The study was performed at the 12-bed medical intensive care unit (ICU) of the University Hospital Zurich, Switzerland. Approval was given by our Institutional Review Board. Due to the retrospective nature of the analysis, the need for informed consent was waived. Twenty-one patients (15 males and 6 females) with circulatory failure monitored with a PAC were included in the study. Treatment was directed by the clinicians in charge of the patients. In 17 patients (81%), PAC was inserted within 1 day after ICU admission. After initial hemodynamic stabilisation but before removal of the PAC, the arterial line was switched to a PiCCO catheter in order to have less invasive continuous monitoring of CO for vasopressor weaning and fluid management. This provided a unique opportunity of simultaneous monitoring with the two methods during a 24-hour period. During this period, the dosage of vasoactive drugs was progressively decreased and volume was substituted or removed according to the clinical treatment strategy. Simultaneous recordings started 2 days (interquartile range [IQR] 1 to 4 days) after ICU admission. In each patient, four consecutive measurements were performed before PAC removal. Median (IQR) time intervals from baseline to the second and third measurements were 5 (4 to 8) and 13 (9 to 16) hours, respectively. All four measurements were realised after 19 (14 to 22) hours. A total of 84 simultaneous hemodynamic measurements were recorded and finally analysed.

Severe sepsis was defined according to the published guidelines as systemic inflammatory response syndrome with infection associated with organ dysfunction 23. AHF was diagnosed in the presence of an underlying heart disease and congestive heart failure, pulmonary edema, or cardiogenic shock 6. Diagnosis of AHF was based on clinical signs of congestion (dyspnea, orthopnea, rales, or elevated jugular venous pressure), low CO with organ hypoperfusion, and bilateral alveolar consolidations on chest x-ray. Echocardiography and coronary angiography were performed only when clinically indicated. The severity of illness was described by the Simplified Acute Physiology Score (SAPS II) as calculated with the worst values within 24 hours following ICU admission 24.

AHF and severe sepsis or septic shock were diagnosed in 12 and 9 patients, respectively. Baseline characteristics on ICU admission are shown in Table 1. Coronary heart disease was present in 7 patients with AHF. Other underlying heart diseases included dilatative cardiomyopathy (n = 2), non-compaction cardiomyopathy (n = 1), valvular heart disease (n = 1), and congenital heart disease (n = 1). Cardiac imaging by echocardiography or coronary angiography or both was available in all heart failure patients except in two with known ischemic heart disease. The septic patients suffered from proven bacterial infection, namely pneumonia (n = 6), abdominal infection (n = 1), urogenital tract infection (n = 1), and puerperal sepsis (n = 1). Twelve patients (57%) required norepinephrine (0.1 to 0.3 μg/kg per minute), 13 patients (62%) needed inotropic support with dobutamine (1.5 to 6 μg/kg per minute), milrinone, or levosimendan, and 6 patients (29%) received intravenous vasodilatators such as nitroglycerin or nesiritide. Furthermore, 16 patients (76%) were mechanically ventilated, and 11 patients (52%) had renal replacement therapy by continuous veno-venous hemofiltration.

A continuous CO thermodilution PAC (model VIP 139F75; Edwards Lifesciences LLC, Irvine, CA, USA) was inserted via a central vein into the right pulmonary artery. Correct placement of the catheter was checked by appropriate pressure traces and fluoroscopy. The PAC was used for measurements of pulmonary artery pressure, PAOP, and cardiac index. Special care was taken to define the zero reference at midchest level and to perform measurements at end-expiration. Continuous assessment of CO was measured using the modified thermodilution technique provided by the PAC manufacturer and described elsewhere 2526.

A thermister-tipped arterial PiCCO catheter (Pulsiocath 5F, 20 cm, PV2015L20; Pulsion Medical Systems AG, Munich, Germany) was placed in the descending aorta and connected to a bedside PiCCO plus monitor. Cardiac index and volumetric variables were measured with the single-indicator transpulmonary thermodilution technique. The PiCCO values were obtained by repeated injections of 15- or 20-mL boluses of ice-cold normal saline via a central line. The mean value of three consecutive measurements was used for analysis. If the difference between the three obtained values for cardiac index was greater than 10%, two additional measurements were performed subsequently. Finally, the mean of all consecutive measurements was used.

By means of the thermodilution curve, the PiCCO calculates CO by the modified Stewart-Hamilton equation, the mean transit time (MTt), and the exponential downslope time (DSt) of the curve. The product of CO times MTt gives the intrathoracic thermal volume (ITTV) 1227. The product of CO times the DSt gives the pulmonary thermal volume (PTV) 122829. The difference between ITTV and PTV is called global end-diastolic volume (GEDV), or GEDVI if indexed for the body surface area.

Stroke volume (SV) is calculated by dividing CO by heart rate. A 'global' ejection fraction (GEF) can be obtained by dividing SV by a quarter of GEDV. Similarly, dividing CO by the preload parameter GEDV gives an indicator of cardiac systolic function, the so-called CFI. Both GEF and CFI may provide information on left ventricular systolic function 30. In patients with shock and multi-organ failure, GEF and CFI correlated closely with left ventricular fractional area of change using echocardiography 30.

The PiCCO method and definitions of intrathoracic blood volume and EVLW are described in more detail elsewhere 31. For this study, EVLW was indexed to predicted body weight (ELWI), as proposed by Phillips and colleagues 16.

The ratio of EVLW to pulmonary blood volume is used as an index of pulmonary vascular permeability (PVPI). Additionally, we calculated the ratio of EVLW indexed for body weight to GEDVI (that is, ELWI/GEDVI × 10²) as another index of pulmonary vascular permeability 13.

In addition to mean arterial pressure (MAP), heart rate, continuous CO, and right atrial pressure, the following hemodynamic parameters were simultaneously recorded four times in each patient: cardiac index by both methods, mixed venous oxygen saturation (SmvO₂), left ventricular stroke work index (LVSWI), PAOP, GEDVI, CFI, GEF, ELWI, and PVPI. For each recording, all variables were determined within 10 minutes. LVSWI was calculated by the formula SVI × (MAP – PAOP) × 0.0136, where SVI denotes SV index (SV divided by body surface area). For comparison purposes, we also calculated cardiac power (CP) using the formula CP = MAP × CO/451. The CP has been described as a valuable marker of outcome in patients with cardiogenic shock 323334. Definitions are provided in Table 2.

Clinical data were collected from the patients' charts, anonymised, and entered into a computerised database. Medians, 25th–75th percentiles (IQR), or percentages were calculated for the overall sample and subgroups. Comparisons between groups were made with the use of the Mann-Whitney U test or the Fisher exact test, as appropriate. Repeated measures within groups were compared with a Wilcoxon signed rank sum test. Including all consecutive hemodynamic measurements per patient, correlations between data pairs were established using linear regression analysis and are expressed as the square of Pearson's correlation coefficients (r²). To investigate the relationship between the cardiac index measured by PAC and PiCCO, bias and limits of agreement of data pairs were calculated as described by Bland and Altman 35. Bias represents the systemic error between the two methods. Upper and lower limits of agreement, calculated as mean bias ± two standard deviations, define the range in which 95% of the differences are expected. The percentage error was calculated as 100 × (CO indexed for body surface area [CI] by PiCCO - CI by PAC)/[(CI by PiCCO + CI by PAC)/2], as proposed by Rödig and colleagues 36. All analyses were performed using SPSS version 12.0 for Windows (SPSS Inc., Chicago, IL, USA). Statistical significance was defined as P values of below 0.05, and all hypothesis testing was two-tailed.

Measurement of PAOP was unavailable in two AHF patients, and the SmvO₂ was missing in another AHF patient. Hemodynamic measurements obtained at the first and fourth recordings are shown in Table 3. Between the first and the forth measurements, hemodynamic variables remained nearly unchanged. Exceptions were LVSWI (increase in septic patients), PAOP and GEDVI (decrease in AHF patients), and SmvO₂ (increase in AHF patients). According to the mild changes during the observation period, we pooled the results within each group for further correlation purposes (Table 4). In comparison with patients with AHF, those with sepsis had higher cardiac index, CP, LVSWI, SmvO₂, CFI, GEF, PVPI, and ELWI/GEDVI ratio but a lower PAOP. ELWI was higher in patients with sepsis, but this trend did not reach statistical significance (P = 0.09).

A Bland-Altman analysis of cardiac index measurements by PiCCO and PAC resulted in a mean bias of 0.19 L/minute per square metre. Limits of agreement were -0.97 and 1.35 L/minute per square metre. The median percentage error of comparisons was 2.5%. It was within 15% for 68% of comparisons between CI by PiCCO and CI by PAC. In septic patients, r² between the two cardiac indexes was 0.81 (P < 0.001) compared with 0.58 in patients with AHF (P < 0.001).

Comparisons between CFI and other markers of cardiac performance (CP and LVSWI) are displayed in Figure 1. Figure 1 demonstrates the significant correlation between CFI and LVSWI (sepsis: r² = 0.30, P = 0.001; AHF: r² = 0.23, p = 0.002) as well as CFI and CP (sepsis: r² = 0.39, P < 0.001; AHF: r² = 0.45, P < 0.001) in both patient groups. In Figures 1a and 1b, the CFI values of four septic patients with depressed cardiac function can easily be identified. The correlations between GEF and LVSWI (sepsis: r² = 0.26, P = 0.001; AHF: r² = 0.18, P = 0.006) plus GEF and CP (sepsis: r² = 0.22, P = 0.004; AHF: r² = 0.13, P = 0.01), as shown in Figure 2, were comparable to the corresponding CFI correlations in Figure 1. The overall correlation between CFI and GEF was r² = 0.81 (P < 0.001). Figure 3 shows the relationships between CFI and PAOP and between CFI and SmvO₂. It demonstrates the significant negative correlation between CFI and PAOP (r² = -0.18, P = 0.006) in AHF patients but not in patients with sepsis (P = 0.89). On the other hand, CFI was significantly correlated with SmvO₂ in septic patients (r² = 0.22, P = 0.004) but not in those with heart failure (P = 0.26).

All AHF patients had an SmvO₂ of not more than 70% and a CFI of less than 4.5 per minute, except one suffering from congenital heart disease, who presented with low central venous oxygen saturation and shock. In this patient (classified as AHF because of her history), PAC showed a CI of 3.6 L/minute per square metre and an SmvO₂ of 68%. PiCCO revealed a CFI of at least 4.5 per minute in two of four measurements and a GEF of greater than 20% in all four measurements.

All septic patients with cardiac dysfunction (CFI of less than 4.5 per minute) had an SmvO₂ of not more than 70%. Among those with a CFI of at least 4.5 per minute, 1 patient had four SmvO₂ values of less than 70%, most likely because of hypovolemia. The remaining four points of less than 70% (2 patients) were associated with an arterial oxygen saturation of below 92% (Figure 3b).

PAOP did not correlate with ELWI and PVPI either in septic or in heart failure patients (Figure 4). Five of 12 patients with AHF and 6 of 9 with sepsis had at least one PVPI value of greater than 3.0, indicating that PVPI may not discriminate between heart failure and sepsis. No correlations were found between PAOP and GEDVI (data not shown).