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Recovery From Deep-Plane Rhytidectomy Following Unilateral Wound Treatment With Autologous Platelet Gel
A Pilot Study
David M. Powell, MD;
Edward Chang, MD;
Edward H. Farrior, MD
Arch Facial Plast Surg. 2001;3:245-250.
ABSTRACT
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Objective To determine the effects of treatment with
autologous platelet-rich plasma mixed with thrombin and calcium
chloride to form an autologous platelet gel (APG) on postoperative
recovery from deep-plane rhytidectomy.
Study Design A prospective, randomized, controlled pilot
study.
Setting An accredited ambulatory facial plastic surgery
center.
Patients Healthy volunteer women (N = 8)
undergoing rhytidectomy.
Intervention Unilateral autologous platelet-rich plasma wound
treatment during standard deep-plane rhytidectomy.
Main Outcome Measures Staged postoperative facial photographs
were graded in a blinded fashion by 3 facial plastic
surgeon reviewers for postoperative ecchymosis and edema. Each facial
side treated with APG that demonstrated less edema or ecchymosis than
the non–APG-treated side was designated a positive response;
otherwise, the response was equal (no difference) or
negative (untreated side had less edema or
ecchymosis).
Results Twenty-one positive and 21 equal responses were
observed compared with 8 negative ones. Of 20 unanimous observations,
15 were positive, only 3 equal, and 1 negative.
Conclusions Treatment with APG may prevent or improve edema or
ecchymosis after deep-plane rhytidectomy. This trend is more apparent
for ecchymosis than for edema, and is chiefly demonstrable in the early
phases of recovery. These observations are consistent with previous
reports of cell tissue culture and wound response to concentrated
platelet product.
INTRODUCTION
PLATELET-DERIVED growth factors—released from the platelet's  granules when the
platelets are activated—have been recognized as crucially important
regulatory elements in wound repair.1 A substantial amount
of work has demonstrated the efficacy of these angiogenic peptides both
in vitro with cell tissue culture and in vivo in bony and soft tissue
wound-healing models.1-4 The best understood of these
factors are platelet-derived growth factor and transforming growth
factor ß, 2 families of growth factors that modulate healing through
a variety of mechanisms. In general, both platelet-derived growth
factor and transforming growth factor ß exert most of their effects
on wound healing through their stimulation of macrophages, which in
turn release a variety of other directly acting angiogenic growth
factors.3
Because these 2 growth factors are naturally concentrated in platelets
at levels up to 100 times those found in most other body
tissues,5 platelets may be an accessible, inexpensive
source for such agents. Generation of the so-called autologous platelet
gel (APG) from the platelet-rich plasma (PRP) layer of centrifuged
blood requires the technically simple steps of platelet harvest and
mixture with commercially available thrombin and calcium chloride.
Clinical trials have been reported detailing improvement of wound
healing after treatment with APG in such clinical endeavors as dental
rehabilitation, treatment of macular degeneration, and management of
chronic lower extremity ulcers caused by systemic illnesses such as
diabetes or venous stasis.6-8
Furthermore, investigators have commented on the
adhesive properties of APG that may be exploited as a tissue sealant in
some instances.9
The positive results observed in clinical trials such as these, as well
as the ever-present search for improved outcomes in a highly
competitive market, have led investigators to examine the applications
of PRP and APG in the field of cosmetic surgery. Marketed as a simple
technology with few risks and the potential to greatly reduce recovery
from elective surgery, treatment with APG has recently been reported
for cosmetic surgery procedures such as face-lift, brow lift, and laser
skin resurfacing.10 Companies providing dual-speed
centrifuge platelet-harvesting services have begun aggressive
advertising campaigns in the field of facial plastic surgery,
purporting dramatic benefits and guaranteeing more rapid patient
recovery from cosmetic procedures in healthy patients. These claims
have been supported chiefly by the clinical studies previously
mentioned.5-11
Although crossover trials have demonstrated improved wound healing in
patients with systemic illnesses after treatments with
PRP,8 a MEDLINE review fails to reveal data from
similarly well-designed studies investigating wound healing in healthy
patients undergoing cosmetic surgery. This investigation was designed
to determine the effects of APG on recovery from
deep-plane face-lift in a randomized, controlled
study. The goal of this investigation is to document whether there is
detectable improvement in wound healing after treatment with APG in the
typically healthy patient population undergoing facial plastic
surgery.
PATIENTS, MATERIALS, AND METHODS
This study was a randomized, prospective, controlled
clinical trial. Study participants were a volunteer sample of healthy
women undergoing rhytidectomy in an accredited facial plastic and
reconstructive surgery center. During a preoperative informed consent
process, it was emphasized to the patient that during the procedure a
randomly selected side of the patient's face would be treated with
APG. Although this study was executed in a private-practice setting, an
informed consent protocol was followed using as a model the elements of
informed consent required by the institutional review board of The Ohio
State University Medical Center, Columbus.
A total of 8 patients volunteered to participate in this study.
Participants underwent standard deep-plane facelift under general
anesthesia. The surgical technique is outlined in detail
elsewhere.12 All rhytidectomies were performed by the
senior author (E.H.F.), using identical technique on each side of the
face and on every patient.
Before the surgical procedure, one side of the patient's face was
randomly selected to be treated with the APG. Furthermore, the side of
the patient's face to be operated on first was randomly selected as
well. This generated 4 patient groups (left first/left APG, right
first/left APG, left first/right APG, and right first/right
APG).
Platelet-rich plasma was harvested intraoperatively. After the
patient was placed under general anesthesia and intubated, an antecubital venotomy was performed and
approximately 450 mL of blood was collected using standard sterile
technique. Blood was centrifuged, first at 5600 rpm then at 2400 rpm,
to isolate and harvest the PRP. Thirty to 50 mL of PRP was harvested
from the initial volume of 480 mL of blood, and platelets were
concentrated at a level 3 to 6 times that found in blood
(500 000/mL to 1 million/mL).
The remaining platelet-poor plasma and red blood cells may be discarded
or retransfused (since the autologous material has no potential for
infection). Patients who have a latex allergy, or who express anxiety
about receiving processed blood, may forgo autotransfusion without
significant effects because the overall volume is hemodynamically
insignificant.
Seven or 8 mL of harvested PRP was stored in 10-mL syringes at room
temperature until elevation of flaps and excision of excess soft tissue
had been completed. When wound closure was imminent, a small amount (1
mL) of mixed topical thrombin and 10% calcium chloride were drawn into
the syringe with the PRP, and the syringe was inverted repeatedly until
the liquid began to solidify, forming a gel of moderate viscosity, the
APG. Gel formation began within a few seconds.
The APG was applied by injecting it into the wound on the flap
undersurface through an 18- or 14-gauge angiocatheter or needle. The
PRP and thrombin/calcium chloride might also be concurrently sprayed
through an atomizer, mixing the solutions as they are deposited on the
wound surface. Further solidification occurred after the gel was allowed to sit undisturbed on the exposed surface for at least 5
minutes for maximum solidification. A thin layer is deposited because a
very thick layer results in excess dead space and is not recommended by
those experienced with PRP technique. In this protocol, 10 mL of APG
was deposited under the deep-plane flap of buccal fat and superficial
musculoapneurotic system; another 10 mL was deposited under the skin
flap. See Figure 1,
Figure 2,
Figure 3, and
Figure 4 for more detail on PRP harvest and APG
deposition.
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Figure 1.
A dual-speed centrifuge is used to spin down the platelet-rich plasma
("buffy coat")—the thin, clear layer between the red outer layer
(red blood cells) and the inner platelet-poor plasma layer.
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Figure 2.
The platelet-rich plasma is starting to collect in the right pouch;
platelet-poor plasma has already been temporarily siphoned off in the
left pouch.
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Figure 3.
Platelet-rich plasma is stored in 10-mL syringes at room temperature
after harvest. It is mixed with commercially available bovine topical
thrombin and calcium chloride immediately before application;
solidification starts within seconds.
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Figure 4.
Platelet-rich plasma is applied under the more superficial cutaneous
flap during deep-plane face-lift and may be seen as a glossy, clear
layer in the wound (the deep-tissue plane has already been
closed).
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Wounds were also treated with pressure dressings and low-pressure
suction drains. Drains were not attached to suction until after the
wounds were completely closed, at least 20 minutes after maximum gel
solidification. Drains were removed the following morning; dressings
were continued for 2 to 3 days postoperatively.
Patients were evaluated postoperatively on a regular basis. Standard
frontal and right and left oblique facial photographs were taken under
uniform conditions with identical technique and equipment at each
visit. Photographs were typically taken at regular intervals in the 4
weeks following surgery.
After all patients were enrolled and photographs documenting
postoperative recovery were completed, photographs were reviewed in a
blinded fashion by 3 judges experienced with facial plastic surgery.
Patients were randomized, then individual patient photograph series
were presented in chronological order from the immediate to late
postoperative periods. Judges were asked to evaluate the buccal,
preauricular, and cervical regions on both sides of the
patient's face at each stage of recovery, then to record the side of
the patient's face that had greater edema and ecchymosis (these
outcomes were recorded separately). Specifically, judges were
asked to carefully inspect the frontal and right and left oblique
photographs to identify if there was any detectable difference in the
amount of edema or ecchymosis. If any difference was detected, the side
with the greater amount of swelling or bruising was recorded;
otherwise, the patient received a score of equal for that
particular postoperative visit. Some patients had concurrent
blepharoplasties through separate incisions, so judges were
specifically requested to ignore this region.
Data were then tabulated for descriptive statistics. We defined a
positive observation as one in which 2 or 3 judges identified
more edema or ecchymosis on the untreated side of the patient's face
than on the treated side. Greater edema or ecchymosis on the side
treated with APG, if noted by 2 or 3 judges, was defined as a
negative observation. When 2 or 3 judges recorded equal edema
or ecchymosis on both sides of the face we recorded an equal
observation. If conflicting data were entered (ie, each judge recorded
a different observation), the final observation was recorded as equal
for that particular photograph set.
McNemar's test of equality of paired proportions was used for
statistical analysis to determine whether there was a statistically
significant difference between the scores received for the treated vs
the untreated sides of the patients' faces, with a P value of
.05 or lower designated as statistically significant.
RESULTS
A total of 8 patients were enrolled in this pilot clinical trial. No
intraoperative or postoperative complications were observed in the
patient group. A total of 25 postoperative visits were photographically
documented, an average of 3 visits per patient (range, 2-4).
The range of days patients were seen and photographed was postoperative
day 1 to day 26 (mean, day 9). Three judges made 150
individual assessments for postoperative edema and ecchymosis (75 in
each category).
The average day of the first assessment was day 3 (range, 1-7); 7
patients were successfully photographed during their first
postoperative visit. The remaining patient was photographed, but the
film was overexposed during development, and these photographs were not
acceptable for evaluation by the judges. The average day of the second
assessment was postoperative day 7 (range,
2-13); all 8 patients were photographically
documented at this visit. The average day of the third assessment was
postoperative day 12 (range, 6-22); 6 patients were photographed; 2
refused photographs secondary to time constraints. The average day of
the fourth assessment was postoperative day 18 (range, 9-26); 4
patients were photographed; 4 were not photographed because recovery
was thought to be complete by the performing surgeon and senior author
(E.H.F.).
Scores for postoperative edema and ecchymosis were recorded by
postoperative visit. Data points defined as identical observations by 2
or more judges are presented in comprehensive format in Table
1. Condensed data are presented in
Table 2. Two examples of
evaluated sets of photographs are presented in Figure
5 and Figure
6.
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Table 1. Pooled Observations by 3 Blinded Reviewers
of Photographs Examined for Edema and Ecchymosis
After Unilateral Autologous Platelet Gel (APG) Treatment During Deep-Plane Face-lift
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Table 2. Condensed Data From Postoperative
Photograph Review by Postoperative Visit*
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Figure 5.
Oblique photographs of patient 3 at the first postoperative visit. Note
the greater submandibular swelling and ecchymosis on the left side of
her face and neck (patient was treated with autologous platelet gel on
the left and received largely negative scores; see Tables 1 and 2). Patient received concurrent blepharoplasties, and judges
were instructed to ignore the periorbital region when making their
observations.
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Figure 6.
Patient 5 at her third postoperative visit. Autologous platelet gel was applied to the left side.
Judges observed equal edema but greater ecchymosis on the right side (compare buccal and cervical regions; see Tables 1 and 2 for recorded observations).
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Some trends were noted when the data were condensed. There were more
than twice as many positive and equal responses as negative
ones (21, 20, and 9, respectively). In general, a greater
difference between the treated and untreated sides was observed for
ecchymosis than for edema (13 positive, 9 equal, and 3 negative for
ecchymosis vs 8 positive, 11 equal, and 6 negative for
edema). Positive observations were clustered early in
recovery and were most dense at the second visit; by the fourth
postoperative visit, this trend had disappeared in favor of heavily
equal observations (Table 2).
Data were further contracted by analysis only of observations where all
3 judges were in unanimous agreement. There were 15 unanimously
positive observations (11 for ecchymosis, 4 for edema) vs 1 unanimously
negative one (ecchymosis) and 3 unanimously equal scores (1 edema, 2
ecchymosis).
No trends were noted when data were analyzed with respect to the side
treated with APG or the side operated on first. None of the comparisons
between groups were found statistically significant using the McNemar
test.
COMMENT
Although no statistically significant differences were identified in
the data, trends suggest that APG may enhance recovery or reduce
postoperative swelling or bruising in healthy women after deep-plane
face-lift. This trend was most apparent early in the recovery period
(postoperative days 3-12; visits 1-3), and disappeared by the fourth
and final visit (day 18) among the examined cohort of volunteer
patients. In general, this trend toward clinical improvement was more
apparent with observations of ecchymosis than edema. Interestingly, the
only predominantly negative cluster of observations occurred in the
edema scores for the first postoperative visit (Table 2). The
major data trends were revealed chiefly by the greater number of
positive (21) and equal (21) observations than negative ones (8) among
the pooled data, and by the vastly greater number of positive (15) than
equal (3) and negative (1) unanimous observations.
These trends for improved healing are similar to results of other
clinical trials evaluating wounds treated with APG. Knighton et
al8 observed that 17 of 21 chronic lower extremity ulcers
reepithelialized during an 8-week course of twice-daily wound treatment
with an autologous platelet concentrate, vs 2 of 13 similar wounds
treated with placebo. Crossover treatment resulted in
reepithelialization among all of the previously unresponsive control
patients. An earlier study by the same group
demonstrated a 93% reepithelialization rate among 71 chronic wounds in
41 patients after daily treatments with autologous platelet
concentrate.11 A similar clinical protocol was reported in
a case series of 171 patients with 355 wounds present an average of 75
weeks; results included a 78% rate of limb salvage after daily 12-hour
treatments with APG for an average of 10 weeks.1 Marx et
al6 reported enhanced bone formation in mandibular bone
grafts treated with PRP, an effect lasting up to 6 months
postoperatively that was documented by biopsy-proven enhanced bone
deposition among PRP-treated grafts. In the field of facial plastic
surgery, one nonrandomized case series documented a single
postoperative hematoma among a cohort of 100 consecutive patients
undergoing face-lifts treated with bilateral APG, an outcome reported
as a significant reduction in postoperative complication incidence by
the clinical investigator.10
One attribute of APG that was not examined during this investigation
was its reported efficacy as a tissue sealant. In this study, drains
were placed bilaterally in all cases (the usual practice of the senior
author) to isolate the effect of APG on postoperative recovery. In
contrast, Welsh10 placed no drains in his series of 100
consecutive face-lifts treated with APG, and encountered only the
single hematoma mentioned above. These results are comparable to those
described by advocates of fibrin glue in face-lift
surgery.13 Hood et al9 reported a case series
detailing the use of APG to seal multiple dural tears, a renal
incision, and an aorta graft. Whitman et al14 report
the use of APG for various applications in oral
and maxillofacial surgery, such as achieving hemostasis in iliac crest
bone graft donor sites, repair of oral-antral and oral-nasal fistulas,
and adhesion of particulate bone matter when reconstructing mandibular
defects. Although these reports are anecdotal, the
knowledge that platelets contain thrombin and other factors
participating in the clotting cascade, and the supraphysiologic
concentration of platelets generated in APG, suggest the likely
mechanisms responsible for these observations.
Significant wound-healing and tissue-sealant properties of
APG have been suggested by multiple investigators. Two other
characteristics of APG have also generated comment. One is the
autologous source for APG, which eliminates the potential for infection
previously observed with pooled, donated blood products. Another is the
relative affordability of the procedure. Cardioperfusionists typically
charge $400 to $500 for this service in Florida, a small expense
compared with the typically larger ones associated with rhytidectomy
surgery such as the surgeon and operating room fees. These 2 features
are of particular importance because they bring the cost and ease of
use of wound-modulating agents into the realm of clinical
applicability. Local delivery systems for wound-modulating agents such
as APG have previously had limited clinical application in the field of
cosmetic surgery owing to the expense of such agents when harvested or
bioengineered using conventional techniques.
The observations from this pilot study are consistent with reports from
multiple other investigators, and suggest possibly beneficial effects
of APG for healthy patients undergoing cosmetic surgery. Further data
are needed, ideally in the form of results from a large,
multi-institutional trial. Although this study was conceived chiefly to
determine if a difference in wound healing could be detected after
unilateral wound treatment with APG, a more comprehensive study design
would assign scores or grades to denote degrees of edema, ecchymosis,
and other indicators of surgical injury. Tissue sealant properties
influencing the requirement for or avoidance of drain placement should
also be investigated. A clinical comparison between fibrin glue and APG
would help characterize this anecdotally reported quality. Such an
investigation has the greatest potential to define and quantify the
true wound-modulating properties of APG.
AUTHOR INFORMATION
Accepted for publication August 15, 2001.
We wish to thank Blood Recovery Systems Inc of Fort Myers, Fla, for
donating platelet sequestration equipment and technical expertise
during the generation of APG for the patients in this study.
Corresponding author and reprints: David M. Powell, MD, Division of
Facial Plastic and Reconstructive Surgery, Department of
Otolaryngology, The Ohio State University, 4100 UHC, 456 W 10th Ave,
Columbus, OH 43210 (e-mail: powell.210{at}osu.edu).
From
the Division of Facial Plastic and Reconstructive Surgery, Department
of Otolaryngology, The Ohio State University, Columbus (Dr
Powell), and the Farrior Facial Plastic and Reconstructive Surgery
Center, Tampa, Fla (Drs Farrior and Chang). The authors have
no financial relationship to Blood Recovery Systems Inc and received no
financial compensation for using its services in the performance of
this investigation.
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