FEATURE
Developing and Evaluating Outcomes of an
Evidence-based Protocol for the Treatment of
Osteomyelitis in Stage IV Pressure Ulcers:
A Literature and Wound Electronic Medical
Record Database Review
Robert Rennert, BA; Michael Golinko, MD; Alan Yan, MD; Anna Flattau, MD; Marjana TomicCanic, PhD; and Harold Brem, MD, FACS
Abstract
Osteomyelitis affects up to 32% of full-thickness pressure ulcers and increases treatment costs and the risk of systemic
complications. Current diagnosis and treatment practices are variable. A literature and retrospective chart review, using a
wound electronic medical record (WEMR), were conducted to develop an evidence-based protocol of care for treatment
of osteomyelitis in pressure ulcers and to evaluate outcomes of care. The seven steps in the protocol of care include: 1)
acknowledgment of osteomyelitis risk in patients with Stage IV pressure ulcers, 2) clinical evaluation for local or systemic
signs of infection upon initial presentation, 3) radiographic evaluation (magnetic resonance imaging or bone scan), 4) surgical debridement to remove all nonviable tissue and/or scarred and infected bone, 5) obtaining pathology reports from
sterile bone biopsy and deep microbial cultures, 6) targeted systemic antimicrobial therapy, and 7) tissue reconstruction
following resolution of infection. WEMR data review (177 patients) identified 50 patients with osteomyelitis (prevalence
28%). Of those, 41 underwent 87 bone debridements for osteomyelitis. Eight (20%) patients experienced complications
related to treatment. Average time to discharge following debridement was 4.3 ± 5.7 days and 76% of wounds with more
than two consecutive WEMR entries showed a decrease in area at their final visit. The outcomes observed are encouraging
and the WEMR facilitates implementation and evaluation of the treatment protocol. Ongoing data acquisition will help assess outcomes and refine the current management protocol and should improve diagnosis and care.
Key Words: osteomyelitis, pressure ulcer, Stage IV ulcer, bone debridement, outcomes
Index: Ostomy Wound Management 2009;55(3):42–53
Potential Conflicts of Interest: This work was funded by the National Institutes of Health/National Library of Medicine
(NIH/NLM) grant 5R01LM008443 (Brem), R21 AG030673 (Tomic-Canic). Dr. Brem and Dr. Tomic-Canic received support
from Organogenesis for Continuing Medical Education programs.
Mr. Rennert is a medical student, The Ohio State University School of Medicine, Columbus, OH. Dr. Golinko is a surgical resident and previous post-doctoral
fellow and Dr. Yan is a fellow, Division of Wound Healing and Regenerative Medicine, Department of Surgery, New York University School of Medicine, New York,
NY. Dr. Flattau is an Assistant Professor, Montefiore Medical Center, Department of Social and Family Medicine, Bronx, NY. Dr. Tomic-Canic is Professor of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL. Dr. Brem is Associate Professor of Surgery and Division Chief,
Division of Wound Healing and Regenerative Medicine, Helen & Martin Kimmel Wound Center, Department of Surgery, New York University School of Medicine.
Please address correspondence to: Harold Brem, MD, FACS, Helen & Martin Kimmel Wound Center, Department of Surgery, New York University School of Medicine, 301 East 17th Street, Room 1027, New York, NY 10003; email: [email protected].
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OSTOMY WOUND MANAGEMENT MARCH 2009
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OSTEOMYELITIS IN PRESSURE ULCERS
ith 1.3 to 3 million cases diagnosed annually in the US,1
and average charges reaching $37,800,2 pressure ulcers
present a serious medical problem for hospitalized and/or
bed-bound patients. Pressure ulcers have an estimated prevalence as high as 26% among hospitalized patients,3 53%
among nursing home patients,4 and 39% among patients with
spinal cord injuries.5 Pressure ulcers are associated with underlying physiologic impairments6-8 and can be difficult to
heal even when appropriately treated.
Pressure ulcers increase the length of hospital stay, risk of
nosocomial infection, and treatment costs.9 Evidence shows
that pressure ulcers are associated with increased mortality
rates10 and have been reported as a cause of death in more
than 104,000 persons in the US annually.11 Septicemia was an
underlying or contributing cause in 39.7% of all pressure
ulcer-associated deaths.11
Stage IV pressure ulcers are particularly morbid. As much
as 54% of Stage IV pressure ulcers require multiple hospital
admissions12 and approximately 95% do not heal within 8
weeks.13 The 6-month mortality rate of patients with Stage IV
ulcers can be as high as is 68.9%.14
Osteomyelitis is characterized by a mixture of inflammatory cells (including neutrophils, lymphocytes, and plasma
cells), fibrosis, bone necrosis, and new bone formation.When
diagnosed in Stage IV pressure ulcers, osteomyelitis is associated with nonhealing wounds,15 surgical flap complications,16,17 and an increased length of hospitalization.16
Osteomyelitis may develop within the first 2 weeks of pressure
ulcer formation and despite treatment may require amputation in lower extremity cases.18 The prevalence of osteomyelitis
in full-thickness pressure ulcers ranges from 17%19 to 32%18
and in a prospective histologic and pathologic studies20 of
bone cultures, the average cost of treatment was found to be
$59,600. Despite the high prevalence of osteomyelitis, no large
randomized controlled studies have been conducted with antibiotics nor have specific guidelines been promulgated.
W
Pathogenesis of Pressure Ulcers
Many studies have tried to explain the etiological pathways
involved in the development of pressure ulcers, although precise understanding remains unclear. Similarly, little is known
about the pathogenesis of pressure ulcers. Immobilized, bedbound, elderly patients are the most likely to develop these ulcers.21 One postulated contributing factor is that ischemia
occurs when static stress on the tissue is greater than the pressure in capillaries, restricting the blood flow to the area.22 It
has been shown that aged rabbits with chronically ischemic
ear wounds fail to heal, suggesting that wound healing impairment is additive, if not synergistic, when age and ischemia are
combined.23 However, the skin break occurs in the epidermis,
which is not vascularized, indicating that pressure has multiple pathogenic effects in addition to local ischemia. The initial
break occurs in the epidermis and the process progresses toward the deep tissue. However, other studies using animal
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Ostomy Wound Management 2009;55(3):42–53
Key Points
• Osteomyelitis is a serious complication of full-thickness pressure ulcers; data to guide treatment are limited.
• Using existing literature, the authors developed an
osteomyelitis protocol of care and conducted a medical chart review to evaluate outcomes of care.
• Overall complication rates of the seven-step protocol
of care, which includes bone debridement, were low
and reduction in wound area was observed in the majority of pressure ulcers.
• Additional studies to optimize treatment of this serious complication are needed.
models have demonstrated damage to the deeper tissues such
as muscle before changes in skin occur.24 This also raises the
question of how compression (pressure) affects mechanical
properties of the skin and epidermis in particular, leading to
this breach. Recent in vitro studies25,26 have shown that the deformation of cells within tissues following sustained compression could be an important inducer of cell damage. Other in
vivo studies27 have shown that large tissue deformation, in
conjunction with ischemia, provide the main trigger for irreversible muscle damage.
Other factors such as age and diabetes also may play a role;
however, wounds in elderly patients can be expected to heal,
if at a slower rate.28 Recent data from a study29 comparing
young db/db mice, aged db/db mice, age-matched non-db/db
control, and wild type mice suggest it is the combination of
age and diabetes that has been shown to have the most detrimental impact on a wound’s mechanical properties, collagen
deposition, and epithelialization.
Pressure ulcers do not naturally occur in animals; therefore,
establishing a true animal model has been difficult. These restrictions resulted in limited knowledge of the etiology and
pathogenesis of pressure ulcers; the knowledge gained thus far
comes only from analyses of human tissues, limited observations, biopsies, and wound fluid analyses.30-37 Research endeavors found elevated levels of IL1; TNF- ; MMP-1, 2, 3, 9, 10, 13;
degradation of tenascin-c and fibronectin; and increased procollagen expression. However, the possible implications of mechanical load (pressure, static compressive stress) on cellular
and molecular processes are yet to be elucidated because Stage
I pressure ulcer biopsies from patients are impossible to obtain.
Once formed, pressure ulcers are chronic wounds with physiologic impairments to the wound healing process.6-8 Normal
wounding activates keratinocyte migration and proliferation,
paralleled by changes in cellular adhesion and cytoskeletal content that promote healing.8 In chronic wounds, keratinocyte
migration is inhibited and growth and differentiation are deregulated by the Wnt signaling pathway.8 Specifically, activation
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FEATURE
Panel45 has classified four Stages of ulcers, with Stage IV ulcers
at risk for underlying osteomyelitis. Multiple scales have been
developed to identify high-risk patients13,46-48; however, these
scales are variable and clinical judgment was found to be the
most reliable indicator of risk.49,50 Early diagnosis and proper
treatment of lower stage ulcers are crucial to prevent wound
progression. Misdiagnosis and inadequate or improper treatment can lead to progression of the pressure ulcer and consequently increase the risk of complications such as
osteomyelitis, sepsis, and amputation.51-53
1a
1b
Figure 1. Examples of patients with Stage IV pressure ulcers with underlying osteomyelitis: ischium (1a) and
trochanteric (1b).
of the protein β-catenin (as evidenced by its nuclear presence)
and induced expression of the oncogene c-myc lead to inhibition of keratinocyte migration, resulting in a chronic wound
that is susceptible to infection. In summary, the development
of severe pressure ulcers is generally considered to be multifactorial in nature.
Pressure Ulcer Stages
Pressure ulcers most often occur in the trochanteric, ischial,
heel, and sacral areas.38 Susceptibility increases with external
(pressure, friction, shear force, and moisture) and internal factors
(age, malnutrition, anemia, nervous regulation of local blood
flow, and diabetes).39-44 The National Pressure Ulcer Advisory
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OSTOMY WOUND MANAGEMENT MARCH 2009
Osteomyelitis: Pathogenesis, Clinical
Presentation, and Complications
In Stage IV pressure ulcers, causative micro-organisms or
bacteria can migrate to nearby bone, causing osteomyelitis.
Common pathogens in pressure ulcer-associated osteomyelitis
include Staphylococcus aureus, Enterobacteriaceae, Streptococcus,
Pseudomonas species, and anaerobic bacteria.17-19 Following infection, leukocytes release enzymes that combine with other inflammatory factors to promote tissue necrosis and the
destruction of bone cells.54,55 The inflammatory process spreads
into the bone’s blood vessels, impairing flow; the resulting ischemia creates areas of devitalized, infected bone. Delivery of
certain antibiotics is impaired to this avascular area,56-58 limiting
efficacy. During infection, growth factors and cytokines associated with osteoclast and osteoblast activity are also present in
abnormal local concentrations, affecting bone structure.59-61
These changes are not well characterized in osteomyelitis.
In general, osteomyelitis can manifest as a poorly healing
wound with or without systemic effects, including fever, leukocytosis, and sepsis.17,18,51,62 The infection can involve bone marrow, cortex, and periosteum as well as surrounding soft tissue
and may result from a contiguous source of infection.63,64 Older
patients have an increased risk due to a higher general incidence
of diseases and conditions (ie, pressure ulcers) and/or surgical
procedures that predispose them to osteomyelitis.29,62
Osteomyelitis may be classified in several ways,65,66 most
commonly acute or chronic.67,68 Acute osteomyelitis is a first
episode that is resolved in fewer than 6 weeks. Chronic osteomyelitis lasts longer than 6 weeks or recurs after initial infection and is characterized by persistence of micro-organisms,
low-grade inflammation, the presence of dead bone (sequestrum), and fistulous tracts.69 However, these classification
schemes do not affect evaluation or management in osteomyelitis associated with Stage IV pressure ulcers largely because these ulcers are treated the same regardless of
osteomyelitis classification.
Bone infection under an ulcer often is present for an indeterminate period before diagnosis; all bone infections resulting from a Stage IV pressure ulcers should be considered
chronic. The development of a standardized protocol for the
prevention, diagnosis, and therapy of pressure ulcers with underlying osteomyelitis is vital to preventing complications
such as sepsis associated with Stage IV pressure ulcers. The
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OSTEOMYELITIS IN PRESSURE ULCERS
2a
2c
2b
2d
Figure 2. A 51-year-old woman with paralysis presented with gangrene and osteomyelitis (she grew MRSA from
her bone) of her sacral ulcer (Figure 2a). The wound eventually healed after implementing the treatment protocol.
(Figure 2b-d).
purpose of this literature and chart review was to develop and
evaluate outcomes of an evidence-based protocol for the treatment of osteomyelitis in Stage IV pressure ulcers.
Methods
Literature review. To identify treatment options and evaluate the evidence for all treatment steps regarding osteomyelitis and pressure ulcers, a Pubmed literature search of
English-language articles published from 1980 to 2007 was
conducted using the search phrases osteomyelitis pressure ulcer,
osteomyelitis, pressure ulcer, osteomyelitis antibiotics, oswww.o-wm.com
teomyelitis diagnose, and osteomyelitis radiography. All located
articles and their associated reference lists were reviewed for
clinical relevance; all levels of evidence were included for articles meeting the search criteria.
Patient chart review using wound electronic medical record
(WEMR). The records of patients with osteomyelitis underlying
pressure ulcers at a university-based hospital inpatient wound
clinic were analyzed to provide a specific treatment protocol.
Records review was supervised by the senior author. A
trained research fellow and a post-doctoral fellow reviewed
the records of all patients treated over 3 years (2004–2007),
MARCH 2009 OSTOMY WOUND MANAGEMENT
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FEATURE
using Microsoft Excel (Microsoft Co., Redmond, WA). This research was approved by the Institutional Review Board of Columbia University (IRB–AAAB4487).
Table 1: Bone Debridement Complications
N = 41 patients, 49 pressure ulcers
Bone debridements analyzed (n)
Number (%) of unexpected patient returns
to OR
Average (SD) days to discharge following
bone debridement
Number (%) of patients with complications
Death before discharge
87
1 (2%)
4.3 ± 5.7*
48 (21%)
0
*Calculated from earliest bone debridement date per admission.
Table 2: Long-term Outpatient Outcome Following
Final Bone Debridement*
N = 20 patients, 21 pressure ulcers
Number (%) of ulcers with decreased
ulcer area
Number (%) of ulcers with increased
ulcer area
Average (SD) follow-up time
16 (76%)
5 (24%)
20.6 ± 26.7 weeks
*For patients with at least two WEMR records following final bone
debridement.
specifically examining data entered into the WEMR. The
WEMR was designed using Microsoft Access® and is a relational database with 137 fields for clinical data entry including
a digital photograph of the wound; a real-time wound healing
rate graph (length, width, depth, and area as a function of
time); wound location (as specific as toe or malleolus);
drainage, cellulitis, and/or pain; fever; ambulation status; degree of undermining; current treatment; summary of the patient’s medical history; laboratory data; radiology and
pathology reports; wound culture reports; medications; and
wound treatments. The database output function displays a
single data sheet and can be viewed online or printed. This
data sheet contains digital photographs of the wound, a graph
that trends wound area and depth, and the most recent laboratory data with color-coding for abnormal results.
The WEMR database was culled to identify pressure ulcer
patients diagnosed with osteomyelitis, as defined by a positive
bone scan or MRI and/or pathology reports showing bone
necrosis or acute inflammation. Although the evidence-based
guidelines presented herein were not formalized in the authors’
hospital before publication of this manuscript, previous treatment of all patients with osteomyelitis underlying a pressure
ulcer was based on, and in accordance with, the same principles.
Unexpected returns to the OR, complications, deaths before discharge, and condition upon discharge were recorded for all patients undergoing bone debridement. Data from patients with
at least two WEMR records (and corresponding wound areas)
following final bone debridement were further analyzed to determine healing trends. Descriptive statistics were calculated
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OSTOMY WOUND MANAGEMENT MARCH 2009
Results
More than 300 articles of various levels of evidence and
study type (eg, randomized trials, prospective studies, and retrospective studies) were found. The following protocol was developed based on a review of the literature on treatment options
for osteomyelitis as well as a retrospective chart review of outcomes (using the WEMR) for patients treated for osteomyelitis.
It must be emphasized that this protocol to treat osteomyelitis
in Stage IV pressure ulcers must be initiated with the patient
(or the guardian) and the primary medical physician and bedside nurse. The protocol consists of the following:
1. Acknowledge that every patient with Stage IV pressure
ulcer is at risk for developing osteomyelitis.
2. Clinically evaluate for local or systemic signs of infection
upon initial presentation.
3. Radiographically evaluate (magnetic resonance imaging
[MRI] or bone scan)
4. Surgically debride all nonviable tissue and/or scarred
and infected bone (may be repeated).
5. Obtain pathologic reports from sterile bone biopsy and
support findings with deep microbial cultures.
6. Provide systemic antimicrobial therapy based on the
micro-organisms identified.
7. Perform tissue reconstruction following resolution of
infection.
1. Acknowledge that every patient with Stage IV pressure
ulcer is at risk for developing osteomyelitis. Early recognition and intervention are vital to successful treatment of osteomyelitis in Stage IV pressure ulcers. Diagnosis is often
difficult due to variability in symptom manifestation, overlying soft-tissue inflammation, and reactive bone formation.
Clinical studies have shown that delayed wound healing may
be the only clinical sign of osteomyelitis.52,70 Every patient
must have pressure ulcer areas examined daily.71 Together, the
primary care physician and the wound care specialist must establish a plan and initiate the treatment protocol once osteomyelitis is suspected. Studies72 of the efficacy of traditional
diagnostic methods in the presence of overlying ulceration
have been shown to have variable results because of inconsistent methodology. Therefore, an accurate diagnosis may require a combination of diagnostic approaches.
2. Clinically evaluate the patient for local or systemic
signs of infection upon initial presentation. Although neither sensitive nor specific enough for definitive diagnosis, clinical evaluation is a vital first step in identifying osteomyelitis
complications in pressure ulcers. Typical signs of soft tissue
infection such as warmth, erythema, local tenderness, purulent discharge, odor, and exposed bone should raise suspicion
for osteomyelitis and prompt further study, but these signs
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OSTEOMYELITIS IN PRESSURE ULCERS
3a
3d
3e
3b
3c
3f
Figure 3. A 62-year-old man with an infected sacral pressure ulcer with osteomyelitis demonstrated by pathology
(Figure 3a). Histologically, osteomyelitis is
characterized by viable bone surrounded
by an infiltrate inflammatory composed of
neutrophils and in the case of chronic osteomyelitis, histocytes and lymphocytes.
Following the described protocol including operative debridement, significant improvement was noted during subsequent
visits. (Figure 3b-f).
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alone do not confirm the diagnosis.18,19 In studies19 assessing
the accuracy of clinical evaluation of osteomyelitis, when patients clinically evaluated for
osteomyelitis subsequently underwent percutaneous needle
bone biopsy, the sensitivity and
specificity of clinical evaluation
in diagnosing osteomyelitis has
been shown to be between 33%
and 60%.
Laboratory values. Laboratory data collected during the
initial evaluation should include complete blood count
with manual differential, prothrombin time, partial thromboplastin time, basic metabolic
panel, lipid profile, hemoglobin A1c level, hepatic function
panel, pre-albumin level, erythrocyte sedimentation rate
(ESR), thyroid stimulating
hormone level, and urinary
micro-albumin level. These
tests are important to establish
baseline values and should be
routinely measured during the
treatment of chronic wounds
because they reflect the status
of comorbid medical conditions such as diabetes and hypercholesterolemia as well as
nutrition status.73 Elevated levels of C-reactive protein, increased ESR, leukocytosis, and
positive blood cultures are
common signs of infection, but
have low specificity for osteomyelitis.17,74-77 These tests
are not specific enough to diagnose osteomyelitis; abnormal values should only be used
to raise clinical suspicion and
evaluate treatment.
3. Radiographically evaluate (MRI or bone scan).
X-rays. Although x-rays are
commonly used in evaluating
osteomyelitis in patients with
Stage IV pressure ulcers, the literature suggests that the role of
x-rays for diagnosis is limited.
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FEATURE
Plain films show soft tissue swelling, narrowing or widening
of joint spaces, bone destruction, periosteal and endosteal reactive changes, heterotopic new bone formation, sclerosis, and
cortical thickening and irregularities.78-80 The bony changes
associated with osteomyelitis, such as periosteal reactive
changes or erosion, also may manifest in noninfected bone.62,79
Although it is important to interpret old and new radiographs
together to accurately assess change, a literature review conducted by Wrobel et al72 concluded that in the presence of an
overlying ulcer, the diagnostic sensitivity and specificity of
plain films are approximately 50% and 80%, respectively.
Therefore the main role of plain-film radiography is to support clinical suspicion of infection, to diagnose severe osteomyelitis, or to guide further diagnostic methods and/or
bone biopsy.81
CT scan. Prospective studies have shown that high-resolution techniques such as computed tomography (CT) and MRI
may reveal bone destruction or alteration even when plain radiographs are normal.78-80 CT is capable of viewing cortical
bone and identifying dead bone, yet its sensitivity has been
found to be only 11% for diagnosing osteomyelitis underlying
pressure ulcers in a prospective trial of 61 spinal cord-injured
patents whose CT scan reports were compared to pathology
reports.70 Nevertheless, it may be most useful in assessing the
extent of soft tissue damage.85,86
MRI. MRI is capable of viewing both bone and soft tissue
changes — it is the test of choice because it provides an anatomical guide for adjacent bone disease and soft tissue involvement.
In a prospective study of 62 patients with diabetes to detect the
presence and extent of osteomyelitis, biopsy and clinical followup were used to establish the diagnosis; the primary MRI characteristics of osteomyelitis result from marrow edema and
infiltration of inflammatory cells.87,88 The two most consistent
MRI characteristics of osteomyelitis involve abnormal bone
marrow signals.89 MRI is particularly valuable for early diagnosis because it reveals initial bone marrow edema.90 In their retrospective study of 59 patients with pressure ulcers, Huang et
al91 showed that MRI had a sensitivity and specificity of 98%
and 89%, respectively, in detecting osteomyelitis, meaning a
negative MRI result nearly rules out osteomyelitis.72
A commonly perceived drawback of MRI is its high cost,
yet it is cost-effective compared to other diagnostic modalities
such as combination three-phase bone scan (TPBS) and indium-111-labeled white blood cell (WBC) or gallium-67 citrate scanning.88
Indium scans. Indium (111)-labeled WBC scans use radiolabeled leukocytes that accumulate in sites of inflammation
and infection and in the bone marrow. The scans have a reported sensitivity and specificity of 100% and 50%, respectively, after studying 11 patients with Stage IV pressure
ulcers.92 High sensitivity and low specificity make this technique best suited to rule out osteomyelitis. The high costs and
variable specificity of radionuclide scintigraphy for osteomyelitis limits its use as a primary diagnostic test.92
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OSTOMY WOUND MANAGEMENT MARCH 2009
4. Surgically debride all nonviable tissue and/or scarred
and infected bone. Current guidelines for the treatment of
osteomyelitis in Stage IV pressure ulcers include bone and
ulcer debridements, specific antimicrobial therapy, and a comprehensive regimen that includes daily assessment of the skin,
mechanical debridement of nonviable tissue, establishing a
moist wound healing environment, nutritional supplementation, pressure relief for the wound, elimination of drainage
and cellulitis, physical therapy, and palliative care.71,93 Patients
with limb ulcers also should be screened for peripheral arterial
disease using noninvasive flow studies (eg, ankle brachial
index <0.9 and/or suppressed waveforms in pulse-volume
recordings [PVRs]) and revascularization should be considered in patients with peripheral arterial disease.28,73
Surgical debridement of nonviable tissue and/or scarred and
infected bone is the foundation for treatment of osteomyelitis
underlying Stage IV pressure ulcers.94-96 Antibiotics alone are
not adequate because studies have shown that dead bone and
surrounding infected areas have minimal vascular supply, which
may result in decreased local antibiotic levels.56,58, 95,97,98 Resected
bone should be sent for pathology and culture and samples
from the remaining bone also should be obtained. If the deepest
bone sample is positive for the presence of bacteria or has evidence of necrosis or scar tissue by pathology, further sharp debridement is indicated.95 Debridement should be continued
until deep bone cultures are negative95 and the wound is decreasing in area. Expert opinion suggests that bony prominences
underlying the ulcer, even if healthy, should be removed to prevent potential ulceration points in the permanently bed-bound
patient.99 An area of undermining often may be found over the
bone; in such cases, the soft tissue including muscle may have
to be debrided. Most Stage IV pressure ulcers heal from the base
up; in the authors’ experience, removal of infected tissue below
undermining will expose the entire wound base and promote
more rapid healing.
5. Obtain pathologic reports from sterile bone biopsy and
support with deep microbial cultures. Pathologic examination of the bone is the most accurate way to diagnose osteomyelitis associated with pressure ulcers. Regardless of
radiological diagnosis, a bone biopsy should be obtained when
osteomyelitis is suspected. A positive diagnosis is based on evidence of necrosis or acute inflammatory cells, including polymorphonuclear leukocytes (PMN), aggregates of lymphocytes,
and/or plasma cells and bacteria.17-19,99,100 Pressure-related
changes are usually characterized by reactive bone formation
or fibrosis without inflammatory changes.18 If possible, multiple bone samples should be obtained from different locations
to increase diagnostic accuracy.18 A prospective trial of 61 pressure ulcers by Lewis et al70,76 showed that bone biopsy sensitivity ranges from 73% to 87% and specificity ranges from 93%
and 96%. Although no studies have been conducted on the diagnostic sensitivity and specificity of bone samples taken during wound debridement, pathology results of aseptically
obtained samples are considered the gold standard.18,101
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OSTEOMYELITIS IN PRESSURE ULCERS
The diagnostic value of bone cultures for pressure ulcer-related osteomyelitis is controversial due to problems differentiating
between bone and adjacent soft tissue infection.16,18,19 There is a
general consensus that bone cultures should be used to guide antimicrobial therapy because they may identify the responsible organisms not present in superficial or deep cultures.18,102,103
6. Provide systemic antimicrobial therapy based on the
micro-organisms identified. Systemic broad-spectrum antibiotics should be given immediately after bone debridement
for osteomyelitis underlying pressure ulcers. Patients initially
treated with intravenous antibiotics may be switched to oral
medications when appropriate. Antibiotic selection should be
based on cultures obtained from bone biopsy, although initial
treatment with broad-spectrum antibiotics may be indicated
while culture results are pending. Common intravenous
treatment regimens based on microbial susceptibility include
linezolid,104 vancomycin,105,106 or daptomycin107 for methicillin-resistant S. aureus (MRSA), and piperacillin-tazobactam,108 ticarcillin,109 cefepime or ceftazidime110 for
Pseudomonas organisms. Anaerobes are susceptible to clindamycin.111 The drug of choice in the absence of MRSA or
Pseudomonas is ertapenem because it is broad-spectrum, convenient (once-a-day dosing), and cost-effective compared to
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piperacillin-tazobactam; evidence from a randomized controlled trial112 demonstrated efficacy in other types of wounds
(ie, diabetic foot ulcers). Due to variable efficacies and the
prevalence of resistant organisms, antibiotic selection may require consultation with an infectious disease specialist.
7. Perform tissue reconstruction following resolution of
infection. Debridement of bone and tissue may leave dead
space that requires significant growth or a myocutaneous flap
following the resolution of bone infection. One option is bone
grafting, which utilizes cancellous bone capable of revascularization to replace osseous loss.113,114 The modified Papineau
technique utilizes open cancellous bone grafting on a granulated tissue base with vacuum-assisted closure (V.A.C.®; KCI,
San Antonio, TX).114 Prospective studies115,116 in patients with
fractures have shown that the recurrence rate of osteomyelitis
following cancellous bone grafts is between 4% and 9%.
Local myocutaneous flaps also can be used for ulcer coverage. The success rate for a myocutaneous flap following
pressure ulcer debridement has been found to be as high as
90% in eligible patients when used in conjunction with proper
antibiotic coverage.117 Myocutaneous flaps have the advantage
of providing vascular supply to both muscle and skin and have
been shown to be superior to skin flaps in treating pressure
MARCH 2009 OSTOMY WOUND MANAGEMENT
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FEATURE
ulcers and containing infection.118 One retrospective study119
of 114 patients reported an 83% healing rate for the treatment
of chronic pressure ulcers with myocutaneous flaps, with 14%
exhibiting wound edge dehiscence, 9% showing partial flap
necrosis, and an overall complication rate of 37%. Fasciocutaneous rotational flaps have been reported to have similar
outcomes but are less durable.120 Experimentation with osteocutaneous flaps to the tibia has shown promise121,122 but future
studies are needed to determine their relevance to pressure ulcers. Myocutaneous flaps are currently preferred for covering
deep pressure ulcers.
Standard Pressure Ulcer Protocol
Standard protocol for treatment of pressure ulcers should
be followed throughout the treatment of underlying osteomyelitis. Protocols include using dressings to create a moist
wound healing environment, nutritional supplementation,
pressure relief, objective wound measurements, elimination
of drainage and cellulitis, mechanical debridement of all nonviable tissue, and physical therapy.71 Topical moist wound
healing may be provided using cadexomer iodine,123-125 collagenase,126,127 or silver sulfadiazine.128 Optional biological therapies include growth factors — ie, platelet-derived growth
factor (PDGF)-BB,129-131 acellular matrices132 and a bilayer of
human living keratinocytes and fibroblasts (also known as
human skin equivalent).133 According to animal and in vitro
studies,134-138 multiple compounds that stimulate bone regeneration remain the promising therapeutic approach to healing
these wounds, yet none to date have been tested for bone regeneration and healing.
Protocol of Care Outcomes
Using the WEMR, charts from 177 consecutive patients
with at least one pressure ulcer were reviewed for the presence
of osteomyelitis. Of those, 50 had osteomyelitis in 62 out of
233 pressure ulcers.The estimated prevalence of osteomyelitis
based on pathology in patients with pelvic pressure ulcers at
the time of initial debridement from this review was 33%.
Nine patients with 13 pressure ulcers were not debrided to
bone and therefore were excluded from the outcome analysis.
The remaining 41 patients with 49 pressure ulcers complicated
by osteomyelitis underwent 87 bone debridements (see Table
1). Patients initially were encountered as inpatients (as they
were receiving operative debridement) and were subsequently
seen in the outpatient clinic for follow-up. The WEMR was
used to track wound area and other variables regardless of the
setting where the patient was seen. The average time to discharge following bone debridement was 4.3 ± 5.7 days. The average follow up time after final bone debridement was 20.6 ±
26.7 weeks. Eight patients experienced complications associated with the treatment of osteomyelitis: two developed
Clostridium difficile infection, two experienced postoperative
hypotension, one experienced postoperative anemia (requiring
transfusion), one patient was discharged to palliative care with
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OSTOMY WOUND MANAGEMENT MARCH 2009
unresolved fever spikes, one returned to the OR for bleeding,
and one patient had a below-knee amputation (BKA) approximately 2 months after the last heel bone debridement. For all
admissions, no deaths occurred prior to discharge.
Twenty (20) patients with 21 pressure ulcers had at least
two WEMR records following final bone debridement (see
Table 2). Digital photographs (see Figure 1) show an example
of a patient with an ischial ulcer and a trochanteric ulcer. Sixteen wounds (76%) had decreased in area at the time of their
final visit following final bone debridement. As shown in Figure 2, one patient who presented with gangrene of her Stage
IV pressure ulcer, completely re-epithelialized, though another
patient in this same group had a BKA. Another patient in this
group also had a severe pressure ulcer but under treatment
protocol improved significantly (see Figure 3). Five wounds
increased in area following final bone debridement.
Discussion
Osteomyelitis of Stage IV pressure ulcers should be treated
with systemic antibiotics and surgical debridement followed
by topical therapy. Serial debridements are often necessary to
remove all the infected bone. Despite the inherent limitations
of retrospective chart reviews, results of the authors’ data confirm the safety of this procedure and that wound area may
begin to decrease once bone infection is resolved.18,19
In one clinical study14 of a VA population, the 6-month
mortality rate for patients with Stage IV ulcers was been reported to be as high as is 68.9%. In this study, no operative
mortalities were reported during an average follow-up of 21
weeks, suggesting that the procedure is safe, although further
longitudinal study is needed to determine whether a surgical
treatment protocol of osteomyelitis may improve long-term
mortality. If the patient is eligible, myocutaneous flaps are recommended.117-119 However, it is important to note that many
candidates for myocutaneous flap surgery have an unacceptable complication risk — their other morbidities may adversely affect healing and/or necessitate invasive procedures
or transfers that preclude them from remaining bed-bound
for a month.
Preventing Stage IV pressure ulcers will reduce the prevalence of osteomyelitis. Educating patients, their families, and
clinicians on the severity of the disease, risk factors, and treatment is critical to minimizing associated morbidity and mortality. It has been shown in multiple prospective studies139-141
that moderate reductions in pressure ulcer prevalence can be
been achieved by limiting the external risk factors of pressure,
friction, moisture, and shear force. An alternative approach
focuses on the early diagnosis and proper treatment of lower
Stage pressure ulcers, which may halt ulcer progression to
deeper tissue and/or bone.71
The WEMR is an effective tool for the documentation of
clinical data relevant to care of the patient with severe pressure
ulcers and provides a convenient platform to follow outcomes
such as wound area. Because most studies of patients with
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OSTEOMYELITIS IN PRESSURE ULCERS
pressure ulcers evaluate a particular treatment and therefore
usually exclude osteomyelitis, few reports exist in the literature
pertaining to healing outcomes in patients with osteomyelitis.
This study suggests that by implementing an evidence-based
approach, most patients’ wounds can ultimately decrease in
area, although extended treatment may be necessary. This study
was limited because of its retrospective design but the findings
highlight the need for a prospective study evaluating the efficacy
of the described protocol for treatment of osteomyelitis.
The majority of patients with osteomyelitis in a Stage IV
pressure ulcer present from a long-term healthcare setting after
development of sepsis. In this study, 76% of the wounds that
had been seen for more than two consecutive visits and documented in the WEMR demonstrated a decrease in area. Thus,
the expectation is that with a daily objective examination and
appropriate treatment, nearly all pressure ulcers can improve.
Emphasis must be placed on working with the patient, family,
and caregivers to ensure weekly follow-up when treating osteomyelitis. With an electronic medical record such as the
WEMR, the clinician can make objective treatment decisions.
Conclusion
Based on a review of the literature, a seven-step protocol
for treatment of osteomyelitis in pressure ulcers was developed. Bed-bound and/or critically ill patients require daily
skin inspections. An electronic documentation system, which
includes a photograph of the skin, such as the one described
in this study, may alert clinicians to worsening pressure ulcers,
allowing intervention before progression to Stage IV. When
osteomyelitis is diagnosed, utilization of the aforementioned
treatment protocol has been found to be safe and supported
by current literature. The majority of Stage IV pressure ulcers
can decrease in area, even with osteomyelitis, under treatment
protocol implemented with a WEMR.
Acknowledgments
The authors thank all members of the Wound Healing Program, especially Jeannine Lewis and Fay-Marie Hall, for their
thoughtful review and suggestions on this project. ■
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