High Central Venous Pressure and Right Ventricle Size are Related to Increased Stroke Volume to Negative Fluid Balance in Critically Ill Patients

Methods

Study design and patient enrollment

The primary aim of this study was to evaluate the relationship between hemodynamic parameters and VTI changes after negative fluid management in patients with high CVP. The study was designed as a prospective observational cohort study. All patients with abnormally high CVP (i.e., outside the normal range of 0–7 mmHg) treated at the Critical Medicine Department of Peking Union Medical College Hospital from May 2017 to October 2017 were included in the study sample. This study was approved by the ethics committee of Peking Union Medical College Hospital (S-617) and written informed consent was provided by the next of kin of all participants.

Inclusion and exclusion criteria

The inclusion criteria were (i) CVP ≥ 8 mmHg and (ii) age > 18 years. The exclusion criteria were (i) non-curative goals of therapy, (ii) a history of cardiac disease, and (iii) pulmonary hypertension or precaval malformations. Patients were divided into two groups according to RV_D/LV_D ratio: Group 1 comprised patients exhibiting RV dilatation (RV_D/LV_D ratio ≥ 0.6) and Group 2 comprised patients without RV dilatation (RV/LV ratio < 0.6).

Study protocol

All patients were treated as follows:

(1) All enrolled patients underwent the routine procedures of the Critical Care Department of Peking Union Medical College Hospital. Arterial and venous lines were inserted. Time 0(T0)was recorded at ICU admission, and T1 was recorded after a negative fluid balance of 500 mL within 30–60 minutes. Central venous and arterial blood gases analysis were performed at T0 and T1.

(2) Critical ultrasound was also performed at T0 and T1 by competent attending physicians or fellows using an ultrasound system equipped with an array probe(X-Porte,Sonosite, Bothell༌WA༌USA). At least five standard views (acoustic windows) were obtained and recorded for each scan: parasternal long axis, parasternal short axis, apical four-chamber, subcostal, and inferior vena cava (IVC). The following parameters were analyzed༈Figure 1༉: RV_D/LV_D ratio, tricuspid annular plane systolic excursion (TAPSE), diameter of the inferior vena cava (DIVC), left ventricular eject fraction (LVEF), and left ventricular stroke volume (LVSV). LVSV was calculated by combining the averaged left ventricular outflow tract velocity time integral (LVOT VTI) by pulsed wave Doppler for the whole respiratory cycle with 2D measurement of the related diameter[11]. RV size was also evaluated at end-expiration by the RV_D/LV_D ratio. RV_D and LV_D were measured in the apical 4-CH view by identifying the maximal distance between the ventricular endocardium and the interventricular septum perpendicular to the long axis at the beginning of the QRS complex[12]. All results were confirmed by two competent attending physicians.

(3) The method of negative fluid balance (application of diuretic drugs or continuous renal replacement therapy) was determined by the physician. No changes were made to mechanical ventilation, the set of vasoactive drugs, or the sedation level (Δ Richmond Agitation-Sedation Scale score < 1 point). Furthermore, no changes were made to the thoracic/abdominal pressure that may cause changes in CVP. In the case of patient hypoxia, the inhaled oxygen concentration was adjusted to ensure SP02 > 95%, Pa02 > 60 mmHg.

Data collection

Clinical data were extracted from the ICU computerized database and medical records, including patients’ socio-demographic data, biometric parameters, comorbidities, respiratory support mode, and Acute Physiology and Chronic Health Evaluation II scores. Hemodynamic parameters (heart rate, mean arterial blood pressure, and CVP) and echo parameters (such as DIVC, RV_D/LV_D ratio, LVEF, LVOT VTI, and TAPSE) were recorded at T0 and T1. Central venous oxygen saturation (ScVO2), central venous-arterial carbon dioxide difference (GAP), and serum lactate levels (lac) were also recorded at the same time. The primary outcome of the study was to clarify VTI change after negative fluid management in patients with high CVP. The secondary outcome was to evaluate the relationship between hemodynamic parameters and VTI change after negative fluid management.

Statistical analysis

Statistical analysis was performed using SPSS software version 20.0 for Windows (IBM, Armonk, NY). Results for continuous variables with a normal distribution (e.g., age, Acute Physiology and Chronic Health Evaluation II score) are reported as the mean ± standard deviation. Student’s t-test was used to compare means between two groups. Results for continuous variables that were not normally distributed are reported as the median (25th and 75th percentiles) and compared using nonparametric tests. The paired sample t-test was used for comparisons between groups before and after treatment. Cox regression models were used to measure the relative risk (RR) and 95% CI for each factor to discover how SV can increase after negative fluid balance. The correlation between RV and ∆VTI/T0VTI variables was analyzed using Pearson correlation analysis. Receiver operating characteristic (ROC) curves were used to determine the ability of the indices to predict LVOT VTI increase > 10% after negative fluid balance. The areas under the ROC curves (AUCs) were compared using DeLong’s test. The AUC, sensitivity, and specificity are expressed as values with 95% confidence intervals (CIs). A P value < 0.05 was considered to be statistically significant.

Results

Demographic and clinical characteristics of patients

During the study period, a total of 154 patients were admitted with CVP ≥ 8 mmHg. Of these, 65 did not meet the study criteria. In addition, nine patients were excluded due to poor TT image quality or incomplete image acquisition; six patients were excluded due to inconsistent judgments of the ultrasound results by the two physicians; and three patients were excluded due to new tachyarrhythmia during the trial. Thus, the final sample for analysis comprised 71 patients (33 males, 38 females)(Figure 2).

Of the final sample, 35 patients (49.3%) were in Group 1 (RV_D/LV_D ratio ≥ 0.6) and 36 patients (50.7%) were in Group 2 (RV_D/LV_D ratio༜0.6). Overall, 40 (56.3%) patients showed increased VTI after negative fluid balance. The demographical and clinical characteristics of all patients are shown in Table 1. In terms of hemodynamic parameters, patients in Group 1 had a higher CVP and GAP and lower ScV02 relative to Group 2 (all p < 0.05). No group differences were observed for HR, MAP, or lactate levels. Regarding the echo parameters, the RV_D/LV_D ratio, DIVC, ∆VTI,and ∆VTI /T0VTI were higher, while T0 VTI was lower, in Group 1 patients (all p < 0.05). There were no group differences in LVEF or TAPSE. Furthermore, there were no significant differences in demographic characteristics between the two groups.

Table 1

The demographic and clinical Characteristics of the Patients Included in This Study
Variable	All patients (N = 71)	Group 1(N = 35)	Group 2(N = 36)	P value
Gender(male/female)	71(33/38)	35(16/19)	36(17/19)	0.321
Age(year)	49 ± 16	47 ± 14	50 ± 15	0.334
APACHE II score(mean ± SD)	18 ± 8	19 ± 7	16 ± 6	0.478
Comorbidities(%)
Coronary artery disease	13	5	8	0.312
Hypertension	28	16	12	0.254
Diabetes mellitus	24	15	9	0.092
Choric renal failure	12	8	4	0.112
Choric liver failure	4	2	2	0.531
Stroke	8	3	5	0.546
Cancer	6	2	4	0.254
Hemodynamic parameters
Central venous pressure CVP(mmHg)	11.42 ± 2.27	12.74 ± 2.02	10.14 ± 1.70	< 0.001
Mean arterial blood pressure MAP(mmHg)	75.70 ± 8.724	75.23 ± 8.74	76.17 ± 7.81	0.635
Heart rate HR(bpm)	94.06 ± 15.86	96.43 ± 17.55	91.75 ± 153.88	0.216
GAP (mmHg)	5.42 ± 1.98	6.65 ± 1.66	4.23 ± 1.48	< 0.001
ScVO2%	68.44 ± 7.71	64.28 ± 6.10	72.49 ± 6.97	< 0.001
Arterial blood lactate level lac(mmol/l)	3.23 ± 0.79	3.41 ± 0.80	3.04 ± 0.74	0.050
Echo parameters
LVOT VTI	18.38 ± 2.72	16.75 ± 1.58	19.95 ± 2.67	< 0.001
Left ventricular eject fraction EF %	62.08 ± 5.04	61.51 ± 5.14	62.64 ± 4.94	0.351
DIVC (cm)	1.93 ± 0.28	2.11 ± 0.25	1.77 ± 0.20	< 0.001
TAPSE (cm)	2.16 ± 0.26	2.15 ± 0.28	2.18 ± 0.25	0.551
∆VTI	1.15 ± 1.45	1.97 ± 1.01	0.35 ± 1.38	< 0.001
∆VTI/T0VTI(%)	7.06 ± 8.09	11.89 ± 5.74	2.36 ± 7.28	< 0.001
∆VTI/T0VTI > 10%	40/71(56.3)	27/31	9/36(25)	< 0.001
RV_D/LV_D ratio	0.59 ± 0.10	0.67 ± 0.06	0.51 ± 0.05	< 0.001
RASS Score	-2.33 ± 1.16	-2.31 ± 1.22	-2.43 ± 1.17	0.674
Ventilation modes%
Non-invasive ventilation	13(18.3)	5(14.3)	6(16.7)	0.256
Invasive ventilation	58(81.7)	30(86.4)	30(83.3)	0.354
Pa02/Fi02(mmHg)	240.62 ± 46.19	213.37 ± 43.52	267.11 ± 31.01	< 0.001
T1 to T0 Time (minute)	50 ± 14	46 ± 14	53 ± 16	0.275
APACHE II Acute Physiology and Chronic Health Evaluation II scores, GAP Central venous-arterial carbon dioxide difference,ScV02 Central venous oxygen saturation༌DIVC Diameter of the inferior vena cava༌TPASE Tricuspid annular plane systolic excursion༌∆VTI Aortic velocity time integral(T1-T0)༌RV_D/LV_D ratio Right to left ventricular end-diastolic dimensions ratio༌RASS Score Richmond Agitation-Sedation Scale score.

Comparison of hemodynamic parameters at T0 and T1 between groups

As shown in Fig. 3, CVP, DIVC, and RV_D/LV_D ratio decreased significantly in both groups after negative fluid management (p < 0.05). None of the patients in our study experienced cardiac and/or tissue perfusion insufficiency. Cardiac output related parameters (LVOT VTI, GAP, ScV02) improved in Group 1 (p < 0.05), and the lactate level decreased in Group 2 ( p < 0.05). In addition, the P/F ratio increased significantly in both groups (p < 0.05).

Correlation between RV parameters and ∆VTI/T0VTI

Figure 4 presents the individual parameter values for RV and ∆VTI/T0VTI among all patients. CVP, RV_D/LV_D ratio, and DIVC were significantly correlated with ∆VTI/T0VTI (r = 0.64 (p < 0.05), 0.64(p < 0.053), and 0.59 (p < 0.05), respectively). By contrast, no relationship was observed between TAPSE and ∆VTI/T0VTI.

Risk factors for a LVOT VTI increase > 10% at T1

Cox regression analysis was used to examine possible risk factors for the outcomes of negative fluid management. Each of the hemodynamics variables was taken into account. The results revealed that CVP and RV_D/LV_D ratio were the most significant predictors (p < 0.05). The RRs of CVP and RV_D/LV_D ratio were 2.425 (95% CI, 1.458–4.003) and 8.588 (95% CI, 1.947–37.887), respectively. (Table 2)

Table 2

Multifactor Cox Logistic Regression Analysis for Possible Risk Factors
Variables	B	SE	Wald’s coefficient	OR	95% CI for OR	p value
					Lower Upper
CVP	0.886	0.260	11.648	2.425	1.458 4.033	0.001
RV_D/LV_D ratio	2.150	0.757	8.064	8.588	1.947 37.887	0.005
CVP central venous pressure,RV_D/LV_D ratio

Effect of risk parameters for predicting a LVOT VTI increase > 10% at T1

The AUC of CVP for predicting a LVOT VTI increase > 10% at T1 was 0.883 (95% CI 0.804–0.902) The best diagnostic threshold was 10.5 mmHg, which provided a sensitivity of 87.5% and a specificity of 77.4%. (Fig. 5)

The regression equation for all of the risk parameters is:

Logit (P) =-10.474 + CVP *0.886 + RV_D/LV_D ratio *2.854 (≥ 0.6 = 1,<0.6 = 0).

The AUC of CVP combined with RV_D/LV_D ratio for predicting a LVOT VTI increase > 10% at T1 was 0.926 (95% CI 0.866–0.96). The best diagnostic threshold was 0.3689, which provided a sensitivity of 92.5% and a specificity of 80.6%. (Fig. 5)

Discussion

In the steady state, venous return is equal to cardiac output [13]; thus, right ventricular function is essential for venous return[14, 15]. The challenge of fluid management is to find the ideal preload to avoid the negative effect of ventricular interdependence on LV function and cardiac output. The right half of the heart behaves very differently from the left. Tyberg et al. [11] measured pericardial pressure and right atrial pressure in patients with acute excessive fluid loading before cardiopulmonary bypass. They found that these two types of pressure increased at the same rate, while the right atrial transmural pressure was unchanged. Previous studies have reported no relationship between right transmural pressure and right ventricular end-diastolic volume and stroke volume[16-18]. The healthy human RV fills at or below its unstressed volume, such that RV end-diastolic volume changes occur without any changes in RV diastolic wall stretch. Presumably, conformational changes in RV shape rather than stretch allow such volume changes to occur without measurable changes in the transmural right atrial pressure. With increased volume loading of the RV, right ventricular end-diastolic pressure and SV both increased. The relation of SV to venous return has a plateau: once this plateau is reached, any further increases in filling pressure will not augment cardiac output[19]. As a result, when RV reaches the flat part of the pressure-volume curve, the left heart no longer determines cardiac output. If the RV further increases in size and the right ventricular end-diastolic pressure rapidly increases, this can cause leftward ventricular septal (VS) shift. VS shift can result in decreased SV, leading to a phenomenon colloquially termed “falling off the Starling curve”[14]^14141414[14][14][14].

The present study is a prospective study about the relationship between hemodynamic parameters during negative fluid management. The intervention was performed in a short period of time (39±17 minutes), while other factors affecting CVP were unchanged. Notably, 56.3% of our patients showed increased VTI after negative fluid balance, which is not exactly the same as the comment cognition. As the Starling curve does not have descending branches, it cannot explain the increase in SV after reducing the intravascular volume. Thus, we assume that patients experienced RV volume overload. A negative fluid balance can reduce RV volume, resulting in a rightward VS shift, an increase in left ventricular end-diastolic volume, and an increase in CO. However, it remains unclear if determining RV volume overload is key to therapy. In terms of the hemodynamic and echo parameters in our cohort, CVP, GAP, ScVO2, RV/LV diastolic area ratio, LVOT VTI, and DIVC differed significantly between the two groups. A high RV_D/LV_Dratio and CVP value were identified as risk factors for RV volume overload. Due to its geometrical complexity, assessment of RV volume is a very difficult task. Although quantitative validation is lacking, the correlation of RV linear dimensions with RV end-diastolic volumes appears to worsen with increased preload[20-22]. RV_D/LV_D ratio has been shown to be an indicator of RV size, and can thus provide reliable information about RV shape and size. A ratio ≥0.6, regardless of whether RV is within the normal reference limits, may relate to certain conditions such as RV volume overload[20]. In our study, we found that a R/V ratio ≥0.6 was a risk factor for VTI increase after negative fluid balance. Our results are similar to those of previous studies[23]. However, our measurement method is more clinically operable and repeatable. Wiesenack et al. measured RV volume in patients with mechanical ventilation to help guide fluid resuscitation. However, in patients with pulmonary embolism and chronic pulmonary hypertension, only RVEDA/LVEDA>1 indicates RV volume overload[24, 25]. When R/V ratio is applied clinically, it should be considered in combination with the patient’s underlying disease and ventricular septal morphology.

We also identified high CVP as a significant risk factor for RV volume overload. The gold standard for evaluating RV filling pressure is invasive monitoring using a centrally placed venous catheter[26]. CVP can be used as a surrogate of intravascular volume, and is often applied at the bedside to guide fluid administration in critically ill patients. Since the filling pressure and SV of the RV do not have a linear relationship, it has recently been acknowledged that CVP is ineffective for evaluating a patient’s fluid responsiveness[27-29]. While the absolute value of CVP alone cannot predict fluid responsiveness, it is necessary to understand that CVP is a marker of pressure and a regulating factor of venous return. Thus, an increase in CVP can be used as a clinical safety mechanism to avoid fluid overload and high RV filling pressure. We consider CVP to be a safety-related indicator rather than a cardiac preload indicator in clinical settings [30]. In the present study, we found that a high CVP may reflect that the RV volume load has exceeded the normal range; failure to appreciate this limit may result in a VS rightward shift and reduced SV. It has been proposed that, once CVP has exceeded 10–14 mm Hg in non-intubated patients with acute RV myocardial infarction, further volume loading is detrimental. A mean CVP > 14 mmHg is almost always associated with a reduced RVSWI[31, 32]. Garcia-Montilla et al. [33] reported that the optimal RV filling pressure in patients with acute respiratory distress syndrome (ARDS) is 13±2 mm Hg. Furthermore, they demonstrated that once CVP reaches 15 mmHg, further increments in filling pressure did not increase RVSPG; rather, due to overstretching of myocardial fibers, RVSPG decreased. These values may be considered the optimal RV filling pressure in patients with acute RV infarction or ARDS. Our results suggest that CVP > 10.5 mmHg can predict whether VTI increases after a negative fluid balance in patients without underlying cardiac disease with high sensitivity but low specificity. When we combined the two risk factors, the predictive ability improved.

Notably, none of our patients experienced CO and tissue perfusion insufficiency after negative fluid management. However, the oxygenation index improved in both groups—especially Group 1. It is well known that fluid overload may lead to pulmonary edema and failure of weaning from mechanical ventilation. A milestone study by Wiederman et al.[34] showed that a conservative fluid management protocol aimed to lower CVP resulted in a major reduction in net fluid balance, improving lung function and shortening the duration of mechanical ventilation. Clinicians should be alert to high CVP as it may indicate increased RV tension and leftward VS, potentially leading to increased left ventricular filling pressure and pulmonary edema. Accurate fluid therapy for patients with high CVP will not lead to hypoperfusion, but will be beneficial for other organs.

Lastly, this study is subject to several limitations. Firstly, our study included a convenience sample of participants from a single institution, and may have thus systematically excluded some participant groups. As a pragmatic study, this population had similar characteristics to previous clinical audits using the same inclusion criteria. Nevertheless, additional clinical research is needed to confirm our findings. Secondly, although we excluded patients with any pre-existing heart disease based on clinical records or echocardiography, some patients might have developed subclinical heart disease after their last echocardiography. Thirdly, the determination of RV volume load may be imperfect. In our experience, estimation of RV/LV size ratio is fairly accurate, even when assessed by trainees relative to an experienced clinicians.

References

Acheampong A, Vincent JL: A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015, 19:251.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative G: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345(19):1368-1377.
Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA: Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011, 39(2):259-265.
Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT: Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? JAMA 2016, 316(12):1298-1309.
Mitchell JR, Whitelaw WA, Sas R, Smith ER, Tyberg JV, Belenkie I: RV filling modulates LV function by direct ventricular interaction during mechanical ventilation. Am J Physiol Heart Circ Physiol 2005, 289(2):H549-557.
Atherton JJ, Moore TD, Lele SS, Thomson HL, Galbraith AJ, Belenkie I, Tyberg JV, Frenneaux MP: Diastolic ventricular interaction in chronic heart failure. Lancet 1997, 349(9067):1720-1724.
Martyn JA, Snider MT, Farago LF, Burke JF: Thermodilution right ventricular volume: a novel and better predictor of volume replacement in acute thermal injury. J Trauma 1981, 21(8):619-626.
Krishnan S, Schmidt GA: Acute right ventricular dysfunction: real-time management with echocardiography. Chest 2015, 147(3):835-846.
Puchalski MD, Williams RV, Askovich B, Minich LL, Mart C, Tani LY: Assessment of right ventricular size and function: echo versus magnetic resonance imaging. Congenit Heart Dis 2007, 2(1):27-31.
Dandel M, Hetzer R: Evaluation of the right ventricle by echocardiography: particularities and major challenges. Expert Rev Cardiovasc Ther 2018, 16(4):259-275.
Tyberg JV, Taichman GC, Smith ER, Douglas NW, Smiseth OA, Keon WJ: The relationship between pericardial pressure and right atrial pressure: an intraoperative study. Circulation 1986, 73(3):428-432.
Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB: Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010, 23(7):685-713; quiz 786-688.
Pinsky MR: Instantaneous venous return curves in an intact canine preparation. J Appl Physiol Respir Environ Exerc Physiol 1984, 56(3):765-771.
Pinsky MR: The right ventricle: interaction with the pulmonary circulation. Crit Care 2016, 20:266.
Takata M, Harasawa Y, Beloucif S, Robotham JL: Coupled vs. uncoupled pericardial constraint: effects on cardiac chamber interactions. J Appl Physiol (1985) 1997, 83(6):1799-1813.
Pinsky MR: My paper 20 years later: Effect of positive end-expiratory pressure on right ventricular function in humans. Intensive Care Med 2014, 40(7):935-941.
Reuse C, Vincent JL, Pinsky MR: Measurements of right ventricular volumes during fluid challenge. Chest 1990, 98(6):1450-1454.
Dhainaut JF, Pinsky MR, Nouria S, Slomka F, Brunet F: Right ventricular function in human sepsis: a thermodilution study. Chest 1997, 112(4):1043-1049.
Funk DJ, Jacobsohn E, Kumar A: The role of venous return in critical illness and shock-part I: physiology. Crit Care Med 2013, 41(1):255-262.
Lai WW, Gauvreau K, Rivera ES, Saleeb S, Powell AJ, Geva T: Accuracy of guideline recommendations for two-dimensional quantification of the right ventricle by echocardiography. Int J Cardiovasc Imaging 2008, 24(7):691-698.
Haddad F, Hunt SA, Rosenthal DN, Murphy DJ: Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 2008, 117(11):1436-1448.
Meyer G, Vieillard-Baron A, Planquette B: Recent advances in the management of pulmonary embolism: focus on the critically ill patients. Ann Intensive Care 2016, 6(1):19.
Wiesenack C, Fiegl C, Keyser A, Laule S, Prasser C, Keyl C: Continuously assessed right ventricular end-diastolic volume as a marker of cardiac preload and fluid responsiveness in mechanically ventilated cardiac surgical patients. Crit Care 2005, 9(3):R226-233.
Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H: Hemodynamic effects of fluid loading in acute massive pulmonary embolism. Crit Care Med 1999, 27(3):540-544.
Fremont B, Pacouret G, Jacobi D, Puglisi R, Charbonnier B, de Labriolle A: Prognostic value of echocardiographic right/left ventricular end-diastolic diameter ratio in patients with acute pulmonary embolism: results from a monocenter registry of 1,416 patients. Chest 2008, 133(2):358-362.
Beigel R, Cercek B, Luo H, Siegel RJ: Noninvasive evaluation of right atrial pressure. J Am Soc Echocardiogr 2013, 26(9):1033-1042.
Eskesen TG, Wetterslev M, Perner A: Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness. Intensive Care Med 2016, 42(3):324-332.
Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S et al: Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med 2015, 41(9):1529-1537.
Osman D, Ridel C, Ray P, Monnet X, Anguel N, Richard C, Teboul JL: Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007, 35(1):64-68.
Sondergaard S, Parkin G, Aneman A: Central venous pressure: we need to bring clinical use into physiological context. Acta Anaesthesiol Scand 2015, 59(5):552-560.
Greyson CR: Pathophysiology of right ventricular failure. Crit Care Med 2008, 36(1 Suppl):S57-65.
Berisha S, Kastrati A, Goda A, Popa Y: Optimal value of filling pressure in the right side of the heart in acute right ventricular infarction. Br Heart J 1990, 63(2):98-102.
Garcia-Montilla R, Imam F, Miao M, Stinson K, Khan A, Heitner S: Optimal right heart filling pressure in acute respiratory distress syndrome determined by strain echocardiography. Echocardiography 2017, 34(6):851-861.
National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF, Jr., Hite RD et al: Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006, 354(24):2564-2575.