retrospective study in 123 ICU patients who had undergone respiratory virus testing for CAP by mPCR and with known one-year survival status. Functional status including dyspnea (mMRC score), autonomy (ADL Katz score) and need for new home-care ventilatory support was assessed at a one-year post-ICU follow-up. Mortality rates and functional status were compared in patients with CAP of a bacterial, viral or unidentified etiology one year after ICU admission.
The bacterial, viral and unidentified groups included 19 (15.4%), 37 (30.1%), and 67 (54.5%) patients, respectively. In multivariate analysis, one-year mortality in the bacterial group was higher compared to the viral group (HR 2.92, 95% CI 1.71-7.28, p = 0.02) and tended to be higher compared to the unidentified etiology group (p = 0.06); but no difference was found between the viral and the unidentified etiology group (p = 0.43). In 64/83 one-year survivors with a post-ICU follow-up consultation, there were no differences in mMRC score, ADL Katz score and new home-care ventilatory support between the groups (p = 0.52, p = 0.37, p = 0.24, respectively). Severe dyspnea (mMRC score = 4 or death), severe autonomy deficiencies (ADL Katz score ≤ 2 or death), and major adverse respiratory events (new home-care ventilatory support or death) were observed in 52/104 (50.0%), 47/104 (45.2%), and 65/104 (62.5%) patients, respectively; with no difference between the bacterial, viral and unidentified group: p = 0.58, p = 0.06, p = 0.61, respectively.
CAP of bacterial origin had a poorer outcome than CAP of viral or unidentified origin. At one-year, impairment of functional status was frequently observed, with no difference according to the etiology.
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