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Purpose: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). Materials and methods: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020–December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. Results: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1–18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6–96.9), a specificity of 95.6% (95% CI: 90.6–98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3–92.3), a negative PV of 97.1% (95% CI: 74.6–96.9) and an accuracy of 94.2% (95% CI: 89.6–97.2) in predicting PMD/PNX (AUC:0.924). Conclusions: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.

OBJECTIVE: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. PARTICIPANTS: Adult patients receiving mechanical ventilation due to COVID-19. INTERVENTIONS: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. MAIN OUTCOME MEASURES: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. RESULTS: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87–16.22; P = 0.013) and the Pao2/Fio2 ratio (median difference, 23.17; 95% CI, 3.46–42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09–0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). CONCLUSIONS: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and Pao2/Fio2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366.

Background: The use of angiotensin II (ANGII) in invasively ventilated COVID-19 patients is controversial. Its effect on markers of organ function is unknown.Methods: We used ANGII either as rescue vasopressor agent or as low dose vasopressor support. Patients treated before ANGII availability or in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of ANG on markers of organ function.Results: We compared 46 ANGII patients with 53 controls. Compared with controls, ANGII increased MAP (median difference, 9.05 mmHg [95% confidence interval, 1.87 to 16.22]; p = 0.013) and PaO2/FiO2 ratio (median difference, 23.17 [95% confidence interval, 3.46 to 42.88]; p = 0.021). ANGII had no effect on lactate, urinary output, serum creatinine, C-Reactive protein, platelet count, or thromboembolic complications. However, it significantly decreased the odd ratio of liver dysfunction (odds ratio: 0.32; 0.09 to 0.94) and, on Bayesian modelling, in patients with abnormal baseline serum creatinine, ANGII carried a 95.7% probability of decreasing renal replacement therapy use. Conclusions: In ventilated COVID-19 patients, ANGII therapy was associated with increased blood pressure and PaO2/FiO2 ratios, decreased odds ratio of liver dysfunction, and a high probability of decreasing renal replacement therapy use in patients with abnormal baseline serum creatinine.

This prospective randomized clinical study was designed to compare the effects of equal volumes of 7.5% hypertonic saline solution (HS) or 20% mannitol (M) on brain bulk and lumbar cerebrospinal fluid pressure (CSFP) during elective neurosurgical procedures (aneurysm, arteriovenous malformation, or tumor). After informed consent, 50 American Society of Anesthesiologists physical Status I (ASA I) patients were randomly assigned to M (n = 25) or HS (n = 25) groups. Anesthesia protocol was identical for both, and variables monitored included mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), CSF pressure (CSFP), arterial blood gases (PaCO2 30-35 mm Hg), serum sodium, potassium, and osmolality, and diuresis. The study period started before hypertonic solution administration (T0) and ended at the opening of the dura mater or 60 min after T0. Data were assessed with repeated measures analysis of variance and Student t test with Bonferroni correction (p < or = 0.05). MAP and CVP were the same in the two groups. After treatment, osmolality increased, and the increase at T15 was higher in HS-treated patients [316.6 +/- 9.3 vs. 304.0 +/- 12.0 (SD) mOsmol/kg; p < 0.001]. Sodium decreased after M and increased after HS. During the study, brain bulk was always considered satisfactory. CSFP was not different between M and HS groups and significantly decreased overtime (p = 0.0056) with no difference between treatments. The results of the present study demonstrate that hypertonic saline is as effective as mannitol in reducing the brain bulk and the CSFP during elective neurosurgical procedures under general anesthesia.