Multivariable haemodynamic approach to predict the fluid challenge response: A multicentre cohort study.

BACKGROUND: Beat-to-beat stroke volume (SV) results from the interplay between left ventricular function and arterial load. Fluid challenge induces time-dependent responses in cardiac performance and peripheral vascular and capillary characteristics. OBJECTIVE: To assess whether analysis of the determinants of the haemodynamic response during fluid challenge can predict the final response at 10 and 30 min. DESIGN: Observational multicentric cohort study. SETTING: Three university ICUs. PATIENTS: 85 ICU patients with acute circulatory failure diagnosed within the first 48 h of admission. INTERVENTION(S): The fluid challenge consisted of 500 ml of Ringer's solution infused over 10 min. A SV index increase at least 10% indicated fluid responsiveness. MAIN OUTCOME MEASURES: The SV, pulse pressure variation (PPV), arterial elastance, the systolic-dicrotic pressure difference (SAP-Pdic) and cardiac cycle efficiency (CCE) were measured at baseline, 1, 2, 3, 4, 5, 10, 15 and 30 min after the start of the fluid challenge. All haemodynamic data were submitted to a univariable logistic regression model and a multivariable analysis was then performed using the significant variables given by univariable analysis. RESULTS: The multivariable model including baseline PPV, and the changes of arterial elastance at 1 min and of the CCE and SAP-Pdic at 5 min when compared with their baseline values, correctly classified 80.5% of responders and 90.7% of nonresponders at 10 min. For the response 30 min after starting the fluid challenge, the model, including the changes of PPV, CCE, SAP-Pdic at 5 min and of arterial elastance at 10 min compared with their baseline values, correctly identified 93.3% of responders and 91.4% of nonresponders. CONCLUSION: In a selection of mixed ICU patients, a statistical model based on a multivariable analysis of the changes of PPV, CCE, arterial elastance and SAP-Pdic, with respect to baseline values, reliably predicts both the early and the late response to a standardised fluid challenge. TRIAL REGISTRATION: ACTRN12617000076370.

Systolic-dicrotic notch pressure difference can identify tachycardic patients with septic shock at risk of cardiovascular decompensation following pharmacological heart rate reduction.

BACKGROUND: During sepsis, heart rate (HR) reduction could be a therapeutic target, but identification of responders (non-compensatory tachycardia) and non-responders (compensatory for 'fixed' stroke volume [SV]) is challenging. We tested the ability of the difference between systolic and dicrotic pressure (SDPdifference), which reflects the coupling between myocardial contractility and a given afterload, in discriminating the origin of tachycardia. METHODS: In this post hoc analysis of 45 patients with septic shock with persistent tachycardia, we characterised features of haemodynamic response focusing on SDPdifference, classifying patients according to variations in arterial dP/dtmax after 4 h of esmolol administration to maintain HR <95 beats min-1. A cut-off value of 0.9 mm Hg ms-1 was used for group allocation. RESULTS: After reducing HR, arterial dP/dtmax remained above the cut-off in 23 patients, whereas it decreased below the cut-off in 22 patients (from 0.99 [0.37] to 0.63 [0.16] mm Hg ms-1; mean [SD], P<0.001). At baseline, patients with decreased dP/dtmax after esmolol had lower SDPdifference than those with higher dP/dtmax (40 [19] vs 53 [16] mm Hg, respectively; P=0.01). The SDPdifference remained unchanged after esmolol in the higher dP/dtmax group (49 [16] mm Hg), whereas it decreased significantly in patients with lower dP/dtmax (29 [11] mm Hg; P<0.001). In the latter, the HR reduction resulted in a significant cardiac output reduction with unchanged SV, whereas in patients with higher dP/dtmax SV increased (from 48 [12] to 67 [14] ml; P<0.001) with maintained cardiac output. CONCLUSIONS: A decrease in SDPdifference could discriminate between compensatory and non-compensatory tachycardia, revealing a covert loss of myocardial contractility not detected by conventional echocardiographic parameters and deteriorating after HR reduction with esmolol. CLINICAL TRIAL REGISTRATION: NCT02188888.

Cardiac cycle efficiency and dicrotic pressure variations: new parameters for fluid therapy: An observational study.

BACKGROUND: During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank-Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. OBJECTIVE: To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP - Pdic and MAP - Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. DESIGN: Observational study. SETTING: Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. PATIENTS: Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. INTERVENTIONS: A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. MAIN OUTCOME MEASURES AND ANALYSIS: The changes in CCE, arterial elastance, SAP - Pdic and MAP - Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. RESULTS: At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP - Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. CONCLUSION: In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP - Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. TRIAL REGISTRATION: ACTRN12616001479493.

Accuracy of invasive arterial pressure monitoring in cardiovascular patients: an observational study.

INTRODUCTION: Critically ill patients and patients undergoing high-risk and major surgery, are instrumented with intra-arterial catheters and invasive blood pressure is considered the "gold standard" for arterial pressure monitoring. Nonetheless, artifacts due to inappropriate dynamic response of the fluid-filled monitoring systems may lead to clinically relevant differences between actual and displayed pressure values. We sought to analyze the incidence and causes of resonance/underdamping phenomena in patients undergoing major vascular and cardiac surgery. METHODS: Arterial pressures were measured invasively and, according to the fast-flush Gardner's test, each patient was attributed to one of two groups depending on the presence (R-group) or absence (NR-group) of resonance/underdamping. Invasive pressure values were then compared with the non-invasive ones. RESULTS: A total of 11,610 pulses and 1,200 non-invasive blood pressure measurements were analyzed in 300 patients. Ninety-two out of 300 (30.7%) underdamping/resonance arterial signals were found. In these cases (R-group) systolic invasive blood pressure (IBP) average overestimation of non-invasive blood pressure (NIBP) was 28.5 (15.9) mmHg (P <0.0001) while in the NR-group the overestimation was 4.1(5.3) mmHg (P < 0.0001). The mean IBP-NIBP difference in diastolic pressure in the R-group was -2.2 (10.6) mmHg and, in the NR-group -1.1 (5.8) mmHg. The mean arterial pressure difference was 7.4 (11.2) mmHg in the R-group and 2.3 (6.4) mmHg in the NR-group. A multivariate logistic regression identified five parameters independently associated with underdamping/resonance: polydistrectual arteriopathy (P = 0.0023; OR = 2.82), history of arterial hypertension (P = 0.0214; OR = 2.09), chronic obstructive pulmonary disease (P = 0.198; OR = 2.61), arterial catheter diameter (20 vs. 18 gauge) (P < 0.0001; OR = 0.35) and sedation (P = 0.0131; OR = 0.5). The ROC curve for the maximal pressure-time ratio, showed an optimum selected cut-off point of 1.67 mmHg/msec with a specificity of 97% (95% CI: 95.13 to 99.47%) and a sensitivity of 77% (95% CI: 67.25 to 85.28%) and an area under the ROC curve by extended trapezoidal rule of 0.88. CONCLUSION: Physicians should be aware of the possibility that IBP can be inaccurate in a consistent number of patients due to underdamping/resonance phenomena. NIBP measurement may help to confirm/exclude the presence of this artifact avoiding inappropriate treatments.

FloTrac/Vigileo(TM) (third generation) and MostCare(®)/PRAM versus echocardiography for cardiac output estimation in vascular surgery.

OBJECTIVE: To compare the FloTrac/Vigileo(TM) cardiac output (COFT/V) and the MostCare(®)/PRAM cardiac output (COMC/P) versus transthoracic echocardiographic cardiac output estimation (reference method; CO(ECHO)). DESIGN: Prospective observational study. SETTING: Single center, Cardio-Thoracic and Vascular Surgery/Intensive Care Unit. PARTICIPANTS: Patients undergoing elective vascular surgery. INTERVENTIONS: Cardiac output measurement with two pulse contour methods: the FloTrac/Vigileo(TM) and the MostCare(®)/PRAM before (T1) and after (T2) fluid loading versus echocardiography (reference method). MEASUREMENTS AND MAIN RESULTS: One hundred fifty-six CO measurements were performed in 26 patients. The data showed poor agreement between CO(ECHO) and CO(FT/V): r(2) = 0.29 (T1) and 0.27 (T2); bias -0.37 (T1) and -0.40 (T2) L/min; limits of agreement from -3.10 to 2.42 (T1) and from -3.0 to 2.2 (T2) L/min. The percentage error was 51.7% (T1) and 49.3% (T2). Conversely, COMC/P resulted in agreement with echocardiography: r(2) = 0.76 (T1) and 0.80 (T2); bias -0.01 (T1) and -0.06 (T2) L/min; limits of agreement from -1.13 to 1.11 (T1) and from -0.90 to 0.80 (T2) L/min, with a PE of 22.4% (T1) and of 17.0% (T2). CONCLUSIONS: In patients undergoing vascular surgery, the FloTrac/Vigileo(TM) did not demonstrate that it was a reliable system for CO monitoring when compared with echocardiography-derived CO. However, MostCare(®)/PRAM was shown to estimate CO with a good level of agreement with echocardiographic measures.

Levosimendan produces an additional clinical and hemodynamic benefit in patients with decompensated heart failure successfully submitted to a fluid removal treatment.

A pivotal role in treating decompensated heart failure (HF) is played by inotropes and calcium sensitizers such as levosimendan. In this study, the authors evaluated whether levosimendan could determine further clinical and hemodynamic benefits in 31 HF patients (New York Heart Association [NYHA] class III or IV), after successful treatment with diuretics (n=15) or ultrafiltration (n=16). Systolic, diastolic, dicrotic, and mean arterial pressures; systemic vascular resistance (SVR); some classic hemodynamic variables (cardiac output [CO], stroke volume [SV], dP/dt(max) ); and indices of cardiovascular system performance (cardiac cycle efficiency [CCE], cardiac power output) have been assessed by the pressure recording analytical method (PRAM), a minimally invasive monitoring system, before levosimendan infusion, at the end of treatment (EoT), and 36 hours after EoT (post-36). A significant increase in CCE, CO, SV, and dP/dt(max) and a significant decrease in diastolic and dicrotic arterial pressures and in SVR have been observed at EoT and at post-36. After the addition of levosimendan, a further reduction in signs and symptoms of HF and NYHA class was observed. Five patients showed an opposite trend of several hemodynamic parameters without any significant clinical improvement (nonresponders). In conclusion, most HF patients treated with diuretics or ultrafiltration receive additional clinical and hemodynamic benefits from levosimendan. The characterization of nonresponders could help in optimizing its use.

Cardiac efficiency improvement after slow continuous ultrafiltration is assessed by beat-to-beat minimally invasive monitoring in congestive heart failure patients: a preliminary report.

BACKGROUND: We have evaluate the effect of slow continuous ultrafiltration (SCUF) on cardiac output (CO) and other hemodynamic parameters related to the overall performance of the cardiovascular system in patients with congestive heart failure (CHF). Minimally invasive hemodynamic monitoring was performed via the radial artery using a pressure recording analytical method (PRAM) during SCUF treatment. PATIENTS AND METHODS: Using PRAM, hemodynamic changes were assessed in 15 CHF patients (New York Heart Association (NYHA) class III-IV) treated with fluid overload removal by ultrafiltration. We analyzed the clinical and hemodynamic data recorded from 6 h before to 36 h after SCUF treatment. RESULTS: Fluid removal was associated with clinical improvements, reductions in weight (7.4%, p < 0.01), edema and dyspnea, increased response to diuretics, and reductions in NYHA class (3.5 +/- 0.52 to 2.4 +/- 0.63, p < 0.01) and plasma pro-B-type natriuretic peptide (BNP) levels (21,810 +/- 13,016 to 8,581 +/- 5,549 pg/ml, p < 0.05). Clinical improvement was associated with significant variations in stroke volume (+17%, p < 0.05), CO (+19%, p < 0.05), cardiac power output (+19%, p < 0.05), dP/dt(max) (+49%, p < 0.01), cardiac cycle efficiency (CCE; +0.44 units, p < 0.01), systemic vascular resistances (SVR; -12%, p < 0.05) and dicrotic pressure (-10%, p < 0.05) with respect to their baseline values. No significant variations in heart rate, and systolic and mean blood pressure were observed. Pro-BNP levels were found to correlate positively with both SVR (r = 0.96, p = 0.002) and NYHA class (r = 0.96, p = 0.037) and negatively with dP/dt(max) (r = -0.83, p = 0.039), CCE (r = -0.93, p = 0.011) and CO (r = -0.94, p = 0.014). CONCLUSIONS: In CHF patients, ultrafiltration improves not only CO, as previously reported, but also contractile cardiac efficiency and performance. The PRAM system, a minimally invasive method, was able to record hemodynamic changes during SCUF treatment.

Assessment of cardiac output in children: a comparison between the pressure recording analytical method and Doppler echocardiography.

OBJECTIVE: To assess cardiac output in pediatric patients with the pressure recording analytical method (PRAM) and the Doppler echocardiography method. PRAM derives cardiac output from beat-by-beat analysis of the arterial pressure profile (systolic and diastolic phase) in the time domain. DESIGN: A prospective observational study. SETTING: Pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Forty-eight patients between the ages of 1 month and 18 yrs. INTERVENTIONS: Femoral or radial artery catheterization and mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Cardiac output was simultaneously estimated by Doppler echocardiography and PRAM. Cardiac output values obtained by Doppler echocardiography (2.7 +/- 1.6 L/min, range 0.92-8.20) were significantly correlated with those estimated by PRAM (2.6 +/- 1.7 L/min, range 0.89-7.48; r2 = .99, p < .01). The mean difference between the two estimates was 0.12 +/- 0.27 L x min(-1) (95% confidence interval, -0.54 to 0.77 L x min(-1)). CONCLUSIONS: In the range of ages evaluated, PRAM provides reliable estimates of cardiac output when compared with noninvasive techniques.

Systemic arterial waveform analysis and assessment of blood flow during extracorporeal circulation.

BACKGROUND: The pressure recording analytical method (PRAM) is a method for real-time beat-to-beat quantification of peripheral blood flow based on the analysis of arterial waveform morphology. Since PRAM can be implemented in any conditions of flow, whether physiological or artificial, we assessed its accuracy in patients undergoing cardiac surgery during extracorporeal circulation (ECC), using the roller-pump device as the reference gold standard. METHODS: We prospectively studied 32 patients undergoing elective coronary surgery. Flow values obtained by PRAM from the radial artery were compared with simultaneous values by thermodilution in physiological conditions of flow and with the roller-pump device readings during ECC. RESULTS: Before and after ECC, the overall estimates of flow measured by PRAM closely agreed with thermodilution (mean difference 0.07 +/- 0.40 L/min). During ECC, PRAM estimates of flow also closely correlated with simultaneous pump readings (mean difference 0.11 +/- 0.33 L/min). At time of weaning from ECC, two patterns of hemodynamic adaptation were documented by PRAM following resumption of cardiac contraction: in most patients (n =26; 80%), cardiac output (CO) was stable (reduction < or = 10% compared to the steady ECC phase); six patients (20%) showed a fall in CO exceeding 10% and up to 38%. CONCLUSIONS: PRAM provided accurate, continuous quantification of peripheral blood flow during each phase of cardiac surgery, including ECC, and allowed early recognition of patients with low CO during weaning from the pump.

The incidence and timing of major arrhythmias following successful primary angioplasty for acute myocardial infarction.

BACKGROUND: The potential benefits of direct percutaneous transluminal coronary angioplasty (PTCA) on malignant arrhythmias in the hospital phase of acute myocardial infarction have not yet been established. METHODS: We prospectively investigated the incidence and timing of major arrhythmias occurring during direct PTCA and within 24 hours of mechanical reperfusion in 90 consecutive patients with acute myocardial infarction undergoing successful direct PTCA within 12 hours of symptom onset. RESULTS: Ventricular fibrillation and complete atrioventricular block occurred exclusively during direct PTCA and both resolved in the catheterization laboratory. Holter monitoring showed that ventricular tachyarrhythmias, such as runs of more than 3 extrasystoles, were detectable only during the first 8 hours after direct PTCA. CONCLUSIONS: In our group of patients undergoing successful direct PTCA, no in-hospital life-threatening arrhythmias occurred after this procedure.

Beat-to-beat analysis of pressure wave morphology for pre-symptomatic detection of orthostatic intolerance during head-up tilt.

OBJECTIVES: The aim of this study was to noninvasively define the hemodynamic profile characterizing the early response to tilting. BACKGROUND: The mechanisms causing orthostatic intolerance have not been fully elucidated. Usually, patients undergoing tilt test are studied in a time-consuming way. Moreover, the test can cause discomfort to the patient and even be potentially hazardous. METHODS: Nineteen orthostatic intolerant patients (OIP), compared with 22 healthy subjects (HS), performed head-up tilt test while their arterial pressure waveform was noninvasively recorded. We elaborated data using the Pressure Recording Analytical Method to obtain hemodynamic parameters, then analyzing the variables by discriminant analysis. RESULTS: Compared with HS, OIP showed lower stroke volume index (SVI) values even in baseline conditions associated with higher values of systemic vascular resistance (SVR) and heart rate (HR). From the third minute of the tilted position and until symptoms appeared, patients exhibited lower values of blood pressure (BP) and SVI and higher HR values but no difference in SVR. At termination, patients showed a further significant reduction in BP and SVI and a persistent increase in HR. CONCLUSIONS: This investigation underlines: 1) the possibility of beat-to-beat monitoring of hemodynamic changes during tilting; 2) the cardiovascular profile of OIP at rest, characterized by lower SVI and higher SVR and HR; 3) the maladaptive response to postural challenge of OIP mainly identifiable in impaired vascular regulation; and 4) the possibility of detecting parameters that enable prompt identification of the positive response to tiltingin these patients, thus guiding the duration of the test.

Baroreflex function in vasodepressive syncope: detection of early impairment.

BACKGROUND: Defective baroreflex function has been suggested as a potential mechanism accounting for the development of syncopal episodes. The present study was therefore aimed at assessing the non-invasive, indirect hemodynamic profile and baroreflex function by means of tilting, which is a natural stimulation crucial to physiological baroreflex activity, in syncopal patients and healthy controls. MATERIAL/METHODS: Seventeen consecutive patients with a positive response to head-up tilting and fourteen healthy subjects as controls underwent continuous and non-invasive beat-to-beat heart rate and arterial pressure measurements in order to evaluate systolic, diastolic, and dicrotic pressures, as well as heart rate. Baroreflex function was calculated as the slope of the linear regression line relating systolic arterial pressure to RR interval changes during upward and downward phases of tilting, respectively. RESULTS: When compared to healthy subjects, vasodepressive patients showed a significantly weaker correlation between systolic pressure and RR interval changes both in upward tilting, (r = 0.68 vs r = 0.91, p<0.05) and downward tilting (r = 0.48 vs r = 0.93, p<0.01). CONCLUSIONS: Our results show that an impairment in baroreflex-mediated adjustment to postural challenge can be detected in syncopal patients also during upward tilting, that is, in the early phase of the test. Moreover, our investigation emphases the utility of a noninvasive, complete hemodynamic evaluation of the early phase of tilting in order to detect peculiar behaviours of pulse wave contour and related parameters.

Assessment of cardiac output from systemic arterial pressure in humans.

OBJECTIVE: To evaluate the reliability, by comparison with established techniques, of a new method to assess cardiac output, called pressure recording analytical method (PRAM), deriving from the analysis of the arterial pressure profile in the time domain the arterial-pressure-blood flow relationship. DESIGN: Criterion standard. SETTING: Hemodynamics laboratory at an university medical center. PATIENTS: Twenty-two hemodynamically stable cardiac patients scheduled for diagnostic right and left heart catheterization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac index was simultaneously estimated by direct-oxygen Fick method, thermodilution, and PRAM applied to pressure signals recorded either invasively from an aortic catheter (PRAMa) or noninvasively at the finger (PRAMf) by photoplethysmography. Cardiac index values obtained by established techniques were significantly correlated with those estimated by PRAM: Fick method vs. PRAMa, r(2) =.88, vs. PRAMf, r(2) =.94; thermodilution vs. PRAMa, r(2) =.77, vs. PRAMf, r(2) =.77. The Bland-Altman analysis showed agreement between the Fick method and PRAM, with all data points comprised within the limits of agreement (+/-2SD) (mean difference +/- SD: -0.012 +/- 0.187 L x min(-1) x m(-2) for PRAMa; 0.024 +/- 0.167 L x min(-1) x m(-2) for PRAMf). Agreement was also found between thermodilution and PRAM, with all but one data point lying within the limits of agreement (mean difference +/- SD: -0.154 +/- 0.348 L x min(-1) x m(-2) for PRAMa; -0.108 +/- 0.348 L x min(-1) x m(-2) for PRAMf). CONCLUSIONS: In the range evaluated (cardiac index from 1.65 to 3.91 L x min(-1) x m(-2) by the Fick method), PRAM provides reliable invasive and noninvasive estimates of cardiac output in hemodynamically stable cardiac patients. PRAM may prove clinically useful for the beat-to-beat monitoring of cardiac output.

Continuous recording of dicrotic and pulse pressures during head-up tilting test: the vasodepressive profile. Preliminary data.

BACKGROUND: The aim of this study was to assess whether a non-invasive automatic evaluation of the pulse wave characteristics could provide clinical clues when monitoring the hemodynamic adjustments to head-up tilting. METHODS: A continuous assessment of the peripheral pulse wave characteristics (systolic, diastolic, dicrotic and pulse pressures) in 8 control subjects with a negative response to head-up tilting (60 degrees for 45 min) compared to 13 syncopal patients with a vasodepressive one was performed. RESULTS: Controls exhibited, when up-tilted, an increase in blood pressure as well as in the dicrotic and pulse pressures and no changes in heart rate. On the contrary, syncopal patients showed a progressive increase in heart rate associated with a progressive decrease in dicrotic pressure and a trend towards lower values of pulse pressure, but no changes in systolic pressure. Thereafter and until the pre-syncopal symptoms supervened, the systolic, diastolic and dicrotic pressures progressively declined. A decrease in dicrotic pressure mainly characterized the early vasodepressive response while its increase identified the negative one. CONCLUSIONS: Our data, even though preliminary, strongly suggest that automatic hemodynamic evaluation is to be used in the clinical setting as a monitor of the sudden changes in blood pressure induced by head-up tilting. Furthermore, the dicrotic and pulse pressures, even those measured during the early phases of the test, should be considered as non-invasive parameters characterizing the vasodepressive response to head-up tilting.