High-Flow Oxygen Therapy Application in Chronic Obstructive Pulmonary Disease Patients With Acute Hypercapnic Respiratory Failure: A Multicenter Study.

OBJECTIVES: To evaluate the effect of high-flow oxygen implementation on the respiratory rate as a first-line ventilation support in chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. DESIGN: Multicenter, prospective, analytic observational case series study. SETTING: Five ICUs in Argentina, between August 2018 and September 2019. PATIENTS: Patients greater than or equal to 18 years old with moderate to very severe chronic obstructive pulmonary disease, who had been admitted to the ICU with a diagnosis of hypercapnic acute respiratory failure, were entered in the study. INTERVENTIONS: High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation. MEASUREMENTS AND MAIN RESULTS: Forty patients were studied, 62.5% severe chronic obstructive pulmonary disease. After the first hour of high-flow nasal cannula implementation, there was a significant decrease of respiratory rate compared with baseline values, with a 27% decline (29 vs 21 breaths/min; p < 0.001). Furthermore, a significant reduction of Paco2 (57 vs 52 mm Hg [7.6 vs 6.9 kPa]; p < 0.001) was observed. The high-flow nasal cannula application failed in 18% patients. In this group, the respiratory rate, pH, and Paco2 showed no significant change during the first hour in these patients. CONCLUSIONS: High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation was an effective tool for reducing respiratory rate in these chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Early determination and subsequent monitoring of clinical and blood gas parameters may help predict the outcome.

Microcirculation alterations in severe COVID-19 pneumonia.

PURPOSE: To assess the presence of sublingual microcirculatory and skin perfusion alterations in COVID-19 pneumonia. MATERIALS AND METHODS: This is a preliminary report of a prospective observational study performed in four teaching intensive care units. We studied 27 mechanically ventilated patients with acute respiratory distress syndrome secondary to COVID-19. Sublingual microcirculation was assessed by hand-held videomicroscopy. A software-assisted analysis of videos was performed. We also measured capillary refill time. RESULTS: Patients were hemodynamically stable with normal lactate (1.8 [1.6-2.5] mmol/L) and high D-dimer (1.30 [0.58-2.93] µg/mL). Capillary refill time was prolonged (3.5 [3.0-5.0] s). Compared to previously reported normal values, total and perfused vascular density (21.9 ± 3.9 and 21.0 ± 3.5 mm/mm2) and heterogeneity flow index (0.91 ± 0.24) were high; and the proportion of perfused vessels (0.96 ± 0.03), microvascular flow index (2.79 ± 0.10), and red blood cell velocity (1124 ± 161 µm/s) were reduced. The proportion of perfused vessels was inversely correlated with total vascular density (Pearson r = -0.41, P = 0.03). CONCLUSIONS: COVID-19 patients showed an altered tissue perfusion. Sublingual microcirculation was characterized by decreases in the proportion of perfused vessel and flow velocity along with high vascular densities. This last finding might be related to enhanced angiogenesis or hypoxia-induced capillary recruitment.

Titration and characteristics of pressure-support ventilation use in Argentina: an online cross-sectional survey study. / Uso y titulación de presión soporte en Argentina: estudio transversal de tipo encuesta online.

OBJECTIVE: To identify common practices related to the use and titration of pressure-support ventilation (PC-CSV - pressure control-continuous spontaneous ventilation) in patients under mechanical ventilation and to analyze diagnostic criteria for over-assistance and under-assistance. The secondary objective was to compare the responses provided by physician, physiotherapists and nurses related to diagnostic criteria for over-assistance and under-assistance. METHODS: An online survey was conducted using the Survey Monkey tool. Physicians, nurses and physiotherapists from Argentina with access to PC-CSV in their usual clinical practice were included. RESULTS: A total of 509 surveys were collected from October to December 2018. Of these, 74.1% were completed by physiotherapists. A total of 77.6% reported using PC-CSV to initiate the partial ventilatory support phase, and 43.8% of respondents select inspiratory pressure support level based on tidal volume. The main objective for selecting positive end-expiratory pressure (PEEP) level was to decrease the work of breathing. High tidal volume was the primary variable for detecting over-assistance, while the use of accessory respiratory muscles was the most commonly chosen for under-assistance. Discrepancies were observed between physicians and physiotherapists in relation to the diagnostic criteria for over-assistance. CONCLUSION: The most commonly used mode to initiate the partial ventilatory support phase was PC-CSV. The most frequently selected variable to guide the titration of inspiratory pressure support level was tidal volume, and the main objective of PEEP was to decrease the work of breathing. Over-assistance was detected primarily by high tidal volume, while under-assistance by accessory respiratory muscles activation. Discrepancies were observed among professions in relation to the diagnostic criteria for over-assistance, but not for under-assistance.

Uso y titulación de presión soporte en Argentina: estudio transversal de tipo encuesta online / Titration and characteristics of pressure-support ventilation use in Argentina: an online cross-sectional survey study

RESUMEN Objetivo: Identificar las prácticas habituales de uso y titulación del modo presión soporte (PC-CSV - pressure control continuous spontaneous ventilation) en pacientes bajo ventilación mecánica y analizar las formas de reconocimiento de sobreasistencia y subasistencia. Secundariamente, comparar las respuestas según profesión en relación al diagnóstico de sobreasistencia y subasistencia. Métodos: Se realizó una encuesta online utilizando la herramienta Survey Monkey. Se incluyeron a médicos, enfermeros y kinesiólogos de Argentina que tuvieran acceso al uso de PC-CSV en su práctica habitual. Resultados: Se recolectaron 509 encuestas desde octubre a diciembre 2018. El 74,1% de ellas correspondió a kinesiólogos. Un 77,6% refirió utilizar PC-CSV para iniciar la fase de soporte parcial. Un 43,8% selecciona el valor de presión de soporte inspiratorio basándose en volumen corriente. El principal objetivo de la selección de PEEP fue disminuir el trabajo respiratorio. El volumen corriente alto fue la variable primordial de detección de sobreasistencia, mientras que el uso de músculos accesorios fue la más elegida para subasistencia. Se observaron diferencias entre médicos y kinesiólogos en relación a las formas de detección de sobreasistencia. Conclusión: El modo más utilizado para la fase de soporte parcial es PC-CSV. La variable más elegida para titular la presión de soporte inspiratorio es volumen corriente y el principal objetivo de la PEEP es disminuir el trabajo respiratorio. La sobreasistencia es detectada prioritariamente por un volumen corriente elevado, mientras que la subasistencia mediante el uso de músculos accesorios. Se halló diferencias entre profesiones en relación a los criterios de detección de sobreasistencia.

ABSTRACT Objective: To identify common practices related to the use and titration of pressure-support ventilation (PC-CSV - pressure control-continuous spontaneous ventilation) in patients under mechanical ventilation and to analyze diagnostic criteria for over-assistance and under-assistance. The secondary objective was to compare the responses provided by physician, physiotherapists and nurses related to diagnostic criteria for over-assistance and under-assistance. Methods: An online survey was conducted using the Survey Monkey tool. Physicians, nurses and physiotherapists from Argentina with access to PC-CSV in their usual clinical practice were included. Results: A total of 509 surveys were collected from October to December 2018. Of these, 74.1% were completed by physiotherapists. A total of 77.6% reported using PC-CSV to initiate the partial ventilatory support phase, and 43.8% of respondents select inspiratory pressure support level based on tidal volume. The main objective for selecting positive end-expiratory pressure (PEEP) level was to decrease the work of breathing. High tidal volume was the primary variable for detecting over-assistance, while the use of accessory respiratory muscles was the most commonly chosen for under-assistance. Discrepancies were observed between physicians and physiotherapists in relation to the diagnostic criteria for over-assistance. Conclusion: The most commonly used mode to initiate the partial ventilatory support phase was PC-CSV. The most frequently selected variable to guide the titration of inspiratory pressure support level was tidal volume, and the main objective of PEEP was to decrease the work of breathing. Over-assistance was detected primarily by high tidal volume, while under-assistance by accessory respiratory muscles activation. Discrepancies were observed among professions in relation to the diagnostic criteria for over-assistance, but not for under-assistance.

Expression and functional evidence of the prostaglandin F2alpha receptor mediating contraction in human umbilical vein.

Our purposes were to perform the pharmacological characterization of PGF(2alpha) receptor (prostanoid FP-receptor) involved in human umbilical vein contraction and confirm its expression in this tissue. Umbilical cords from healthy patients after full-term deliveries were employed. The vein was dissected out of cords and used for either isolated organ bath or reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. The natural prostanoid FP-receptor agonist, PGF(2alpha), and its selective analogues, latanoprost and bimatoprost free acids are full agonists (produce more than 80% of the maximal contractile response to 5-HT) in human umbilical vein. The agonist potency (pEC(50)) order was PGF(2alpha) (6.01+/-0.05)>latanoprost free acid (5.65+/-0.07)=bimatoprost free acid (5.59+/-0.08). The contractile effects of PGF(2alpha) and latanoprost free acid were blocked competitively by the prostanoid FP-receptor antagonist, AL-8810. The antagonist potencies (pK(B)) of AL-8810 vs. PGF(2alpha) (5.93+/-0.05) and vs. latanoprost free acid (6.40+/-0.08) in human umbilical vein are in good agreement with its ability to antagonize prostanoid FP receptors of rat, mouse and human cells. In all samples, clear signal was detected for cDNA amplification of prostanoid FP receptor and the specific prostanoid FP-receptor antibody recognized a protein of approximately 64 kDa. In conclusion, taking into account the obtained functional and biochemical data, we propose for the first time that human umbilical vein express prostanoid FP-receptors and these receptors could be involved in the vasoconstriction action of PGF(2alpha) in this tissue.

Potentiation of adrenaline vasoconstrictor response by sub-threshold concentrations of U-46619 in human umbilical vein: involvement of smooth muscle prostanoid TP(alpha) receptor isoform.

Considering the potential physiological, pharmacological and therapeutic relevance of synergistic interaction of thromboxane A(2) with adrenaline at postjunctional receptor sites, we examined whether sub-threshold concentrations of thromboxane A(2) mimetic U-46619 (9,11-dideoxy-9alpha, 11alpha-methanoepoxy prostaglandin F(2alpha)) could amplify adrenaline-induced contraction in human umbilical vein. The receptor involved in U-46619-induced potentiation of adrenaline contractility was also investigated. Umbilical cords (n=125) from healthy patients after full-term vaginal or caesarean deliveries were employed. The vein was dissected out of cords and rings used for isolated organ bath experiments or reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Presence of endothelium did not modify U-46619-induced contraction in human umbilical vein. Prostanoid TP-selective receptor antagonist, SQ-29548 (7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-[1S(1alpha,2alpha(Z),3alpha,4alpha)]-5-Heptenoic acid), inhibited U-46619-induced contraction (pA(2)=8.22+/-0.11). U-46619 sub-threshold concentrations (0.1-0.3 nM) potentiated adrenaline-vasoconstriction response in a concentration-dependent manner. SQ-29548 (0.1 microM) abolished this potentiation. Using RT-PCR, we found that human umbilical vein rings with or without endothelium express the prostanoid TP(alpha), but not the prostanoid TP(beta) receptor isoform. Western blot allowed the identification of proteins with an electrophoretic mobility (47- and 55-kDa) indistinguishable from human platelet prostanoid TP receptor, a rich source of prostanoid TP(alpha) receptor isoform. Collectively, present results demonstrate that prostanoid TP(alpha) is the major receptor isoform localized on smooth muscle cells which participate in both direct vasoconstriction and potentiating effects of U-46619 on adrenaline contractions in human umbilical vein. These results suggest that thromboxane A(2) may interact synergistically with adrenaline in pathophysiological situations that lead to an increase of its umbilical venous levels (e.g. preeclampsia associated with fetal distress) raising the possibility of vasoconstriction affecting fetal blood flow.