Use of Airway Pressure Release Ventilation in Patients With Acute Respiratory Failure Due to COVID-19: Results of a Single-Center Randomized Controlled Trial.

OBJECTIVES: Airway pressure release ventilation is a ventilatory mode characterized by a mandatory inverse inspiratory:expiratory ratio with a very short expiratory phase, aimed to avoid derecruitment and allow spontaneous breathing. Recent basic and clinical evidence suggests that this mode could be associated with improved outcomes in patients with acute respiratory distress syndrome. The aim of this study was to compare the outcomes between airway pressure release ventilation and traditional ventilation targeting low tidal volume, in patients with severe coronavirus disease 2019. DESIGN: Single-center randomized controlled trial. SETTING: ICU of a Mexican referral center dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. PATIENTS: Ninety adult intubated patients with acute respiratory distress syndrome associated with severe coronavirus disease 2019. INTERVENTIONS: Within 48 hours after intubation, patients were randomized to either receive ventilatory management with airway pressure release ventilation or continue low tidal volume ventilation. MEASUREMENTS AND MAIN RESULTS: Forty-five patients in airway pressure release ventilation group and 45 in the low tidal volume group were included. Ventilator-free days were 3.7 (0-15) and 5.2 (0-19) in the airway pressure release ventilation and low tidal volume groups, respectively (p = 0.28). During the first 7 days, patients in airway pressure release ventilation had a higher Pao2/Fio2 (mean difference, 26 [95%CI, 13-38]; p < 0.001) and static compliance (mean difference, 3.7 mL/cm H2O [95% CI, 0.2-7.2]; p = 0.03), higher mean airway pressure (mean difference, 3.1 cm H2O [95% CI, 2.1-4.1]; p < 0.001), and higher tidal volume (mean difference, 0.76 mL/kg/predicted body weight [95% CI, 0.5-1.0]; p < 0.001). More patients in airway pressure release ventilation had transient severe hypercapnia, defined as an elevation of Pco2 at greater than or equal to 55 along with a pH less than 7.15 (42% vs 15%; p = 0.009); other outcomes were similar. Overall mortality was 69%, with no difference between the groups (78% in airway pressure release ventilation vs 60% in low tidal volume; p = 0.07). CONCLUSIONS: In conclusion, when compared with low tidal volume, airway pressure release ventilation was not associated with more ventilator-free days or improvement in other relevant outcomes in patients with severe coronavirus disease 2019.

Acute kidney injury in renal trauma patients.

BACKGROUND: The kidney is the most commonly injured organ of the genitourinary system during trauma. We describe the associated risk factors for the development of acute kidney injury (AKI) in patients with renal trauma (RT). MATERIALS AND METHODS: We prospectively analyzed data from 65 patients who suffered RT from 2015 to 2019 at the Hospital Civil de Guadalajara. Demographic variables, clinical characteristics, and AKI risk factors were described. We assessed the risk factors related to AKI development. RESULTS: In our study cohort, 60 (92.3%) patients were men, mean age 25 (20 - 30) years; the most common cause of RT was firearm injury in 26 (40%) of patients and 46 (70%) required surgery. AKI associated with RT developed in 39 (60%) patients. There were no differences between patients with or without AKI requiring nephrectomy (35.9 vs. 19.2%, p = 0.15). RT was classified as high-grade in 37 (56.9%) cases; high-grade RT increased four-fold the probability of AKI (adjusted OR 3.95, p = 0.05). A model for AKI prediction during RT was built with the most relevant variables: firearm injury, shock, emergency surgery, high-grade RT, and liver injury, all predicting AKI (ROC-AUC of 0.74 p = 0.02). CONCLUSION: AKI occurred in 60% of cases with RT, and it was significantly associated with high-grade RT. Further studies will be required to confirm this association in other populations, which could lead to an earlier and proactive management of AKI in this setting.

Prone positioning in non-intubated patients with COVID-19 associated acute respiratory failure, the PRO-CARF trial: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the effect of prone positioning therapy on intubation rate in awake patients with COVID-19 and acute respiratory failure. TRIAL DESIGN: This is a two-center parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hospital Civil de Guadalajara and Hospital General de Occidente in Mexico for COVID-19 associated acute respiratory failure and in need of supplementary oxygen through high-flow nasal cannula are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the COVID-19 unit who test positive for COVID-19 by PCR-test and in need for oxygen are eligible for inclusion. Randomization starts upon identification of requirement of a fraction of inspired oxygen ≥30% for an oxygen capillary saturation of ≥90% Exclusion criteria: less than 18 years-old, pregnancy, patients with immediate need of invasive mechanical ventilation (altered mental status, fatigue), vasopressor requirement to maintain median arterial pressure >65 mmHg, contraindications for prone positioning therapy (recent abdominal or thoracic surgery or trauma, facial, pelvic or spine fracture, untreated pneumothorax, do-not-resuscitate or do-not-intubate order, refusal or inability of the patient to enroll in the study. INTERVENTION AND COMPARATOR: Patients of the intervention group will be asked to remain in a prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of 92%-95%. For patients in the control group, prone positioning will be allowed as a rescue therapy. Staff intensivists will monitor the patient's status in both groups on a 24/7 basis. All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: Endotracheal intubation rate for mechanical ventilation at 28 days. RANDOMISATION: Patients will be randomly allocated to either prone positioning or control group at 1:1 ratio. Such randomization will be computer generated and stratified by center with permuted blocks and length of 4. BLINDING (MASKING): Due to logistical reasons, only principal investigators and the data analyst will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): With an intubation rate of 60% according to recent reports from some American centers, and assuming a decrease to 40% to be clinically relevant, we calculated a total of 96 patients per group, for a beta error of 0.2, and alpha of 0.5. Therefore, we plan to recruit 200 patients, accounting for minimal losses to follow up, with 100 non-intubated patients in the prone position group and a 100 in the control group. TRIAL STATUS: The local registration number is 048-20, with the protocol version number 2.0. The date of approval is 3rd May 2020. Recruitment started on 3rd May and is expected to end in December 2020. TRIAL REGISTRATION: The protocol was retrospectively registered under the title: "Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure. The PRO-CARF trial" in ClinicalTrials.gov with the registration number: NCT04477655. Registered on 20 July 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Timing, method and discontinuation of hydrocortisone administration for septic shock patients.

AIM: To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes. METHODS: This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone. It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic (ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects. RESULTS: All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h (range, 47.5-90.5) vs 108 h (range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 µg/kg per minute (range, 0.11-0.28 µg)] compared with patients who were given bolus [0.34 µg/kg per minute (range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus (83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock (r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81 (P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 µg/kg per minute, with an area under the curve of 0.75 (P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse (RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio (OR), 5.3; P = 0.04] and hypokalemia (OR = 10.6; P = 0.01). CONCLUSION: Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

Respiratory variation in carotid peak systolic velocity predicts volume responsiveness in mechanically ventilated patients with septic shock: a prospective cohort study.

BACKGROUND: The evaluation of fluid responsiveness in patients with hemodynamic instability remains to be challenging. This investigation aimed to determine whether respiratory variation in carotid Doppler peak velocity (ΔCDPV) predicts fluid responsiveness in patients with septic shock and lung protective mechanical ventilation with a tidal volume of 6 ml/kg. METHODS: We performed a prospective cohort study at an intensive care unit, studying the effect of 59 fluid challenges on 19 mechanically ventilated patients with septic shock. Pre-fluid challenge ΔCDPV and other static or dynamic measurements were obtained. Fluid challenge responders were defined as patients whose stroke volume index increased more than 15 % on transpulmonary thermodilution. The area under the receiver operating characteristic curve (AUROC) was compared for each predictive parameter. RESULTS: Fluid responsiveness rate was 51 %. The ΔCDPV had an AUROC of 0.88 (95 % confidence interval (CI) 0.77-0.95); followed by stroke volume variation (0.72, 95 % CI 0.63-0.88), passive leg raising (0.69, 95 % CI 0.56-0.80), and pulse pressure variation (0.63, 95 % CI 0.49-0.75). The ΔCDPV was a statistically significant superior predictor when compared with the other parameters. Sensitivity, specificity, and positive and negative predictive values were also the highest for ΔCDPV, with an optimal cutoff at 14 %. There was good correlation between ΔCDPV and SVI increment after the fluid challenge (r = 0.84; p < 0.001). CONCLUSIONS: ΔCDPV can be more accurate than other methods for assessing fluid responsiveness in patients with septic shock receiving lung protective mechanical ventilation. ΔCDPV also has a high correlation with SVI increase after fluid challenge.