Background
Cardiac surgeries are commonly performed procedures that almost universally require fluid resuscitation during the intraoperative and perioperative period (Lange et al.
2011; Hirleman and Larson
2008; Verheij et al.
2006). The effects of fluid type, fluid amount, timing of fluid administration, and techniques for determining fluid responsiveness are actively debated topics (Lange et al.
2011; Cherpanath et al.
2014; van Haren and Zacharowski
2014). Specific disease and/or conditions of surgery involving cardiopulmonary bypass (CPB) and related patient pathophysiology have become increasingly recognized as key determinants for successful fluid resuscitation. For example, the balance between the hydrostatic pressure gradient which pushes water outward into the interstitial space and the colloid oncotic pressure (COP) which pulls water inward into the vessel (classic Starling’s Principle believed to govern fluid movement across the capillary wall) does not fully apply to conditions involving systemic inflammation and vascular barrier damage (Aditianingsih and George
2014; Jacob and Chappell
2013). Moreover, the endothelial glycocalyx layer (EGL), which comprises membrane-bound glycoproteins and proteoglycans with side chains of heparan sulfate, chondroitin, and dermatan sulfate, is recognized as an important factor in vascular barrier function (Jacob and Chappell
2013; Weinbaum et al.
2007; Becker et al.
2010; Myburgh and Mythen
2013). Whereas large molecules (e.g., albumin in colloid solutions) are retained inside the vessel, generating COP in the intravascular compartment (Aditianingsih and George
2014; Jacob and Chappell
2013; Myburgh and Mythen
2013); small molecules (e.g., electrolytes in crystalloid solutions) can travel freely through the vessel wall and thus can draw water into the interstitial space. Cardiopulmonary bypass can produce changes in fluid physiology and fluid responsiveness in patients (Lange et al.
2011; Hirleman and Larson
2008; Verheij et al.
2006), characterized by increased interstitial fluid as a consequence of decreased COP, damaged EGL, and inflammatory changes (Lange et al.
2011; Hirleman and Larson
2008; Jacob and Chappell
2013; Hoeft et al.
1991; Ortega-Loubon et al.
2015). This shift of fluid from the intravascular space to the interstitial space, in addition to blood and fluid losses during the surgical procedure, can result in an intravascular hypovolemia that requires fluid resuscitation.
A survey of current fluid usage by health care professionals (HCPs) involved in cardiovascular surgeries in the USA was developed to (a) examine the use of different fluid types for resuscitation (i.e., crystalloids, plasma-derived colloid [albumin], synthetic colloids [hydroxyethyl starches, HES]) in patients undergoing cardiovascular surgery, (b) determine whether certain patient characteristics and/or practice settings influence the type of fluid utilized for resuscitation, (c) determine whether the fluid selected for resuscitation varies by clinical specialties of the treating HCPs, and (d) determine the fluids used to prime the CPB circuit in patients undergoing on-pump procedures.
Methods
Study design
This study was cross-sectional and collected survey data from 124 cardiothoracic surgeons, cardiovascular anesthesiologists, and perfusionists to investigate the patterns of fluid utilization in cardiovascular surgery. The online survey was conducted November 4 through 17, 2015, with an average survey completion time of 9 min. The 38-item self-administered questionnaire (Additional file
1) obtained information on fluids used for hemodynamic management in the operating room and in the first 24-h postoperative period, as well as on volume status indicators most often used to determine volume expansion needs. Survey participants were presented with five different hypothetical patient scenarios encountered frequently in cardiovascular surgery and asked to identify their first choice of fluid for volume expansion for each patient type from a list of colloid and crystalloid fluids. The five patient scenarios were:
(1)
Volume expansion during CPB when not experiencing significant blood loss
(2)
Volume expansion in the presence of blood loss during CPB when blood transfusion is not indicated (adequate hemoglobin [Hb])
(3)
Volume maintenance during acute normovolemic hemodilution (ANH, autologous blood collection)
(4)
Volume expansion while patients were supported with extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD)
(5)
Intraoperative volume expansion for off-pump coronary artery bypass graft (OPCABG) surgery or transcatheter aortic valve replacement (TAVR)
The six types of fluids were crystalloids, 5% albumin, 25% albumin, first-generation HES or HES 450/600 (e.g., 6% HES 450/0.70 and 6% HES 600/0.75), third-generation HES or HES 130 (e.g., 6% HES 130/0.4), and blood-derived blood products other than albumin. The participants rated the frequency with which they used various fluid types for volume expansion using a 5-point scale (from 1 for “always” to 5 for “never”). Participants were also asked to indicate the bolus volumes (mL) of the crystalloids and of colloids that they typically use for volume expansion. Participants rated the importance of certain colloid characteristics (e.g., more sustained volume expansion, faster volume expansion) and non-oncotic properties of albumin (e.g., transport of metabolites, free radical scavenging) on the patient treatment decision-making process using a 5-point scale (from 1 for “not important” to 5 for “absolutely essential”). Four of the 38 questions addressed pump priming preferences for CPB circuits and were asked of perfusionists only.
Participants
A total of 124 participants were recruited from the e-Rewards Medical panel. e-Rewards Medical is a leading provider of market research services to the professional health care community. The panel consists of HCPs who have opted to become members of the panel and were paid for their time. Email invitations for participation in this study were sent from e-Rewards to the non-probability sample of its panelists, meaning this sample set was not a random selection of all physicians. Of note, the panelists remained anonymous to the investigators in this study. The email invitation provided a general description of the survey topic (i.e., “Fluid and Hemodynamic Management”) and a link by which to access the online survey. Each invitation contained a unique identifier that prevented any one respondent from taking the survey more than once. To qualify for participation, respondents had to specialize in cardiac surgery, adult cardiovascular anesthesiology, or be a perfusionist; had been in practice for at least 2 years since residency or training in the USA but not in the states of Minnesota, Vermont, West Virginia, Massachusetts, nor the District of Columbia as these states prohibit or limit compensation to physicians; and had performed or were involved in at least four cardiac bypass surgeries per month. Anesthesiologists who specialized in pediatrics were excluded because fluid management for pediatrics is different than for adults due to vast differences in the pathophysiology of their circulatory system. To ensure a minimum number of completed surveys were received from each group, subquotas were set for each clinical specialty: 50 surgeons, 50 anesthesiologists, and 50 perfusionists.
This research project involved obtaining the opinions of physicians and perfusionists about their choices for the use of various fluids for volume expansion in five different hypothetical patient situations. No patient data were obtained, and no questions were asked of the participants that would help in identifying them. All participant data were de-identified. Hence, this study was exempt from requiring institutional review board approval under United States Code of Federal Regulations Title 45 Part 46.101(b)(2) by Copernicus Group Independent Review Board (CGIRB). The study did receive a formal Letter of Exemption from the CGIRB.
Statistical analyses
Most questions were based on 5-point scales and provided ordinal data which, by definition, are not normally distributed. As such, descriptive statistics were performed using a Kruskal-Wallis test to evaluate differences among the respondent groups on the ordinal measures. Follow-up tests were conducted to evaluate differences within and between patient scenarios. T tests were used to evaluate differences across ratio variables (i.e., bolus volume). Statistical significance was assessed at the alpha level of less than 0.05. Descriptive analyses were performed using SPSS (Version 23.0).
Discussion
This cross-sectional study provided insights on the patterns of fluid utilization in cardiovascular surgery from a survey of 52 cardiovascular anesthesiologists, 47 cardiothoracic surgeons, and 25 perfusionists in the USA. This survey examined the fluids chosen for volume resuscitation by these 124 HCPs to treat five different hypothetical patient scenarios. The 25 perfusionists were surveyed to determine the solutions that they utilized to prime the CPB circuit. There were remarkable variability in clinical practice and a lack of consensus about the use of various fluid types in cardiovascular surgery patients.
In this survey, the most commonly preferred indicators of volume status were blood pressure, urine output, cardiac output, central venous pressure, and heart rate. Anesthesiologists preferred transesophageal echocardiography, pulse pressure variation, and stroke volume variation as indicators of volume status significantly more frequently than surgeons. Different fluid types were chosen as the first choice of IV fluids depending on the clinical context of the patients. For example, crystalloid fluid was the predominant first choice for patients needing volume expansion during CPB without bleeding (scenario 1), for fluid maintenance during ANH (scenario 3), and for intraoperative volume expansion during OPCABG or TAVR (scenario 5). On the other hand, 5% albumin was the primary fluid choice for patients needing volume expansion in the presence of blood loss during CPB not requiring transfusion (scenario 2) or during ECMO or VAD (scenario 4). When choosing colloids for volume expansion, HCPs felt that “less interstitial edema” and “more sustained volume expansion” were more important colloid traits than “faster volume expansion,” “better respiratory function,” and “less weight gain.” “Other blood-derived products” were chosen infrequently (less than 10%) as the first choice for fluid resuscitation by both university- and non-university-affiliated physicians; the only situation in which it was chosen by more than 10% of the respondents was for patients on ECMO and VAD.
In addition, there were differences in practice patterns among the clinical specialties of the treating HCPs. Significantly larger numbers of surgeons, relative to anesthesiologists, preferred 25% albumin for patients who need volume expansion in the presence of blood loss (scenario 2), for fluid maintenance during ANH (scenario 3), and for volume expansion during EMCO or VAD (scenario 4). Sixty percent of the perfusionists in this study preferred to use only crystalloids for priming the CPB circuit, while the other 40% used a mixture of albumin and crystalloids. The data from this study demonstrate that volume repletion practices vary dramatically and clinical data do not allow for consensus recommendations. While there are no large, randomized trials available to inform HCPs of definitive protocols for optimal volume resuscitation during cardiovascular surgeries, it is well accepted that fluid overload increases the risk of major complications after CABG (Morin et al.
2011). Whereas several studies (Hoeft et al.
1991; Russell et al.
2004; Sade et al.
1985; Kuitunen et al.
2004) have suggested that the use of colloid fluids in the priming solution during CPB is beneficial for maintaining COP.
Additional data indicate that utilization of colloid fluid results in a larger intravascular volume expansion than an equal volume of crystalloid fluid (Verheij et al.
2006; Finfer et al.
2011; Jacob et al.
2012; Skhirtladze et al.
2014), and the role of the EGL may be important. Studies have suggested that the EGL becomes damaged in numerous systemic inflammatory states (i.e., ischemia-reperfusion injury (Rehm et al.
2007), trauma (Johansson et al.
2011), and sepsis (Steppan et al.
2011; Ait-Oufella et al.
2010)), which may lead to interstitial edema (Aditianingsih and George
2014; Myburgh and Mythen
2013). In such conditions, colloids may behave more like crystalloids when there is significant damage to the EGL, and several large studies (Finfer et al.
2011; Myburgh et al.
2012; Annane et al.
2013; Perner et al.
2012) have failed to show any benefit from colloids in this context. On the other hand, two randomized trials in patients undergoing cardiac surgery support the suggestion that smaller volumes of colloids (HES and albumin) are required for volume resuscitation when compared to crystalloid solutions (Verheij et al.
2006; Skhirtladze et al.
2014). In this context, it has been argued that the addition of colloids to crystalloid mixture may theoretically have benefits over crystalloids alone (Roger et al.
2014). In a retrospective, hospital-discharge database study of 19,578 cardiac surgery patients, albumin administration for volume expansion during CABG appeared to be associated with a 25% reduction in postoperative mortality, relative to other non-protein colloids (Sedrakyan et al.
2003). However, a recent retrospective study of one cardiac surgery program comparing outcomes from 9 months before vs 3 months after its protocol changed to restrict the use of albumin in patients who required more than 3-L crystalloids within the first 24 h, had an albumin concentration < 3.0 g/dL, or had volume overload, found that there was no difference in morbidity or mortality between the two groups (Rabin et al.
2017). Both of these studies have all the shortcomings of being retrospective. Of note, a recent single-center, double-blind, randomized, controlled trial of albumin administration for a serum albumin level of less than 4.0 g/dL prior to OPCABG revealed a significant decrease in stage 1 acute kidney injury in the albumin group (Lee et al.
2016).
A well-designed, prospective, randomized trial would be required to address the question of whether albumin has a benefit on patient outcomes in cardiac surgery.
While this survey cannot elucidate the reasons behind why clinicians preferred a particular fluid type over another, the respondents did refer to “a more sustained volume response” as one of the major reasons for choosing a colloid for volume expansion.
It is noteworthy that more surgeons than anesthesiologists in this survey preferred HES solutions for patients needing volume expansion during CPB without bleeding (scenario 1). HES should be given with caution or possibly avoided altogether due to warnings from the FDA (United States Food and Drug Administration
2013), European Medicines Agency (
2013), and Surviving Sepsis Campaign (Dellinger et al.
2013). In a recently published survey of fluid management in cardiac surgery that was conducted in 18 European countries, it was noted that the use of HES products has decreased dramatically in the last several years (Protsyk et al.
2017). The most commonly used fluids for intraoperative and postoperative fluid management were crystalloids, and if colloids were used, the colloids were used in combination with crystalloids. The colloids that were used most frequently in this recent European survey were the gelatins, followed by HES and albumin. The warnings about the risks of HES use in critically ill patients issued by the FDA and EMA may have had an effect on the use of HES in the USA as well. In the present survey, which was performed about 2 years after the regulatory agency warnings, HES was chosen as the fluid of first choice by less than 10% of the respondents in most of the clinical scenarios. In agreement with the European survey, crystalloids were the most commonly chosen first fluid choice in three of the five clinical scenarios. However, in the USA, gelatins are not available and the only non-HES colloid that is easily available is albumin.
Limitations
A limitation of this study is that it describes current practices of fluid volume expansion in cardiovascular surgeries conducted only in the United States; these study results cannot be generalized to other countries in the rest of the world. We did not report on clinical outcomes, as this study is based on a survey of HCP preferences. We also recognize that the decision-making processes of HCPs are complex and may vary from the situations we put forth in the survey. While our study design cannot provide details on the underlying reasons for treatment decisions, the results allow HCPs to compare their own practice patterns to those of their colleagues, which could be helpful given the lack of expert consensus on fluid resuscitation in patients undergoing cardiovascular surgeries. The results in this survey also provide basic background information for the design of future trials that address complicated issues, such as fluid volume expansion strategies in the hypothetical scenarios we described.