Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow.

OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.

Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19: A Randomized Clinical Trial.

IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.

Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O2 extraction during septic shock.

Derangements of microvascular blood flow distribution might contribute to disturbing O2 extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O2 extraction ratio ([Formula: see text]) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg-1·min-1) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in [Formula: see text] in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas [Formula: see text] exhibited a corresponding significant decrease (repeated-measures ANOVA, P = 0.02 and P = 0.04 for time × group interactions and intergroup differences for villi-PPV and [Formula: see text], respectively). Variations in villi-PPV were paralleled by variations in [Formula: see text] (R2 = 0.88, P < 0.001) and these, in turn, by mesenteric lactate changes (R2 = 0.86, P < 0.001). There were no significant differences in cardiac output and systemic O2 delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O2 extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O2 uptake during development and resuscitation from septic shock.NEW & NOTEWORTHY Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O2 extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O2 uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O2 consumption.

Relajación residual posoperatoria en la unidad de cuidados postanestésicos de un hospital universitario: Estudio de corte transversal / Postoperative residual curarization at the post-anesthetic care unit of a university hospital: A cross-sectional study

Abstract Introduction: Postoperative residual curarization has been related to postoperative complications. Objective: To determine the prevalence of postoperative residual curarization in a university hospital and its association with perioperative conditions. Method: A prospective registry of 102 patients in a period of 4 months was designed to include ASA I-II patients who intraoperatively received nondepolarizing neuromuscular blockers. Abductor pollicis response to a train-of-four stimuli based on accelleromyography and thenar eminence temperature (TOF-Watch SX®. Organon, Ireland) was measured immediately upon arrival at the postanesthetic care unit and 30 s later. Uni-bivariate analysis was planned to determine possible associations with residual curarization, defined as two repeated values of T4/T1 ratio <0.90 in response to train-of-four stimuli. Results: Postoperative residual curarization was detected in 42.2% of the subjects. Pancuronium was associated with a high risk for train-of-four response <0.9 at the arrive at postoperative care unit [RR:2.56 (IC95% 1.99-3.30); p = 0.034]. A significant difference in thenar temperature (°C) was found in subjects with train-of-four <0.9 when compared to those who reach adequate neuromuscular function (29.9 ± 1.6 vs. 31.1 ± 2.2; respectively. p = 0.003). However, we were unable to demonstrate a direct attribution of findings in train-of-four response to temperature (R² determination coefficient = 0.08%). Conclusions: A high prevalence of postoperative residual curarization persists in university hospitals, despite a reduced use of "long-lasting" neuromuscular blockers. Strategies to assure neuromuscular monitoring practice and access to therapeutic alternatives in this setting must be considered. Intraoperative neuromuscular blockers using algorithms and continued education in this field must be priorities within anesthesia services.

Introducción: La relajación residual postoperatoria ha sido asociada con mayores complicaciones postoperatorias. Objetivo: determinar la prevalencia de relajación residual postoperatoria en un hospital universitario y su relación con condiciones perioperatorias. Métodos: Se diseñó un registro prospectivo de 4 meses de duración, que incluyó pacientes ASA I-II que intraoperatoriamente recibieran bloqueadores neuromusculares. Se registró la respuesta del abductor pollicis a un estímulo de tren de cuatro mediante aceleromiografía y se midió la temperatura de la eminencia tenar (TOF-Watch SX®.Organon, Ireland) inmediatamente al ingreso a recuperación y a los 30 segundos. Se realizó análisis uni y bivariado para determinar posibles asociaciones con relajación residual postoperatoria, definida como dos respuestas sucesivas al estímulo tren-de-cuatro con una relación T4/T1 <0.90. Resultados: Se reclutaron 102 pacientes, encontrando una prevalencia de relajación residual del 42.2%. Pancuronio fue asociado con un riesgo elevado de TOF < 0.9 al ingreso a recuperación [RR:2,56 (IC95% 1.99-3.30); p = 0.034]. Se evidenció una diferencia significativa en la temperatura tenar de los pacientes que presentaban relajación residual, al compararla con pacientes que recuperaron su función neuromuscular [Grupo evento = 29.9 ± 1.6 (n = 43); Grupo control = 31.1 ±2.2 (n = 59)]. Sin embargo no se logró determinar una atribución directa de relajación residual a esta medición (coeficiente de determinación = 0.08%). Conclusión: Persiste una alta prevalencia de relajación residual postoperatoria en los hospitales universitarios, a pesar del uso reducido de bloqueadores neuromusculares de larga duración. Se hace indispensable encaminar estrategias para incentivar la monitoria neuromuscular y establecer algoritmos que permitan un manejo eficiente de los bloqueadores neuromusculares.