Edited by: Kris Gommeren, University of Liège, Belgium
Reviewed by: Anthony Barthélemy, VetAgro Sup, France; Vincent Gauthier, Centre Vétérinaire Laval, Canada
Specialty section: This article was submitted to Veterinary Emergency and Critical Care, a section of the journal Frontiers in Veterinary Science
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The use of synthetic colloids (SCs), particularly hydroxyethyl starch (HES), in people has changed in recent years following new evidence raising concerns about their efficacy and safety. Although fluid therapy guidelines for small animals are often extrapolated from human medicine, little information exists on current practice in veterinary medicine. The objective of the present study was to investigate current fluid selection, use of plasma volume expanders including SCs, and recent changes in their use in small animal practice. An Internet-based survey was conducted, inviting veterinarians to report their practices in fluid resuscitation and colloid osmotic pressure support, their choice of SC, and perceived adverse effects and contraindications associated with SC use. There were 1,134 respondents from 42 countries, including 46% general practitioners and 38% diplomates. Isotonic crystalloids, HES, and hypertonic saline were chosen by most respondents for fluid resuscitation, and HES by 75% of respondents for colloid osmotic support. Dextran and gelatin were used by some European respondents. Human serum albumin was used more than canine albumin but 45% of respondents, particularly those from Australia and New Zealand, used no albumin product. The majority (70%) of respondents changed their practice regarding SCs in recent years (mostly by limiting their use), largely due to safety concerns. However, only 27% of respondents worked in an institution that had a general policy on SC use. Impaired renal function, coagulopathy, and hypertension were most often considered contraindications; impaired coagulation tests and increased respiratory rate were the most frequently perceived adverse effects. The use of HES remains widespread practice in small animals, regardless of geographic location. Nevertheless, awareness of safety issues and restrictions on the use of SCs imposed in human medicine seems to have prompted a decrease in use of SCs by veterinarians. Given the paucity of evidence regarding efficacy and safety, and differences in cohorts between human and veterinary critical care patients, studies are needed to establish evidence-based guidelines specific for dogs and cats.
Crystalloids and colloids have been widely used for plasma volume expansion in human and veterinary medicine for many decades (
Recommendations for fluid resuscitation in small animals are often based on extrapolation from human medicine and veterinary experts’ opinions (
This paper presents the results of an international Internet-based survey evaluating current fluid therapy practices and factors influencing fluid selection in small animals. The survey was designed to question how fluids are used by veterinarians from different institutions and countries, the extent to which their practice may have changed over recent years, and examine the perceived risks and benefits associated with SC use.
A commercial cloud-based survey development service (SurveyMonkey®,
The survey was designed in two parts. An initial general part (Part 1) asked questions regarding respondent characteristics, qualifications, experience and area of practice, general use of fluids for resuscitation and COP support, and the preferred type of SC used. The second specific part (Part 2) asked questions about SC use, perceived adverse effects and contraindications, and participants’ recent changes in SC practices.
The study was approved by the Vetsuisse University IRB procedures. A preliminary survey was distributed to a pilot group (21 people) of in-house diplomates, residents, and interns. Questions were then amended for the final survey based on their feedback regarding question perspicuity and survey completion time.
A cover letter with the main investigator’s contact information, explaining the purpose of the survey, assuring confidentiality and encouraging recipients to invite their colleagues to participate was then distributed with a link to the survey to veterinary organizations (Data Sheet S2 in Supplementary Material). This was achieved by contacting organizations and requesting them to distribute the link to their members and/or post it on their homepages, and directly by email to members of organizations
All questions in Part 1 required an answer and only data from respondents answering all 17 questions were included for data analysis. For Part 2, the number of questions that required a response differed between respondents due to contingency questions. Responses to all questions in Part 2 were included.
A total of 1,134 respondents completed at least Part 1 of the survey (Data Sheet S4 in Supplementary Material).
Respondents were 394 men and 740 women from 42 different countries. These included 658 (58%) from the USA and Canada, 395 (35%) from Europe, 54 (5%) from Australia and New Zealand, and 27 (2%) from 17 other countries (Figure
Frequency chart showing the geographic distribution of the 1,134 survey respondents. Countries represented by 30 or more respondents are shown separately within each geographic area.
Frequency chart showing the qualifications and case types seen by the 1,134 survey respondents.
Respondents included 525 (46%) general practitioners, 435 (38%) board-certified diplomates, 95 (8%) residents, 28 (3%) interns, and 51 (5%) others/unspecified. Diplomates included 216 (45%) emergency and critical care specialists (ACVECC and ECVECC), 90 (19%) internists (ACVIM and ECVIM), 84 (17%) anesthetists (ACVAA and ECVAA), 75 (16%) surgeons (ACVS and ECVS), 6 (1%) neurologists (ECVN), and 15 (3%) unspecified board-certified specialists.
Isotonic crystalloids, HES, and hypertonic saline were reported to be used sometimes or often for fluid resuscitation by 1,123 (99%), 730 (64%), and 577 (51%) of respondents, respectively (Figure
Frequency chart showing the relative frequency with which the 1,134 survey respondents use intravenous solutions for fluid resuscitation. CRYS, crystalloids; HTS, hypertonic saline; HES, hydroxyethyl starch; DEX, dextran; GEL, gelatin; ALB, albumin.
Frequency chart showing the type of intravenous solutions used by the 1,134 survey respondents for fluid resuscitation in specific disease conditions. SIRS, systemic inflammatory response syndrome; GDV, gastric dilatation-volvulus; GI loss, gastrointestinal loss.
Hydroxyethyl starch and plasma were reported to be used sometimes or often for COP support by 848 (75%) and 523 (46%) of respondents, respectively (Figure
Frequency chart showing the relative frequency with which the 1,134 survey respondents use intravenous solutions for colloid osmotic support. HES, hydroxyethyl starch; GEL, gelatin; DEX, dextran; ALB, albumin.
Frequency chart showing the type of intravenous solutions used by the 1,134 survey respondents for colloid osmotic support in specific disease conditions. SIRS, systemic inflammatory response syndrome; PLE, protein-losing enteropathy; PLN, protein-losing nephropathy.
Five and 20–25% human serum albumin was used by 262 (23%) and 321 (28%) of respondents, respectively, and canine albumin was used by 182 (16%) of respondents, whereby some respondents used more than one albumin product. No albumin product was used by 505 (45%) of respondents, including 89% of respondents from Australia and New Zealand. Canine albumin was used by 21% of respondents from the USA and Canada but was seldom used in other geographic regions (Data Sheet S5 in Supplementary Material).
The most frequently used SC was HES in 958 (85%), gelatin in 49 (4%), and dextran in 31 (3%) of respondents (Figure
Frequency chart showing the primary synthetic colloid used by the 1,134 survey respondents from different geographic areas.
Only 304 (27%) reported that a general policy or guideline for the use of SCs existed in their workplace. Most respondents (726, 64%) reported no general policy and a further 104 (9%) did not know if one existed (Data Sheet S6 in Supplementary Material).
Of the 1,134 respondents who completed the general part of the survey, 1,051 also responded to questions in the second specific part (Part 2).
Of 947 respondents using HES, 64% used tetrastarch, 25% hetastarch, 8% pentastarch, and 3% did not specify HES type (Data Sheet S7 in Supplementary Material). Use of dextran and gelatin was generally limited to respondents in Europe, whereby gelatin was the main SC in 24% of respondents from the UK and dextran in 15% of respondents from Spain. The criterion reported most often as having high importance in influencing the choice of SC was availability (58% of respondents); the criterion reported most often as having low importance was price (42% of respondents) (Figure
Frequency chart showing the relative importance of criteria reported as considerations in the selection of synthetic colloids by 1,024 survey respondents.
The bolus dose of SCs reported for fluid resuscitation varied somewhat but was generally lower in cats than dogs (Table
Bolus dose of synthetic colloids used for fluid resuscitation by survey respondents.
ml/kg | Hydroxyethyl starch users |
Gelatin users |
Dextran users |
|||
---|---|---|---|---|---|---|
Dogs | Cats | Dogs | Cats | Dogs | Cats | |
≤5 | 11 (24%) | 5 (20%) | ||||
6–10 | 97 (11%) | 7 (16%) | 4 (16%) | |||
11–15 | 58 (6%) | 26 (3%) | 2 (4%) | 1 (2%) | 4 (16%) | 1 (4%) |
16–20 | 60 (7%) | 8 (1%) | 3 (7%) | 1 (2%) | 4 (16%) | 2 (8%) |
>20 | 5 (1%) | 3 (< 1%) | 0 (0%) | 0 (0%) | 1 (4%) | 0 (0%) |
I don’t know/not applicable | 20 (2%) | 46 (5%) | 4 (9%) | 5 (11%) | 3 (12%) |
Maximum daily dose of synthetic colloids used for fluid resuscitation by survey respondents.
ml/kg/day | Hydroxyethyl starch users |
Gelatin users |
Dextran users |
|||
---|---|---|---|---|---|---|
Dogs | Cats | Dogs | Cats | Dogs | Cats | |
≤10 | 59 (6%) | 4 (9%) | 2 (8%) | 6 (24%) | ||
11–20 | 8 (32%) | |||||
21–30 | 217 (23%) | 115 (12%) | 6 (13%) | 5 (20%) | 1 (4%) | |
31–40 | 70 (8%) | 18 (2%) | 1 (2%) | 1 (2%) | 2 (8%) | 1 (4%) |
41–50 | 65 (7%) | 23 (3%) | 2 (4%) | 1 (2%) | 1 (4%) | 0 (0%) |
>50 | 6 (<1%) | 3 (<1%) | 1 (2%) | 1 (2%) | 1 (4%) | 0 (0%) |
I don’t know/not applicable | 50 (5%) | 75 (8%) | 7 (16%) | 9 (20%) | 6 (24%) |
Criteria most frequently reported to be used sometimes or often to guide the decision to use SCs in CRI were albumin concentration (85%) and presence of edema (87%, Figure
Frequency chart showing the relative importance of criteria used to guide the decision to use synthetic colloids as a constant rate infusion reported by 681 survey respondents.
Constant rate infusion dose of synthetic colloids used by survey respondents.
ml/kg/h | Hydroxyethyl starch users |
Gelatin users |
Dextran users |
|||
---|---|---|---|---|---|---|
Dogs | Cats | Dogs | Cats | Dogs | Cats | |
≤1.0 | ||||||
1.1–2.0 | 120 (19%) | 3 (14%) | 1 (9%) | |||
2.1–3.0 | 28 (4%) | 14 (2%) | 0 (0%) | 0 (0%) | 1 (9%) | 0 (0%) |
>3.0 | 15 (2%) | 5 (<1%) | 1 (4%) | 1 (5%) | 0 (0%) | 0 (0%) |
I don’t know/not applicable | 46 (7%) | 76 (12%) | 3 (13%) | 5 (22%) | 1 (9%) | 1 (9%) |
Maximum limit for the duration of constant rate infusions of synthetic colloids by survey respondents.
Limit | Respondents ( |
|||
---|---|---|---|---|
Hydroxyethyl starch | Dextran | Gelatin | All | |
1 day | 131 | 2 | 8 | 141 (21%) |
3 days | 332 | 7 | 13 | 352 (52%) |
1 week | 18 | 1 | 0 | 19 (3%) |
No limit | 166 | 1 | 2 | 169 (25%) |
Of the 65 respondents who had stopped using HES, 59 (91%) had stopped during the past 5 years. The most frequent reason given was concerns regarding its safety (Table
Reasons reported by survey respondents for stopping or changing their use of hydroxyethyl starch (HES).
Reasons given | Respondents |
||
---|---|---|---|
Stopped using HES ( |
Changed using HES ( |
All ( |
|
Concerns regarding its safety | 59 (91%) | 536 (82%) | 595 (83%) |
Concerns regarding its efficacy | 38 (59%) | 300 (46%) | 338 (47%) |
Availability issues | 12 (19%) | 158 (24%) | 170 (24%) |
Other reasons | 10 (15%) | 18 (3%) | 28 (4%) |
A further 654/927 (71%) of HES users agreed that they had changed their use of HES over the last 5 years but continued using HES. The most frequent reason was concerns regarding its safety (Table
Frequency chart showing the changes in synthetic colloid use over the past 5 years and/or because of new recommendations reported by survey respondents (650 hydroxyethyl starch users; 27 gelatin users; 11 dextran users).
Frequency chart showing incidence of adverse reactions noted by survey respondents since changing their use of synthetic colloids (654 hydroxyethyl starch users; 27 gelatin users; 12 dextran users).
Of 927 HES users, 25 dextran users and 45 gelatin users answering the question, no specific adverse reaction associated with SC use was reported by more than 30% of respondents (Data Sheet S9 in Supplementary Material). The most frequently reported adverse reaction was increased respiratory rate/effort (29% of HES users; 22% of gelatin users; 32% of dextran users) and impaired coagulation tests for HES users (29% of respondents).
Of 632 HES users responding to the question, impaired renal function and coagulopathy were the two most common conditions considered either relative or absolute contraindications for using HES, and more than a quarter of respondents considered impaired renal function and hypertension as absolute contraindications (Figure
Frequency chart showing relative and absolute contraindications for the use of hydroxyethyl starch perceived by 632 survey respondents.
This is the first major international survey on the use of SCs in small animals. Respondents represented a varied group of veterinarians with diverse qualifications and experience, working in different clinical settings. However, the majority (58%) of respondents were from North America, which likely created some degree of bias. As respondents from USA and Canada almost never used gelatin and dextran and represented 64% of HES users, survey results may be distorted toward practices particular to this geographic area. This must be borne in mind when interpreting findings of this survey. Furthermore, gelatin and dextran users were very low in numbers, and results given as percentages of these users were affected by responses from few individuals.
Based on this survey, the most common resuscitation fluids used are isotonic crystalloids followed by HES. Similarly, isotonic crystalloids are preferred to SCs for fluid resuscitation in human ICUs (
Despite widespread use of HES by respondents from all countries, and gelatin and dextran in Europe, most respondents declared having no guideline or policy on the use of SCs in their workplace. However, our findings suggest that guidelines may be more common in Europe and some other geographic areas than in North America, possibly reflecting differences in new legislation for SC use in people or differences in attitudes toward the freedom of veterinarians to treat their cases as they see fit. Nevertheless, a small number of veterinarians have stopped using SCs and a large majority have changed their SC practices in recent years (mostly by using them less frequently). These changes were largely due to concerns regarding safety and, to a lesser extent, efficacy. Although evidence investigating the safety of SCs in small animals is growing, most published clinical studies on mortality and SC-related AKI are non-randomized and retrospective studies on HES. One retrospective cohort study in dogs showed a significantly higher incidence of AKI in dogs treated with 10% pentastarch (6%,
Although safety concerns lead most respondents to alter their use of SCs, more respondents reported availability to be of high importance in their choice of SC than risk of adverse effects. This apparent discrepancy in the relative importance given to safety issues likely reflects differences in opinions between those who did change their practice and all other SC users responding to the survey. Given the relative paucity of veterinary literature on HES safety, changes in SC practices are likely due largely to respondents’ awareness of recent human studies and new guidelines in people. In addition, in some countries, such as the UK, HES solutions were recalled from the market following the European Medicines Agency alert in 2013 (
Despite concerns regarding safety, a minority of respondents reported experiencing adverse effects of SCs in their cases. This apparent discrepancy between human and veterinary medicine is likely the result of major differences in cohorts and treatment complexity. Furthermore, HES-related human RCTs were often criticized for their poor quality and more recently for refusal to share raw data (
Although these findings together suggest a disparity between perceived and reported risks associated with SCs, it is unlikely that many respondents logged such events in their cases. Moreover, increased respiratory rate/effort, impaired coagulation tests, and hypertension were indeed observed by users of all three SCs. Previous studies have reported impaired coagulation tests associated with SC use in both people and small animals (
Coagulopathy and impaired renal function were most often considered contraindications for the use of HES although increased serum creatinine was rarely reported to be an observed adverse effect. This is in accordance with recent studies demonstrating a transient impairment of canine platelet function and whole blood coagulation (
Although dosages of SCs varied, these were largely similar between respondents. The most commonly used HES preparation was tetrastarch, but the most frequent maximal daily dose used was ≤20 ml/kg/day. This may be due to previous use of hetastarch, for which the recommended doses in people were not exceeding 20 ml/kg/day (
Doses used for gelatin were similar to those used for HES although daily limits for gelatin use are neither recommended by manufacturers nor reported elsewhere to the authors’ knowledge (
The preferred HES carrier solution (buffered electrolyte-balanced versus saline) was not investigated in this survey, but may be important in the selection of HES products. Indeed, several human trials showed an association between saline-based colloids and acid–base and electrolytes disturbances, including hyperchloremia, and decreased base excess, bicarbonate and anion gap (
Most survey respondents use SCs in CRIs, a practice unique to veterinary medicine. Continuous rate infusion doses were within the currently recommended ranges of 20–30 ml/kg/day (
A limitation on the duration of SC CRIs was variably reported by respondents in this survey. This may reflect both varied knowledge about the effects of cumulative doses and tissue storage in humans as well as the lack of published facts about such effects in dogs and cats (
Even though RCTs failed to show benefits of albumin infusions in human ICU patients (
Data from this survey suggest that, regardless of their geographic location or qualifications, veterinarians continue using HES and other SCs. Nevertheless, and despite a lack of practice guidelines, a notable proportion of respondents have limited their use of SCs based on an awareness of potential deleterious effects. As little data exist in veterinary medicine, changes in SC practice uncovered in this survey are likely due largely to results of human RCTs. Given differences in cohorts between veterinary and human ICU patients, studies are needed to establish evidence-based guidelines for the use of SCs in dogs and cats.
IY helped design the survey questionnaire, interpreted data, and wrote the manuscript. JH designed the survey questionnaire, interpreted data, and revised the manuscript. NS helped design the survey questionnaire and revised the manuscript. KNA designed the study questionnaire, interpreted data, and revised the manuscript. All authors read and approved the final manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank everyone who participated in answering the survey.
The Supplementary Material for this article can be found online at
AKI, acute kidney injury; COP, colloid osmotic pressure; CRI, constant rate infusion; HES, hydroxyethyl starch; ICU, intensive care unit; RCT, randomized clinical trial; SC, synthetic colloid.