A Prospective Observational Study on Short and Long-Term Outcomes of COVID-19 Patients with Acute Hypoxic Respiratory Failure Treated with High-Flow Nasal Cannula.

(1) The use of high-flow nasal cannula (HFNC) combined with frequent respiratory monitoring in patients with acute hypoxic respiratory failure due to COVID-19 has been shown to reduce intubation and mechanical ventilation. (2) This prospective, single-center, observational study included consecutive adult patients with COVID-19 pneumonia treated with a high-flow nasal cannula. Hemodynamic parameters, respiratory rate, inspiratory fraction of oxygen (FiO2), saturation of oxygen (SpO2), and the ratio of oxygen saturation to respiratory rate (ROX) were recorded prior to treatment initiation and every 2 h for 24 h. A 6-month follow-up questionnaire was also conducted. (3) Over the study period, 153 of 187 patients were eligible for HFNC. Of these patients, 80% required intubation and 37% of the intubated patients died in hospital. Male sex (OR = 4.65; 95% CI [1.28; 20.6], p = 0.03) and higher BMI (OR = 2.63; 95% CI [1.14; 6.76], p = 0.03) were associated with an increased risk for new limitations at 6-months after hospital discharge. (4) 20% of patients who received HFNC did not require intubation and were discharged alive from the hospital. Male sex and higher BMI were associated with poor long-term functional outcomes.

Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS-CoV-2 infection.

The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia increases neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and induces expression of a prothrombotic NEDD9 peptide (N9P) on the extracellular plasma membrane surface. We hypothesized that the SARS-CoV-2-ARDS pathophenotype involves increased pulmonary endothelial N9P. Paraffin-embedded autopsy lung specimens were acquired from patients with SARS-CoV-2-​​​​​​ARDS (n = 13), ARDS from other causes (n = 10), and organ donor controls (n = 5). Immunofluorescence characterized the expression of N9P, fibrin, and transcription factor 12 (TCF12), a putative binding target of SARS-CoV-2 and known transcriptional regulator of NEDD9. We performed RNA-sequencing on normal HPAECs treated with normoxia or hypoxia (0.2% O2) for 24 h. Immunoprecipitation-liquid chromatography-mass spectrometry (IP-LC-MS) profiled protein-protein interactions involving N9P relevant to thrombus stabilization. Hypoxia increased TCF12 messenger RNA significantly compared to normoxia in HPAECs in vitro (+1.19-fold, p = 0.001; false discovery rate = 0.005), and pulmonary endothelial TCF12 expression was increased threefold in SARS-CoV-2-ARDS versus donor control lungs (p < 0.001). Compared to donor controls, pulmonary endothelial N9P-fibrin colocalization was increased in situ in non-SARS-CoV-2-ARDS and SARS-CoV-2-ARDS decedents (3.7 ± 1.2 vs. 10.3 ± 3.2 and 21.8 ± 4.0 arb. units, p < 0.001). However, total pulmonary endothelial N9P was increased significantly only in SARS-CoV-2-ARDS versus donor controls (15 ± 4.2 vs. 6.3 ± 0.9 arb. units, p < 0.001). In HPAEC plasma membrane isolates, IP-LC-MS identified a novel protein-protein interaction between NEDD9 and the ß3-subunit of the αvß3-integrin, which regulates fibrin anchoring to endothelial cells. In conclusion, lethal SARS-CoV-2-ARDS is associated with increased pulmonary endothelial N9P expression and N9P-fibrin colocalization in situ. Further investigation is needed to determine the pathogenetic and potential therapeutic relevance of N9P to the thrombotic pathophenotype of SARS-CoV-2-ARDS.

Fluid Management in Patients with Acute Respiratory Distress Syndrome and Diabetes Mellitus: A propensity score matched analysis of the fluid and catheter treatment trial.

Diabetes mellitus results in an attenuated inflammatory response, reduces pulmonary microvascular permeability, and may decrease the risk of developing acute respiratory distress syndrome (ARDS). Studies have shown that patients with ARDS are better managed by a conservative as compared to liberal fluid management strategy. However, it is not known if the same fluid management principles hold true for patients with comorbid diabetes mellitus and ARDS.As diabetes mellitus results in reduced pulmonary microvascular permeability and an attenuated inflammatory response, we hypothesize that in the setting of ARDS, diabetic patients will be able to tolerate a positive fluid balance better than patients without diabetes.The Fluid and Catheter Treatment Trial (FACTT) randomized patients with ARDS to conservative versus liberal fluid management strategies. In a secondary analysis of this trial, we calculated the interaction of diabetic status and differing fluid strategies on outcomes. Propensity score subclassification matching was used to control for the differing baseline characteristics between patients with and without diabetes.Nine hundred fifty-six patients were analyzed. In a propensity score matched analysis, the difference in the effect of a conservative as compared to liberal fluid management strategy on ventilator free days was 2.23 days (95% CI: -0.97 to 5.43 days) in diabetic patients, and 2.37 days (95% CI: -0.21 to 4.95 days) in non-diabetic patients. The difference in the effect of a conservative as compared to liberal fluid management on 60 day mortality was 2% (95% CI: -11.8% to 15.8%) in diabetic patients, and -7.9% (95% CI: -21.7% to 5.9%) in non-diabetic patients.When comparing a conservative fluid management strategy to a liberal fluid management strategy, diabetic patients with ARDS did not have a statistically significant difference in outcomes than non-diabetic patients.

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome.

BACKGROUND: Acute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS). OBJECTIVE: To investigate whether statin treatment is protective against AKI in sepsis-associated ARDS. DESIGN: Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. SETTING: 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. PATIENTS: 644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis. MEASUREMENTS: Our primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness. METHODS: We used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization. RESULTS: Among individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84). LIMITATIONS: Sample size, lack of urine output data, and prehospitalization baseline creatinine. CONCLUSION: Treatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI.

CONTEXTE: L'insuffisance rénale aiguë (IRA) survient fréquemment chez les patients atteints d'une septicémie et du syndrome de détresse respiratoire aiguë (SDRA). OBJECTIF DE L'ÉTUDE: Déterminer si un traitement aux statines offre une protection contre l'IRA chez les patients atteints d'un SDRA associé à une septicémie. TYPE D'ÉTUDE: Il s'agit d'une analyse secondaire des données de l'étude SAILS (Statins for Acutely Injured Lungs in Sepsis), un essai contrôlé à répartition aléatoire qui se penchait sur l'effet d'un traitement à la rosuvastatine sur le taux de mortalité des patients atteints d'un SDRA associé à une septicémie. CADRE DE L'ÉTUDE: Les données proviennent de 44 centres hospitaliers du réseau National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. PATIENTS: Les 644 participants à l'essai SAILS (sur un total de 745) non dialysés à vie et pour qui on disposait de valeurs initiales de créatinine sérique. MESURES: La principale mesure observée était une atteinte d'IRA, définie selon les critères liés aux valeurs de la créatinine avancées par la fondation Kidney Disease : Improving Global Outcomes. Le facteur prédictif essentiel était la répartition aléatoire des sujets (traitement à la rosuvastatine ou par placébo). Les caractéristiques sociodémographiques des patients, l'étiologie du SDRA et la gravité de l'atteinte constituaient les covariables additionnelles colligées. MÉTHODOLOGIE: La survenue d'une IRA a été analysée par régression logistique multivariée chez deux sous-groupes : 511 patients qui ne présentaient initialement aucun signe clinique d'IRA et 93 patients initialement atteints d'IRA de stade 1. RÉSULTATS: Chez les sujets non atteints d'IRA au moment de la répartition, le traitement à la rosuvastatine n'a eu aucun effet sur le risque de survenue d'IRA (rapport de cotes corrigé : 0,99; IC 95 % : 0,67-1,44). Chez les sujets initialement atteints d'IRA de stade 1, le traitement à la rosuvastatine a été associé à un risque plus élevé d'aggravation de l'atteinte existante (rapport de cotes corrigé : 3,06; IC 95 % : 1,14-8,22). Cependant, chez ces mêmes sujets, lorsque la créatinine sérique a été ajustée selon le bilan hydrique cumulatif, l'effet néfaste de la rosuvastatine n'a plus été observé (rapport de cotes corrigé : 1,85; IC 95 % : 0,70-4,84). LIMITES: La taille de l'échantillon ainsi que l'absence de certaines données (concernant notamment la créatinine préhospitalisation et la diurèse) limitent les constats de notre étude. CONCLUSION: Un traitement par rosuvastatine n'a eu aucun effet protecteur contre le développement ou l'aggravation d'une IRA chez des patients atteints du SDRA associé à une septicémie.

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case. CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Relationship between Race and the Effect of Fluids on Long-term Mortality after Acute Respiratory Distress Syndrome. Secondary Analysis of the National Heart, Lung, and Blood Institute Fluid and Catheter Treatment Trial.

RATIONALE: Short-term follow-up in the Fluid and Catheter Treatment Trial (FACTT) suggested differential mortality by race with conservative fluid management, but no significant interaction. OBJECTIVE: In a post hoc analysis of FACTT including 1-year follow-up, we sought to estimate long-term mortality by race and test for an interaction between fluids and race. METHODS: We performed a post hoc analysis of FACTT and the Economic Analysis of Pulmonary Artery Catheters (EAPAC) study (which included 655 of the 1,000 FACTT patients with near-complete 1-year follow up). We fit a multistate Markov model to estimate 1-year mortality for all non-Hispanic black and white randomized FACTT subjects. The model estimated the distribution of time from randomization to hospital discharge or hospital death (available on all patients) and estimated the distribution of time from hospital discharge to death using data on patients after hospital discharge for patients in EAPAC. The 1-year mortality was found by combining these estimates. RESULTS: Non-Hispanic black (n = 217, 25%) or white identified subjects (n = 641, 75%) were included. There was a significant interaction between race and fluid treatment (P = 0.012). One-year mortality was lower for black subjects assigned to conservative fluids (38 vs. 54%; mean mortality difference, 16%; 95% confidence interval, 2-30%; P = 0.027 between conservative and liberal). Conversely, 1-year mortality for white subjects was 35% versus 30% for conservative versus liberal arms (mean mortality difference, -4.8%; 95% confidence interval, -13% to 3%; P = 0.23). CONCLUSIONS: In our cohort, conservative fluid management may have improved 1-year mortality for non-Hispanic black patients with ARDS. However, we found no long-term benefit of conservative fluid management in white subjects.

Challenges in end-of-life care in the ICU. Statement of the 5th International Consensus Conference in Critical Care: Brussels, Belgium, April 2003.

The jurors identified numerous problems with end of life in the ICU including variability in practice, inadequate predictive models for death, elusive knowledge of patient preferences, poor communication between staff and surrogates, insufficient or absent training of health-care providers, the use of imprecise and insensitive terminology, and incomplete documentation in the medical records. The jury strongly recommends that research be conducted to improve end-of-life care. The jury advocates a "shared" approach to end-of-life decision-making involving the caregiver team and patient surrogates. Respect for patient autonomy and the intention to honour decisions to decline unwanted treatments should be conveyed to the family. The process is one of negotiation, and the outcome will be determined by the personalities and beliefs of the participants. Ultimately, it is the attending physician's responsibility, as leader of the health-care team, to decide on the reasonableness of the planned action. In the event of conflict, the ICU team may agree to continue support for a predetermined time. Most conflicts can be resolved. If the conflict persists, however, an ethics consultation may be helpful. Nurses must be involved in the process. The patient must be assured of a pain-free death. The jury of the Consensus Conference subscribes to the moral and legal principles that prohibit administering treatments specifically designed to hasten death. The patient must be given sufficient analgesia to alleviate pain and distress; if such analgesia hastens death, this "double effect" should not detract from the primary aim to ensure comfort.