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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
Hyperbaric oxygen therapy: Types of injury
and number of sessions – a review of 1506
cases
M. D’AGOSTINO DIAS1 ,B. FONTES2 ,R. S. POGGETTI3 ,D. BIROLINI4
Medical Supervisor, Intensive Care Unity, Emergency Surgery Service of the III Division of Surgical Clinics of the Clinics
Hospital of the University of São Paulo School of Medicine; 2 Medical Supervisor, Emergency Surgery Service of the III Division
of Surgical Clinics of the Clinics Hospital of the University of São Paulo School of Medicine; 3Associate Professor, University
of São Paulo School of Medicine; Director, Emergency Surgery Service of the III Division of Surgical Clinics of the Clinics
Hospital of the University of São Paulo School of Medicine; 4Full Professor, Trauma Discipline, Department of Surgery,
University of São Paulo School of Medicine.
1
D’Agostino Dias M, Fontes B, Poggetti RS, Birolini D. Hyperbaric oxygen therapy: Types of injury and
number of sessions – a review of 1506 cases. Undersea Hyperb Med 2008; 35(1):53-60. Objective: The
aim of this work was to identify clinical data indicative of the number of hyperbaric oxygen therapy HBO2
sessions that should be prescribed for adjuvant treatment of tissue injuries of differing severity. Patients:
A total of 1730 cases of patients treated with HBO2 using an open protocol (without a predetermined
number of sessions) was examined in this study. Method: A retrospective study involving charts review
was conducted. Severity had been previously determined for the treatment of acute (fasciitis, myositis,
gangrene, contaminated/infected perineal or lower extremity traumatic injuries) or chronic (osteomyelitis,
pressure sore, diabetic or ischemic ulcer) injuries. Only patients that met or exceeded the supposed effective
minimal treatment doses (5 sessions for acute, 10 sessions for chronic injuries) were included in the present
study Results. The data analysis included 1506 cases. These consisted of 1014 patients with acute injuries,
who required 11 to 18 sessions (depending on injury severity), and 492 patients with chronic injuries, who
required a greater (p < 0.001) number of sessions (approximately 30/patient, independent of injury severity).
Global mortality was 79/1506 patients. Conclusion: These results seem to support the initial indication of 15
HBO2 sessions for the treatment acute injuries, and 30 for treatment of chronic injuries. Prospective studies
may better determine the number of sessions for the treatment of different types of injuries.
INTRODUCTION
Therapeutic application of pure oxygen
above atmospheric pressure, termed hyperbaric
oxygen therapy (HBO2), has been used since
the 1960s (1) as an adjuvant treatment of
infectious, ischemic, inflammatory and
necrotizing injuries. Experimental (2,3) and
clinical studies (4,5,6) have demonstrated that
HBO2 treatment reduces injury resolution time,
preserving tissue and sparing lives. However,
controversies remain regarding its use, with the
Copyright © 2008 Undersea and Hyperbaric Medical Society, Inc
results of adjuvant HBO2 application in clinical
studies being considered sometimes favorable
(7,8,9) and sometimes unfavorable (10). This
inconsistency suggests that further research is
required (11,12). When analyzing HBO2 use data,
the treatment application mode, including the
number of sessions employed, should be taken
into account. For example, in a retrospective
multicenter study carried out in Canada (13),
24 patients with infectious necrotizing truncal
injuries received conventional treatment only,
whereas 30 received adjuvant HBO2 using 2.5
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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
to 3 atmospheres absolute (ATA), 90 minutes
(min) duration sessions. The mortality rates of
the conventional treatment group (42%, 10/24)
and the HBO2 group (30%, 9/30) did not differ
statistically. However, 80% of the patients in
the HBO2 group received just 1 to 4 sessions;
only six patients received five or more sessions.
Thus, it is questionable whether the HBO2
group in that study (13) should be considered
representative of HBO2 treated patients in
general.
HBO2 effects depend on the O2 pressure
employed, as well as on session duration,
frequency, and the number of sessions applied.
The O2 pressure recommended by the Undersea
and Hyperbaric Medical Society (UHMS) and
used in most protocols is at least 2.5 ATA (150
KPa) (14,15). Pressures of 2.1 to 2.4 ATA (110
to 140 KPa) may be employed in special cases,
e.g. in children, but pressure less than 2 ATA
(100 KPa) should never be used. The duration
of each session is usually 90 min (13).
Although there is no agreement regarding
the length of the time interval between HBO2
sessions, one session per day is commonly
used, while some authors recommend 2 or
even 3 sessions per day at the beginning of
the treatment of particularly devastating tissue
injuries such as gaseous gangrene, or rapidly
progressing necrotizing fasciitis (16). Although
the total treatment duration prescribed, either
in terms of cumulative time or number of
sessions, generally differs depending on injury
characteristics and severity, the relationship
between these factors and the amount of HBO2
that is optimal has not been clearly established.
Furthermore, although some authors have
suggested a minimal effective dose for acute
or chronic injuries (16,17,18), the minimal
effective doses, in terms of number of HBO2
sessions for the treatment of various types
of injuries have not been firmly established.
In this context, and with the purpose of
identifying data which suggests the number of
HBO2 sessions that should be prescribed for
adjuvant treatment of different types of tissue
injury, we performed a retrospective analysis of
1506 patients that were subjected to HBO2 for
treatment of various types of tissue injuries.
METHODS
The patients included in this study had
received routine HBO2 treatment in a hyperbaric
chamber (Sechrist 2500B) at the University of
São Paulo over a ten-year period (1992-2002).
Based on the data obtained at the beginning of
the treatment, the injuries were classified into
two groups: acute injuries (fasciitis, trauma,
surgical incision dehiscence, etc), and chronic
injuries (diabetic foot, Crohn’s disease fistula,
skin ulcer [pressure, ischemic or mixed], and
osteomyelitis, etc) (Table 1).
Table 1.
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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
The severity of the cases was classified
according to the USP Severity Scale (19) (Table
2).
This scale comprises 21 variables
including diverse injury characteristics, patient
age, and co-morbidities. Each variable is
quantified as 1, 2, or 3 points, and the sum
of the points for the variables present in each
patient (total range: 1 to 41 points) indicates
the severity score for the patient: score I (mild
severity) = 1 to 10 points, score II (moderate
severity) = 11 to 20 points, score III (high
severity) = 21 to 30 points, score IV (very high
severity) = 31 to 41 points (19).
Each HBO2 session consisted of pure
oxygen application for 2 h (including total
compression and decompression time of 20 to
30 min), at 2.2 to 2.8 ATA (120 to 180 KPa)
pressure. Pressure variations depended on
the type of tissue involved, the response to
treatment, the treatment phase, and the patient’s
tolerance to the treatment. The inter-session
interval was 24 hours for the first sessions,
in general up to the tenth session and then 48
hours until resolution of the injuries.
Of the patients with acute injuries, 271
(18%) were in the intensive care unit (ICU) at
the beginning of the treatment, with mechanical
ventilation assistance and/or being medically
treated with vasoactive drugs. Sessions applied
to patients with extensive and complex injuries,
such as burns and traumatic injuries requiring
surgery, were interrupted for the performance of
surgical procedures, and continued thereafter.
The collected data included injury type and
severity, number of HBO2 sessions applied,
time of day of application, total treatment
duration, and mortality. Initially, data from a
total of 1730 cases were considered.
For this study, a minimum HBO2
treatment criterion was adopted, consisting of 5
sessions for acute, and 10 sessions for chronic
injuries. Consequently, patients who did not
reach this minimum number of sessions, either
due to death, treatment withdrawal or being
discharged from the hospital, were excluded
from the analysis. Also patients who abandoned
Severity score: 1 to 10 points = score I (mild severity)
11 to 20 points = score II (moderate severity)
21 to 30 points = score III (high severity)
31 to 41 points = score IV (very high severity)
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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
the hyperbaric treatment after having received
any number of sessions, but before the injuries
were clinically resolved, were excluded. Thus,
a total of 1506 patients who met the initially
established minimum number of sessions and
who were discharged with cured injuries, or
who died before the complete resolution of the
injuries, were included in this study.
interval for the mean (20). For mortality rate
analysis, the absolute and relative frequencies
were calculated. In all tests, a 5% level of
significance was adopted.
DISCUSSION
In the present study the aim was to
identify data which may contribute to the
determination of the number of HBO2 sessions
that should be prescribed for adjuvant treatment
of different types of tissue injuries.
RESULTS
The population of 1506 cases analyzed
comprised 1014 (67.3%) patients with acute
injuries, and 492 (32.7%) patients with chronic
injuries. The patient distributions among the
four severity levels for each injury type (acute
or chronic) are summarized in Figure 1. The
number of HBO2 sessions administered until
injury resolution, according to severity, with
the exclusion of patients who died, is shown
in Figure 2. In the statistical analysis, a 95%
confidence interval (with exclusion of 5%
patients with great dispersion values) was
adopted. There was a total of 79 deaths (5.24%)
comprising 63 of the patients with acute
injuries, and 16 with chronic injuries (Figure
3). Death distributions among the different
patient groups, according to severity, are also
shown in Figure 3.
The homogeneity of the groups, regarding
mortality rate, was statistically evaluated by
the chi-squared test or Fisher’s exact test (20).
For comparison of two independent groups,
regarding number of sessions (quantitative
variables), the non-parametric Mann-Whitney
test for two independent samples (20) was
used. For comparison of three groups, the
non-parametric Kruskal-Wallis test for
three independent samples, with multiple
comparisons by the Dunn test (20) was used. A
descriptive analysis of the number of sessions
was performed by determining the minimum and
maximum values, and calculating means and
standard deviations, using the 95% confidence
Minimum number of HBO2
sessions.
Although common in other therapeutic
modalities, an established dose regimen in terms
of minimum number of sessions and session
duration required for HBO2 efficacy is lacking
(13). Several studies have employed closed
protocols, in which a predetermined number
of sessions was used for all cases, independent
of injury type or severity, or patient response
to the initial treatment (12,21,22,23). This
approach may impede the evaluation of HBO2
efficacy (13,14). For example, in the treatment
of burns, the use of a maximum number of
sessions equal to the percentage of burned
body area, independent of the depth of injury or
response to initial treatment, has been reported
(22).
However, the difference in mortality
rate between HBO2-treated and control patients
was not significant.
The patients examined herein were
on open protocols (without a pre-determined
number of sessions), with continuation of the
sessions until injury resolution or death. The
minimum session exposure adopted for the
present study (5 sessions for acute injuries, and
10 sessions for chronic injuries) was based on a
review of several studies of HBO2 for acute and
chronic injuries (16,17,18). According to the
official recommendation of the UHMS (16) and
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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
Figure 1
Fig. 1. Numbers of acute and chronic patients, according
to the severity score and percent distribution in the acute
or chronic group.
Figure 2
Fig. 2. Number of sessions required by acute and
chronic injuries according to their severity. The number
of sessions for chronic injuries did not vary with injury
severity, and was higher (*p < 0.001) than that for acute
injuries of the same severity level. Increased acute
injury severity correlated with number of sessions (**P
< 0.001, vs. low severity or high severity groups). There
was no patient with very high severity chronic injury in
this study. Only patients discharged with healed lesions
were included in this analysis.
Figure 3
Fig. 3. Mortality according to the severity of acute or
chronic injuries. The number of deaths as a fraction of
the total of patients in each group is indicated above each
bar. Total numbers of acute and chronic injury patients
are indicated in the legend. Mortality of patients with
chronic injuries did not vary significantly with injury
severity. Patient groups with high or very high severity
acute injuries had higher mortality rates than groups
with less severe injuries (*p < 0.001 vs. all other groups;
**p < 0.001 vs. groups with mild or medium severity
injuries). A similar correlation was observed when the
acute and chronic patients of the same injury severity
level were pooled (p < 0.001).
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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
the view that “less than a total of five sessions
should never be performed” for the treatment
of gaseous gangrene (18), the presently adopted
criteria allow one to suppose that patients who
may not have received the normal benefit of
the treatment due to inadequate treatment
exposure were excluded. In a review of 267
patients with USP scores III and IV injury
severity, who were treated in an ICU, Dias
reported that, compared to survivors, patients
who died received on average 4.8 sessions of
HBO2, which was significantly less than the
average of 14.2 sessions received by patients
who survived until being discharged; the global
mortality observed in Dias’ study was 27.5%
(18). These data support the establishment of a
5-session minimum for initial HBO2.
optimal number of HBO2 sessions for treatment
of acute and chronic injuries in general has not
been established, it has been observed that the
treatment tends to be prolonged for chronic
injuries,(26) and the UHMS recommends that
diabetic ulcer patients be administered at least
10 sessions(16). Our study revealed that in
acute injury patients, the number of applied
sessions increased with injury severity (Figure
2). Meanwhile the number sessions did not
vary with severity in chronic injury patients,
and was greater than that that was required for
acute injuries with severity degrees I, II and
III. It was also observed that the mean number
of sessions applied until patient discharge or
death was approximately 15 (range: 11 to 18
sessions) for acute injuries, and 30 (range: 25 to
37 sessions) for chronic injuries, for 95% of the
patients. These findings support the adoption of
minimum treatment criteria, and double-dosage
for chronic relative to acute injury treatment. The
total number of sessions required, both in acute
and in chronic cases, is likely to be influenced
by several factors, including procedures that
may disrupt the HBO2 regimen but that are
commonly needed by HBO2 patients, such as
surgical debridement, grafting, flap rotation,
wound border approximation, and performance
of wound dressings (27,28), as well as transfer
of the patient to the ICU while he or she is still
undergoing HBO2 (16).
The global mortality rate of 5.24%
(70/1506 cases) observed in this study
comprised the 6.21% rate (63/1014 cases) in
the acute group, and the 3.24% rate (16/494
cases) in the chronic group. All deaths were
attributed to the underlying pathology, and none
to HBO2, thus conforming with the assertion
that “respecting safety rules, treatment with
HBO2 presents minimal side effects and a
high safety level” (14,29). Similar to the
observation regarding the number of sessions,
in patients with acute, but not chronic injuries,
mortality rate increased with injury severity.
Injury classification.
The diversity of lesions commonly
treated with HBO2, in terms of injury type
and severity, suggests that there is a need for
an injury classification rubric that includes
severity grade and that provides an indication
of the adequate number of sessions that should
be prescribed for optimal therapeutic efficacy.
There is evidence of differences between acute
and chronic patient responses to HBO2 in the
literature. For instance, treatment of patients
with crush trauma was very successful after
application of 12 HBO2 sessions (8), while, on
average 38 sessions were required for effective
treatment of diabetic ulcers (7). In one study,
diabetic ulcers that had not been resolved after
three months of conventional treatment alone
showed improvement after 20 HBO2 sessions
(24). In a double-blind study involving 16
patients (8 treated with HBO2 and 8 controls),
it was observed that 30 HBO2 sessions led to
complete ulcer closure in 62% and partial
closure in 38% of the cases (25).
Most of the 1014 acute and the 492
chronic patients in this study had medium or
high severity levels (Figure 1). Although an
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UHM 2008, Vol. 35, No. 1 – HBOT-types of injuries and number of sessions.
The relatively low mortality of the present
study could be a result of exclusion of patients
with the most severe acute injuries, who did
not receive an effective minimum treatment.
A study assessing the mortality rate of patients
receiving less than 5 HBO2 sessions for diverse
severity score injuries, relative to a control
group with no HBO2 treatment, would be
needed to determine whether this is the case.
Because there was not an a priori
established maximum number of sessions for
this study, some may question whether patients
would have continued to improve after HBO2
was discontinued, which might then suggest
that HBO2 continuation was unnecessary. On
the other hand, it is important to consider that
premature discontinuation of HBO2 therapy
could have negative or even tragic consequences
for the patient. Prospective studies examining
the effects of a wide range of HBO2 session
numbers for the treatment of diverse types of
injury are needed to resolve these questions.
3.
4.
5.
6.
7.
8.
CONCLUSIONS
9.
The present data support the initial
indication of 15 HBO2 sessions for the
treatment of acute injuries, and 30 sessions for
the treatment of chronic injuries. Our findings
further suggest that establishment of an injury
classification rubric may help ensure that each
patient receives an HBO2 treatment regimen
that is appropriate for the nature and severity of
his or her injuries. Future prospective studies
may enable the optimal number of sessions for
the treatment of different types of injuries to be
determined.
10.
11.
12.
13.
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