Hemodynamic Characteristics of Mechanically Ventilated COVID-19 Patients: A Cohort Analysis.

BACKGROUND: Solid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients. METHODS: A retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system. RESULTS: The mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p < 0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p < 0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Q s/Q t) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p < 0.001), but static lung compliance remained unchanged. CONCLUSIONS: In general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange.

Relationship between norepinephrine dose, tachycardia and outcome in septic shock: A multicentre evaluation.

PURPOSE: Septic shock is associated with massive release of endogenous catecholamines. Adrenergic agents may exacerbate catecholamine toxicity and contribute to poor outcomes. We sought to determine whether an association existed between tachycardia and mortality in septic shock patients requiring norepinephrine for more than 6 h despite adequate volume resuscitation. MATERIALS AND METHODS: Multicentre retrospective observational study on 730 adult patients in septic shock consecutively admitted to eight European ICUs between 2011 and 2013. Three timepoints were selected: T1 (first hour of infusion of norepinephrine), Tpeak (time of highest dose during the first 24 h of treatment), and T24 (24-h post-T1). Binary logistic regression models were constructed for the three time-points. RESULTS: Overall ICU mortality was 38.4%. Mortality was higher in those requiring high-dose (≥0.3 mcg/kg/min) versus low-dose (<0.3 mcg/kg/min) norepinephrine at T1 (53.4% vs 30.6%; p < 0.001) and T24 (61.4% vs 20.4%; p < 0.0001). Patients requiring high-dose with concurrent tachycardia had higher mortality at T1; in the low-dose group tachycardia was not associated with mortality. Resolving tachycardia (from T1 to T24) was associated with lower mortality compared to patients where tachycardia persisted (27.8% vs 46.4%; p = 0.001). CONCLUSIONS: Use of high-dose norepinephrine and concurrent tachycardia are associated with poor outcomes in septic shock.

Right Ventricular Function and Long-Term Outcome in Sepsis: A Retrospective Cohort Study.

BACKGROUND: Sepsis-related myocardial dysfunction is associated with impaired outcome. Traditionally, in this setting the main focus has been on left ventricular performance. Currently, specific knowledge on the prognostic importance of right ventricular dysfunction is scarce. The aim of this study was to determine whether right ventricular ejection fraction (RVEF) is predictive of long-term mortality in sepsis. METHODS: Single-centre retrospective cohort study in adult patients admitted to the ICU with severe sepsis and septic shock, and equipped with a pulmonary artery catheter within the first day after admission. RVEF was recorded as an average over the first 24 h (sample rate of 1 per min). Patients were separated a priori into subgroups according to their RVEF: RVEF less than 20% (A), RVEF 20% to 30% (B), and RVEF more than 30% (C). The primary endpoint was 1-year all-cause mortality. RESULTS: In a 7-year period, 101 patients fulfilled all entry criteria and 98 were included in the study. One-year all-cause mortality was significantly different between groups: 57% in group A (n = 21), 18% in group B (n = 55), and 23% in group C (n = 22); P = 0.003. Kaplan-Meier survival analysis revealed a clear separation between groups A and B/C (X = 14.00, P = 0.001). In a multivariate logistic regression analysis RVEF, both as a categorical variable (RVEF <20%) and as a continuous variable remained independently associated with the primary endpoint (odds ratio [OR] 4.1; 95% confidence interval [CI], 1.3-13.4; P = 0.018 and OR 0.92; 95% CI, 0.85-0.99; P = 0.018, respectively). CONCLUSIONS: RVEF was independently associated with 1-year all-cause mortality in a highly selected group of patients with severe sepsis and septic shock.

Microcirculatory blood flow as a tool to select ICU patients eligible for fluid therapy.

PURPOSE: The aim of this study is to assess the incidence of sublingual microcirculatory flow alterations, according to a predefined arbitrary cutoff value, in patients with "clinical signs of impaired organ perfusion". Secondary endpoints were the changes in microvascular flow index (MFI), "clinical signs of impaired organ perfusion", and stroke volume (SV) after fluid administration, and the differences between groups. METHODS: Prospective, single-center, observational study in a 22-bed mixed intensive care unit (ICU). Patients ≥18 years with invasive hemodynamic monitoring and "clinical signs of impaired organ perfusion" as the principal reason for fluid administration were included. Before and after fluid challenge, systemic hemodynamics and direct in vivo observation of the sublingual microcirculation with sidestream dark-field imaging were obtained. Microvascular flow index (MFI) <2.6 was predefined as abnormal. RESULTS: N = 50. At baseline, MFI <2.6 was present in 66 % of the patients. In these patients, MFI increased from 2.3 (2-2.5) at baseline to 2.5 (2.1-2.8) after fluid challenge (p = 0.003). This was accompanied by a reduction in the number of "clinical signs of impaired organ perfusion" from 2 (1-2) to 1 (0-2) (p < 0.001). However, in patients with MFI >2.6 at baseline, MFI and clinical signs changed insignificantly [2.8 (2.8-2.9) versus 2.8 (2.7-3), p = 0.45, respectively, 1 (1-2) versus 1 (1-2), p < 0.32]. These changes were not restricted to patients with a rise in SV ≥10 %. CONCLUSIONS: These data add to the understanding that noninvasive assessment of microvascular blood flow may help to identify patients eligible for fluid therapy, and to evaluate its effect.

Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial.

OBJECTIVES: Microcirculatory alterations have been associated with morbidity and mortality in human sepsis. Such alterations occur despite pressure-guided resuscitation. Earlier data suggested that impaired microcirculatory blood flow could be corrected with intravenous nitroglycerin in these patients. We tested this concept after fulfillment of preset systemic hemodynamic resuscitation end points in the early phase of sepsis. DESIGN: Prospective, single center, randomized, placebo-controlled, double-blind clinical trial. SETTING: Closed-format 22-bed mixed intensive care unit in a tertiary teaching hospital. PATIENTS: Patients > or =18 yrs with sepsis, according to international criteria, and at least one early sign of organ dysfunction, as the principal reason for intensive care unit admission, were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive nitroglycerin (n = 35) or placebo (n = 35) after fulfillment of protocol-driven resuscitation end points. This trial is registered with ClinicalTrials.gov as NCT00493415. MEASUREMENTS AND MAIN RESULTS: Primary outcome was sublingual microcirculatory blood flow of small vessels, as assessed by side-stream dark field imaging. After protocolized resuscitation, we observed recruitment of sublingual microcirculation in both groups, as indicated by a significant improvement in the microcirculatory flow index after 24 hrs, in comparison to baseline. However, no difference in the sublingual microvascular flow index was observed between groups. The median microvascular flow index in sublingual small-sized vessels was 2.71 (1.85-3) in the nitroglycerin group and 2.71 (1.27-3), p = .80, in the placebo group. In medium-sized vessels, the respective values were 3 (2.75-3) vs. 2.86 (2.19-3), p = .21, and in large-sized vessels, 3 (3-3) vs. 3 (2.89-3), p = .06. In-hospital mortality, as a secondary outcome, was 34.3% in the nitroglycerin group and 14.2% in the placebo group, p = .09. CONCLUSIONS: In the context of a strict resuscitation protocol, based upon fulfillment of systemic hemodynamic end points in patients with early-phase severe sepsis or septic shock, we conclude that intravenous nitroglycerin does not promote sublingual microcirculatory blood flow.