In the current era of critical care, increasing evidence supports the adoption of hemodynamic goal-directed therapies (GDT) to improve patient outcomes.12 For a hemodynamic GDT to be beneficial, objective feedback from reliable assessments of cardiac output and a patient's status on the Frank-Starling curve seem mandatory, as only half of hemodynamically unstable patients are fluid responders and fluid excess may actually lead to dismal prognosis.34

Despite technical advances, the postoperative course following cardiac surgery in the intensive care unit (ICU) is often complicated by hemodynamic perturbations, alarming the need for an effective GDT. However, appropriate preload assessment can be especially challenging in patients after valvular heart surgery, as it invariably accompanies various degrees of myocardial and vasomotor dysfunction and changes in loading conditions of the heart related to surgery and cardiopulmonary bypass (CPB).56

In the cardiac surgical setting, pulmonary artery catheters (PAC) have been traditionally used to guide hemodynamic management. However, it is now widely accepted that invasive cardiac filling pressures derived from PACs are no longer valid in predicting fluid responsiveness, and the role of PACs in high-risk patients has been constantly questioned.78 In contrast, dynamic preload indices derived from arterial pressure waveforms have emerged as accurate predictors of fluid responsiveness over the last decade.9 However, these indices cannot be applied to patients with spontaneous breathing efforts or arrhythmia, limiting their postoperative use after cardiac surgery.10

The totally Noninvasive Cardiac Output Monitoring device (NICOM™, Cheetah Medical, Portland, OR, USA) is based on thoracic bioreactance and measures the phase shift in voltage across the thorax created by pulsatile ejection of the left ventricle.11 While its accuracy and reliability have been validated in various clinical settings, including in patients with arrhythmia, it has also been shown to accurately predict fluid responsiveness when coupled with a passive leg raising (PLR) maneuver in critically ill patients, regardless of the presence of spontaneous breathing efforts.12131415 Therefore, the aim of this study was to compare the efficacy of two different postoperative GDTs based on conventional PAC derived parameters versus NICOM derived parameters coupled with PLR in patients with atrial fibrillation undergoing valvular heart surgery in a randomized trial.

Patient characteristics and operative data are described in Table 1. The patients' characteristics including the EuroSCORE were all similar between the groups, except for history of cerebral infarction, which was significantly more prevalent in the NICOM group than the PAC group. The incidence of diabetes mellitus also showed a trend towards being higher in the NICOM group. Operative data including the duration of CPB were all comparable between the groups, except that significantly more patients required double valve replacement (aortic and mitral) in the NICOM group than the PAC group.

Baseline hemodynamic data after surgery before ICU admission were similar between the two groups (data presented in the order of PAC and NICOM group): central venous pressure 8.7±2.9 mm Hg vs. 8.5±2.8 mm Hg, p=0.798; mean pulmonary arterial pressure 24.0±6.2 mm Hg vs. 23.5±5.3 mm Hg, p=0.729; MAP 70±10 mm Hg vs. 69±11 mm Hg, p=0.586; and CI 2.8±0.6 L/min/m² vs. 2.6±0.8 L/min/m², p=0.194.

Postoperative data in the ICU regarding fluid balance and resource utilization are shown in Table 2. The amount of chest tube drainage for 24 h showed a trend towards being larger in the PAC group, compared with the NICOM group. PAC group required significantly larger amounts of colloid than the NICOM group. Inotropic and vasopressor requirements in terms of number of patients and duration were all larger in the PAC group than the NICOM group without statistical significance. The number of patients requiring epinephrine was significantly larger in the PAC group than the NICOM group (5 vs. 0, p=0.019).

Data regarding postoperative outcomes are shown in Table 3. There was no in-hospital mortality in either group and the incidences of the major morbidity endpoints were all similar between the two groups, except the number of patients requiring ventilator care >24 h, which was significantly higher in the PAC group than the NICOM group. The length of hospital stay was 1.5 days shorter in the NICOM group than the PAC group without statistical significance (12.2±4.8 days vs. 10.8±4.0 days, p=0.239).

In this prospective, randomized trial comparing the efficacy of PAC- and NICOM-based postoperative hemodynamic GDT in patients with atrial fibrillation undergoing valvular heart surgery, NICOM-based GDT coupled with PLR was associated with significant reductions in resource utilization (colloid and epinephrine requirement). These beneficial influences led to significantly fewer patients requiring ventilator care >24 h, without any significant difference in length of hospital stay, compared with the conventional PAC group.

Despite pharmacologic and technical advances aimed to reduce systemic inflammation and myocardial injury during CPB, approximately 10% of patients experience hemodynamic instability or multiple organ dysfunctions following cardiac surgery.617 CPB with cardioplegic arrest inevitably results in various degrees of myocardial injury and edema, resulting in both systolic and diastolic dysfunction, not to mention that valvular heart surgery alone causes significant changes in the loading conditions of the heart. The postoperative course is also frequently complicated by severe vasodilation as a result of systemic inflammatory response. As the systemic inflammatory response persists for several hours to days after surgery,18 clinicians are confronted with hemodynamic perturbations in the ICU, mandating the need for hemodynamic GDTs based on proper feedback of the hemodynamics and volume status. Indeed, studies of GDTs at any time point during the perioperative period have shown benefits, although a variety of different surgical patients, algorithms, and goals have been assessed.12

To ensure optimal oxygen delivery to the tissues, maintenance of sufficient cardiac output and perfusion pressure is imperative. Before advancing to vasopressors and/or inotropes, preload optimization by fluid resuscitation is often considered as the first line of therapy. However, it has been consistently reported that only 50% of the critically ill patients are fluid responsive and fluid excess may actually worsen these patients' outcomes.34

While cardiac filling pressures derived by PAC are no longer considered to be valid preload indices,7 dynamic indices derived from arterial pressure waveforms, such as pulse pressure variation, have emerged as useful and accurate predictors of fluid responsiveness over the last decade.9 Albeit exhibiting almost a 90% power in predicting fluid responsiveness, these indices require mechanical ventilation and sinus rhythm, and thus, cannot be applied to patients with spontaneous breathing efforts or atrial fibrillation.10 Also, the validity of these devices in terms of cardiac output measurement may be compromised in patients with arrhythmia.19

NICOM is a totally non-invasive method of measuring cardiac output, and is reported to have high accuracy in various clinical situations, compared with PAC or other devices using arterial waveform analysis.12131420 The thoracic bioreactance system involves the application of a high-frequency electrical current across the chest, and measures changes in voltage via topical electrodes placed around the thorax. Pulsatile changes in thoracic blood volume result in changes in electrical impedance, and its rate of change during systole is measured, allowing a value of cardiac output to be derived.1221 Besides being totally non-invasive, other potential advantages of NICOM include that it provides accurate cardiac output measurement in patients with arrhythmia and has been validated to accurately reflect changes in stroke volume following PLR, and thereby, to reliably predict fluid responsiveness, even in patients who are breathing spontaneously.15

PLR causes a reversible increase in preload (200-300 mL), resulting in increases in stroke volume in potential fluid responders.22 These changes need to detected within minutes.23 Continuous cardiac output measurement, and thus stroke volume, by PAC requires 8 to 10 min of delay, whereas real-time intermittent bolus measurement is often not clinically feasible, as it requires stopping all pharmacologic agents delivered through central venous access. Moreover, at least three measurements are recommended for real-time intermittent thermodilution method using PAC, with its inherent problems regarding operator dependency and drift causing a discrepancy of up to 15%.2425

Taken together, NICOM-based GDT coupled with PLR may have theoretical advantage over PAC or arterial waveform analysis devices in the immediate postoperative period, following valvular heart surgery in patients with atrial fibrillation, although it has not yet been validated.

In the current trial, the common goals of the applied hemodynamic GDTs were to maintain a MAP between 60-80 mm Hg and CI ≥2.0 L/min/m², starting with preload assessment based on PCWP or changes in SVI by PLR in the PAC and NICOM groups, respectively. Use of vasopressors and inotropics were standardized according to an institutional protocol in a stepwise additive fashion.

As our results indicate, NICOM-based GDT was associated with significantly less resource utilization in terms of the amount of colloid used and epinephrine requirement to meet the predefined hemodynamic goals despite that significantly more patients in the NICOM group received double valve replacement. Use of epinephrine is well known to be associated with increased lactic acidosis and mortality.2627 Thus, its use is usually not recommended as a first line of therapy for hemodynamic support, as was in the current trial.28 Likewise, fluid excess in critically ill patients promotes tissue edema and congestion hindering the patients' recovery, thus exerting adverse influence on the patients' prognosis.4 Apparently, these favorable influences led to significantly fewer patients requiring ventilator care >24 h. Although we did not observe any statistically significant differences in other major morbidity endpoints and length of hospital stay, NICOM-based hemodynamic GDT coupled with PLR showed favorable trends in all aspects regarding resource utilization.

The limitations of this trial are as follows. First, the primary endpoint of this trial was to assess whether NICOM-based hemodynamic GDT would exert any beneficial influence on the length of hospital stay, upon which the sample size calculation was performed. Although patients in the NICOM group were discharged 1.5 days earlier than the PAC group, this difference lacked statistical significance, clearly due to insufficient sample size, as opposed to our expectations, which merits further trials. However, statistically significant differences were noted in secondary end-points. Second, it may be argued that the observed difference in the use of colloids may be related to a trend observed in postoperative bleeding amounts, which were higher in the PAC group without statistical significance. However, the mean difference in postoperative bleeding was less than 200 mL between the groups, while the difference in the amount of colloid was 500 mL. Moreover, considering the approximately 110 mL of difference in the amount of packed erythrocytes transfusion, its influence should be negligible. Third, despite being a randomized controlled trial adhering strictly to the respective GDT protocols, caregivers in the ICU could not be blinded due to differences in the nature of the monitoring systems.

In conclusion, appropriate preload assessment and hemodynamic management may be especially challenging after valvular heart surgery in patients with arrhythmia for the reasons described above. While conventional PAC or arterial waveform analysis devices have inherent limitations, our study demonstrates promising results regarding the application of NICOM-based hemodynamic GDT coupled with PLR in terms of resource utilization.