From the early prototypes constructed by Maximilian von Frey in Leipzig in 18851 to the first known cardiotomy with extracorporeal circulatory support by Clarence Dennis et al in 19512 and subsequent development by Gibbon,3 cardiopulmonary bypass has become an integral component of modern cardiac surgery. As time passed, the complexity of bypass has evolved with a wide range of different options for pump priming and cardioplegia available to the surgeon, anesthesiologist, and clinical perfusionist.
Despite the seemingly ubiquitous nature of this important device, regional patterns in cardiopulmonary bypass practice worldwide remain poorly understood. Although a number of surveys concerning specific countries have been undertaken,4–7 there is little understanding of how different countries, regions, and continents differ from one another in pump priming and anticoagulation. The recent literature in this field concerning colloid versus crystalloid priming strategies and the consequences of Joachim Boldt’s activities8–10 add further confusion as to what constitutes best practice.
In light of this confusion, and with the assistance of a number of regional specialist anesthesiology societies, we undertook a global survey of cardiopulmonary bypass practice to clarify what practices were being used in 2016 as well as to determine if any specific regional variations in pump priming, cardioplegia, and anticoagulation strategies existed.
Institutional ethics approval was received from the Human Ethics Research Committee at Austin Health (Melbourne, Australia). We devised a 16-question survey tool (see Supplemental Digital Content 1, Survey, http://links.lww.com/AA/B713), of which 5 questions concerned preferences for pump priming and associated additives and 1 question concerned anticoagulation strategies. Of the remainder, 6 questions concerned cardioplegia choices and additives, and 4 dealt with institutional location and caseload. The use of blood products (including their use as a pump prime in isolation) was not included in the survey. The questions were then loaded into an online survey cloud-based software tool (SurveyMonkey, Palo Alto, CA) for distribution. Pediatric cardiac anesthesiologists were not specifically excluded from participating, although the nature of some of the questions in the survey was designed to maximize the responses of those with an adult practice.
We then contacted a wide range of anesthesiology societies with a regional and specialist focus (Table) to enlist their help with distributing the questionnaire to their membership via their mailing lists. The survey was open between June 2015 and May 2016 to allow the maximal possible number of responses. Distribution to each region was staggered because of the differences in time taken among each of the specialist societies to approve the release of the survey. A reminder notice was sent to all anesthesiologists approximately 2 weeks after initial contact. The survey was translated into Spanish and Portuguese for the South American arm.
After the survey was closed, the results were collated and analyzed. Those regions for which there was a poor response (ie, <100 individually identifiable participants) were eliminated from the final analysis as were duplicate responses. The data from all regions (including those eliminated for poor responses) are available as Supplemental Digital Content 2, http://links.lww.com/AA/B812.
All data were obtained as categorical variables. Data were first analyzed descriptively using graphic methods. Statistical differences between region responses were evaluated using the Pearson χ2 test. The null hypothesis was rejected if the P < .05. An a priori sample size was derived using a χ2sample size calculation. This used an effect size (w) value of 0.3 (estimating a moderate effect size), a significance level of 0.05, degrees of freedom set to 16, and a power of 0.95. This indicated that a total sample size of 317 individual responses across all the groups was required to achieve 95% power. Assuming a 15% response rate, this required the survey to be sent to at least 2114 individual participants. A post hoc power calculation using the final number of total responses (n = 923) suggested that the study had a 99.999% power to detect a difference between the groups. All statistical analysis was performed using Stata version 12 (StataCorp, College Station, TX).
A total of 1019 responses were received; of these, 10 (0.98%) were identified as belonging to a participant who had previously completed the survey and were removed from the data set (Figure 1). An additional 10 (0.98%) respondents did not state their region of origin, and were also removed. The raw responses and percentage responses from the included regions are displayed in the Table. A further 76 responses (7.46%) were from regions where there were less than 100 responses. Because of the low response rate from these regions, they were not analyzed further. The final cohort comprised 923 responses, comprised of regional practice groups in Europe (29.1%), North America (36.2%), South America (23.3%), and Australia/New Zealand (11.4%). Contingency tables for individual analyses showed fewer than 20% of the expected cell counts were <5 with no expected counts <1. Interregional responses differed for all questions asked (P < .001).
Some differences between annual caseloads were noted between regions (Figure 2). The most marked difference demonstrated was that the majority of European respondents worked in higher volume centers with 57.2% indicating their hospital undertook more than 750 cases per annum. Relative to other regions, a higher proportion of North and South American respondents worked in centers that performed fewer than 250 cardiopulmonary bypass cases per year (27.4% and 26.6%, respectively). It should be noted that the high rate of nonrespondents in the South American cohort for this question (36.7%) implies that this result should be interpreted with caution.
Activated Clotting Time
A range of acceptable activated clotting times (ACTs) for initiating cardiopulmonary bypass were recorded with broad confidence intervals (Figure 3). Overall, the most common “safe” range for initiating bypass worldwide was reported to be between 401 and 450 seconds, whereas 72.7% of respondents were satisfied with an ACT between 400 and 500 seconds. Interestingly, 2 respondents in Europe (0.74%) and 15 in South America (6.98%) did not make use of ACT when titrating anticoagulation before the initiation of and during cardiopulmonary bypass.
Differences in the broad prime types used are shown in Figure 4. The majority of centers worldwide (61.9%) made use of a crystalloid component in their prime, either alone (38.1%) or together with a colloidal component (23.8%). Respondents working in centers where colloidal primes were used in isolation were an extreme minority across all regions (1.0%). Retrograde autologous priming had limited uptake worldwide with the exception of North America. Some 31.1% of respondents from this region used this technique, almost double that of the next most enthusiastic adopters in Australia/New Zealand (16.2%).
Crystalloid choice (Figure 5) was limited with a preference for balanced crystalloid solutions (which were used by 52.5% of all respondents). European respondents expressed a preference for relatively hyponatremic solutions such as Hartmann’s and lactated Ringer’s solutions, whereas in Australia/New Zealand and North America, Plasmalyte (Baxter International, Inc, Deerfield, IL) and other balanced crystalloids such as Normosol (Hospira, Inc, Lake Forest, IL) and Isolyte (B. Braun Medical, Inc, Irvine, CA) were preferred. Normal saline was still used by a number of respondents; highest use of this fluid was reported in South America (15.8%).
Colloid type (Figure 6) was restricted to those solutions routinely used in anesthetic practice (ie, gelatins, hydroxyethyl starches [HES], and albumin) and was relatively limited worldwide. Although North American and Australian respondents who did use colloid were restricted largely to albumin (both 4%–5% and concentrated albumin solutions), European institutions, demonstrated a higher use of HES (9.3%) and gelatins (18.6%) in pump prime solutions relative to other regions.
Cardiopulmonary bypass prime additives varied in keeping with regional practices described earlier in this article (Figure 7). The addition of heparin to the prime was particularly popular among Australian and New Zealand respondents (65.7%) and markedly reduced in South America (16.3%). Antipodean centers were limited in their use of other prime additives in comparison with other regions, particularly with respect to mannitol (14.3%).
Our group has completed a global survey of cardiac anesthesiologists concerning cardiopulmonary bypass practice with representative cohorts displayed from Europe, North America, Australia/New Zealand, and South America. Key findings related to anticoagulation and pump priming practices.
Most respondents deemed a minimum ACT between 400 and 449 seconds necessary before initiating cardiopulmonary bypass, although participants from Australia/New Zealand seemed to prefer an ACT of 450 or even higher. Crystalloid primes are still more commonly used worldwide, although a substantial minority will combine these with a colloidal solution. Where crystalloid was used, Plasmalyte and other balanced crystalloids were most popular in North America and Australia/New Zealand, whereas European and South American centers preferred the relatively hyperchloremic solutions (Hartmann’s, lactated Ringer’s, and normal saline). Albumin remains the most commonly used colloid where such a fluid is used, although European centers demonstrate a preference for HES or gelatin solutions. Prime additives demonstrated considerable variation, although one clear trend was a higher proportion of Antipodean respondents with heparin added to the pump prime.
Within the limitations of the data, this study implies that there is no clear consensus for management of cardiopulmonary bypass coagulation and priming. In the face of this conflicting evidence, the reasons why regional practice groups made the choices they have are not known, and the clinical implications are uncertain. This equipoise opens the way for well-conducted randomized studies. Although it is unlikely that these differences in practice will result in clinically significant mortality differences in all patients, it is possible that high-risk patients may benefit from alternative management (for example, anticoagulation management in patients with significant bleeding risk). Similarly, morbidity outcomes such as renal and lung injury may be viable targets for future studies in this region.
Over the last decade, considerable confusion has emerged over the role of crystalloids and colloids as pump priming solutions for cardiopulmonary bypass. Beginning with a series of small studies that examined pump priming solutions specifically, the evidence to guide therapy was limited at best. Colloids were felt to initially provide no benefit11–18 or, at best, some improvement in plasma colloid oncotic pressure and extravascular lung water, the effect of which on mortality was uncertain.19 A Cochrane Review published in 1998 examining the role of albumin solutions in the critically ill20 suggested that the use of colloidal solutions (particularly albumin) may be associated with excess mortality. Although apparently refuted by the SAFE trial21 and a subsequent systematic review,22 sufficient equipoise had been introduced to allow further studies into the role of colloidal solutions, particularly HES, in cardiopulmonary bypass. Some of these research efforts were led by the German anesthesiologist, Joachim Boldt, who was subsequently found to have fabricated large amounts of data and was declared a fraud.8-10,23 In the years since Boldt’s unmasking, little has been done to mitigate the associated confusion with a paucity of large, randomized controlled trials examining the difference between the various priming solutions in clinical use and determining the effects on morbidity and mortality that result as a consequence.
This confusion was reflected in the results of our survey. Pump priming practices vary considerably with respondent preferences for specific solutions and additives appearing to coalesce for reasons of geographic and regional significance.
With respect to prime types, colloidal solutions appear to be used by a minority of centers, particularly as an isolated pump prime. Balanced crystalloid solutions (particularly Plasma-Lyte 148) were preferred in the Antipodes and North America. This may reflect the findings of a series of articles by local (particularly in Australia) authors suggesting that the use of older fluids such as Hartmann’s and lactated Ringer’s solutions (which maintain popularity in Europe) led to a greater derangement of acid-base status during cardiopulmonary bypass,24 despite supraphysiologic acetate concentrations.25 Nonprotein colloids such as gelatins and HES solutions were used rarely outside of Europe. HES use appears to be limited to a minority of respondents in this cohort with gelatin solutions more popular. This may be explained by the aftermath of the Boldt affair, although there are a number of small studies suggesting that HES may have benefits in blood rheology and maintenance of colloid oncotic pressure26–28 without negative effects on coagulation29,30 and renal function,31,32 particularly in the pediatric population.33,34 The absence of large-scale studies into this subject combined with the enormous variation in practice might corroborate the somewhat cynical finding of a UK and Ireland survey into pump priming practices that “…the most common reason for fluid choice was historical belief.”35
Anticoagulation preferences did not vary substantially between regions, in keeping with previous surveys in this area.36 Overall, the judged safe range for initiating cardiopulmonary bypass in the regions surveyed tended to be between 400 and 500 seconds with a small minority of respondents preferring an ACT above or below that figure. It is not known what proportion of respondents used heparin-bonded circuits as part of their practice and whether or not this correlated with a lower acceptable ACT for the initiation of cardiopulmonary bypass.
Some questions had a high rate of failure to respond despite respondents having elected to complete the survey in general. Examples include pump prime type (36.8% failure to respond), prime additives (43.6% failure to respond), and crystalloid type (38.5% failure to respond). This is contrasted with the question concerning ACT, which had a 4.3% rate of failure to respond.
In keeping with this observation, clinical perfusionists and surgeons would certainly have a greater knowledge of pump priming practices and cardioplegia choices than anesthesiologists, who are the target of this survey. Anesthesiologists were targeted largely for methodological reasons; specifically, the background of the authors and their knowledge of various subspecialty cardiac anesthesiology societies allowed the reach of the survey to be maximized. However, it is certainly noted that anesthesiologists may not have the understanding of their surgical and perfusion colleagues of certain cardiopulmonary bypass choices, and as a result, the response rate of the survey may have been hindered. Although some of these examples may reflect that the institution of the respondent simply does not use the practice in question (such as colloid in, or additives to the pump prime), this result may reflect that the respondent answering the survey (and indeed, cardiac anesthesiologists in general) may have a limited understanding of what substances are used in their cardiopulmonary bypass circuits and, by extension, the implications for clinical practice.
The major strength of our study is the scope of the undertaking. By using specialist anesthesiology societies, we were able to reach a large number of practicing cardiac anesthesiologists from most parts of the world, suggesting that, within the limits of responder bias, these results are generally representative of regional practice. The survey was limited to 16 questions only, and the question style was deliberately designed to maximize the response rate.
A number of limitations are noted. Note that although some questions dealt with cardioplegia choices, the size of the data set precluded publication of all results in a single manuscript.
First, specialist societies were judged as the best means of reaching a large number of cardiac anesthesiologists relatively easily rather than trying to identify and contact major cardiac centers on every continent. Although this allowed us to considerably increase the number of potential participants that we reached, it must be noted that as larger centers employ a larger number of anesthesiologists, smaller centers may be relatively unrepresented. This could potentially confound the results, particularly with respect to caseload.
Second, some continents remain unrepresented in this survey, notably Asia and Africa. Despite contacting a number of specialist societies in Asia and distributing the survey through them, we had difficulty in achieving a reasonable response rate from this region. We suspect this reflects the associated language barrier, because there have been Asian practice surveys published in the past.4 Inclusion of a large Asian cohort in any subsequent research effort would be of great value to determine how these regions of the world differ from the cohorts represented in this survey. A reasonable response rate was received from South Africa. Despite great individual efforts in the region, we had difficulty contacting specialist groups in other large, African countries currently practicing cardiac surgery (ie, Nigeria, Egypt, Kenya, etc) and therefore felt that a South African cohort in isolation would not be representative of continental practice as a whole.
It should also be noted that for certain continents, the survey was distributed through more than one society, and some specialist groups (particularly the Society of Cardiovascular Anesthesiologists and the European Association of Cardiothoracic Anesthesiology) have a global reach. Hence, it is possible that some participants may have received the survey from more than one group (if they held memberships in multiple societies) or that a recipient may have received the survey through a group that was primarily based outside of their region (for example, an Australian member of the Society of Cardiovascular Anesthesiologists). Hence, calculation of a precise percentage response from a specific region is difficult.
Third, because of the deidentified nature of the data collection, it is possible that some respondents may have been sent and completed the survey twice, because some participants may have been members of more than 1 specialist society. Once this possibility was realized, an additional question was added to the survey to prevent this from occurring; however, it is still possible that a small number of early responses may have been affected. It is unlikely that this would have an effect sufficient to skew the data presented. In addition, pediatric anesthesiologists were not specifically prohibited from participating in the survey. However, some questions (particularly those relevant to caseload and surgery type) were designed to maximize the response of those with an adult practice.
Within South America, the survey was distributed through nonspecialist societies, namely the Confederacion Latinoamericana de Sociedades de Anestesiología and the Brazilian Society of Anesthesiology. The fact that a large number of anesthesiologists with either no or limited cardiac practice were sent the survey might help to explain why the response rate in South America was lower than elsewhere and the higher rates of failure to respond to all questions. It is possible that the relatively low rates of response in certain regions that have been reported in the survey (particularly South America) may impact on how well the results reflect continental practice. Nevertheless, it is felt that given the overall number of responses received, the results of this survey are worth reporting as a hypothesis-generating exercise for why these differences exist and whether or not they may influence outcomes between regions.
Overall, these low rates of response, particularly to some questions, mean that it is difficult to draw firm inferences from the data presented. To ensure that the degree of precision of the survey data has been adequately reflected, we have reported 95% confidence intervals as a component of all bar graphs. We have taken special care in the results section to comment only on overall global results (for example, commenting on the most commonly used pump prime type worldwide) and, where we have compared results between regions, reporting specifically on only those results within the data set where there is no or minimal overlap in confidence intervals between 1 region and its fellows. Nevertheless, readers should carefully examine the data as it is displayed graphically before determining if their own practice differs substantially from those techniques used within and between regions.
In summary, our group has performed the first global cardiopulmonary bypass survey and is able to present data representing practice in North America, Europe, Australia/New Zealand, and South America. Our results demonstrate some differences in anticoagulation and pump priming practice between regions, the reasons for which and consequences of are uncertain. The high rates of failure to respond to certain questions may reflect poor anesthesiologist understanding of what substances are used in their pump primes and the rationale behind them. The limitation of the survey data means that drawing firm inferences from this data set on the reasons behind detected differences is difficult. Further research into this topic is required and also particularly into the consequences of cardiopulmonary bypass choices on outcomes after cardiac surgery, particularly because there continues to be a paucity of evidence regarding crystalloid and colloid choices as a priming solution. Equipoise continues to exist for an up-to-date systematic review of the literature and a large, randomized controlled trial examining this question.
The authors would like to extend their gratitude to Dr Gudrun Kunst from the European Association of Cardiothoracic Anesthesiology, Dr Paul Heerdt from the Society of Cardiovascular Anesthesiologists, Dr Michael Fanshawe from the Cardiovascular, Thoracic and Perfusion Special Interest Group of the Australian and New Zealand College of Anaesthetists, Tarryn Oschadleus and Professor Justiaan Swanevelder from the Groote Schuur Hospital in Cape Town, and Dr Suhaini Kadiman and Professor Ruban Poopalalingam from the Asian Society of Cardiac Anesthesia for assisting in the distribution of the survey. They would also like to acknowledge the contribution of Dr Guillermo Martinez and Mr Pedro Catarino in translating the survey and Dr Damian Ianno in providing additional statistical support.
Name: Lachlan F. Miles, MBBS (Hons), PGCertCU, FANZCA.
Contribution: This author helped design the study, collect and analyze the data, and prepare the manuscript.
Name: Timothy G. Coulson, MBBS, FANZCA.
Contribution: This author helped analyze the data and prepare the manuscript.
Name: Carlos Galhardo, MD.
Contribution: This author helped analyze the data and prepare the manuscript.
Name: Florian Falter, MD, FRCA, FFICM, PhD.
Contribution: This author helped design the study, collect and analyze the data, and prepare the manuscript.
This manuscript was handled by: Roman M. Sniecinski, MD.
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