Venous return and mean systemic filling pressure: physiology and clinical applications.

Venous return is the flow of blood from the systemic venous network towards the right heart. At steady state, venous return equals cardiac output, as the venous and arterial systems operate in series. However, unlike the arterial one, the venous network is a capacitive system with a high compliance. It includes a part of unstressed blood, which is a reservoir that can be recruited via sympathetic endogenous or exogenous stimulation. Guyton's model describes the three determinants of venous return: the mean systemic filling pressure, the right atrial pressure and the resistance to venous return. Recently, new methods have been developed to explore such determinants at the bedside. In this narrative review, after a reminder about Guyton's model and current methods used to investigate it, we emphasize how Guyton's physiology helps understand the effects on cardiac output of common treatments used in critically ill patients.

Effects of Prone Positioning on Venous Return in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine the effects of prone positioning on venous return and its determinants such as mean systemic pressure and venous return resistance in patients with acute respiratory distress syndrome. DESIGN: Prospective monocentric study. SETTINGS: A 25-bed medical ICU. PATIENTS: About 22 patients with mild-to-severe acute respiratory distress syndrome in whom prone positioning was decided. INTERVENTIONS: We obtained cardiac index, mean systemic pressure, and venous return resistance (the latter two estimated through the heart-lung interactions method) before and during prone positioning. Preload responsiveness was assessed at baseline using an end-expiratory occlusion test. MEASUREMENTS AND MAIN RESULTS: Prone positioning significantly increased mean systemic pressure (from 24 mm Hg [19-34 mm Hg] to 35 mm Hg [32-46 mm Hg]). This was partly due to the trunk lowering performed before prone positioning. In seven patients, prone positioning increased cardiac index greater than or equal to 15%. All were preload responsive. In these patients, prone positioning increased mean systemic pressure by 82% (76-95%), central venous pressure by 33% (21-59%), (mean systemic pressure - central venous pressure) gradient by 144% (83-215)%, while it increased venous return resistance by 71% (60-154%). In 15 patients, prone positioning did not increase cardiac index greater than or equal to 15%. In these patients, prone positioning increased mean systemic pressure by 28% (18-56%) (p < 0.05 vs. patients with significant increase in cardiac index), central venous pressure by 21% (7-54%), (mean systemic pressure - central venous pressure) gradient by 28% (23-86%), and venous return resistance by 37% (17-77%). Eleven of these 15 patients were preload unresponsive. CONCLUSIONS: Prone positioning increased mean systemic pressure in all patients. The resulting change in cardiac index depended on the extent of increase in (mean systemic pressure - central venous pressure) gradient, of preload responsiveness, and of the increase in venous return resistance. Cardiac index increased only in preload-responsive patients if the increase in venous return resistance was lower than the increase in the (mean systemic pressure -central venous pressure) gradient.

Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock.

BACKGROUND: Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR). METHODS: In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%. RESULTS: Norepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose. CONCLUSIONS: Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.

Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge.

BACKGROUND: The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. METHODS: We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. RESULTS: Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68-1.71) vs. 1.27 mIU/L (0.75-1.79), p = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. CONCLUSIONS: Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome.

Transpulmonary thermodilution detects rapid and reversible increases in lung water induced by positive end-expiratory pressure in acute respiratory distress syndrome.

PURPOSE: It has been suggested that, by recruiting lung regions and enlarging the distribution volume of the cold indicator, increasing the positive end-expiratory pressure (PEEP) may lead to an artefactual overestimation of extravascular lung water (EVLW) by transpulmonary thermodilution (TPTD). METHODS: In 60 ARDS patients, we measured EVLW (PiCCO2 device) at a PEEP level set to reach a plateau pressure of 30 cmH2O (HighPEEPstart) and 15 and 45 min after decreasing PEEP to 5 cmH2O (LowPEEP15' and LowPEEP45', respectively). Then, we increased PEEP back to the baseline level (HighPEEPend). Between HighPEEPstart and LowPEEP15', we estimated the degree of lung derecruitment either by measuring changes in the compliance of the respiratory system (Crs) in the whole population, or by measuring the lung derecruited volume in 30 patients. We defined patients with a large derecruitment from the other ones as patients in whom the Crs changes and the measured derecruited volume were larger than the median of these variables observed in the whole population. RESULTS: Reducing PEEP from HighPEEPstart (14 ± 2 cmH2O) to LowPEEP15' significantly decreased EVLW from 20 ± 4 to 18 ± 4 mL/kg, central venous pressure (CVP) from 15 ± 4 to 12 ± 4 mmHg, the arterial oxygen tension over inspired oxygen fraction (PaO2/FiO2) ratio from 184 ± 76 to 150 ± 69 mmHg and lung volume by 144 [68-420] mL. The EVLW decrease was similar in "large derecruiters" and the other patients. When PEEP was re-increased to HighPEEPend, CVP, PaO2/FiO2 and EVLW significantly re-increased. At linear mixed effect model, EVLW changes were significantly determined only by changes in PEEP and CVP (p < 0.001 and p = 0.03, respectively, n = 60). When the same analysis was performed by estimating recruitment according to lung volume changes (n = 30), CVP remained significantly associated to the changes in EVLW (p < 0.001). CONCLUSIONS: In ARDS patients, changing the PEEP level induced parallel, small and reversible changes in EVLW. These changes were not due to an artefact of the TPTD technique and were likely due to the PEEP-induced changes in CVP, which is the backward pressure of the lung lymphatic drainage. Trial registration ID RCB: 2015-A01654-45. Registered 23 October 2015.