Keywords
hydrogen peroxide - hemostasis - embolization
This literature and case review is prepared in an effort to determine the efficacy,
indications, and contraindications of using a 3% hydrogen peroxide (H2O2) solution during this procedure. The use of H2O2 in open dissection can be found throughout recent literature, in various medical
disciplines. Literature review is limited to post-1980 and will address three topics;
visual field clearance, topical antiseptic, and hemostasis.[1]
H2O2 was first described in 1818 by Louis Jacques Thenard, but pure H2O2 was not synthesized until 1894. H2O2 has been used throughout history as a disinfectant and for antisepsis based on solution
strength. This solution is an important endogenous structure in phagocytosis in the
immune system. H2O2 has harmful characteristics at higher concentrations and is considered unsafe for
topical use over 6%.[2] The solution's vapors are used for sterilization of surgical instruments. Solutions
of 3% are sold over the counter and used as an antiseptic. H2O2 demonstrates broad-spectrum efficacy against viruses, bacteria, yeasts, and bacterial
spores.
The ability for catalase to break down H2O2 into a foaming agent and create microembolisms in the vasculature can be used to
the surgeon's advantage during microvascular flap reconstruction surgery. The breakdown
of H2O2 into oxygen gas and water allows for increased visibility through dilution. In addition,
the ability for H2O2 to act on a clot as a dissolution agent may increase the viability of muscle cells
during the procedure. Excessive clotting during a long, extensive procedure allows
for unwanted muscle hypoxia. Although there is abundant literature concerning the
risk of embolism when H2O2 is used as an irrigation agent in a closed space, this is mitigated due to the open
dissection used during this procedure.
Literature Review
Visual Field Clearance
Wu et al[3] conducted a study in which 20 patients with acute upper gastrointestinal bleeding
(13 males and 7 females) were included. The site of bleeding was sprayed with 200
mL of saline and again with 25 to 175 mL of 3% H2O2. Pictures of the visual fields were taken and compared by three gastroenterologists
and graded on a visual scale. Cauterization of the bleeding field was performed and
a biopsy was taken to evaluate the effects of the H2O2 on the area. The results showed a significant improvement in the mean visual score
with H2O2 compared with saline alone. In addition, during endoscopic evaluation, 19 patients
were seen to have active oozing from an adherent blood clot at the ulcer base. Altogether
12 of these individuals achieved initial hemostasis after being sprayed with 3% H2O2. Finally, there were no significant changes in the histology of the biopsied sites.
A second, similar study conducted by Kalloo et al[4] at the John Hopkins University found similar results. In six patients with acute
upper gastrointestinal bleeding, H2O2 spray resulted in good to excellent visualization of the bleeding source. Hemostasis
occurred in two patients who were actively bleeding. There were no adverse effects
or complications. The authors concluded that H2O2 significantly enhanced clot dissolution and endoscopic visualization in patients
with acute upper gastrointestinal bleeding. This study differed from the previous
study, by Wu et al, with the addition of an antifoaming agent, simethicone, being
mixed with the H2O2. Simethicone decreases the surface tension of gas bubbles allowing them to combine
into larger bubbles.
Antisepsis
H2O2 has long been known as a topical antiseptic due to the breakdown of bacterial cell
walls due to the catalase reaction. According to Hyslop et al, a concentration of
500 mM is needed to completely kill Staphylococcus aureus cells when exposed[5]; 3% H2O2 (980 mM) sufficiently succeeds this threshold. The authors concluded that levels
of 25 to 50 mM of H2O2 are bacteriostatic. There is a debate on whether this concentration of H2O2 is cytotoxic at longer duration of contact. There is no definitive answer to this
question at this time. Consequently, these procedures are concluded with a wash of
normal saline in an effort to decrease the incident, if any, of cytotoxicity to healthy
tissue.
Hemostasis
There are two possible reactions in terms of hemostasis when H2O2 is used as an irrigation solution. First is the catalase reaction wherein H2O2 is broken down into water and oxygen gas: 2 H2O2 → 2 H2O + O2. Second is the Fenton reaction: Fe3+ + H2O2 → Fe2+ + HOO• + H+, where a free radical is created using iron from the hemoglobin as a catalyst.
Foaming is created with either reaction as gas by-products are released.
H2O2 injection has been shown to reduce blood loss during surgery by Lichtenbaum et al.[6] Further studies involving this technique by Mastronardi and DeWaele[7] revealed the creation of intraluminal bubbles from this reaction in mice.[7] This has led many to caution the use of H2O2 in a closed space environment such as the spine, brain, or deep abscesses. This study
highlighted the possibility of gas collection leading to embolism in close spaces.
It has been theorized that collection of these bubbles may act as a barrier through
high surface tension on a low pressure capillary bed causing retention of blood flow,
thus decreasing blood loss during surgery. Gas embolization is a concern in a closed
space where the gas may have the ability to collect and travel in small vessels, leading
to embolization. Morikawa et al[8] described an embolism in their article concerning the use of H2O2 in cervical spinal surgery. Despite the transient nature of the embolization that
occurred, they concluded that there is a concern for use of H2O2 in closed spaces. However, in the meningioma surgery study by Lichtenbaum et al[6], they concluded that embolization did not occur in the spinal surgery. The differences
in location are key to understanding the possibility of embolization. Cervical spinal
surgery is a smaller field with deeper access than the surgery described herein. Spinal
surgeries and the procedures described here are performed in an open field allowing
the gas to dissipate, as well as having a wider field in which to remove any remaining
H2O2. There is a possibility for the flap itself to experience a small amount of embolization
along the periphery due to lingering presence of H2O2. The saline wash along with gentle palpation along the periphery of the flap during
the wash ensures the remaining pockets to dissipate prior to implantation.
Procedural Use of Hydrogen Peroxide
At the beginning of each microvascular flap reconstructive case, a basin is filled
with 120 mL of H2O2. A bulb syringe or a Luer lock 60 mL syringe is used to administer the H2O2 to the patient. The H2O2 is used intermittently throughout the case. No tourniquet is used.
After initial skin incision, 10 to 20 mL of H2O2 is used along with direct pressure. The H2O2 controls the smaller capillaries and allows the larger vessels to be more easily
visualized for Bovie cauterization. After dissection through the subcutaneous fat
to the level of the fascia, another application of H2O2 (5–10 mL) is used, along with direct pressure. Subsequently, through the level of
the fascia, another 5 to 10 mL of H2O2 and direct pressure is used to control any additional deep bleeding vessels. This
stepwise procedure is constant for every case.
When performing a nerve repair case, additional H2O2 is used during dissection of the nerve from the surrounding tissue. When a minor
segmental flap procedure is performed, H2O2 is used for the muscle flap dissection. A total of 20 mL of H2O2 is used in both cases. In total, approximately 60 to 70 mL of H2O2 is used. The average blood loss for a nerve repair case or a minor segmental muscle
flap is 25 to 40 mL. Total fluid collection including blood and H2O2 is 85 to 110 mL.
For a large muscle flap with resection of tibia and fibula, an additional three to
four applications of H2O2 are needed. In total, 120 mL of H2O2 is used in these larger procedures. Blood loss for a large muscle flap is in the
range of 150 mL leading to a total fluid collection of 400 to 500 mL. Normal saline
is used at the completion of all procedures prior to closing.
Conclusion
In regard to the actions created through the use of H2O2 in an open field procedure, it may be possible that these two reactions are forming
and reforming simultaneously, in regard to hemostasis. H2O2, when introduced exogenously in repeated washes, allow the following to occur:
-
Catalase reaction allows dilution of the hemoglobin in the visual field, increasing
visibility.
-
The Fenton reaction taking place, wherein a free radical is formed, leading to the
breakdown of the cell wall and to clot formation.
-
Catalase reaction may also act as disagglutination process on newly forming clots
with subsequent washes.
-
Both reactions liberate gas, leading to microembolization of smaller vessels and capillary
beds.
H2O2 and its effect on homeostasis is important when viewed in terms of reducing blood
loss during these procedures. There is marked visual improvement in the surgical field.
Blood loss is kept to a minimum and antisepsis is achieved throughout the procedure.
A final wash with normal saline throughout the open field and along incision lines
allows the surgeon to dilute any lingering H2O2. Dilution clears the capillary beds of cell breakdown debris and ensures that there
are no pockets of H2O2 left against healthy cells during the healing process.
Understanding the biochemical pathways concerning platelet aggregation and breakdown,
the chemical reactions that occur and the procedural details of when H2O2 is used will further the surgeon's ability to successfully minimize blood loss during
an open field microvascular muscle flap procedure.
