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Medicare Coverage Database
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Decision Memo for Hyperbaric Oxygen Therapy for Hypoxic
Wounds and Diabetic Wounds of the Lower Extremities (CAG-00060N) |
Hypoxic
Wounds: The evidence is
not adequate to conclude that hypoxic wounds are a distinct wound type for
purposes of Medicare coverage, and, thus, Medicare has decided not to expand
coverage.
Diabetic
Wounds of the Lower Extremities: The evidence is adequate to conclude that HBO therapy is clinically
effective and, thus, reasonable and necessary in the treatment of certain patients
with limb-threatening diabetic wounds of the lower extremity. Accordingly,
Medicare has decided to announce its intention to issue a national coverage
determination for HBO therapy in the treatment of diabetic wounds of the lower
extremities in patients who meet each of the following three criteria:
1.
patient has type I or type II
diabetes and has a lower extremity wound that is due to diabetes;
2.
patient has a wound classified as
Wagner grade III or higher; and
3.
patient has
failed an adequate course of standard wound therapy (defined below).
The use of HBO therapy will be
covered as adjunctive therapy only after there are no measurable signs of
healing for at least 30-days of treatment with standard wound therapy and must
be used in addition to standard wound care. CMS has used 30 days as the cut-off
for determining whether or not a particular wound treatment, such as standard
wound therapy, has produced measurable signs of healing in an individual
patient in previous national coverage determinations (e.g., Coverage Issues
Manual 60-19 Air- Fluidized Beds decision). Measurable signs of improved
healing include a decrease in wound size either in surface area or volume,
decrease in amount of exudates and decrease in amount of necrotic tissue.
Standard wound care in patients with diabetic wounds includes: assessment of a
patient’s vascular status and correction of any vascular problems in the
affected limb if possible, optimization of nutritional status, optimization of
glucose control, debridement by any means to remove
devitalized tissue, maintenance of a clean, moist bed of granulation tissue
with appropriate moist dressings, appropriate off-loading, and necessary
treatment to resolve any infection that might be present, such as systemic
antibiotics and surgical debridement. Failure to
respond to standard wound care occurs when there are no measurable signs of
healing for at least 30 consecutive days. Wounds must be evaluated at least
every 30 days during administration of HBO therapy. Continued treatment with
HBO therapy is not covered if measurable signs of healing have not been
demonstrated within any 30-day period of treatment.
Medicare intends to retain its
non-coverage of HBO therapy in the treatment of diabetic wounds of the lower
extremities in all other subgroups. Medicare will also retain its non-coverage
policy for use of HBO therapy as an initial treatment for diabetic ulcers of
the lower extremities. We encourage interested parties to undertake
well-designed clinical trials to assess the clinical effectiveness of HBO
therapy in other subgroups of diabetic lower extremity ulcers.
Physician
Supervision and Credentialing: CMS concludes that special supervision and credentialing requirements
should not be imposed on physicians who perform HBO therapy. Contractors may
not impose a higher level of supervision than direct supervision as is required
for all ?incident to? therapies.
CMS encourages physicians who perform HBO therapy to obtain adequate training
in the use of HBO and in advanced cardiac life support.
This decision memorandum does not constitute a national coverage determination (NCD). It states CMS's intent to issue an NCD. Prior to any new or modified policy taking effect, CMS must first issue a manual instruction giving specific directions to our claims-processing contractors. That manual issuance, which includes an effective date, is the NCD. If appropriate, the Agency must also change billing and claims processing systems and issue related instructions to allow for payment. The NCD will be published in the Medicare Coverage Issues Manual. Policy changes become effective as of the date listed in the transmittal that announces the Coverage Issues Manual revision.
TO: |
Administrative File: CAG-00060N |
From: |
Jeffrey Shuren, M.D., J.D. |
Subject: |
Coverage Decision Memorandum for Hyperbaric Oxygen
Therapy |
Date: |
August 30, 2002 |
This memorandum serves seven
purposes: (1) provides a brief description of hyperbaric oxygen (HBO) therapy;
(2) describes wound types covered by the existing Medicare policy on HBO
therapy; (3) reviews the history of Medicare's HBO therapy policy as it applies
to wounds; (4) analyzes relevant scientific and clinical literature on the use
of HBO therapy for the treatment of hypoxic wounds and diabetic wounds of the
lower extremities; (5) describes our position concerning physician supervision
and physician credentialing; (6) announces our intent to not recognize hypoxic
wounds as a distinct category of ulcers; and, (7) announces our intent to issue
a positive national coverage determination for HBO therapy for Wagner grades
III and higher diabetic ulcers of the lower extremities that do not heal with
standard wound therapy.
I. Clinical
Background
Hyperbaric oxygen (HBO) therapy
involves the inhalation of 100% oxygen at an elevated (i.e., greater than
sea-level) atmospheric pressure. In the treatment of wounds, this is typically
between 2 to 2.5 atmospheric absolute (ATA). Originally developed for the
treatment of decompression sickness, HBO therapy is used by some physicians in
the management of a variety of wound types. The theory is that wounds have a
reduced oxygen supply that impairs wound healing. By delivering oxygen to the
body under hyperbaric conditions, tissue oxygen levels are raised, and this,
some believe, enhances wound healing. Some physicians use transcutaneous
oxygen tension (TcPO2) with vascular assessment to help predict the healing
potential in patients before they undergo HBO therapy. TcPO2 is a non-invasive
quantitative assessment of the amount of oxygen in the tissue.
The delivery system for HBO uses
either a monoplace (single person) chamber or multiplace (multiple person)
chamber. In monoplace chambers, the entire chamber is
pressurized with 100% oxygen to the desired ATA. Multiplace
chambers, which can accommodate between 2-12 patients, are pressurized (using
compressed air) and the patients breathe 100% oxygen either via mask, head
tent, or endotracheal tube. In either setting, the
time the patient spends in the chamber under hyperbaric conditions is decided
by the attending physician and generally ranges from one to two hours.
Potential risks for patients
undergoing treatment with HBO therapy include pressure related traumas (e.g., barotraumatic otitis, pneumothorax) and adverse effects due to oxygen toxicity
(e.g., myopia, seizures). Some patients may experience claustrophobia due to
the confined space of the chambers. Most adverse events are selflimited
and resolve after termination of therapy. Patients with barotraumatic
otitis may require the placement of myringotomy tubes.
II.
History of Medicare’s Coverage of HBO Therapy and Timeline of
Recent Activities
Current
Coverage Issues Manual (CIM) Policy: The Centers for Medicare & Medicaid Services (CMS) has a
long-standing national coverage policy for the use of HBO therapy for certain
indications. Section 35-10 of the Coverage Issues Manual (CIM) states that HBO
therapy is a modality in which the entire body is exposed to oxygen under
increased atmospheric pressure. The CIM lists 14 covered conditions, nine of
which involve wounds. All other indications are not covered.
Benefit
Category Determination:
CMS has determined that the appropriate benefit categories for HBO therapy are
hospital outpatient services set forth in sections 1861(s)(2)(B) of the Social
Security Act, physician services set forth in section 1861(q) and 1861(s)(1) of
the statute, or incident to physician services under sections 1861(s)(2)(A) of
the statute. HBO therapy is not a therapy service as defined in section 1832(a)(2)(C) of the statute.
Timeline
of Recent Activities:
·
On November 29, 2000, CMS accepted a
formal request for a coverage determination on the use of HBO therapy in the
treatment of hypoxic wounds that was submitted by the Undersea and Hyperbaric
Medical Society (UHMS), the Hyperbaric Oxygen Therapy Association (HOTA), the
·
On January 17, 2002 CMS received a
letter from the HOTA asking that the original request (HBO therapy for hypoxic
wounds) be expanded to include HBO therapy of diabetic lower extremity wounds.
CMS accepted the HOTA’s request.
·
February 11, 2002 CMS decided to also
consider physician supervision and physician credentialing of HBO therapy.
·
On April 1, 2002, CMS received a
letter from the IHMA suggesting the following subpopulation of patients were
most appropriate for HBO therapy: (1) infected diabetic foot wounds, or (2) diabetic
foot wounds with minimal or no signs of cellulites that are occurring in an
extremity with peripheral vascular disease and a hypoxic TcPO2 < 35-40 mmHg
on room air.
·
On April 12, 2002, CMS received a
letter from the UHMS suggesting the diabetic foot wound patient subpopulation
they felt were most appropriate for HBO therapy. The UHMS defined these
patients as Wagner grade III or greater diabetic foot wound with (1) evidence
of persistent or progressive infection, or (2) evidence of dysvascularity
as evidenced by abnormal pulse examination, other clinical parameters such as
ischemic rubor or distal cyanosis, Doppler study,
arteriogram, and TcPO2, or (3) evidence of failure to respond with demonstrable
improvement after 8 weeks of appropriate conventional therapy.
III. FDA Status
The Food and Drug Administration
(FDA) has granted monoplace and multiplace
hyperbaric chambers clearance to market through their 510(k) process. Both monoplace and multiplace chambers
were on the market prior to May 28, 1976, the enactment date of the Medical
Device Amendments of the Federal Food, Drug and Cosmetic Act, and, therefore,
were grandfathered under the statute. Later versions of these chambers were
cleared under the 510(k) process, because they were substantially equivalent to
the models on the market prior to May 1976.
IV. General Methodological Principles of Clinical
Study Design
When making national coverage
decisions, we evaluate relevant trials to determine whether or not the data is
of sufficient quality to support a finding of clinical effectiveness. It has
been our experience that many studies performed to evaluate wound treatments
are of poor quality. CMS considers several generally accepted methodological
principles when assessing a clinical trial. For example, we evaluate whether or
not general methods of study design have been followed, such as calculating
sample size a priori, specifying inclusion and exclusion criteria, describing
the process for the selection of study participants and the ways in which the
consistency of this process was maintained, ensuring comparability of
experimental groups at baseline to the extent possible, describing baseline
characteristics of the participants, randomizing study subjects, masking of
patients and investigators to the therapy administered to the extent feasible,
describing co-interventions in detail, and performing appropriate statistical
analyses, such as statistical tests of differences in baseline characteristics
between the comparison groups. CMS evaluates other study design issues, which,
in the case of wound care trials, include, among other things, the following:
·
Has an appropriate outcome been used?
For example, the optimal outcome to measure is the number and proportion of
wounds that reach complete closure. Assessing partial healing provides less
assurance of clinical effectiveness, because the clinical benefit of partial
healing has not been demonstrated.
·
Have appropriate measures of
endpoints been selected, identified prior to initiating the trial, and
standardized across all study sites? Have clear measurement criteria been
provided? Has the process used to measure the selected outcomes and methods in
which the study investigators insured the consistency of this process across
different study sites been described?
·
Was the appropriate patient
population studied? For example, was the study performed on patients with the
wound type for which coverage is sought?
·
Has a single reference wound been
selected for each patient? Generally, including multiple wounds on a single
patient in the analysis provides limited additional data of value, because
individual wounds are not independent.
·
Have all subjects, regardless of the
protocol arm to which they are assigned (e.g., investigational treatment,
control), received good standard care and the same standard care procedures?
Have the standard care procedures been described in detail?
·
Have variables that may affect
results been addressed in the analysis, including surface area, depth, and chronicity of wounds, condition of the subject, age of the
subject?
·
Has the effect of the therapy under
investigation on the wound been evaluated? Adverse effects on healing can
manifest in several ways, including tissue necrosis requiring more debridement, erythema, and
discharge.
·
Have adequate follow-up evaluations
been performed? Clinical benefits from wound therapies can be short-lived and,
therefore, of limited clinical value.(June 2000).
Physicians, 1998.
The FDA has also issued guidance
that may be useful to investigators.1 In addition, numerous useful texts have
been published on general trial design and evidencebased
medicine review of studies.2
V. Summary
of Evidence
Hypoxic Wounds
The requestors submitted a list
of 25 references to support their request for coverage of hypoxic wounds. The
bibliographies of each of these references were reviewed to identify additional
relevant articles. In addition, CMS also conducted a literature search using
the terms ?hyperbaric oxygen,? ?hypoxic wounds,"
and "hypoxia." The literature search was limited to English language
articles involving humans. Review articles were excluded.
To aid CMS in its review, and to
address a broader range of questions CMS had regarding HBO therapy, CMS
requested a technology assessment (TA) from the Agency for Healthcare Research
and Quality (AHRQ) on the use of HBO therapy. AHRQ contracted with the New England
Medical Center (NEMC) to perform this TA. A list of questions to be addressed
in this TA was created (see below). This TA, received in its final form on
November 29, 2001, was reviewed and considered in our decision making process.
Questions 4, 5, and 7 of the TA specifically addressed hypoxia in HBO therapy,
and the TA’s findings in regards to these questions are noted herein. The full
list of questions NEMC addressed in this TA was the following:
1.
Is there sufficient objective
evidence that the use of HBO, as adjunctive therapy to standard wound care,
aids in wound healing?
1.
Chronic refractory wounds
2.
Wound conditions covered under
current Medicare Policy.
1.
At what point in treatment should HBO
therapy be introduced?
2.
What other treatment modalities must
be employed along with HBO therapy in order to maximize therapeutic benefits?
3.
Wounds are generally classified based
on diagnosis. Could wounds be classified based on a level of “hypoxia” rather
than diagnostic specific (such as diabetic)?
4.
Are there useful criteria to
determine when an individual is likely to benefit from HBO therapy or when an
individual will be non-responsive to HBO therapy?
5.
Are there absolute contraindications
when considering HBO therapy in mono-place or multi-place chambers?
6.
Which method of measuring tissue
oxygen is most reliable and lends itself to standardization?
In the NEMC TA, eight studies
were reviewed in addressing questions surrounding HBO therapy and hypoxic
wounds (Faglia 1996, Faglia
1998, Zamboni 1997, Mathieu 1990, Wattel
1990, Wattel 1991, Smith 1996 and Schirmaer,
1996). Regarding the above questions, NEMC concluded that there was
insufficient evidence to use hypoxia as a criterion for classifying wounds
(question #4). Concerning question #5, NEMC noted that several studies
considered whether tissue oxygen levels during HBO therapy were predictive of
response, however, the TA did not make a conclusion regarding this issue. NEMC
noted that question #7 could not be answered adequately by the studies
reviewed.
In addition to the articles
reviewed in the NEMC TA, the requestors, in a presentation submitted to CMS,
identified four articles that they believed supported TcPO2 use in HBO therapy
(Burgess 1982, Franzeck 1982, Pecorraro
1991, White 1982). Finally, CMS identified and reviewed four additional
articles (Dooley 1996, Padberg 1995, Grolman 2001, Bunt 1996) and the requestors supplied CMS
with an article that has been submitted for publication (
To answer the question of whether HBO therapy
improves net health outcomes in patients with hypoxic wounds, CMS believes that
two issues need to be addressed in the literature:
1.
are
wounds adequately classified primarily on the basis of their tissue oxygen level?
2.
are
tissue oxygen levels predictive of wound healing following HBO therapy?
No articles were identified,
either in the NEMC TA or in CMS’s review, in which wounds were primarily
identified as hypoxic or classified based on their oxygen level. Indeed, no
articles were identified in which tissue oxygen level was used as an inclusion
criterion. All of the studies reviewed classified wounds by their disease
etiology.
All of the articles the requestor
submitted, all of the articles NEMC reviewed, and all of the articles CMS
identified, considered, in some manner, the relationship of tissue oxygen level
to wound healing. While that does not specifically answer the question of
whether wounds can be classified primarily by oxygen level, it could
potentially answer the second question posed above. Therefore, these articles
were reviewed. The four articles used by the requestor in a presentation to CMS
to support the use of TcPO2 in HBO therapy (Burgess 1982, Franzeck
1982, Pecorraro 1991, White 1982) did not address
TcPO2 measurements in the course of treating wounds with HBO. As such, their
findings were not felt to be applicable to the question of HBO use in hypoxic
wounds, and they will not be further addressed in this decision memorandum.
Four of the articles (Bunt 1996, Faglia 1996, Faglia 1998, Wattel 1991)
measured TcPO2 at some point in their study, but provided no discussion of the
ability of TcPO2 to predict healing with HBO therapy. Therefore, they were not
useful in drawing conclusions about the role of TcPO2 in HBO therapy. Eight
studies (Bouchour 1996, Dooley 1996, Fife submitted, Grolman 2001, Mathieu 1990, Padberg
1995, Smith 1996, Wattel 1990) did provide some
discussion on the use of TcPO2 in predicting response to HBO therapy for wounds
of various etiologies. The relevant findings of these eight studies are
summarized below.
Of these eight studies, Bouchour et al (1996) was the only randomized controlled
clinical trial (RCT). Thirty-six patients with crush limb injuries were
randomized to either HBO or non-HBO therapy within 24 hours of initial
evaluation and initial surgical procedure. Patients in the HBO arm received
therapy at 2.5 ATA twice daily (90 minutes each session) for 6 days. Non-HBO
patients were placed in an HBO chamber and breathed room air via facemask at
1.1 ATA for the same time, frequency, and duration. Thus, they served as a
placebo-control. The study’s primary endpoints included wound healing without
tissue necrosis, need for new surgical procedures, time to heal, and length of hospitalization.
Prediction of outcome based on initial TcPO2 was not a primary endpoint.
Nonetheless, the authors stated that when they looked at completely healed
limbs and compared the TcPO2 in the injured limbs to the TcPO2 in the contralateral non-injured limb, the ratio was constantly
greater than 0.9.
The remaining seven articles were
either prospective or retrospective case series. In six of these articles, the
authors concluded that some aspect of TcPO2 was predictive of the wounds’
outcome with HBO therapy. However, as the following review of the articles
discusses, there were no typical TcPO2 values or indices consistently used to
predict outcome.
Grolman (2001) followed 36 patients with
non-healing ulcers to investigate the hypothesis that a difference in TcPO2
measured near the lesion while breathing room air, and then while breathing
100% O2 at normobaric pressure, was predictive of
wound healing. The authors concluded that patients whose TcPO2 increased by
more than 10mmHg on 100% had a 70% chance of healing while those patients whose
TcPO2 changed by less than 10 mmHg had only an 11% chance of healing.
Mathieu’s study (1990) was a case
series involving 23 patients with posttraumatic limb wounds. TcPO2 measurements
were performed in the normal and traumatized limbs and the ratio of values was
compared. The authors found that if the ratio was less than 0.4 the TcPO2
sensitivity in predicting outcome was 100% and the specificity was 94%.
The case series by Padberg (1996) reported on 112 patients with ischemic lower
extremity wounds due to diabetes or chronic renal failure. Patients were
evaluated using TcPO2, arterial segmental pressure (ASP) and arterial segmental
indices (ASI) to determine which readings provided objective risk
stratification for healing of these wounds. The TcPO2 values which predicted
healing varied from 10 to 40 mm Hg. Baseline values of TcPO2 were not
discussed. Using multivariate regression analysis, TcPO2 was superior to both
ASP and ASI in predicting healing, however, on univariate analysis ASP and ASI were as predictive of
healing as TcPO2.
Smith et al (1996) reported a
case series of 26 patients with chronic leg wounds and noted that patients with
a TcPO2 of >800 torr at 2.4 ATA had a greater
improvement in wound score as compared to patients with a TcPO2 measurement
>800 torr.</p />
Wattel et al (1990) reported a case series of 20
patients with either arterial or diabetic lower extremity wounds and noted that
TcPO2 measurements distal to the wound were a reliable predictor of outcome.
All patients with TcPO2 < 100 mm Hg distal to the wound failed to improve
while all patients with TcPO2 > 100 mm Hg distal to the wound healed.
Not all of the studies, however,
noted a strong predictive role for TcPO2. Dooley et al (1996) investigated 60
patients with chronic lower extremity wounds and performed TcPO2 before and
after a regimen of HBO therapy. They noted that while HBO therapy reduced periwound edema, they were not able to identify a single TcPO2
measurement that was predictive of changes in periwound
edema or overall wound severity.
Finally, CMS did not receive any
public comment, other than from the requestors, either supportive or not supportive
of HBO therapy’s use in treating hypoxic wounds.
Diabetic Wounds of the Lower
Extremities
The requestors provided CMS with
a list of 129 references they believed supported the use of HBO therapy in
treating lower extremity diabetic wounds. Each of these references was
reviewed. The majority were either non-human studies,
reviews in textbooks, review articles, or did not specifically address HBO
treatment of diabetic wounds. Eleven articles directly investigated the use of
HBO therapy in treating diabetic lower extremity wounds (Abidia
2001, Baroni 1987, Davis 1987, Doctor 1992, Faglia 1996, Kalani 2002, Oriani 1990, Oriani 1992, Stone
1995, Wattel 1991, Zamboni
1997). The bibliographies of these eleven articles were reviewed in an attempt
to identify additional studies. Also, a literature search was performed using
the search terms “diabetes”,”diabetic”,’wound”,
“leg”, “foot”, “hyperbaric oxygen”, and “HBO”. This additional search was
limited to English language articles that involved human subjects (either
clinical trials or case series). CMS identified one additional article (Ciaravino 1996) through these other search methods.
The NEMC TA, discussed earlier
under hypoxic wounds, also contained information on chronic non-healing wounds,
which included diabetic ulcers, and was considered in this assessment of HBO
therapy in diabetic lower extremity wounds. Two additional technology
assessments (Blue Cross Blue Shield 1999 and Australian Medicare Service
Advisory Committee (MSAC) 2000) discussed diabetic ulcers and were reviewed.
Finally, a 1999 consensus statement on diabetic foot care written by the
American Diabetes Association (ADA) was considered in our assessment.
Two of the twelve clinical
articles CMS reviewed were RCTs (Doctor 1992, Faglia 1996), one was a combination of a randomized and
non-randomized trial (Kalani 2002), seven were case series articles with or without a comparison
group (Baroni 1987, Ciaravino
1996, Davis 1987, Oriani 1990, Oriani
1992, Wattel 1991, Zamboni
1997), and two were abstracts (Abidia 2001, Stone
1995).
Doctor et al (1992) was a RCT
designed to study the effect of HBO therapy in treating chronic diabetic foot
lesions and to assess the effect of HBO therapy on wound culture results.
Thirty diabetic patients with chronic foot ulcers were enrolled. The authors
did not define “chronic foot ulcer”, and did not provide information on the
length these wounds had been present or what the patients? past
wound care had been. Patients were randomized to receive either HBO treatment
plus standard wound care or standard wound care alone. Regular debridement and drainage of abscesses was done in all
patients. Patients received four HBO sessions over a 2-week period. HBO therapy
was administered at 3 ATA for 45 minutes each session. All patients received a
baseline wound culture and then a wound culture at the end of the two-week
study. The baseline wound sizes or vascular status was not reported, and it is
not clear if follow-up exams or the decision to amputate were performed in a masked
fashion.
In the HBO group, 2/15 (13%) of
patients had a major amputation (i.e., amputations of more than the forefoot
resulting in the patient’s inability to ambulate on the extremity without a
prosthesis) as compared to 7/15 (47%) of patients in the standard care only
group. This difference was statistically significant (p<0.05). The number of
positive wound cultures also decreased with HBO treatment. In the HBO group 19
positive cultures were noted pre-study (some patients had more than one bacteria
grow out on a culture and this resulted in the number of positive cultures
being greater than the number of patients) while at the end of two weeks the
number in the HBO group was only three. Conversely, there were 16 positive
cultures in the standard wound care group pre-study and 12 post-study. This
difference was significant with a p value of <0.05. The control of wound
bacteria growth was most notable for Pseudomonas and E. Coli.
The 1996 study by Faglia et al was a RCT designed to evaluate the effectiveness
of HBO therapy in decreasing major amputations in diabetics hospitalized for
severe foot ulcers. Seventy consecutive diabetics patient who were admitted to
the authors’ institution for treatment of a foot ulcer during a defined
two-year period were enrolled. Patients were randomized to receive either HBO
therapy plus standard wound care or standard wound care alone. One patient
randomized to HBO refused treatment and one patient randomized to the non-HBO
group died within the first week of treatment. Both of these patients were
excluded from the data analysis. The remaining 35 HBO-treated patients and 33
standard wound care only group were included in the data analysis.
After randomization there were no
significant differences between the HBO and non-HBO treatment groups in
baseline characteristics. All patients underwent an initial, aggressive debridement followed by twice daily dressing changes as
long as necrosis or exudates were present. As the wounds healed, the frequency
of dressing changes was decreased, and debridements
were done periodically whenever necrotic tissue was present. All patients were
treated with systemic antibiotics, had their blood sugars optimized, and were
off-loaded. Patients in the HBO group underwent daily 90-minute treatments at
2.5 ATA. A necessary sample size of 34 patients in each group was calculated in
order to detect a one-third decrease in major amputation rate with an alpha
error of 0.05 and a power of 0.80.
Patients in the HBO group
underwent an average of 38+8 sessions. The only reported complications
associated with HBO therapy reported were two cases of barotraumatic
otitis (2/35 or 6%). This otitis
did not cause an interruption in these two patients? HBO
therapy.
Faglia et al grouped the wounds in their study
by Wagner grade. Wagner grades are a commonly used classification system and
include five grades (Wagner 1981, Cianci 1997). The
five grades are defined as follows: grade 0 = no open lesion; grade 1 =
superficial ulcer without penetration to deeper layers; grade 2 = ulcer
penetrates to tendon, bone, or joint; grade 3 = lesion has penetrated deeper
than grade 2 and there is abscess, osteomyelitis, pyarthrosis, plantar space abscess, or infection of the
tendon and tendon sheaths; grade 4 = wet or dry gangrene in the toes or
forefoot; grade 5 = gangrene involves the whole foot or such a percentage that
no local procedures are possible and amputation (at least at the below the knee
level) is indicated.
Table 1 details the major
amputation rate in the HBO and non-HBO groups as well as the major amputation
rate by Wagner grade. The authors noted that the rate of major amputations was
significantly greater in the non-HBO patients. When analyzed by Wagner grade,
the group that demonstrated the greatest benefit from HBO was those with Wagner
grade IV wounds.
Table
1
|
HBO |
Non-HBO |
P value |
Maj. Amputations (all Wagner grades) |
3/35 (9%) |
11/33 (3%) |
0.016 |
Maj. Amputations- Wagner grad II |
0/4 |
0/5 |
n/a |
Maj. Amputations- Wagner grade III |
1/4(25%) |
0/8 |
0.33 |
Maj. Amputations- Wagner grade IV |
2/22 (9%) |
11/20 (55%) |
0.002 |
Faglia et al performed a multivariate analysis
on the variables they found to be associated with major amputation in the univariate analysis. The authors stated that this
multivariate analysis showed a protective role of HBO with an odds ratio of
0.084 (p=0.033 and 95% CI 0.008-0.821).
Kalani et al (2002) was a combination of a
randomized and non-randomized clinical trial. These authors investigated the
use of HBO therapy in treating chronic diabetic foot ulcers. While the authors
did not state what the Wagner grade of the investigated wounds was, they did
state that none of the wounds had deep infection or were gangrenous, and, as such,
most likely were Wagner grade II or lower. Thirty-eight patients were included
in their study - 17 received HBO therapy and 21 were treated with standard
wound care. The first 14 patients enrolled in the study were randomly allocated
to HBO or standard care, and this produced 7 patients in each group. For two
years the study was interrupted because of lack of availability of HBO therapy.
When the study was restarted, the remaining patients were allocated to
treatment groups in a nonrandomized method depending on HBO availability. Each
patient was followed-up for at least three years. The authors reported that
there was no difference between the HBO and non-HBO treated patients in terms
of baseline blood pressure, hemoglobin A1c (HgA1c)
levels, diabetes duration or peri-wound tissue oxygen
level. There was a statistically significant difference between the number of
patients with insulin dependent diabetes mellitus (IDDM) and non-insulin
dependent diabetes mellitus (NIDDM) in the two groups. Of the HBO patients 65%
(11/17) had IDDM as compared to 43% (9/12) in the non-HBO group (p<0.05).
All of the patients had a baseline vascular work-up that included angiography
and evaluation by a vascular surgeon. None of the patients enrolled were
eligible for surgery. All patients received the same standard wound care
including off-loading, diabetic control, blood pressure control, and
nutritional assessment. The patients in the HBO group underwent 90-minute
sessions five times a week and received between 40-60 sessions.
Kalani et al reported that at the three-year
follow-up point, 76%(13/17) of the HBO-treated
patients were healed as compared to 48% (10/21) of the standard-care group. No
information on statistical significance was presented. Amputations were
necessary in 2/17 (12%) of the HBO-treated group as compared to 7/21 (33%) of
the standard care-only group (no statistical data presented on this
difference). Finally, of those wounds that healed, the mean time to healing was
15+7 months in the HBO group and 15+4 months in the standard care group
(p=0.8).
The case series by Baroni (1987) reported on 28 diabetic leg ulcer patients
referred to their clinic during a two-year period. Gangrene was noted in 23 of
the patients while the authors noted that five patients had ?perforating
ulcers.? They stated that their preliminary observations convinced them that
HBO therapy was beneficial in diabetic patients, and, accordingly, they decided
to use this treatment on all of their patients. Ten of the 28 patients,
however, refused HBO therapy (due to claustrophobia or fear of earache). These
ten patients received standard wound care leaving 18 patients in the HBO group.
The authors stated that all patients received daily debridement
of necrotic tissue, however, further discussion of the wound care received by
the groups was not provided. The two groups were not statistically different in
terms of baseline lesion size, presence of infection, or diabetic control as
defined by HgA1c or mean blood glucose levels. The authors stated that patients
were evaluated for lower extremity vascular disease but did not provide
information on how this assessment was done or what the results were. Although
baseline ulcer size was reported, the Wagner grade was not.
The outcome reported was the
number of ulcers healed. The authors, however, did not define what constituted
complete healing. Also, it is unclear if those who assessed the healing status
of these wounds were masked to the treatment group. Of those patients who
underwent HBO therapy, 16/18 (98%) had their ulcers heal within 62+30 days and
after 34+22 sessions. Conversely, one of the ten (10%)
patients in the standard wound care group had their ulcer heal. The authors did
not state how long it took for this patient’s ulcer to heal. This difference of
98% versus 10% healing between the groups was statistically significant
(p=0.001).
The two articles by Oriani et al (1990 and 1992) were also performed at the
Oriani et al (1990) stated that beginning in
1982 they recommended HBO therapy to all diabetic patients with necrotic leg
ulcers. In their study they provided information on 80 diabetic foot ulcer
patients - 62 were treated with HBO and 18 patients received standard wound
care only. These 18 patients served as a comparison group after refusing HBO
therapy. The authors stated there was no difference between the two groups of
patients in terms of vascular disease. However, the manner by which patients’
vascular status was evaluated, and the degree of vascular disease noted, were not discussed. Oriani noted
that the ulcers in both groups were curettaged each
day although there was no further description of wound care provided to either
group. HBO treatments were administered at 2.8 ATA (length not stated) six days
a week until granulation tissue formed and then five days a week until healed.
The authors
assessed two outcomes - number of ulcers healed and the number of patients who
required amputation. A definition of when healing occurred
was not provided, and it is not stated if the amputations reported were only
major ones (i.e., beyond the forefoot). Amongst the HBO-treated group,
59/62 (95%) ulcers healed versus 12/18 (67%) in the group that did not receive
HBO (p value not stated). In regards to the number of amputations, 3/62 (5%)
HBO patients as opposed to 6/18 (33%) of the non- HBO patients underwent an
amputation (p<0.001).
In Oriani
et al’s 1992 study, they reported their experience using HBO therapy over a 10-year
period. Since this would have started in 1982, the same time that their 1990
study began enrolling patients, it is highly likely
that patients reported in this 1992 study were also reported in their earlier
article. The authors, however, did not address this.
Oriani et al reported on 172 diabetic patients
with 192 lower extremity lesions. It is unclear how long the wounds had been
present prior to beginning HBO therapy. Forty-one patients were excluded from
their analysis. In describing why these patients were excluded, the authors
stated that it was “because they were given only 12 HBO sessions (or due to
general complications, subjective reasons, or poor cooperation with the
attending physician).”3 Exactly how many were excluded for each
reason was not specified. The requirement that patients have at least 12 HBO
sessions was the result of the authors’ observation that patients with fewer
than 12 sessions did not show a benefit. Unlike their 1990 study, the 1992
study was without a comparison group. They did not present baseline data on
wound size or severity of vascular disease. They did define a positive outcome
from HBO therapy as occurring in one of three scenarios, (1) wound either
completely healed or minimal skin lesions destined to heal, (2) demolitive surgery that was less than expected prior to HBO
therapy, or (3) no major amputation required. It is unclear if the provider who
assessed the wounds or who made the decisions regarding surgery was masked to
the fact that patients were undergoing HBO therapy.
The authors stated that the
average number of HBO sessions in this cohort was 40 (range 12-186). Of the 151
lesions that remained in their analysis following the aforementioned
exclusions, 130 (86%) had a positive outcome. Oriani
also stated that the number of HBO sessions correlated to the size of the
lesion but not to the duration of disease. No data or r-values were given to
support this.
The remaining four case series
articles were conducted at different centers by different groups of
investigators. The article by
The prospective case series by Wattel et al (1991) enrolled every diabetic foot ulcer
patient who was referred to their unit for HBO treatment during a two-year
period. Fifty-nine patients were treated with HBO at 2.5 ATA for 90 minutes
twice daily five days a week. There was no comparison group. The presence and
severity of vascular disease, and the wound size/stage at baseline, was not
stated. The authors measured TcPO2 levels near the wound under three
conditions: room air, 100% normobaric oxygen, and
100% oxygen at 2.5 ATA. The mean treatment duration was 3+2 weeks and the mean
number of HBO sessions was 29+19. In the abstract of the article, the authors
stated that 52/59 (88%) ulcers healed, but in the body of the paper it stated
that 48/59 (81%) ulcers healed. In addition, in the abstract it stated that
7/59 (12%) patients required amputation, but in the body of the paper the
number of amputations was reported as 11/59 (19%). These discrepancies were not
discussed and p values for these differences were not provided. Information on the
comparability of the vascular status of the healed and failed groups was not
provided.
Zamboni et al (1997) prospectively evaluated the
effect of HBO therapy on the healing of diabetic lower extremity wounds in 10
consecutive patients with chronic foot wounds. Five of the patients refused HBO
(two due to claustrophobia and three because they lived too far to travel to
the center for daily treatments) and served as a comparison group. Three of the
control patients and four of the HBO-treated patients had evidence of osteomyelitis. The authors stated that there were no
significant differences in characteristics such as baseline wound size (p
values were not provided). The article also noted that all patients underwent a
prior evaluation by a vascular surgeon. Two patients in the control group had
prior lower extremity bypass surgery and “all other patients were without
significant macrovascular disease amenable to
surgical intervention.”4 The actual manner by which patients’ vascular
status was evaluated, however, was not provided. In addition, baseline Wagner grades were
not reported.
HBO sessions were done five days
a week at 2.0 ATA for 120 minutes each. All patients underwent an initial debridement and a standardized wound care regimen of twice
daily dressing changes. A nurse masked to the treatment group measured the
wounds weekly. Patients underwent a total of 30 sessions. After the course of
HBO, each patient was followed for four to six months.
Zamboni defined the study’s endpoint as complete
healing of the wound or need for major amputation. During the course of the
study there was a greater reduction in wound area in the HBO group as compared
to the non-HBO patients (p<0.05). Likewise, after the four-six month
follow-up, only 1/5 (20%) of the HBO patients as compared to 4/5 (80%) of the
non-HBO patients had persistent, non-healing wounds (p=0.0578).
In the retrospective case series
by Ciaravino et al (1996) the 54 patients reviewed
had either peripheral vascular disease or diabetes as their underlying disease.
The authors stated that in reviewing these patients’ charts, 17 patients had
their wounds classified as diabetic although many of the other 37 patients
whose wounds were classified as due to peripheral vascular disease also had
diabetes. Thus, the etiology of the wounds was not clear. In addition, the
method by which patients were selected for HBO treatment and the underlying
disease severity in these patients was not stated. Overall, the authors noted
that 43/54 (80%) of the patients showed no improvement with an average of 30
(range 5- 81) HBO sessions.
Although the flaws in this
study’s methodology make it difficult to use it to draw conclusions regarding
the efficacy of HBO therapy, what was notable was the high number of
HBO-related complications reported. In all of the other studies reviewed in
this decision memorandum, only minor problems, such as barotraumatic
otitis (sometimes requiring myringotomy
tubes) or claustrophobia were reported, and then occurring in less than one
percent of patients. Ciaravino et al, however,
reported that 42% (23/54) of their patients had barotraumatic
otitis and 17 of these (74%) required myringotomy tubes. Also, 4/54 (7%) patients had a cardiac
arrhythmia while in the chamber, one patient (2%) had a seizure, and one (2%)
had a stroke while under hyperbaric treatment. The authors did not address the
high rate of complications reported in their patients as compared to the
complication rates reported in other studies.
CMS identified two abstracts that
reported on the use of HBO therapy in treating diabetic foot wounds. Abidia (2001) studied 18 patients with non-healing leg
ulcers who were randomized in a placebo-controlled study. Patients received
either HBO treatment with 100% oxygen at 2.4 ATA or room air at 2.4 ATA. Each
group received 30 treatments, each for 90 minutes. The authors reported that at
12-weeks, 13/19 (68%) HBO ulcers had healed versus 4/14 (29%) control ulcers
(no p value given). They also reported that there was no difference in the
major amputation rate between the groups.
Stone et al provided a
retrospective review of 469 consecutive patients with diabetes treated at a
referral wound care center over a 33-month period. Eighty-seven of the patients
received HBO therapy while 382 received standard care only. The authors stated
that the patients in the HBO group had more and larger wounds than the standard
care group. The limb salvage rate was 72% in the HBO group versus 53% in the
standard care group (p<0.002). Both of these abstracts provided limited
information on their methodology, patient selection, inclusion criteria,
baseline characteristics, and results.
Finally, CMS received one public
comment from a physician who uses HBO therapy to treat diabetic lower extremity
wounds. This practitioner was supportive of HBO’s use in these patients. The
practitioner did not offer any additional scientific evidence.
Summary of the Technology Assessments
and American Diabetic Association (
The NEMC TA included a section
that reviewed articles on chronic non-healing wounds - both diabetic and
non-diabetic ulcers. NEMC identified two randomized clinical trials (Doctor
1992, Faglia 1996) and four case series articles (Baroni 1987, Faglia 1998, Oriani 1990, Zamboni 1997). With
the exception of the 1998 Faglia study, these
articles were also considered by CMS in our review. The Faglia
1998 article was not considered relevant to our decision memorandum because it
investigated the role of angiography as a prognostic indicator for amputation
in diabetic foot ulcers and did not investigate the use of HBO to treat such
ulcers. NEMC concluded that HBO aids in the healing of chronic non-healing
wounds. However, they also stated that direct evidence on non-diabetic chronic
non-healing wounds was not sufficient, thus it appears that their conclusions
of HBO’s use in chronic non-healing wounds was primarily directed at diabetic
wounds. NEMC had not been asked to nor did it address in which subpopulation of
patients with chronic non-healing diabetic ulcers does HBO
therapy aid in healing. In addition, the TA did not assess the
methodology used by the studies that were reviewed.
The two other TAs reviewed (Blue
Cross Blue Shield 1999, Australian Medicare Service Advisory Committee 2000)
considered the same articles reviewed by NEMC and considered by CMS in this
decision memorandum. These two TAs concluded that there was sufficient evidence
to support the use of HBO therapy in chronic non-healing wounds (Blue Cross
Blue Shield) and diabetic wounds (MSAC). The Blue Cross Blue Shield assessment
reviewed the finding of the articles but did not assess the methodology of
these studies. The MSAC assessment did note methodologic
flaws with some of the studies - flaws that CMS has noted in this decision
memorandum.
The
“There are no randomized controlled trials supporting the use of hyperbaric oxygen therapy to treat neuropathic diabetic foot wounds. Given the limited evidence of positive results in select groups of patients with severe wounds, additional randomized clinical trials are warranted. It is reasonable, however, to use this costly modality to treat severe and limb- or life-threatening wounds that have not responded to other treatments, particularly if ischemia that cannot be corrected by vascular procedures is present.”5
The authors did not define what
was meant by a “select group” of patients.
Physician Supervision and
Credentialing
In July 1999, CMS proposed
changing the national coverage policy on HBO to include physician supervision
and credentialing. At the time, the agency received many comments addressing
these topics and revision to the existing policy was postponed. We have now
been asked by physicians and contractors to provide guidance on the issues of
physician supervision and credentialing and CMS has agreed to revisit these
issues.
The objective of our review was
to acquire information from professional and other technical sources concerning
the safety, operations, procedures and technology of hyperbaric medicine in
order to gain more knowledge about risks that may be involved in the delivery
of HBO therapy. To locate the most credible sources we performed literature
searches and contacted experts in the fields of fire safety, hyperbaric
technology, certification for hyperbaric physicians, nurses and technicians,
and professional associations. On February 11, 2002, we revised the HBO
tracking sheet on the CMS website to reflect our renewed interest in these
issues. We indicated our intention to evaluate the need for these services as a
part of our review and requested public comment.
For information pertaining to the
safety of HBO chambers we gathered information from the FDA, the National Fire
Protection Association (NFPA), the Clinical Hyperbaric Medicine Department at
Brooks Air Force Base, the Undersea and Hyperbaric Medical Society, and the
National Board of Diving and Hyperbaric Medical Technology.
The first safety codes for HBO
therapy were developed by the NFPA in 1968 and were based on safety guidelines
developed for the use of various gases and oxygen in hospital operating rooms.
The NFPA has oversight of non-diving HBO facilities designed for medical
therapeutic use. No fatalities due to fire have been reported in facilities
falling under the jurisdiction of NFPA.
The FDA Enforcement Report, dated
August 14, 1996, reported an explosion with fatalities within a monoplace chamber and listed the reason for the mishap to
be a failure to follow labeled safety procedures. Letters from the FDA to the
manufacturer urged users to review the safety and emergency procedures outlined
in the manufacturer?s
operations manual. In international reports of safety in hyperbaric chambers it
has been noted that although hyperbaric chamber fires are rare, they are
usually fatal to inside occupants.
At the 2001 UHMS Gulf Coast
Chapter meeting James C. Sheffield, BBA, CHT and Paul Sheffield, PhD, CHT
reported on 21 years of operation at three wound care and hyperbaric facilities
in
As a result of our review, CMS
has been unable to find current statistical evidence pertaining to the safety
or the adverse effects precipitated by the administration of HBO therapy in a multiplace or monoplace chamber.
The need for physician
supervision is based on considerations for appropriate and safe administration
of HBO therapy. Routinely, this treatment is prescribed as an adjunct therapy
when standard wound care has failed to produce satisfactory results. In October
2000 the Department of Health and Human Services, Office of Inspector General
(OIG) issued a report: “Hyperbaric Oxygen Therapy: Its Use and Appropriateness.”
The OIG review indicated that physician attendance is strongly correlated with
quality of care. The report also suggested that training requirements might
provide a means of promoting quality care.
On February 11, 2000, a revision was
made to the CMS Coverage Policy web site tracking sheet for HBO therapy in
which we asked for public comment on the issues of physician supervision and
credentialing. Nine comments were received from individual practitioners, but
they provided no clinical data. All of the comments received by CMS were
supportive of the clinical concepts and guidelines put forth by UHMS in a 1999
document:
“The physician attending a patient undergoing
hyperbaric oxygen treatment must be present during all critical and key
portions of the treatment and be immediately available to furnish services
during the entire treatment. The responsibility for determining which
components of treatment are critical and key portions will vary with each
patient and must be determined by the physician attending the patient
undergoing hyperbaric treatment based upon the physician’s training and
experience.”:
In reaching our conclusions we
have given consideration to all of the comments forwarded to CMS.
VI. CMS Analysis
National coverage determinations
(NCDs) are determinations by the Secretary with
respect to whether or not a particular item or service is covered nationally
under title XVIII of the Social Security Act. § 1869(f)(1)(B). In order to be
covered by Medicare, an item or service must fall within one or more benefit
categories contained within Part A or Part B, and must not be otherwise
excluded from coverage. Moreover, with limited exceptions, the expenses
incurred for items or services must be "reasonable and necessary for the
diagnosis or treatment of illness or injury or to improve the functioning of a
malformed body member." § 1862(a)(1)(A).
As previously mentioned in this
decision memorandum, HBO therapy for hypoxic wounds or diabetic wounds of the
lower extremities falls within a Medicare benefit category. In addition, no
statutory provision specifically precludes payment. Finally, we have fully
examined the medical and scientific evidence submitted with the request for a
national coverage decision as well as additional evidence that we have
identified.
Hypoxic Wounds
CMS believes that in order to
cover HBO therapy for hypoxic wounds, the literature must demonstrate:
1.
that
wounds can be primarily classified based on their tissue oxygen level. To this
end, the literature must show that response to HBO therapy is coupled to tissue
oxygen level irrespective of wound etiology, and
2.
that transcutaneous oxygen tension (TcPO2) values are predictive
of a wound’s response to HBO therapy.
No studies were identified that
classified wounds based on their TcPO2, and there is no evidence that wound
care providers classify wounds by tissue oxygen level. In the past, CMS has
taken the position that wounds of different etiologies cannot necessarily be
considered the same in terms of healing, and we have requested that other wound
care treatments be investigated on an etiology-based approach (i.e., diabetic
wounds, pressure ulcers, venous ulcers, etc.).6 CMS believes that in order for coverage
of HBO therapy to be extended to hypoxic wounds evidence must be presented that
demonstrates wounds of similar tissue oxygen pressure respond in the same
manner to HBO irrespective of their disease etiology.
Several studies did report on the
predictability of TcPO2 in the healing response to HBO therapy. These studies,
as discussed earlier, were inconclusive in this regard. The majority of the
studies were case series articles with unclear patient selection criteria,
failure to set the predictability of TcPO2 in wound response as a primary
outcome, and inconsistency in the methods for measuring TcPO2. The one
randomized clinical trial (Bouchour 1996) was well
designed and investigated the use of HBO therapy in the treatment of acute, severe
crush injuries (an etiology for which CMS already covers HBO therapy). The
study’s primary endpoints all centered on healing and not on the utility of
TcPO2 in predicting the outcome with HBO therapy. In addition, the authors did
not give a level of TcPO2 that was predictive of outcome nor did they discuss
the sensitivity/specificity of TcPO2 in predicting a wound’s response to HBO
therapy. Instead, Bouchour provided a ratio of TcPO2
between the injured and non-injured limb that they believe was predictive of
outcome. Other studies were also inconsistent in the level of TcPO2 that was
predictive of an HBO response or in what TcPO2 indices could be used to predict
HBO response. In addition,
In summary, the evidence is not
adequate to conclude that “hypoxic wounds” is a type of wound for purposes of
Medicare coverage. The literature does not adequately demonstrate that wounds
can be primarily classified based on their tissue oxygen level, nor demonstrate
that TcPO2 can reliably predict the wounds’ outcome with HBO therapy.
Diabetic Wounds of the Lower
Extremities
The body of literature consists
of two RCTs, one combination randomized/nonrandomized
trial, seven case series articles, two abstracts, and several TAs. Although the results of TAs are taken into account when
CMS makes coverage determinations, we also review all of the evidence on its
own merits.
With the exception of the studies
by Ciaravino (1996) and Davis (1987), all of the
studies reported a benefit in the healing of diabetic leg ulcers using HBO
therapy. Ciaravino reported a response to HBO therapy
in only 20% of treated patients while
Faglia et al (1996) was the best designed and
conducted study we reviewed. Patients were randomized to either HBO therapy
plus standard wound care or standard wound care only. They reported that HBO
therapy significantly decreased the major amputation in patients with Wagner
grade IV lesions but not in grade II or III lesions (there were no grade I or
grade V patients in this study). The number of patients in this study with
grade II or III lesions, however, was small. In addition, whether or not HBO
therapy improved other outcomes, such as wound healing, was not assessed. This
study was randomized with clear patient selection/inclusion criteria, a defined
outcome, adequate power, and a comparable group of patients in the HBO and
non-HBO arms. In addition, the authors demonstrated that on multivariate
analysis, conducted on variables they found to be associated with major
amputation on univariate analysis, HBO showed a
protective effect.
The Doctor study was also a RCT
and, while it suffered from some methodologic
problems, it too showed that patients treated with HBO also had need for fewer
amputations as compared to those treated with standard care alone. Doctor et al
also demonstrated that patients treated with HBO were more likely to have a
reduction in positive wound cultures as compared to patients not treated with HBO.
This is important because it implies that HBO can be helpful in fighting
serious wound infections, especially those caused by Pseudomonas and E. coli.
The findings by Doctor et al that
HBO reduced the amount of positive wound cultures, along with other findings
reported in the literature, support a biologic plausibility that HBO may have a
beneficial effect in fighting infection. Local hypoxia is known to predispose
patients to infection because neutrophil-mediated
killing of bacteria by free radicals is decreased.7 By increasing the tissue oxygen level,
many authors note that neutrophil-mediated killing
can be increased. In addition, HBO can be directly bactericidal to anaerobic
bacteria and bacteriostatic to such bacteria as E.
coli and pseudomonas. Doctor et al did not specifically report what the Wagner
grade of the lesions in their study were, but the fact that the wounds in their
study were infected, and that they had their abscesses drained, made these
ulcers at least Wagner grade III. Thus, Doctor et al provide evidence that
supports HBO’s use in Wagner grade III lesions.
The Kalani
et al study (2002) combined patients who were randomized to HBO or standard
care alone and patients who were allocated to HBO or standard care alone in a
non-random fashion based on HBO availability. This study presented many methodologic flaws that made it difficult to conclude their
findings are correct. First was the issue of treatment allocation. The majority
of their patients were assigned to a therapy based on the availability of HBO.
This is inherently subject to bias. Also, it is not clear if the wounds that
led to amputation were the wounds that led to the patient’s enrollment in the study.
While they reported statistical significance data for some results, they did
not provide statistical significance data for the number of ulcers healed or
number of limbs amputated. Finally, in patients that did heal, the time to
healing was the approximately the same in each group.
There were five case series that
reported benefits in the treatment of diabetic lower extremity ulcers with HBO
therapy (Baroni 1987, Oriani
1990, Oriani 1992, Wattel
1991, Zamboni 1997). Three of these studies (Baroni 1987, Oriani 1990, Oriani 1992) were conducted at the same institution by the
same group of investigators. The dates of enrollment in these three case series
overlapped, such that each successive article may have reported information on
patients that were also reported in prior studies. In addition, in the two
studies where there was a comparison group (Baroni
1987 and Oriani 1990), the comparison group was
comprised of patients who had refused HBO. It is difficult to consider these
patients a control group since the reasons they refused treatment may have been
related to their outcome. In the Baroni study, the
authors stated “preliminary observations (data not included) convinced us of
the benefits of HBO in the treatment of diabetic gangrene. Accordingly, we decided
to use this treatment (approved by our hospital ethical committee) in all
subjects with diabetic foot lesions.”8 Thus, there is a strong suggestion of treatment
bias (i.e., having a predetermined idea of the response to treatment).
In Baroni
et al, and the two Oriani studies, there was limited
information on the vascular disease status of their patients, and no
information on the grade of the ulcers in these studies. As such, it is not
possible for CMS to conclude that in these two studies (Baroni
1987 and Oriani 1990) the HBO and non-HBO treated
patients groups were comparable. The 1992 Oriani
study did not provide statistical significance data on their results. In
addition, in the 1992 Oriani article one of their
positive outcomes was defined as “wound healed completely or destined to evolve
positively.”9 The authors did not define what was meant
by “destined to heal,” and, therefore, the reader must be concerned that this
could have biased the way wounds were assessed. Finally, in Oriani’s
1992 study 41 patients were excluded from analysis for a variety of reasons
such as if they received less than 12 HBO sessions, general complications,
subjective reasons, and poor cooperation. The limit of 12 sessions was because
the authors noted that patients who received less than 12 sessions were not
likely to heal. This patient censoring is problematic, and may have introduced
bias in favor of the HBO results.
The patients in Wattel’s study also were all referred for HBO - creating
the potential for investigator bias in favor of the treatment - and there was
no comparison group. The authors did not provide detailed information on
baseline characteristics such as wounds size or grade. They did state that
there was no significant difference between the treatment successes and
failures in terms of micro-angiopathy or large vessel
alteration, but they did not say how the vascular status was assessed or what
was the level of vascular disease. Also, it is not clear what their results
actually were. As detailed earlier, the results reported in the abstract of
their paper do not correspond with the results reported in the body of the
paper.
Zamboni’s study involved a small number of patients
- five in each the HBO and non-HBO treatment groups. As with the other case
series articles reviewed, patients in Zamboni’s study
were referred to the investigators for the purpose of receiving HBO therapy.
The five patients in the non-HBO group refused HBO, two because they were
claustrophobic and three because they lived too far to travel to the center for
daily treatments. As mentioned earlier, such a comparison group that is
selected by default may have differences that could affect the outcome of
therapy. Also concerning is that the three patients who could not travel to the
center for daily treatments may also not have received as comparable standard
wound care as the HBO patients. This would then be an independent variable that
could affect the outcome of their wounds. In addition, there is no information
on the baseline vascular status of the patients or on the grade of the lesions.
In summarizing the case series
articles, five of the seven reported positive results with HBO treatment of
diabetic leg wounds (Baroni 1987, Oriani
1990, Oriani 1992, Wattel
1991, Zamboni 1997). Regarding the two case series
that did not report positive results (Ciaravino 1996,
Davis 1987), CMS questions the reliability of the investigators’ conclusions
because the studies contain serious methodologic
flaws. The five supportive case series also have methodologic
flaws (such as problems in the comparability of patients, problems in comparison
groups, possible treatment bias, and censoring of patient data). While these
five case series articles, by themselves, would not be enough to conclude that
a treatment benefit exists with HBO, they do demonstrate a trend that supports
HBO’s effectiveness in helping to heal severe diabetic foot wounds. When the
reports of these case series articles are combined with two RCTs
(Faglia 1996, Doctor 1992) that demonstrated HBO is
useful in treating the most severe diabetic foot wounds, CMS feels confident
that a benefit does exist.
The two abstracts (Abidia 2001, Stone 1995) both reported a benefit from HBO
therapy – Stone’s abstract was a retrospective case series and Abidia’s abstract was a RCT. The manner of patient
selection, detailed information on baseline characteristics, and complete
information on the results and statistical analyses was not presented. As such,
these abstracts provided limited information from which CMS could critically
review the studies. The Abidia abstract did report
that their study was a RCT and CMS encourages that the full text of this study
be published.
CMS reviewed three TAs as part of
this decision memorandum. The NEMC TA was commissioned by CMS to assess the use
of HBO therapy in hypoxic wounds. The review of chronic non-healing wounds was
not its primary purpose. The TA concluded that HBO therapy aids in the healing
of chronic non-healing wounds, however, it appears that this determination was
based on studies that investigated diabetic wounds. Likewise the Blue Cross Blue
Shield TA also addressed a wide range of HBO indications of which HBO’s use in
treating chronic non-healing wounds was only one part. Their review of chronic
non-healing wounds included a RCT by Hammarlund
(1994). This RCT excluded diabetic foot wounds, and, as such, was not felt to
be applicable by CMS for this decision memorandum. Thus, the Blue Cross Blue
Shield assessment conclusion that HBO aids in chronic non-healing wounds was
not a conclusion that singled out HBO effectiveness in diabetic wounds.
Finally, the MSAC was focused on the use of HBO in treating diabetic lower
extremity wounds and did conclude that HBO was effective in treating these
wounds. This TA noted the methodologic limitations of
the studies reviewed (all of which were also reviewed by CMS).
Finally, the American Diabetic
Association’s consensus statement on diabetic foot wound care was reviewed. The
Physician Supervision and
Credentialing
Physician
Supervision: Two
perspectives on the meaning of “attendance” are prominent in the hyperbaric
community: (1) the physician is physically present during the entirety of the
treatment and uses that time to manage the patient’s overall care; and (2) the
physician remains available to manage rare emergency situations. There are
differing opinions within the medical community as to whether a physician can
supervise a treatment without being in constant attendance. Some argue that the
administration of HBO therapy for wound care is routine and relatively risk
free and therefore requires a physician only in cases of emergency or when a
patient demands specialized care for a particular condition. In a letter to CMS
from the
“A physician should be present and in constant
attendance, carefully monitoring the patient should a complication occur,
during treatment of a critically ill patient. Other patients need to have a
physician available should a complication occur.”
CMS has determined the benefit
category for HBO therapy is hospital outpatient services, physician services,
or incident to physician services. To be covered as incident
to physician services, the services and supplies must be furnished as an
integral, although incidental, part of the physician’s professional service in
the course of diagnosis or treatment of an illness or injury. CMS
believes that the level of physician supervision for HBO therapy should not
exceed that required for all “incident to” treatments (i.e., direct
supervision). CMS is not imposing any new requirements when it states that HBO
therapy must be provided under “direct supervision.” The “direct supervision”
requirement for “services and supplies incident to physician services” has been
clearly defined and specified by CMS in regulations (42 CFR. §
410.26 and 42 CFR § 410.27). Additional descriptions of what constitutes
“direct supervision” are contained in the Medicare Intermediary Manual (MIM §
3112.4) and the Medicare Carrier Manual (MCM § 2050).
Physician
Credentialing:
Certification in hyperbaric technology (CHT) is an added qualification for
licensed health care and related professionals. The certification is open to
several disciplines in allied health, including therapists, technologists,
chamber technicians, physician’s assistants, diving medical technicians,
corpsmen, physiologists, emergency medical technicians, paramedics, life
support technicians, researchers and physicians. Registered nurses and licensed
nurses may also take the CHT examination, although there is a separate
certification process and examination for nurses.
CMS recognizes the need for
specialized skills to administer hyperbaric oxygen technology and encourages
members of the medical community directly involved with administering HBO
therapy to patients who are members of the Medicare population to take
advantage of the training offered by credible professional organizations as
well as training in advanced cardiac life support.
Summary of CMS Analysis
In summary, the medical
literature does not support a finding that HBO therapy warrants coverage for
hypoxic wounds. The evidence is not adequate to conclude that wounds can be
primarily classified as hypoxic, nor that tissue oxygen levels are predictive
of the healing outcome of wounds with HBO therapy.
There are several studies that
report a benefit with HBO treatment for diabetic lower extremity wounds. In
general, these studies looked at the use of HBO therapy in cases where the limb
was in immediate jeopardy of amputation. While many of the reviewed studies had
serious methodologic flaws, two studies were
reasonably well designed clinical trials (Faglia
1996, Doctor 1992) and demonstrated a lower rate of major amputation following
HBO therapy. In Faglia et al the reduction was noted
in patients with Wagner grade IV ulcers that received HBO therapy. This same
study found no statistically significant benefit, in terms of major amputation
rate, in patients with less severe ulcers (i.e., Wagner grade II or III)
although the number of patients with these less severe wounds was small and
other outcomes, such as wound healing, were not assessed. The study by Doctor
et al also demonstrated that HBO therapy reduced the number of infected wounds
(i.e., Wagner grade III). As such, CMS believes that the evidence supports the
use of HBO therapy in the treatment of lower extremity diabetic wounds that are
limb-threatening andare Wagner grade III or greater.
The literature reviewed used HBO as an adjunctive therapy in patients who had
not responded to conventional therapy. Consistent with our other national
coverage policies on wound care, failure to respond to a minimum of 30-days of
conventional diabetic wound care will be required before patients are otherwise
eligible for CMS coverage of HBO therapy.
DECISION:
Hypoxic
Wounds: The evidence is
not adequate to conclude that hypoxic wounds are a distinct wound type for
purposes of Medicare coverage, and, thus, Medicare has decided not to expand
coverage.
Diabetic
Wounds of the Lower Extremities: The evidence is adequate to conclude that HBO therapy is clinically
effective and, thus, reasonable and necessary in the treatment of certain
patients with limb-threatening diabetic wounds of the lower extremity.
Accordingly, Medicare has decided to announce its intention to issue a national
coverage determination for HBO therapy in the treatment of diabetic wounds of
the lower extremities in patients who meet each of the following three
criteria:
1.
patient has type I or type II diabetes
and has a lower extremity wound that is due to diabetes;
2.
patient has a wound classified as
Wagner grade III or higher; and
3.
patient has
failed an adequate course of standard wound therapy (defined below).
The use of HBO therapy will be
covered as adjunctive therapy only after there are no measurable signs of
healing for at least 30-days of treatment with standard wound therapy and must
be used in addition to standard wound care. CMS has used 30 days as the cut-off
for determining whether or not a particular wound treatment, such as standard
wound therapy, has produced measurable signs of healing in an individual
patient in previous national coverage determinations (e.g., Coverage Issues
Manual 60-19 Air- Fluidized Beds decision). Measurable signs of improved
healing include a decrease in wound size either in surface area or volume,
decrease in amount of exudates and decrease in amount of necrotic tissue.
Standard wound care in patients with diabetic wounds includes: assessment of a
patient’s vascular status and correction of any vascular problems in the
affected limb if possible, optimization of nutritional status, optimization of
glucose control, debridement by any means to remove
devitalized tissue, maintenance of a clean, moist bed of granulation tissue
with appropriate moist dressings, appropriate off-loading, and necessary
treatment to resolve any infection that might be present, such as systemic
antibiotics and surgical debridement. Failure to
respond to standard wound care occurs when there are no measurable signs of
healing for at least 30 consecutive days. Wounds must be evaluated at least
every 30 days during administration of HBO therapy. Continued treatment with
HBO therapy is not covered if measurable signs of healing have not been demonstrated
within any 30-day period of treatment.
Medicare intends to retain its
non-coverage of HBO therapy in the treatment of diabetic wounds of the lower
extremities in all other subgroups. Medicare will also retain its non-coverage
policy for use of HBO therapy as an initial treatment for diabetic ulcers of
the lower extremities. We encourage interested parties to undertake
well-designed clinical trials to assess the clinical effectiveness of HBO
therapy in other subgroups of diabetic lower extremity ulcers.
Physician
Supervision and Credentialing: CMS concludes that special supervision and credentialing requirements
should not be imposed on physicians who perform HBO therapy. Contractors may
not impose a higher level of supervision than direct supervision as is required
for all “incident to” therapies. CMS encourages physicians who perform HBO
therapy to obtain adequate training in the use of HBO and in advanced cardiac
life support.
1 FDA Draft Guidance for
Industry: Chronic Ulcer and Burn Wounds - Developing Products for Treatment
(June 2000).
2 For example, Egger M., Smith G.D., Altman DG (eds.),
Systematic Reviews in Health Care: Meta-Analysis in Context. BMJ Publishing
Group, 2001; Gray J.A.M., Evidence-Based Healthcare: How to Make Health Policy
and Management Decisions. Churchill Livingstone, 1998; Mulrow
C., Cook D. (eds.), Systematic Reviews: Synthesis of Best Evidence for Health
Care Decisions.
3 Oriani 1992, page 217.
4 Zamboni 1997, p.176.
5 Ibid, page 1359.
6 Decision memorandum for Noncontact Normothermic Wound
Therapy. http://www.cms.hhs.gov/ncdr/memo.asp?id=80
7 Tibbles 1996, page 1643.
8 Baroni 1987, page 82.
9 Oriani 1992, page 216.