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Update on Managing Serious Wound Infections in Horses
1. Wounds Involving Joints and Other Synovial Structures (part A)
Christine King BVSc, MANZCVS, MVetClinStud
This update on managing serious wound infections in horses comprises a series of 4 articles:
1. Wounds involving joints and other synovial structures (part A).
2. Wounds involving joints and other synovial structures (part B).
3. Wounds involving bone.
4. Wounds involving soft tissues.
Wound infections that involve a joint, tendon sheath, or bursa can have disastrous consequences
for the horse's athletic career. Some infections cause such severe damage that euthanasia is
warranted on humane grounds, so immediate, intensive, and targeted treatment is indicated for
penetrating injuries to a synovial structure. There are many good articles on the treatment of
synovial infections in horses, and the common threads are these:
• early and intensive treatment, guided by clinical signs and synovial fluid analysis
• large-volume lavage of the synovial space, repeated as needed
• local/regional and systemic antibiotic therapy, culture-guided whenever possible
Sometimes, however, despite our best efforts, treatment is unsuccessful. It has been said that to
understand a problem is to know what to do about it. In that spirit, this series explores the
following question: Why do some infections persist and progress despite seemingly appropriate
treatment?
Of the many possible reasons, most serious wound infections involve at least one, and usually a
combination, of these factors:1
• extensive contamination, or bacterial burden that overwhelms the patient's resources
• refugia which protect the bacteria from host defenses and antibiotic drugs
• immunocompromise
• poor perfusion
• antibiotic insensitivity of the wound pathogen(s)
To have the best chance of success, the diagnostic and therapeutic plan must identify and address
each of the factors involved in the case at hand. Identifying the factors involved in the
persistence/progression of the infection allows us to formulate a targeted treatment approach that
optimizes the patient's defensive and reparative processes and the efficacy of the antibiotic drugs
selected.
In these first two articles (parts A and B), we'll explore each of these factors in relation to
wounds involving synovial structures, using examples from clinical studies of synovial sepsis
published over the past 15 years. In the spirit of learning from our failures, the focus is on the
patients with poor outcomes—not to be second-guessing the handling of the cases presented, but
rather to be learning together and expanding our collective ability to effectively treat wounds that
result in synovial contamination and infection.
EXTENSIVE CONTAMINATION
Following a penetrating injury, whether traumatic or surgical, extensive contamination of a
synovial structure may be caused by any or all of the following:
• fecal contamination—most likely with wounds on the distal limb, but may occur with any
wound
• environmental contamination with dirt, plant debris, or insect activity (flies, etc.)
• delay in effective treatment, allowing exponential increase in bacterial numbers within
the protected space of the synovial cavity
One drop of fecal liquor contains about 15 billion colony-forming units (CFU) of bacteria2 and
the generation time of Escherichia coli under optimal growth conditions is 17 minutes,3 so the
wound need not be covered in feces to be extensively contaminated with potentially infective
bacteria.
In each of the situations above, large numbers of bacteria invade and/or multiply within the
synovial space, overwhelming the patient's immediate defenses. Although the specific pathogen
is important for antibiotic selection, this factor is primarily about the sheer numbers of bacteria
within the synovial space.
Are Some Bacteria Worse Than Others?
That said, there is some evidence that certain pathogens are more problematic than others, in any
number, and the reason may lie in specific virulence factors characteristic of the pathogen. While
Gram-negative enteric bacteria such as E. coli and Salmonella sp. are challenging pathogens in a
synovial cavity, Staphylococcus aureus is a particular concern, regardless of its methicillin
sensitivity.
In an in vitro study using articular cartilage explants (i.e., no synovium, synovial fluid, or white
blood cells), co-culture with E. coli caused a 30% loss of glycosaminoglycans (GAGs) from the
cartilage within 48 hours, whereas S. aureus caused an 80% loss, and both pathogens caused
rapid chondrocyte death.4 Addition of serum to the culture medium inhibited the bacterial effects
on cartilage degradation, but it did not prevent chondrocyte death. Other in vitro studies
documented similar rapid (<48 h) deterioration of articular cartilage structure and cell viability
with S. aureus.5,6 Killed S. aureus, however, had no effect on GAG loss,5 which is good news
clinically, as it suggests that inactivating the bacteria as soon as possible after invasion may
minimize cartilage degradation, even if nonviable bacteria remain within the joint space.
The virulence of S. aureus is also demonstrated in how few bacteria it takes to cause joint sepsis.
For example, in experimental studies of septic arthritis in horses, it took as little as 33 CFU of S.
aureus to cause sepsis in healthy joints.7,8 As for clinical studies, Taylor et al. examined whether
positive synovial fluid culture, and specifically the culture of S. aureus, influenced the outcome
in 206 horses with synovial sepsis.9 Horses with positive cultures were 19 times more likely to
be euthanized during hospitalization than horses with negative cultures. Within that statistic,
horses with S. aureus infections were 29.5 times more likely to be euthanized, whereas those
with other infections were only 14 times more likely to be euthanized, than horses with negative
cultures. Furthermore, horses with S. aureus infections were more than twice as likely to fail to
return to their previous level of athletic performance as horses with other infections.
Walmsley et al. found that culture of S. aureus had no significant effect on survival to discharge
or return to athletic function compared with culture of another genus/species in 75 horses with
synovial sepsis.10 However, S. aureus was significantly more likely to cause persistent infection
(synovial fluid abnormalities 4–6 days after the start of treatment) than other genera/species.
Together, these experimental and clinical studies indicate that synovial sepsis involving S.
aureus should be treated with particular urgency and deliberation.
Except for Salmonella sp. infection in young foals with septic arthritis,11 no other specific
bacterial pathogens have stood out as significantly influencing short-term survival or subsequent
athletic performance in horses and foals with synovial sepsis. Herdan et al. suggested that
synovial infection with Enterococcus sp. may have a particularly poor prognosis,12 but other
factors were involved in the 3 cases they presented, as we'll explore later.
Fecal/Environmental Contamination
The impact of fecal/environmental contamination is illustrated by a recent UK study of synovial
contamination or sepsis resulting from penetrating injury to the solar surface of the foot in 95
horses.13 Despite endoscopic lavage of the involved synovial structure(s), only 56% of the horses
survived to hospital discharge, and of those available for follow-up at least 1 year later, only 57%
had returned to their pre-injury athletic use, which represented only 36% of the horses that
recovered from anesthesia where the long-term outcome was known. These figures contrast with
most other reports of synovial sepsis from various causes and in various anatomic locations,
where short-term survival rates for adult horses were in the range of 78% to 100%, and rates of
recovery to previous or higher levels of athletic use in recovered horses were in the range of 54%
to 89%.9,10,14-21
In the solar penetration study, fecal and/or environmental contamination was thought to be a
contributing factor in initial and ongoing wound infection for both the traumatic and the surgical
(endoscopic) wounds.13 Not only the site (the foot), but the nature of the injury was considered
another important factor, as penetrating injuries to the central sulcus of the frog typically resulted
in collapse and sealing of the wound tract after the foreign object was removed, effectively
preventing natural drainage and trapping bacteria deep within the foot. A third factor is discussed
in the next section: treatment delay. Each of these factors likely contributed to the bacterial
burden within the affected synovial space (navicular bursa, digital flexor tendon sheath, and/or
distal interphalangeal joint), and thus to the relatively poor outcomes compared with other
studies.
Fecal contamination may also be assumed in a small case series by Herdan et al. which
documented multidrug-resistant Enterococcus spp. in 3 horses with septic synovitis.12 In the first
case, the infection occurred secondary to a heel bulb laceration, and culture yielded
Enterococcus gallinarum and E. coli. The other 2 cases involved fresh wounds to the carpus or
stifle/tibia that, despite prompt local and systemic antibacterial therapy, evidently sustained
fecal/environmental contamination, as each subsequently yielded Enterococcus faecalis, various
Gram-negative enteric genera, and Streptococcus zooepidemicus. These 3 cases are discussed
further in later sections. They are noteworthy here as examples of the potential impact of
fecal/environmental contamination, even when it is seemingly inconsequential (e.g., fresh, clean
wound at or above the carpus/tarsus that is treated immediately).
Treatment Delay
As one might expect, numerous clinical studies found that a delay between synovial
contamination and hospital admission decreased the odds of a good outcome.11-13,15,16,19 For
example, in the solar penetration study, the likelihood of euthanasia during hospitalization
increased 1.2-fold for every day that elapsed between injury and admission, and the likelihood of
the horse failing to return to its pre-injury exercise level increased 1.1-fold for every day.13
Wereszka et al. similarly found that horses treated within 1 day of showing clinical signs of
septic tenosynovitis were almost 16 times more likely to survive at least 1 year than horses
treated >10 days after onset.19 However, several other studies found no significant effect of the
duration between contamination and admission on short-term survival and/or return to athletic
function.10,17,18,21,22
There are a number of possible reasons why treatment delay did not appear to matter, including
differences in the cause or type of contamination (trauma, intrasynovial injection, postoperative
complication, hematogenous spread, extension from adjacent tissue), the number of bacteria
introduced into the synovial space, their virulence, concurrent tissue trauma (soft tissue, bone, or
tendon/ligament), the competence of the patient's immune response, and treatment methods, as
well as study design, patient population, and statistical methods. However, those differences
were also present in the studies which showed that treatment delay did significantly worsen the
prognosis. The take-home message seems to be that, while prompt treatment of synovial
contamination provides the best possible chance of a good outcome, other factors may be equally
important.
Walmsley et al. found no significant effect of the interval between contamination and admission
on survival to discharge or return to athletic performance, but they noted an interesting
phenomenon: horses that still had synovial fluid abnormalities indicative of synovitis or sepsis
4–6 days post-admission were significantly less likely to return to athletic function than were
those with normal synovial fluid at that time.10 That is, if the infection/inflammatory response
persisted beyond 4 days of treatment, then the prognosis significantly worsened. Along the same
lines, Kidd et al. showed that treatment of septic arthritis significantly decreased synovial fluid
white cell counts and the expression of matrix metalloproteinase-9 (a gelatinase), and that the
initial concentrations of each were inversely associated with survival.18
"The sooner, the better" clearly applies to the treatment of synovial sepsis, but the good news is
that a delay does not inevitably result in a poor outcome. Intensive and targeted treatment can
still lead to a good result.
Relying on empiric antibiotic therapy
Whether or not there is fecal or environmental contamination, or specific "bad actors" such as S.
aureus, a delay in implementing targeted treatment increases the likelihood that bacteria will
multiply in the relatively protected and nutrient-rich environment of the synovial cavity, and
potentially extent to other structures, including bone. Targeted treatment includes antibiotic
therapy that is guided by bacterial culture and antibiotic sensitivity results whenever possible,
and the case series by Herdan et al.12 illustrates the downside of relying on empiric antibiotic
therapy.
The first case involved septic arthritis of the distal interphalangeal joint secondary to a heel bulb
laceration in a 6-week-old foal. The patient was treated for the first 5 days after injury with a
broad-spectrum antibiotic regimen that is a reasonable empiric choice under the circumstances:
systemic ceftiofur and intra-articular gentamicin. However, the organisms subsequently cultured
from the deteriorating joint and wound tissues (E. gallinarum and E. coli) were resistant to both
drugs. Culture-guided antibiotic therapy began 8 days after injury, but response to treatment was
poor and the foal was euthanized 2 weeks later with extensive osteolysis of the distal phalanx
and navicular bone, complete destruction of the joint, and sequestration of the distal epiphysis of
the second phalanx. This delay, while relatively short (8 days), may have been critical.
The other two cases received immediate, appropriate medical and surgical treatment. However, a
combination of fecal/environmental contamination with multidrug-resistant E. faecalis and other
enteric bacteria, reliance on entirely reasonable but ultimately ineffective empiric antibiotic
choices, and delay in culturing and thus identifying the specific pathogens and their sensitivities
(5–7 days in Case 2, and 23 days in Case 3) evidently contributed to the poor outcomes in these
cases as well. (Note: Reviewing these cases in such detail is not intended as a criticism of how
they were managed, because "there, but for the grace of God, go I." The point is to learn from
our individual and collective failures so that we all get better at managing these challenging, and
at times heartbreaking, cases.)
Does Cause Matter?
Beccati et al. recently published an insightful study documenting the ultrasonographic findings
in 38 horses with septic arthritis or tenosynovitis.23 In one of their analyses, they divided the
horses into 2 groups based on cause: Wounds and Other (intra-articular injection, surgery,
extension from septic cellulitis, and idiopathic). Fibrinous loculations within the synovial cavity
were more than 5 times more likely to be found in the Other group than in the Wound group. As
discussed later, fibrinous adhesions may act as refugia for bacteria; and fibrinous loculations may
be expected to reduce the effectiveness of synovial lavage.
Milner et al. found that horses with synovial sepsis caused by a wound were almost 5 times more
likely to survival to hospital discharge than horses whose synovial infection had some other
cause.21 Furthermore, in their univariable analysis, they found that the larger the maximum
diameter of the wound, the better the outcome.
These findings may seem counter-intuitive at first, as open wounds allow further contamination
of the synovial space. However, unless they are sealed naturally or surgically, wounds that
communicate with the synovial cavity also allow spontaneous drainage of fluid from the synovial
space, along with bacteria, their exo- or endotoxins, and various inflammatory products
(cytokines and chemokines, enzymes, free radicals, white cells, fibrin, and cell debris). In
addition, free drainage prevents the buildup of intrasynovial pressure that could decrease
perfusion and even cause damage to the synovial membrane, intrasynovial structures, and
adjacent bone if the subchondral bone plate is compromised. Furthermore, obvious wounds may
prompt the owner to seek immediate veterinary attention.21 So, while the potential for extensive
and ongoing contamination certainly exists with open wounds involving synovial structures, the
nature of these injuries may also be of some initial benefit.
Targeted Treatment
Reducing, and ultimately eliminating, the bacterial burden within the synovial cavity involves
some variation of these procedures:
• debridement (discussed under REFUGIA, below)
• lavage
• drainage
• antibiotic therapy (discussed in the next article in this series)
Some early and uncomplicated synovial infections may be effectively managed without surgical
debridement, and drainage may be accomplished as part of the lavage procedure (i.e., drainage
via the egress port of the lavage system). Nevertheless, these principles apply in general, even
though their application is adapted for the individual case. The goal is substantial reduction in
bacterial numbers by the inactivation and/or removal of free bacteria and contaminated material.
Synovial Lavage
Large-volume lavage (>5 liters initially for most synovial structures in adult horses) is an
essential component of management for synovial sepsis because it physically dilutes and expels:
• free bacteria and any toxins they produced
• substrates needed for bacterial growth
• inflammatory mediators and proteolytic enzymes
• fibrin and debris that may act as a reservoir for infection
Along the lines of the adage, "the solution to pollution is dilution," large-volume lavage
substantially lowers the bacterial burden, renders the synovial space less hospitable to microbial
growth, and removes both bacterial and host products that contribute to persistent inflammation
and, in the case of septic arthritis, to articular cartilage degradation.
Endoscopic lavage is advised whenever possible, as it provides an opportunity to:
• visually examine most or all of the synovial cavity and its contents
• debride devitalized or irreparably damaged tissue without making a large incision or
extending the wound
• direct the lavage fluid into synovial recesses that may be difficult or impossible to
thoroughly flush with needle lavage or via the wound or open synoviotomy
• remove inflammatory debris, blood/fibrin clots, pannus (granulation tissue), and
adhesions that may compromise full recovery and even contribute to persistent infection
Endoscopy may be performed even when an open wound communicates with the synovial
structure, although distension of the synovial space in preparation for endoscopic examination
can result in leakage of the fluid from the wound. In some cases, the wound may be used as an
endoscopy or instrument port.16 Alternatively, the wound may be debrided and sutured, and then
the synovial cavity may be examined endoscopically.
Interestingly, Wereszka et al. found no significant effect of lavage method on 1-year survival or
return to intended use in horses with septic tenosynovitis treated with through-and-through
lavage, tenoscopy (which included lavage), or open tenosynoviotomy with lavage.19 Endoscopic
lavage certainly has its advantages, but this study illustrates that the throughput of large volumes
of sterile fluid is a critical element. When endoscopy is unavailable or prohibited on economic
grounds, or when access is delayed for some reason, it is useful to know that through-and-
through, or needle, lavage is a valid alternative.
With or without antiseptic?
With a severely contaminated or infected wound, it is tempting to add an antiseptic agent such as
povidone-iodine or chlorhexidine to the lavage fluid. However, when the wound communicates
with a synovial space, extra care is needed to ensure that the synovial structures do not sustain
chemical damage.
Povidone-iodine. At concentrations of 0.5% to 1%, povidone-iodine (PVI) appears to have no
adverse effects on articular cartilage metabolism in vitro, even after 2 hours of exposure.24
However, exposure time is a key—and perhaps limiting—factor when protein is present.
For example, a German study examined the in vitro bactericidal effect of Betaisodona® (10%
PVI) solution against strains of methicillin-resistant S. aureus (MRSA).25 When there was no
protein in the culture medium, optimal bactericidal activity occurred at PVI concentrations of
0.1% to 1% with an exposure time of 30 seconds. When protein (0.2% albumin) was added,
concentrations of at least 1% PVI were required with an exposure time of 30 seconds. But when
the protein load was increased 10-fold (to 2% albumin), optimal bactericidal activity required
either a 10-fold increase in concentration for the same exposure time (undiluted Betaisodona for
30 seconds) or a 10-fold increase in exposure time for the same concentration (1% PVI for 5
minutes).
To put that into a clinical context, 2% albumin is 2 g/dl, which is less than half the concentration
of total protein in the synovial fluid of most septic joints and tendon sheaths (often >4
g/dl).10,19,21,22 Extrapolating from the Betaisodona study, exposure times may be required in cases
of synovial sepsis that are impractical if PVI is added to the lavage fluid at bactericidal
concentrations known to be well tolerated by articular cartilage.
Complicating things further, an in vivo equine study found that lavage of the digital flexor tendon
sheath with 0.5% PVI caused severe synovitis, whereas 0.1% PVI caused no more inflammation
than lavage with a balanced electrolyte solution (which was minimal).26 The latter comports with
the findings of another equine study, in which the joints of healthy horses were experimentally
inoculated with S. aureus and then lavaged with either balanced electrolyte solution or 0.1%
PVI. There were no significant differences between these two treatments for synovial fluid total
protein concentration or white cell count, histologic degree of synovial inflammation, or articular
cartilage GAG content—but also no significant differences in bacterial culture results (synovial
fluid and membrane).27
Taking all of these findings together, one could conclude that addition of PVI to the lavage fluid
is likely to be either harmless but useless or useful but harmful (to at least some synovial
structures).
Chlorhexidine. The situation is much more clear with chlorhexidine. In an in vivo equine study,
synovial lavage with 0.05% chlorhexidine (the lowest bactericidal concentration) caused
significant synovial inflammation, ulceration, and fibrin accumulation.28 In another equine study,
potentiation of chlorhexidine with EDTA and Tris buffer allowed a much lower concentration
(0.0005% chlorhexidine) to be used without causing synovial inflammation or articular cartilage
damage in vivo, while maintaining good in vitro bactericidal effect against clinical isolates of S.
aureus, E. coli, and S. zooepidemicus.29 However, that study was published almost 20 years ago,
and clinical studies are still lacking on the safety and efficacy of potentiated chlorhexidine for
lavage in horses with synovial sepsis.
Another consideration is the possible influence of pre-existing joint disease. The aforementioned
equine studies examined healthy joints in normal horses and ponies. However, an in vitro study
using human articular cartilage explants showed that, while exposure to 0.05% chlorhexidine for
1 minute did not significantly affect the metabolism of cartilage from joints without
osteoarthritis, it markedly impaired the metabolism of cartilage from osteoarthritic joints.30 As
synovial sepsis can adversely affect articular cartilage, causing GAG loss and chondrocyte death
in as little as 48 hours,4-6 chlorhexidine at even very low concentrations may be inadvisable for
lavage of septic joints, particularly if there has been a treatment delay of more than 48 hours. If
chlorhexidine is used in lavage fluid, it has been suggested that it then be rinsed from the
synovial space.31
Polyhexanide. Polyhexamethylene biguanide, or polyhexanide, is an antiseptic agent that is used
in human orthopedic surgery because of its broad spectrum of bactericidal activity and relatively
low cytotoxicity compared with other antiseptic agents such as chlorhexidine.32 However, its
activity requires prolonged exposure (5–20 minutes), and even with exposure times of only 5 or
10 minutes, the standard concentration of polyhexanide (0.04%) is toxic to chondrocytes33 and
osteoblasts32 in vitro. Very low concentrations (0.005%) of polyhexanide appear to have no
negative effects on cartilage metabolism in vitro,24 but the clinical efficacy of this concentration
has not been studied in horses with synovial sepsis.
On the one hand, there are few things more destructive to a synovial structure than persistent
infection. But on the other hand, physical expulsion of bacteria, their toxins, and inflammatory
products through large-volume lavage, accompanied by local and systemic antibiotic therapy, is
likely to do the job just as well, without the risks of chemical damage.
Whether and when to repeat?
As a testament to the importance and effectiveness of synovial lavage, a single treatment often is
sufficient, in conjunction with local and systemic antibiotic therapy. Some patients do require a
second or multiple lavages, although the proportion is surprisingly low, given the condition
being treated. In clinical studies published over the past 15 years, about 1 in 4 patients with
synovial sepsis received more than 1 lavage,10,13,19 although it ranged from around 12%15,16,21 to
38% of patients.17 Simply put, in at least 60% of patients, once is enough.
The necessity and frequency of serial lavage may be guided by repeated synovial fluid analysis
and/or clinical response.16,21 However, a number of authors routinely repeated synovial lavage
every other day (q 48 h) until clinical signs of synovial sepsis resolved and/or synovial fluid
normalized.11,14,17,34
In each case, the decision whether and when to repeat synovial lavage must weigh several
factors, including these:
• patient restraint, particularly if general anesthesia is needed
• potential for synovial damage or fibrosis from repeated insertion of catheters/cannulas or
lavage itself (particularly with high-pressure lavage)
• potential for (re)infection, particularly if septic cellulitis complicates synovial sepsis
• excessive dilution of nutritive and protective substances (e.g., hyaluronate), as well as
host defenses and antibiotic drugs, in the synovial fluid
• synovial fistula formation (see below)
That said, there are few things more destructive to a synovial structure than persistent infection
and the inflammatory response it incites, so one-too-many lavage treatments may be less
detrimental than one-too-few.
Drainage
Drainage is a key component of treatment for serious wound infections. However, wounds that
communicate with a synovial cavity present a unique problem because the synovial membrane is
a secretory tissue. Whether or not to close the wound, or even to close just the synovial space, is
somewhat of a judgment call. Several factors need to be considered, including these:
• open synovial cavities are vulnerable to further contamination, so it may be best to close
fresh, minimally contaminated wounds primarily and rely on endoscopic or needle lavage
for controlled drainage as needed
• some chronic wounds may also be debrided and closed surgically at the time of
presentation and then managed as above
• severely contaminated wounds may be best left open to drain, at least initially, for the
reasons discussed earlier (spontaneous drainage expels bacteria, toxins, and inflammatory
exudate, and reduces intrasynovial pressure)
• however, leaving the synovial cavity open to drain necessitates frequent dressing
changes, as it is very difficult to maintain sterile dressings on these effusive wounds
• leaving the synovial cavity open to drain for more than a few days may lead to fistula
formation as the wound heals; repeated synovial lavage may increase this risk (see
below), as may the use of drains and setons, so plan on debriding and closing at least the
synovial structure as soon as the infection is responding to treatment
• if the nature of the injury requires the external support of a cast or Robert Jones bandage,
then even if the wound is severely infected, it may be best to close the synovial space
(before or after thorough lavage), and rely on systemic and local/regional delivery of
antibiotics to control the infection
• closed-cavity infections can be very painful, so if the wound is closed naturally or
surgically and the horse becomes more uncomfortable, then use repeat lavage
(endoscopic or needle) as a means of providing drainage to lower the intrasynovial
pressure and manage the infection
Whether or not the synovial structure is closed, the wound must be protected with a sterile
dressing that is changed at least once a day until wound healing is well underway and there is no
drainage from the wound.
Avoiding synovial fistula formation
Stewart et al. described the use of an indwelling intrasynovial catheter for the treatment of
synovial sepsis in 38 horses.22 An over-the-wire polyurethane cathetera was placed into the
infected joint or tendon sheath while the horse was under general anesthesia so that antibiotics
could be infused into the synovial cavity 3 or 4 times a day until the infection was resolved. In 27
horses, daily synovial lavage was also performed through the catheter, using the open wound, a
synoviotomy incision (created or left open for the purpose), or a needle as the egress port.
This technique is discussed further in the next article, in the section on local/regional antibiotic
delivery. Of note here, 2 horses developed synovial fistulas at the site of an open wound or
arthrotomy incision. The authors commented that daily lavage and consequent fluid drainage
through the synovial defect may have contributed to fistula formation. Since those 2 cases, they
have limited open synovial lavage to a maximum of 5 consecutive days. If the egress site is
healing and the horse is no longer lame, then lavage is discontinued. Since adopting this
approach, no further fistulas had developed. That is probably a good guideline to follow with
repeated lavage of open synovial wounds, whether or not an indwelling catheter is used.
REFUGIA
A refugium in this context is any substance or circumstance that protects bacteria within the
tissues from the host's defenses and effective concentrations of antibiotic drugs, enabling the
infection to persist and potentially to progress.1 With wounds involving synovial structures,
refugia may include:
• foreign material—foreign bodies such as nails or wire, flecks of metal or paint left behind
after foreign body removal, wood splinters, thorns, etc.
• surgical implants—including sutures, staples, drains, and indwelling catheters; bacterial
biofilms may form on any of these materials and serve as a source of persistent
(re)infection
• poorly perfused or devitalized tissue—congested or damaged synovium, cartilage or
osteochondral flaps or fragments, fibrillated tendon, etc.
• inflammatory debris—blood/fibrin clots, purulent material, fibrous adhesions
• infection adjacent—e.g., overlying wound infection or cellulitis; osteomyelitis; infection
of an adjacent joint, tendon sheath, or bursa
In numerous clinical studies of synovial sepsis in horses, involvement of tissues other than the
synovium—such as bone, tendon, or cartilage—worsened the recovery rate.10-14,19,20,22,34 For
example, in horses with synovial contamination or sepsis caused by penetrating injury to the
solar surface of the foot, concurrent injury to the distal phalanx increased the odds of euthanasia
during hospitalization by 32-fold over horses with no such bone injury.13 Involvement of the
distal phalanx was typically accompanied by involvement of other digital structures, particularly
the deep digital flexor tendon and the navicular bursa.
Rates of bone and/or tendon involvement in horses with synovial sepsis from various causes,
including trauma, are reported to be in the range of 25% to 44% of patients.10,19,22 Using
ultrasonography, Beccati et al. documented soft tissue lesions involving structures other than the
synovium and capsule in 53.5% of horses with septic arthritis or tenosynovitis.23 These incidence
rates are a sobering reminder that assessment of wounds involving a synovial structure should
include both radiographic and ultrasonographic examination whenever possible. As osteolysis
may not be evident radiographically for days or even weeks after injury or infection, radiography
is indicated both at presentation (or as soon as possible) and 1–2 weeks later.
The importance of refugia in synovial sepsis may be further illustrated by an unusual
phenomenon that is revealed in numerous clinical studies: unexpected recurrence of infection
days or weeks, and up to 3 months, after apparent recovery. This problem has not been well
studied, but somewhere between 4% and 10% of patients appeared to recover from the infection
and were discharged from the hospital, only to be readmitted or euthanized without treatment in
the following days, weeks, or months because clinical signs of infection (synovial sepsis and/or
infection in adjacent tissues) had recurred.9,11,12,14,19,22 This phenomenon is documented in young
foals and adult horses alike, and it suggests that in some cases the synovial structures or related
tissues may act as refugia.
Surgical Debridement
The studies documenting involvement of other tissues also serve to illustrate that treatment
directed solely at the contaminated synovial space, such as synovial lavage and intrasynovial
antibiotic delivery, may be insufficient to resolve the infection in these cases. Wound infections
involving bone are the focus of the third article in this series. Suffice it to say here that
concurrent bone lesions in a patient with synovial sepsis need additional surgical and medical
treatment, including thorough debridement of the abnormal bone and long-term antibiotic
therapy.
Devitalized or irreparably damaged tissues within the synovial space and also pannus
accumulations are best debrided endoscopically or via the wound or open synoviotomy. In their
study of septic tenosynovitis, Wereszka et al. found that the presence of severe pannus
significantly decreased the likelihood of the horse returning to its previous or higher level of
athletic performance compared with patients in which pannus was mild or absent.19 As this
fibrovascular tissue may serve as a refugium within the synovial space, its presence should be
regarded as more than a mere interference to full athletic function.
The overlying wound may need to be debrided before being closed primarily, left to heal by
second intention, or prepared for delayed primary closure. Whether or not synovial and wound
debridement are performed at the same time depends on the case. The primary concern is to
avoid further contamination of the synovial space via the wound, so to that end it may be best to
address the synovial structure first and the wound second. Alternatively, synovial and wound
closure may be followed immediately by endoscopic examination, debridement, and lavage of
the synovial cavity.
Repeated endoscopic examination and debridement is sometimes needed when the clinical
response is not as good as expected and repeat synovial fluid analysis and/or ultrasonography
suggest that a focus of infection remains within the synovial space. As with the argument for
repeated lavage, on balance it may be better to repeat endoscopic examination on a case that
turned out not to need it than to hold off and discover later that the case would likely have
benefited from it. The need for more than 1 surgery was significantly associated with a poor
outcome in some studies that examined this variable,13,21 and it would be interesting to know
whether delaying the second surgery contributed to these poorer outcomes.
IMMUNOCOMPROMISE
Immunocompromise can profoundly impede recovery from infection.1 Nowhere is that more
apparent than with septic arthritis in young foals.11,14,15,34 Failure of passive transfer of colostral
antibodies is common in these patients11,14 and likely contributed to the common occurrence of
multisystem disease (sepsis involving tissues/organs other than joints), which significantly
decreased survival rates.11,34 In adult horses, numerous intrinsic and extrinsic factors may
compromise the immune response to infection, although this phenomenon is not well studied in
connection with synovial sepsis.
Pregnancy?
Pregnancy may complicate the treatment of synovial sepsis, as it is a relatively immunotolerant
state. This situation is illustrated by one of the cases presented by Herdan et al.12 A pregnant
mare undergoing standing ovariectomy to remove a granulosa-theca cell tumor jumped out of the
stocks and sustained a full-thickness skin laceration to the carpus which exposed part of the third
metacarpal bone and opened the extensor carpi radialis tendon sheath. Despite broad-spectrum
systemic antibiotic therapy pre- and post-operatively and immediate wound care, septic
tenosynovitis developed. Three weeks after injury, the mixed-bacterial infection had extended to
the antebrachiocarpal joint...
Corticosteroids
The mare was euthanized 4½ months after injury (3 months after discharge from the hospital),
shortly after an intra-articular injection of 6 mg triamcinolone. That brings us to the third clinical
scenario which can interfere with successful resolution of synovial sepsis, and in this case
apparently contributed to recrudescence of the infection: corticosteroid administration. The mare
became nonweight-bearing lame in the injured limb after corticosteroid administration and at
necropsy was found to have septic arthritis of both the antebrachiocarpal and the midcarpal
joints, with extensive articular cartilage destruction.12
In a clinical study of 38 horses with synovial sepsis, Stewart et al. noted that synovial fluid
culture in 2 horses grew a mix of Aspergillus sp. and Pseudomonas sp.22 Both horses developed
synovial sepsis after intrasynovial corticosteroid administration. Pseudomonas sp. is a relatively
uncommon finding on synovial fluid culture (<10% of isolates);9,11,19,22 Aspergillus sp. is rare.
Both suggest environmental contamination, and clinical infection with a mix of these two
pathogens suggests immunosuppression which compromised synovial defenses.
Some authors routinely or occasionally administered corticosteroids intrasynovially after clinical
recovery from synovial sepsis;12,14 one author routinely injected 4–8 mg dexamethasone into
(post)septic joints as soon as the synovial fluid normalized (after the last joint lavage),14
presumably in an effort to prevent or treat secondary osteoarthritis. Experimentally, injection of
100 mg methylprednisolone into healthy joints after a small inoculum of S. aureus did not result
in a statistically greater incidence of joint sepsis compared with saline-treated controls (see
below).7 However, as a small percentage of patients experience recurrence of infection up to 3
months after apparent recovery, this practice should probably be applied with great caution.
Polysulfated glycosaminoglycans
Intra-articular administration of polysulfated glycosaminoglycan (PSGAG) has been shown to
cause profound immunosuppression, or at least facilitate joint sepsis, in horses. In an in vivo
study, joints in healthy horses were experimentally infected with 33 CFU of S. aureus and then
treated intra-articularly with sterile saline (control), 250 mg PSGAG, 100 mg
methylprednisolone acetate, or 20 mg sodium hyaluronate (HA).7 There were no significant
differences in the rates of joint sepsis between control (1 of 8 joints) and corticosteroid-treated
(3/8) or HA-treated (4/8) joints, but all 8 joints treated with PSGAG became septic (P=0.001).
This effect was further investigated in a study of similar design which compared sterile saline
(control), 250 mg PSGAG, filtered PSGAG (using a 0.6-micron filter), and PSGAG to which
125 mg amikacin was added.8 Sepsis developed in all horses treated with PSGAG, except for
those in which amikacin was added. The authors concluded that intra-articular administration of
PSGAG increased the infectivity of S. aureus; filtering the PSGAG had no effect, but the
addition of 125 mg amikacin prevented potentiation of infection by PSGAG.
Addition of amikacin to intra-articular injections of PSGAG has since become standard practice.
The point of reviewing these 25-year-old studies is to remind ourselves of the importance of
preserving the vulnerable immunologic landscape of the contaminated synovial space.
Hyaluronate?
As mentioned above, the incidence of joint sepsis after experimental infection with a small dose
of S. aureus was not significantly different for saline-treated (control) and HA-treated joints.7
Thus, hyaluronate does not appear to facilitate or potentiate bacterial infection as PSGAG has
been shown to do.
In fact, hyaluronate may be immunomodulatory, as illustrated by the following study. Septic
arthritis was experimentally induced with S. aureus, then 24 hours later the joints were lavaged
with lactated Ringer's solution; in addition, half of the joints were injected with HA.35 Compared
with the horses whose lavaged joints were not injected with HA, the HA-treated horses were
significantly less lame, there was less articular swelling (smaller joint circumference), synovial
fluid white cell counts and total protein concentrations were lower, and the synovial membrane
had less cellular infiltrate, less pannus, and a more normal villous structure. There was also a
trend for less GAG loss from the articular cartilage in the HA-treated joints.
From these studies, HA appears to be a safe addition to a septic joint following synovial lavage,
and it may help make the patient more comfortable and moderate the inflammatory response that
contributes to cartilage deterioration. That said, HA should be considered a supplemental rather
than a primary treatment for synovial sepsis.
Plasma Therapy
Although this aspect of wound care has not been well studied in horses, antigen-specific
hyperimmune plasma may be of value when the pathogen is known. Commercial hyperimmune
plasma is available in the US specifically for E. coli, Salmonella spp., S. equi, Rhodococcus equi,
and various Clostridium spp.b No commercial equine hyperimmune plasma products are yet
available for S. aureus, but a recent in vitro study showed that plain equine plasma significantly
inhibited the growth of both methicillin-sensitive and methicillin-resistant S. aureus, unless the
plasma was heat-inactivated,36 so fresh plasma from the patient or a healthy herdmate may be of
some benefit.
Supplemental plasma may be administered locally (e.g., to a wound bed) or intravenously.
Unconditioned and calcium-activated platelet-rich plasma products appear to be safe for use in
normal equine joints.37,38 Even so, if administering plasma into a septic synovial structure, it may
be wise to dilute it in sterile saline or polyionic solution until we have more information on this
biologic therapy in synovial sepsis.
POOR PERFUSION
Poor perfusion is another condition that can profoundly challenge the treatment of serious wound
infections.1 The synovium is a well-vascularized tissue, but it encases some other tissues that by
nature are not as well vascularized (tendon, ligament, meniscus) or that are avascular (articular
cartilage). As discussed above, involvement of these structures in synovial infection lowers the
short- and long-term recovery rates, as does the presence of necrotic tissue.19
Surgical debridement, synovial lavage, and effective antibiotic therapy each make positive
contributions to restoring optimal blood flow to compromised synovial tissues. Nonsteroidal
anti-inflammatory therapy may also be of value in this regard, in addition to improving patient
comfort and mobility—which further aids in optimizing tissue perfusion. Oxygen therapy, such
as systemic hyperbaric oxygen therapy39 and local or regional ozone therapy,40 may also be of
benefit in treating severe or persistent infections, although oxygen therapy is not well studied in
horses.
Managing wounds involving synovial structures continues in the second article in this series,
which focuses on the reasons anbitiotic therapy may fail or fall short, and strategies for
optimising the effectiveness of antibiotic therapy in these wounds.
Author’s note: This article was written by me (Christine M. King) on commission in 2016 and published under
another person’s name. This article is some of my best work to date, yet it is credited to someone else—an
act of intellectual dishonesty, the ramifications of which I did not appreciate at the time. This article is
entirely my own original work, exactly as I submitted it. I retain the copyright.
******************
MANUFACTURERS
a MILACATH 2-Piece Guidewire Kit–14 ga x 20 cm [product #1410-2P], MILA International,
Erlanger, KY. www.milainternational.com.
bAntigen Select Equine HI Plasma, Lake Immunogenics, Inc., Ontario, NY.
http://www.lakeimmunogenics.com.
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