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.
Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noninvasive ventilation reduces desaturation during intubation of severely hypoxemic patients, it does not ...allow for per-procedure oxygenation and has not been evaluated in mild-to-moderate hypoxemic patients for whom high-flow nasal cannula oxygen may be an alternative. We sought to compare pre- and per-procedure oxygenation with either a nonrebreathing bag reservoir facemask or a high-flow nasal cannula oxygen during tracheal intubation of ICU patients.
Prospective quasi-experimental before-after study (ClinicalTrials.gov: NCT01699880).
University hospital medico-surgical ICU.
All adult patients requiring tracheal intubation in the ICU were eligible.
In the control (before) period, preoxygenation was performed with a nonrebreathing bag reservoir facemask and in the change of practice (after) period, with high-flow nasal cannula oxygen.
Primary outcome was median lowest SpO2 during intubation, and secondary outcomes were SpO2 after preoxygenation and number of patients with saturation less than 80%. One hundred one patients were included. Median lowest SpO2 during intubation were 94% (83-98.5) with the nonrebreathing bag reservoir facemask versus 100% (95-100) with high-flow nasal cannula oxygen (p < 0.0001). SpO2 values at the end of preoxygenation were higher with high-flow nasal cannula oxygen than with nonrebreathing bag reservoir facemask and were correlated with the lowest SpO2 reached during the intubation procedure (r = 0.38, p < 0.0001). Patients in the nonrebreathing bag reservoir facemask group experienced more episodes of severe hypoxemia (2% vs 14%, p = 0.03). In the multivariate analysis, preoxygenation with high-flow nasal cannula oxygen was an independent protective factor of the occurrence of severe hypoxemia (odds ratio, 0.146; 95% CI, 0.01-0.90; p = 0.037).
High-flow nasal cannula oxygen significantly improved preoxygenation and reduced prevalence of severe hypoxemia compared with nonrebreathing bag reservoir facemask. Its use could improve patient safety during intubation.
High circulating DPP3 (dipeptidyl peptidase 3) has been associated with poor prognosis in critically ill patients with circulatory failure. In such situation, DPP3 could play a pathological role, ...putatively via an excessive angiotensin peptides cleavage. Our objective was to investigate the hemodynamics changes induced by DPP3 in mice and the relation between the observed effects and renin-angiotensin system modulation.
Ten-week-old male C57Bl/6J mice were subjected to intravenous injection of purified human DPP3 or an anti-DPP3 antibody (procizumab). Invasive blood pressure and renal blood flow were monitored throughout the experiments. Circulating angiotensin peptides and catecholamines were measured and receptor blocking experiment performed to investigate the underlying mechanisms.
DPP3 administration significantly increased renal blood flow, while blood pressure was minimally affected. Conversely, procizumab led to significantly decreased renal blood flow. Angiotensin peptides measurement and an AT1R (angiotensin II receptor type 1) blockade experiment using valsartan demonstrated that the renovascular effect induced by DPP3 is due to reduced AT1R activation
decreased concentrations of circulating angiotensin II, III, and IV. Measurements of circulating catecholamines and an adrenergic receptor blockade by labetalol demonstrated a concomitant catecholamines release that explains blood pressure maintenance upon DPP3 administration.
High circulating DPP3 increases renal blood flow due to reduced AT1R activation via decreased concentrations of circulating angiotensin peptides while blood pressure is maintained by concomitant endogenous catecholamines release.
The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals' evolving characteristics. To learn and validate ...optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials.
We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a "crude strategy" maximizing the population-level hospital-free days at day 60 (HFD60) and a "stringent strategy" recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60.
We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 95% CI -5.3 to 35.7 and 14.9 95% CI -3.2 to 39.2 HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices.
Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many.
We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.
Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the ...association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14.
In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation.
The mean Crs in 372 patients was 37.6 ± 13 mL/cmH
O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO
/FiO
ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs OR 1.0 (CI 95% 0.98-1.02) neither Crs/IBW OR 0.63 (CI 95% 0.13-3.1) were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was OR 0.93 (CI 95% 0.88-0.99). In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH
O vs 37.8 ± 11.4 mL/cmH
O, p < 0.001). The decrease in Crs was not associated with day-28 outcome.
In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH
O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.
The occurrence of ventilator-associated pneumonia (VAP) is linked to the aspiration of contaminated pharyngeal secretions around the endotracheal tube. Tubes with cuffs made of polyurethane rather ...than polyvinyl chloride or with a conical rather than a cylindrical shape increase tracheal sealing.
To test whether using polyurethane and/or conical cuffs reduces tracheal colonization and VAP in patients with acute respiratory failure.
We conducted a multicenter, prospective, open-label, randomized study in four parallel groups in four intensive care units between 2010 and 2012. A cohort of 621 patients with expected ventilation longer than 2 days was included at intubation with a cuff composed of cylindrical polyvinyl chloride (n = 148), cylindrical polyurethane (n = 143), conical polyvinyl chloride (n = 150), or conical polyurethane (n = 162). We used Kaplan-Meier estimates and log-rank tests to compare times to events.
After excluding 17 patients who secondarily refused participation or had met an exclusion criterion, 604 were included in the intention-to-treat analysis. Cumulative tracheal colonization greater than 10(3) cfu/ml at Day 2 was as follows (median interquartile range): cylindrical polyvinyl chloride, 0.66 (0.58-0.74); cylindrical polyurethane, 0.61 (0.53-0.70); conical polyvinyl chloride, 0.67 (0.60-0.76); and conical polyurethane, 0.62 (0.55-0.70) (P = 0.55). VAP developed in 77 patients (14.4%), and postextubational stridor developed in 28 patients (6.4%) (P = 0.20 and 0.28 between groups, respectively).
Among patients requiring mechanical ventilation, polyurethane and/or conically shaped cuffs were not superior to conventional cuffs in preventing tracheal colonization and VAP. Clinical trial registered with clinicaltrials.gov (NCT01114022).
Background
Bacterial infections are frequent triggers for diabetic ketoacidosis. In this context, delayed antibiotic treatment is associated with increased morbidity and mortality. Unnecessary ...administration of antimicrobial therapy might however, also negatively impact the prognosis. The usefulness of sepsis markers in diabetic ketoacidosis has not been assessed. Thus, we sought to investigate diagnostic performances of clinical and biological sepsis markers during diabetic ketoacidosis.
Methods
In this monocentric retrospective cohort study, all consecutive episodes of diabetic ketoacidosis (defined as pH ≤ 7.25, glycaemia > 300 mg/dL and presence of ketones) admitted in intensive care unit were included. A proven bacterial infection was defined as bacteriological documentation on any bacterial sample. Clinical (presence of fever: temperature > 38 °C and presence of hypothermia: temperature < 36 °C) and biological markers (whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and procalcitonin), recorded at admission, were compared according to the presence or absence of a proven bacterial infection.
Results
Between 2011 and 2018, among 134 episodes of diabetic ketoacidosis, 102 were included (91 patients). Twenty out of 102 were infected. At admission, procalcitonin (median: 3.58 ng/mL vs 0.52 ng/mL,
p
< 0.001) and presence of fever (25% vs 4%,
p
= 0.007) were different between episodes with and without proven bacterial infection in both univariate and multivariate analysis. Whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and presence of hypothermia were not different between both groups. The diagnostic performance analysis for procalcitonin revealed an area under the curve of 0.87 with an optimal cutoff of 1.44 ng/mL leading to a sensitivity of 0.90 and a specificity of 0.76. Combining procalcitonin and presence of fever allowed to distinguish proven bacterial infection episodes from those without proven bacterial infection. Indeed, all patients with procalcitonin level of more than 1.44 ng/mL and fever had proven bacterial infection episodes. The presence of one of these 2 markers was associated with 46% of proven bacterial infection episodes. No afebrile patient with procalcitonin level less than 1.44 ng/mL had a proven bacterial infection.
Conclusion
At admission, combining procalcitonin and presence of fever may be of value to distinguish ketoacidosis patients with and without proven bacterial infection, admitted in intensive care unit.
Needle aspiration (NA) is recommended as first-line treatment of primary spontaneous pneumothorax (PSP). We aimed to assess NA success and the effect of a longer symptom onset to NA time.
A discovery ...phase was retrospectively conducted in the intensive care unit of Louis Mourier Hospital (January 2000 to December 2011) followed by a prospective validation cohort (January 2012 to August 2015). The primary outcome was immediate NA success defined by the absence of need for chest tube insertion within 24 hours of the procedure.
In the discovery phase, 130 patients were admitted for PSP and 98 had NA as first-line treatment (75%). The immediate success rate of NA was 34.7% and was higher when it was performed ≥48 hours after symptom onset (57.7% vs 25%; p=0.004). In the prospective cohort, 87 patients were admitted for PSP; 71 (82%) had NA as first-step treatment. The immediate success rate was 40.8%. NA was more successful when it was performed after 48 hours of symptoms' onset (34.5% vs 7.1%; p=0.005). A delay between the first symptom and NA procedure ≥48 hours was associated with a higher success of NA (OR=13.54; 95% CI 1.37 to 133). A smaller pneumothorax estimated by Light's index was associated with NA success (OR=0.95; 95% CI 0.92 to 0.98). To what extent some of these pneumothoraces would have had a spontaneous resolution remains unknown.
When managing PSP with NA, a longer symptom onset to NA time was associated with NA success.
NCT02528734.
Objective The prognosis of patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific interstitial pneumonia undergoing invasive mechanical ventilation (MV) for acute respiratory ...failure is known to be poor. The issue of life support in these patients needs to be reconsidered in light of changes during the past decade in ventilator settings and in the management of acute exacerbation. We therefore aimed to reassess the prognosis of such patients. Methods We retrospectively assessed the outcomes of all medical patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific interstitial pneumonia who required invasive MV in 3 university hospitals in the Paris area from January 2002 to April 2009. Results In total, 27 patients (mean age, 66 ± 12.8 years) required invasive MV in the intensive care unit: 8 (30%) were successfully weaned from MV, and 6 and 4 were discharged from the intensive care unit and the hospital, respectively. Survivals for patients who did not undergo lung transplant were 22%, 3.7%, and 3.7%, at 30 days, 6 months, and 12 months, respectively. Conclusions We confirm that use of invasive MV for acute respiratory failure in patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific interstitial pneumonia is associated with a high mortality; however, a subset of patients may be discharged alive from the intensive care unit and hospital, providing an opportunity to consider lung transplant in case of eligibility. Our results suggest that invasive MV should not be systematically denied to these patients but discussed on a case-by-case basis.
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