Validation of a new transpulmonary thermodilution system to assess global end-diastolic volume and extravascular lung water

Transpulmonary thermodilution (TPTD) is increasingly used for hemodynamic evaluations in critically ill patients [1‐4]. After injection of a cold indicator in the superior vena cava, TPTD allows the computation of cardiac output (CO) from a TPTD curve recorded by a thermistor-tipped femoral arterial catheter [4]. Additional physiological parameters can be derived from the dilution curve, such as global end diastolic volume (GEDV), a volumetric marker of cardiac preload [5‐7], and extravascular lung water (EVLW) [7‐10].

The TPTD method currently in clinical use and implemented in the PiCCO™ system (Pulsion Medical Systems, Munich, Germany) is based on mathematical models described in the 1950 s [11, 12]. A new and original method has recently been developed to derive GEDV and EVLW from a TPTD curve (VolumeView™; Edwards Lifesciences, Irvine, CA, USA). The aim of the present animal study was to compare the new VolumeView™ system with the PiCCO™ system, over a wide range up to extreme pathophysiological conditions.

The study was approved for the use of swine by the Institutional Animal Care and Use Committee at the Edwards Lifesciences Biological Resource Center, and all experimentation was done in accordance with the Guide for the Care and Use of Laboratory Animals (1996; ILAR, NAP, Washington, DC, USA).

Eleven anesthetized and mechanically ventilated pigs (90 to 110 kg) were studied. Animals were premedicated with intramuscular midazolam (0.5 mg/kg) and atropine (0.5 mg) and were anesthetized with an injection of propofol (1 mg/kg) followed by continuous infusion of propofol (150 μg/kg/min) and sufentanil (2.5 μg/kg/h). After tracheal intubation, pigs were mechanically ventilated in a volume-controlled mode with a FiO₂ of 50%, a respiratory rate between 12 and 16 breaths/minute (to maintain an end-expiratory partial pressure of carbon dioxide within the normal range), a positive end-expiratory pressure of 0 cmH₂O and a tidal volume of 10 ml/kg.

All animals were instrumented with a right (PulsioCath™; Pulsion Medical Systems) and a left (VolumeView™; Edwards Lifesciences) 5F thermistor-tipped femoral arterial catheter. The correct position of femoral catheters was confirmed by radioscopy (Figure 1).

All animals were also instrumented with a pulmonary artery catheter (CCComboV™, 7.5F; Edwards Lifesciences) inserted through the right jugular vein and with a central venous catheter in the left jugular vein (Figure 1). The pulmonary artery catheter was used for continuous monitoring of CO (Vigilance II; Edwards Lifesciences) and pulmonary arterial pressures during the experimental protocol. The central venous catheter was used for cold indicator injections and for central venous pressure monitoring. Pulmonary artery pressures, continuous CO and central venous pressure data were used to guide therapy at various stages (as described below) but were not recorded nor analyzed.

A total of 137 paired measurements were available for comparisons. Sixty-six paired measurements were collected from stages 1 to 6 (6 stages × 11 pigs) and 71 additional paired measurements (6.5 ± 2.1 per pig) were collected at the final lung injury stage. No data were discarded. The reproducibility of hemodynamic parameters is reported in Table 1.

Overall, CO₁ and CO₂ ranged from 3.1 to 15.4 l/minute and from 3.4 to 15.1 l/minute, respectively. CO₁ and CO₂ were closely correlated (r² = 0.99), with mean bias (± SD) of 0.20 ± 0.30 l/minute and percentage error of 7% (Figure 3). GEDV₁ and GEDV₂ ranged from 701 to 1,629 ml and from 774 to 1,645 ml. GEDV₁ and GEDV₂ were closely correlated (r² = 0.79), with mean bias of -11 ± 80 ml and percentage error of 14% (Figure 4). EVLW₁ and EVLW₂ ranged from 507 to 2,379 ml and from 495 to 2,222 ml. EVLW₁ and EVLW₂ were closely correlated (r² = 0.97), with mean bias of -5 ± 72 ml and percentage error of 15% (Figure 5).

Changes in CO₂, GEDV₂, and EVLW₂ were closely correlated with changes in CO₁, GEDV₁, and EVLW₁, respectively (Figure 6).

The effects of each intervention are summarized in Table 2. Inotropic stimulation (DOBU) was achieved by administering an average 23 μg/kg/minute dose of dobutamine, hypovolemia (HYPO) by an average 1.2 l controlled hemorrhage, and hypervolemia (HYPER) by the average infusion of 4.5 l serum saline and 1.5 l gelatin. Both GEDV₁ and GEDV₂ decreased significantly during bleeding and increased significantly after blood restitution and fluid loading (Table 2). EVLW₁ and EVLW₂ increased slightly but significantly during fluid overload and dramatically (+110%) during ALI (Table 2). At each stage, values measured with the new VolumeView™ and with the current PiCCO™ method were comparable (Table 2).

In animals, and over a wide range of values, the present study demonstrates that GEDV and EVLW derived from the new VolumeView™ method and from the current PiCCO™ method are interchangeable.

Both methods derive CO from the TPTD curve using the Stewart-Hamilton principles and the same equation [4] so, not surprisingly, the agreement was extremely good with a percentage error of 7%, far below the clinically acceptable threshold value of 30% proposed by Critchley and Critchley [13].

In contrast, GEDV was derived from two different equations. The PiCCO™ equation is based on time characteristics of the TPTD curve (mean transit time of the cold indicator and exponential downslope time) while the new VolumeView™ equation additionally relies on the ascending and descending slopes of the dilution curve (Figure 1). The present results show that both methods are interchangeable to assess GEDV even when significant changes in cardiac preload are induced by bleeding and fluid loading. They also confirm that GEDV is not affected by dobutamine-induced changes in CO, and hence that there is no mathematical coupling between both parameters [3, 5]. The GEDV has been shown to be a reliable indicator of cardiac preload [5], varying in the same direction as echocardiographic preload indices [6]. A goal-directed strategy based on the optimization of GEDV has been shown to be useful to improve the postoperative outcome of cardiac surgical patients [15].

Both methods were also interchangeable for the assessment of EVLW; not only during slight modifications induced by fluid overload, but also during dramatic increases related to capillary leak as those observed during the ALI phase (Table 2). Assessing EVLW may be useful for clinicians treating patients with ALI or left ventricular failure [16]. EVLW has been shown to be more sensitive and specific than chest X-ray and ALI criteria to diagnose pulmonary edema [17, 18]. EVLW is also a prognostic parameter since it has repeatedly been shown to be correlated with mortality in patients with ALI as well as in the general intensive care unit population [19‐22]. Moreover, it has been suggested in critically ill patients that goal-directed strategies based on the measurement of EVLW may be associated with a decrease in the duration of mechanical ventilation and length of hospital stay [15, 23, 24].

Surprisingly, EVLW₁ increased slightly but significantly during dobutamine infusion and decreased slightly but significantly during bleeding, while EVLW₂ did not change (Table 2). From a pathophysiological point of view, no change in lung water is expected during inotropic stimulation or hypovolemia, particularly over such a short period of time [25]. Since our study was not designed to compare the PiCCO™ method and the VolumeView™ method with a third reference method (such as gravimetry), however, we cannot draw any definitive conclusions regarding the superiority of one method over the other.

Our study also confirms the very good reproducibility of TPTD measurements. These findings are in line with previous studies [5, 26] reporting reproducibility of CO, GEDV and EVLW of 4 to 7%, 5 to 8% and 11%, respectively.

The gravimetric method in animals and the double indicator (cold green dye) dilution method in humans are considered gold standard methods to quantify EVLW [9, 10]. The goal of the present study was to compare the new VolumeView™ system with the TPTD system currently in clinical use - this is why the PiCCO™ system has been selected as the reference method in our study. A clinical validation is necessary to investigate whether the new VolumeView™ system is also comparable with the PiCCO™ system in critically ill patients. The new VolumeView™ algorithm was originally developed to decrease the sensitivity of TPTD to recirculation and thermal baseline drifts. The present study was not designed to investigate this potential advantage over the existing TPTD technology, but instead to ensure that the new VolumeView™ system and the PiCCO™ system are interchangeable in clinical-like conditions where CO, blood volume and lung water vary significantly. Further studies are therefore required to compare both systems in situations where technical (thermal baseline drift) or other clinical challenges (for example, valvular regurgitation-induced recirculation) are encountered.

In animals, and over a very wide range of values, the new TPTD VolumeView™ system is comparable with the current PiCCO™ system to assess CO, GEDV and EVLW during inotropic stimulation, acute hemorrhage, fluid overload and severe acute lung injury.