Use of intravenous lipid emulsion therapy as a novel treatment for brevetoxicosis in sea turtles

Abstract

The southwest coast of Florida experiences annual red tides, a type of harmful algal bloom that results from high concentrations of Karenia brevis. These dinoflagellates release lipophilic neurotoxins, known as brevetoxins, that bind to sodium channels and inhibit their inactivation, resulting in a variety of symptoms that can lead to mass sea turtle strandings. Traditional therapies for brevetoxicosis include standard and supportive care (SSC) and/or dehydration therapy; however, these treatments are slow-acting and often ineffective. Because red tide events occur annually in Florida, our objective was to test intravenous lipid emulsion (ILE) as a rapid treatment for brevetoxicosis in sea turtles and examine potential impacts on toxin clearance rates, symptom reduction, rehabilitation time, and survival rates. Sea turtles exhibiting neurological symptoms related to brevetoxicosis were brought to rehabilitation from 2018-2019. Upon admission, blood samples were collected, followed by immediate administration of 25 mg ILE/kg body mass (Intralipid® 20%) at 1 mL/min using infusion pumps. Blood samples were collected at numerous intervals post-ILE delivery and analyzed for brevetoxins using enzyme-linked immunosorbent assays. In total, nine (four subadults, one adult female, four adult males) loggerheads (Caretta caretta), five (four juvenile, one adult female) Kemp's ridleys (Lepidochelys kempii), and four juvenile green turtles (Chelonia mydas) were included in this study. We found that plasma brevetoxins declined faster compared to turtles that received only SSC. Additionally, survival rate of these patients was 94% (17/18), which is significantly higher than previous studies that used SSC and/or dehydration therapy (47%; 46/99). Nearly all symptoms were eliminated within 24-48 h, whereas using SSC, symptom elimination could take up to seven days or more. The dosage given here (25 mg/kg) was sufficient for turtles in this study, but the use of a higher dosage (50-100 mg/kg) for those animals experiencing severe symptoms may be considered. These types of fast-acting treatment plans are necessary for rehabilitation facilities that are already resource-limited. Intravenous lipid emulsion therapy has the potential to reduce rehabilitation time, save resources, and increase survival of sea turtles and other marine animals experiencing brevetoxicosis.

Figure 1

Clearance of plasma brevetoxins in (a) all turtles combined, (b) loggerhead (Caretta caretta), (c) Kemp’s ridley (Lepidochelys kempii), and (d) green (Chelonia mydas) sea turtles undergoing rehabilitation for brevetoxicosis. All turtles included in the figure received intravenous lipid emulsion after an initial sample was taken at admission (T = 0 h). Each colored circle represents the mean ± standard error for all turtles at that time point. Light gray circles indicate the raw data. Note that the x-axis is not set to scale, but instead serves to show changes in concentrations through time. The horizontal gray-dashed lines represent the detection limit of the ELISA at 1 ng PbTx-3/mL. Different letters above each point represent significant differences.

Figure 2

Time-series of plasma brevetoxin concentrations determined using enzyme-linked immunosorbent assays (ELISA) in (a) loggerhead (Caretta caretta) and (b) Kemp’s ridley (Lepidochelys kempii) sea turtles receiving intravenous lipid emulsion (ILE: yellow points/line) versus those treated with standard and supportive care (SSC: blue points/line). Points represent raw data for each treatment method with the lines-of-best fit also shown. The locations on the line-of-best fit are indicated where (1) an approximate 50% reduction in toxin concentration occurred in relation to concentration at time 0 h (i.e. admission) and (2) an approximate concentration of 1 ng PbTx-3/mL (the detection limit of the ELISA) was reached, indicating near complete clearance of the toxins from the blood plasma.

Figure 3

Plasma brevetoxin concentrations analyzed using ELISA in N = 5 lipemic samples compared to concentrations in the same samples after lipid-extraction by ultracentrifugation. Raw data are shown in (a), while box plots are shown in (b). The central yellow box represents the values from the lower to upper quartile (25th to 75th percentile), with the middle line representing the median (concentrations are shown). The vertical lines extend from the minimum to the maximum values. No outliers were present.