Endotoxaemia in horses: intravenous polymyxin B vs placebo — POSSIBLE

In horses with endotoxaemia (such as from colic or colitis), does intravenous polymyxin B reduce endotoxin-driven clinical signs and inflammatory mediators compared with placebo, and is there evidence on laminitis or mortality?

Shelf #150 · gate-verified and approved by the developer

POSSIBLE: In experimental endotoxin models — and only there — intravenous polymyxin B consistently blunts the endotoxin response. Pretreatment lowered maximal TNF and IL-6 and rectal temperature and respiratory rate in 6 foals given IV endotoxin (Durando 1994); in 24 healthy mature horses, polymyxin B given before or after endotoxin infusion significantly reduced fever, tachycardia and serum TNF versus saline, with the largest difference at 5,000 u/kg given before endotoxin (Barton 2004); and in 14 neonatal foals challenged with lipopolysaccharide, polymyxin B produced significantly lower lactate, TNF-alpha and thromboxane B2 and better attitude scores than saline at various time points (Wong 2013). No carded study enrolled horses with naturally occurring endotoxaemia from colic or colitis, and none measured laminitis or mortality, so a hard-outcome benefit is unproven rather than shown. This pack is Tier C because its question carries laminitis and survival (hard-outcome) claims, which the carded evidence does not answer. Nephrotoxicity was not demonstrated in these models (urine GGT:creatinine unchanged in Barton 2004; no overt nephrotoxicosis in Wong 2013), but the Barton authors urge caution in azotaemic patients — precisely the clinical population none of these studies enrolled. Drafted Nov 10, 2026 (VetMed build, topic #150); all figures from abstracts fetched and verified at drafting.

Durando 1994: polymyxin B pretreatment lowered maximal TNF and IL-6 and rectal temperature and respiratory rate in 6 foals given IV endotoxin

Experimental endotoxin-model study in foals (the record gives no randomisation or blinding statement)

Who: Horses (foals): 6 foals aged 3 to 5 months in an experimental endotoxin model; each foal was given endotoxin (0.25 micrograms/kg of body weight) IV after no pretreatment, or pretreatment with polymyxin B (6,000 U/kg, IV) or S typhimurium antiserum (1.5 ml/kg, IV).

Result: When given without pretreatment, endotoxin caused transient recumbency and increases in rectal temperature and heart and respiratory rates, plus leukopenia and increases in circulating tumor necrosis factor (TNF) and interleukin 6 (IL-6) activities. Compared with results obtained when endotoxin was given alone, pretreatment with polymyxin B resulted in significantly (P < 0.05) lower maximal plasma TNF and IL-6 activities, and significantly lower rectal temperature and respiratory rate. In contrast, use of antiserum was associated with significantly (P < 0.05) higher respiratory rate, maximal plasma IL-6 activity, and total TNF response (as determined by areas under curves of plasma TNF vs time).

Watch out: Six foals only, each exposed under the three conditions as described, and polymyxin B was given as pretreatment before endotoxin — not as treatment of established clinical endotoxaemia. No randomisation or blinding is stated in the record, and no laminitis or survival outcome was measured. The antiserum arm's worse results are a warning about the model, not about polymyxin B.

Durando MM, MacKay RJ, Linda S, Skelley LA. Effects of polymyxin B and Salmonella typhimurium antiserum on horses given endotoxin intravenously. American journal of veterinary research. 1994;55(7):921-7. PMID: 7978630. Registry ID: none in the record. MeSH: Animals · Body Temperature/drug effects · Endotoxins/toxicity · Escherichia coli · Heart Rate/drug effects · Horses · Immunization, Passive · Interleukin-6/blood · Leukocyte Count/drug effects · Lipopolysaccharides/toxicity · Polymyxin B/therapeutic use · Respiration/drug effects · Salmonella typhimurium/immunology · Toxemia/blood · Toxemia/immunology · Toxemia/prevention & control · Tumor Necrosis Factor-alpha/analysis

Barton 2004: polymyxin B before or after endotoxin significantly reduced fever, tachycardia and serum TNF versus saline in 24 healthy mature horses

Experimental endotoxin-infusion study; the record's MeSH includes Random Allocation, but the abstract does not state randomisation and no blinding is stated

Who: Horses: four groups of 6 healthy mature horses each (24 total) in an experimental model; all received 20 ng endotoxin/kg bwt i.v. over 30 mins, and additionally one of the following i.v.: 5000 u polymyxin B/kg bwt 30 mins before endotoxin infusion; 5000 u polymyxin B/kg bwt 30 mins after endotoxin infusion; 1000 u polymyxin B/kg bwt 30 mins prior to endotoxin infusion; or saline. Clinical response data and samples were collected for neutrophil count, serum tumour necrosis factor (TNF) activity, plasma thromboxane B2 concentration and urine gamma glutamyltranspeptidase (GGT) to creatinine ratio.

Result: Treatment with polymyxin B before or after administration of endotoxin significantly reduced fever, tachycardia and serum TNF, compared to horses receiving saline. The differences in response to endotoxin were greatest between horses that received saline vs. those that received 5000 u polymyxin B/kg bwt prior to endotoxin. Urine GGT:creatinine did not change significantly. The authors concluded polymyxin B may be a safe and effective treatment of endotoxaemia even when administered after onset, while noting that although nephrotoxicity was not demonstrated with this model, caution should be exercised when using polymyxin B in azotaemic patients.

Watch out: Experimentally induced endotoxaemia in healthy mature horses, not naturally occurring endotoxaemia from colic or colitis. Outcomes were clinical signs and mediators over the model period; there was no laminitis or mortality endpoint, and the 'after onset' arm was dosed only 30 minutes after a controlled infusion began — far earlier relative to disease course than most clinical presentations. Blinding is not stated in the record and is not claimed here.

Barton MH, Parviainen A, Norton N. Polymyxin B protects horses against induced endotoxaemia in vivo. Equine veterinary journal. 2004;36(5):397-401. PMID: 15253079. Registry ID: none in the record. MeSH: Animals · Anti-Bacterial Agents/therapeutic use · Body Temperature/drug effects · Dose-Response Relationship, Drug · Drug Administration Schedule/veterinary · Endotoxemia/blood · Endotoxemia/drug therapy · Endotoxemia/veterinary · Endotoxins/administration & dosage · Heart Rate/drug effects · Horse Diseases/blood · Horse Diseases/drug therapy · Horses · Polymyxin B/therapeutic use · Random Allocation · Tumor Necrosis Factor-alpha/analysis

Wong 2013: in 14 neonatal foals challenged with lipopolysaccharide, polymyxin B lowered lactate, TNF-alpha and thromboxane B2 and improved attitude scores versus saline

Prospective experimental study (record's own wording); publication type: Randomized Controlled Trial — no blinding stated in the record

Who: Horses (foals): 14 healthy neonatal foals in a prospective experimental study, randomly assigned to a treatment or control group; all were administered a single dose of lipopolysaccharide (0.5 μg/kg) IV over 30 minutes. The treatment group received polymyxin B (6,000 U/kg, IV) immediately after completion of lipopolysaccharide infusion, with subsequent doses at 8 and 16 hours; the control group was administered an equal volume of saline (0.9% NaCl) solution. Outcome variables included heart rate, respiratory rate, rectal temperature, attitude score, blood lactate and glucose, serum tumor necrosis factor-alpha and plasma thromboxane B2, with urine collected before and after experimentation for nephrotoxicosis assessment (per-group numbers are not given in the record).

Result: The treatment group had significantly lower blood lactate concentration and serum tumor necrosis factor-α and plasma thromboxane B2 concentrations and had higher blood glucose concentrations and better attitude scores, compared with the control group, at various time points during the study. No other significant differences and no evidence of overt nephrotoxicosis were detected. The authors concluded that polymyxin B IV in healthy neonatal foals challenged with lipopolysaccharide attenuated some clinical and serum biochemical derangements associated with endotoxemia.

Watch out: Healthy neonatal foals given a single controlled lipopolysaccharide challenge — an experimental model, not clinical endotoxaemia. The significant contrasts held 'at various time points', i.e. they were time-point-specific rather than uniform, and no laminitis or survival outcome was measured. The record does not state blinding; a saline control arm alone is not stated blinding.

Wong DM, Sponseller BA, Alcott CJ, Agbedanu PN, Wang C, Hsu WH. Effects of intravenous administration of polymyxin B in neonatal foals with experimental endotoxemia. Journal of the American Veterinary Medical Association. 2013;243(6):874-81. PMID: 24004237. Registry ID: none in the record. MeSH: Administration, Intravenous · Animals · Animals, Newborn · Endotoxemia/chemically induced · Endotoxemia/drug therapy · Endotoxemia/veterinary · Female · Horse Diseases/drug therapy · Horses · Lipopolysaccharides/toxicity · Male · Polymyxin B/administration & dosage · Polymyxin B/therapeutic use · Thromboxane B2/blood · Time Factors · Tumor Necrosis Factor-alpha/blood

Synthesis: polymyxin B reproducibly attenuates signs and mediators in experimental endotoxin challenge; clinical benefit on laminitis or survival is untested in the carded evidence

Synthesis

Who: Synthesis of the cards above: Durando 1994 (6 foals, endotoxin with no pretreatment vs polymyxin B or antiserum pretreatment), Barton 2004 (24 healthy mature horses, endotoxin infusion with polymyxin B before/after or saline) and Wong 2013 (14 healthy neonatal foals, randomised, lipopolysaccharide challenge with polymyxin B or saline). All three are experimental endotoxin/lipopolysaccharide models.

Result: (1) Mediators: polymyxin B lowered maximal TNF and IL-6 (Durando), serum TNF (Barton) and TNF-alpha and thromboxane B2 (Wong) versus controls. (2) Clinical signs: lower rectal temperature and respiratory rate (Durando), reduced fever and tachycardia (Barton), lower lactate and better attitude scores (Wong). (3) Timing and dose: benefit appeared with pretreatment, with dosing 30 minutes after endotoxin began (Barton) and immediately after a lipopolysaccharide infusion ended (Wong), and was greatest at 5,000 u/kg given before endotoxin (Barton). (4) Safety in models: no nephrotoxicity signal in either study that looked (urine GGT:creatinine unchanged; no overt nephrotoxicosis). No carded study measured laminitis or mortality.

Watch out: Every carded study is an experimental challenge in healthy animals — foals, neonatal foals or healthy mature horses given a single controlled endotoxin dose. Nothing here is a trial in horses with naturally occurring endotoxaemia from colic, colitis or sepsis, where endotoxin exposure is ongoing, dosing starts hours later, and patients may be azotaemic; the sign and mediator benefits should not be silently transported into survival or laminitis claims.

Synthesis of Durando MM et al. PMID: 7978630; Barton MH et al. PMID: 15253079; Wong DM et al. PMID: 24004237. Registry IDs as on the individual cards.

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