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burns 37 (2011) 559–565



                                                               available at www.sciencedirect.com




                                                     journal homepage: www.elsevier.com/locate/burns



Review

Hemostasis in burn surgery—A review

Jose P. Sterling a, David M. Heimbach b,*
a
    University of Texas, Southwestern Medical School, Dallas, TX, United States
b
    University of Washington, Seattle Washington, USA



article info                                                  abstract

Article history:                                              Over the past 30 years, techniques of early excision and grafting along with enhancement of
Accepted 29 June 2010                                         critical care have significantly improved survival following burn injury. Despite these
                                                              advancements, large volume blood loss associated with surgical intervention continues
Keywords:                                                     to be a challenging aspect of burn surgery. This review article will examine the methods of
Thermal injury                                                limiting blood loss during surgical procedures.
Burns                                                                                                                                                                                                                                Published by Elsevier Ltd and ISBI
Burn surgery
Burn excision
Blood transfusion
Tourniquets
Epinephrine
Thrombin
Fibrin sealant
Electrocautery
Terlipressin
Blood conservation




Contents

    1.   Introduction . . . . . . . . . . . . . . . . . . . . .      .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   560
    2.   Methods . . . . . . . . . . . . . . . . . . . . . . . .     .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   560
         2.1. Literature search strategies . . . .                   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   560
         2.2. Inclusion criteria . . . . . . . . . . . .             .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   560
         2.3. Data extraction and synthesis. .                       .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   560
    3.   Results . . . . . . . . . . . . . . . . . . . . . . . . .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   561
         3.1. Description of included studies.                       .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   561
         3.2. Tourniquets . . . . . . . . . . . . . . . .            .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   561
         3.3. Epinephrine tumescence . . . . . .                     .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   562
         3.4. Thrombin. . . . . . . . . . . . . . . . . .            .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   562
         3.5. Fibrin sealant. . . . . . . . . . . . . . .            .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   562
         3.6. Electrocautery . . . . . . . . . . . . . .             .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   563



 * Corresponding author. Tel.: +1 206 779 9600.
   E-mail address: heimbach@u.washington.edu (D.M. Heimbach).
0305-4179/$36.00 . Published by Elsevier Ltd and ISBI
doi:10.1016/j.burns.2010.06.010
560                                                                                              burns 37 (2011) 559–565



                  3.7. Systemic therapies . . . . . . .              .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   563
                  3.8. Blood conserving protocols .                  .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   563
             4.   Discussion . . . . . . . . . . . . . . . . . . .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   564
                  4.1. Study limitations . . . . . . . . .           .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   564
             5.   Conclusion . . . . . . . . . . . . . . . . . . .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   564
                  References . . . . . . . . . . . . . . . . . . .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   .   564



1.                  Introduction                                                                                                                     Boolean search terms, from the establishment of the
                                                                                                                                                     database until Jan 2010. Searches were conducted without
Over the past 30 years, techniques of early excision and grafting                                                                                    language restriction. The bibliographies of all retrieved
along with enhancement of critical care have significantly                                                                                            articles were then manually searched for relevant missed
improved survival following severe burn. Despite these advance-                                                                                      articles. The search terms were: ‘‘‘‘haemostasis’’[All Fields]
ments, large volume blood loss associated with surgical                                                                                              OR ‘‘hemostasis’’[MeSH Terms] OR ‘‘hemostasis’’[All Fields])
intervention continues to be a challenging aspect of burn surgery.                                                                                   AND (‘‘burns’’[MeSH Terms] OR ‘‘burns’’[All Fields] OR
    Traditionally, blood was transfused when the hemoglobin                                                                                          ‘‘burn’’[All Fields]) AND (‘‘surgery’’[Subheading] OR ‘‘surger-
levels fell bellow 10 mg/dl. This originated from the fear of the                                                                                    y’’[All Fields] OR ‘‘surgical procedures, operative’’[MeSH
deleterious effects of anemia on oxygen consumption, cardiac                                                                                         Terms] OR (‘‘surgical’’[All Fields] AND ‘‘procedures’’[All
function and tissue perfusion [1,2]. However, such liberal use                                                                                       Fields] AND ‘‘operative’’[All Fields]) OR ‘‘operative surgical
of blood has come under question.                                                                                                                    procedures’’[All Fields] OR ‘‘surgery’’[All Fields] OR ‘‘general
    Multiple studies questioned the harmful effects of blood                                                                                         surgery’’[MeSH Terms] OR (‘‘general’’[All Fields] AND ‘‘sur-
component transfusion. Blood component transfusions can be                                                                                           gery’’[All Fields]) OR ‘‘general surgery’’[All Fields]) AND
associated with transfusion related acute lung injury, infec-                                                                                        (‘‘hemorrhage’’[MeSH Terms] OR ‘‘hemorrhage’’[All Fields]
tion, immunomodulation, age of the transfused component,                                                                                             OR (‘‘blood’’[All Fields] AND ‘‘loss’’[All Fields]) OR ‘‘blood
multi organ dysfunction, acute respiratory syndrome and                                                                                              loss’’[All Fields]’’.
increase in mortality [3–7]. Due to the risks associated with
blood component transfusion, restrictive transfusion prac-                                                                                           2.2.                    Inclusion criteria
tices are recommended for both adult and pediatric patients
[7–10]. Furthermore, this has been extrapolated and demon-                                                                                           All articles reporting efficacy and/or outcome with the use of
strated in the burn patient [4,5,11].                                                                                                                hemostatic techniques and/or agents in humans during burn
    Unfortunately, the surgical treatment of burn patients is                                                                                        surgery were included. Individual case reports were excluded.
associated with substantial blood loss [12–16]. Multiple hemo-                                                                                       The techniques were used for the management of excised
static techniques have been proposed for this problem. To                                                                                            wounds and/or donor sites in adults and children. A flowchart
address this issue, a review of the hemostatic techniques was                                                                                        of the search results is provided in Fig. 1. The two reviewers
undertaken and we present here the findings for assessment.                                                                                           independently applied the inclusion criteria and any differ-
                                                                                                                                                     ences were resolved through discussion.

2.                  Methods                                                                                                                          2.3.                    Data extraction and synthesis

2.1.                Literature search strategies                                                                                                     Data was extracted by the researchers, to determine interven-
                                                                                                                                                     tion, management of burn and/or management of donor site,
A systematic search was conducted of Ovid MEDLINE,                                                                                                   number of patients, age (pediatric or adult), and result of
EMBASE, Cochrane Library, CINAHL, and PubMed using                                                                                                   intervention.
[()TD$FIG]




                                                                                 Fig. 1 – Flowchart of search results.
burns 37 (2011) 559–565                                                           561


 Table 1 – Included studies.
 Study ref. Type of study           Site                        Intervention                              N        Type of     Range of
                                                                                                      (patients)   patients    % TBSA

 [17]         Comparative      Burn         Tourniquet versus No Tourniquet                                10      All          3–31
 [18]         Descriptive      Burn         Tourniquet + Topical Epinephrine                              52a      NS           <12
 [19]         Descriptive      Burn         Tourniquet + Thrombin                                          17      All          0.5–15
 [20]         Comparative      Burn         Epinephrine Tumescence or Tourniquet versus                    44      Adult        >5%
                                            Historical Controls
 [25]         Descriptive      Burn/donor   Epinephrine/Bupivicaine Tumescence                            29       Pediatric    1–12
 [26]         Descriptive      Burn         Epinephrine Tumescence                                        10       Adult        5–50%
 [29]         Comparative      Burn/donor   Epinephrine Tumescence + Thrombin                             20       Adult        14–52%
                                            versus 0.45% NS + Thrombin
 [27]         Comparative      Burn/donor   Topical/Tumescence Epinephrine + Thrombin                     42       Pediatric    11–66%
                                            versus 0.45% NS + Thrombin
 [28]         Comparative      Donor        Epinephrine/Lidocaine Tumescence + Topical                    56       All          10–51%
                                            Epinephrine versus 0.45% NS Tumescence + Topical
                                            Epinephrine
 [38]         Descriptive      Burn         Thrombin                                                      72       All          1–4%
 [33]         Comparative      Donor        Topical Epinephrine versus Thrombin                           32       All          NS
 [37]         Comparative      Donor        Topical Phenylephrine versus Thrombin                         24       NS           NS
 [35]         Comparative      Donor        Thrombin versus Bovine collagen sheet                         20       NS           NS
 [36]         Comparative      Donor        Thrombin Ointment versus Thrombin Solution                    11       All          NS
 [46]         Comparative      Donor        Thrombin versus Fibrin Sealant                                46       Adult        NS
 [49]         Comparative      Donor        Fibrin Sealant versus No Fibrin Sealant                       61       All          2–8%b
 [48]         Comparative      Donor        Fibrin Sealant versus No Fibrin Sealant                       47       All          <15%
 [47]         Comparative      Donor        Thrombin + Fibrin versus Thrombin + Placebo                   10       NS           NS
 [50]         Comparative      Burn         Electrocautery knife with air spray versus No air spray        6       NS           10–30%
 [53]         Comparative      Systemic     Terlipressin versus Placebo                                   51       All          10–20%
 [51]         Descriptive      Systemic     rFVIIa                                                         4       All          50–72%
 [52]         Comparative      Systemic     rFVIIa versus No rFVIIa                                       18       Adult        12–60%
 [30]         Descriptive                   Blood Conserving Protocol                                     23       Pediatric    1–55%
 [21]         Comparative                   Blood Conserving Protocol                                   2461       NS           1–>40%
 [22]         Comparative                   Blood Conserving Protocol                                     35       Adult        1–36%
 [23]         Comparative                   Blood Conserving Protocol                                    392       Pediatric    10–>50%
 [24]         Comparative                   Blood Conserving Protocol                                     30       Adult        8–46%

 NS: not stated.
 a
   Upper extremities.
 b
   Donor percent total body area.




3.      Results                                                      However, as part of their intraoperative protocol the wounds
                                                                     in both groups were sprayed with thrombin solution and
3.1.    Description of included studies                              wrapped with epinephrine soaked gauze.
                                                                        Three other studies described the use and benefit of
A total of 27 studies were included (see Table 1.) From the          tourniquets in the treatment of burns [18–20]. Smoot
included studies 8 are descriptive and 19 are comparative            described the use of intermittent release and rapid reinflation
hemostatic interventions. Specifically, 5 studies compared the        of the tourniquet to allow for assessment of tissue viability
implementation of blood conserving protocols at single               [18]. This method was used in combination with epinephrine
institutions. Most studies discussed the use of subcutaneous         soaks and compression wraps. Similarly, Sawada and
and topical agents to assist in hemostasis. However, 3 studies       Yotsuyanagi described the use of a tourniquet and spraying
discussed the use of systemic pharmacoactive agents to assist        the wound with thrombin prior to, and after, removal of the
with hemostasis.                                                     tourniquet along with pressure bandages [19]. Djurickovic
                                                                     et al. described the use of a tourniquet during tangential
3.2.    Tourniquets                                                  excision of the extremity [20]. After completion of the
                                                                     excision the tourniquet was deflated to evaluate areas of
O’Mara et al. directly studied the value of tourniquet               inadequate excision and then reinflated. After reinflation,
application without exsanguination of the limb prior to              areas of major bleeding where coagulated and meshed
tourniquet inflation to improve visualization of viable tissue        autograft was then placed along with cotton gauze dressing
during excision [17]. In this study they found that blood loss       and elastic bandages. Furthermore, four out of the five studies
per area excised was less with tourniquet control                    that describe blood conserving protocols include tourniquets
(0.10 Æ 0.29 cc/cm2) versus no tourniquet (0.32 Æ 0.56 cc/cm2)       as part of the hemostatic protocol [21–24]. It was felt by these
(P = 0.04). Additionally they demonstrated similar graft take        authors that the use of tourniquet is an important adjunct to
between the two groups (98.2% versus 96.8%) (P > 0.1).               limit bleeding.
562                                                  burns 37 (2011) 559–565



3.3.    Epinephrine tumescence                                          Four studies compared the hemostatic efficacy of thrombin
                                                                    (bThrombin) versus other products [33–36]. Brezel et al.
Three articles described the technique of epinephrine subcu-        compared the visual amount of blood loss form donor sites
taneous infiltration as a hemostatic agent [20,25,26]. Djur-         on 32 patients that were treated with thrombin (100 U/ml) or
ickovic et al. described the use of 1:1,000,000 epinephrine         epinephrine solution (1:200,000) [33]. They demonstrated a
solution infiltrated to the burn in 23 patients [20]. They           superior hemostatic effect from the epinephrine treated donor
estimated a 3.42 Æ 0.39% blood volume loss per 1% body              site. Caucci et al. compared the hemostatic effect of
surface area excised. Fujita et al. preoperatively marked the       phenylephrine (1:20,000) versus thrombin (100 U/ml) on the
burn wound of 10 consecutive patients with a 5 Â 5 cm square        donor sites of 24 patients [37]. They demonstrated a superior
grid using crystal violet [26]. This grid was used a guide to       hemostatic effect with phenylephrine compared to thrombin
inject 20 ml of a dilute epinephrine solution (1 mg/l) per          when comparing blood absorbed in a paper filter disk covering
square. They felt that this provided an aide and safeguard to       the donor site after treatment with the agents (P < 0.005).
the amount of epinephrine used with the tumescent tech-             Prasad et al. compared thrombin versus a bovine collagen
nique. Beausang et al. reported on 29 pediatric patients in         dressing on the donor sites of 21 patients [35]. Although, they
which the donor sites and burn wounds were infiltrated with a        did not describe the concentration of the thrombin spray, they
1:500,000 epinephrine with bupivicane [25]. Bupivicane (0.25%       did demonstrated superior hemostatic control with the spray
plain) was added to the solution at a 3 mg per kg body weight       thrombin. Mean blood loss with thrombin (5.25 Æ 8.68 ml)
concentration. They reported no adverse effects and a               versus collagen (8.24 Æ 13.54 ml) (P = 0.057). Sawada et al.
decrease of postoperative pain with this technique.                 compared the use of thrombin ointment versus thrombin
    Three articles compared the use of epinephrine tumes-           solution on the donor sites of 11 patients [36]. They created the
cence to determine effect on hemostasis [27–29]. Barret et al.      ointment by mixing 10,000 units of powdered thrombin with
compared the use of topical and subcutaneous epinephrine on         10 g of petroleum jelly based gentamicin ointment. Again, this
a cohort of 42 pediatric patients [27]. Half of these patients      study did not describe the concentration of the thrombin
received topical epinephrine (1:10,000 sprayed and 1:200,000        solution. However, the mean bleeding time with the thrombin
compresses) to the excised wound and donor sites and                ointment (11.5 s) was less than that of the thrombin solution
subcutaneous infusion (1:300,000) to scalp donor sites only.        (25.5 s, P < 0.01).
The other half of patients followed the same protocol using             One study described the efficacy of the recombinant
0.45% normal saline solution. Additionally, both groups             human Thrombin (rThrombin) as a hemostatic agent in burn
received topical thrombin (1000 units/ml) to the excised            surgery. Greenhalgh et al. conducted a single-arm, open label
wounds and donor sites. They found no difference in the             study of rThrombin (1000 U/ml) on the burn wounds of 72
amount of bleeding per square centimeter excised                    patients after excision [38]. Hemostasis at 20 min was
(0.48 Æ 0.12 ml/cm2 versus 0.51 Æ 0.15 ml/cm2, P = 0.681) be-       achieved in 91.5% of the patients. Further application of
tween the two groups. Robertson et al. compared the results of      rThrombin ensued hemostasis in all but 4 patients. Also, they
20 patients (26 operations) using epinephrine (1 mg/ml)             demonstrated a low rate of anti-rThrombin antibody forma-
tumescence at the excision and donor sites to 10 patients           tion (1.6%) without associated human thrombin neutraliza-
(11 operations) [29]. Also, topical thrombin spray was utilized     tion, a concern that originated from the use of bThrombin [39–
in both groups. They demonstrated almost a 70% reduction in         42]. Furthermore, one out of the four studies that describe a
blood loss per unit area excised in the tumescent group             blood conserving protocol utilize thrombin in their protocol
(0.37 Æ 0.2 ml/cm2 versus 1.15 Æ 0.28 ml/cm2, P 0.0001).            [21].
Gacto et al. performed a prospective, randomized, controlled,
blinded trial of 56 patients [28]. Both groups received             3.5.    Fibrin sealant
subcutaneous infiltration at donor sites with either epineph-
rine (1:500,000) solution with added lidocaine (5%, w/v) or with    Fibrin sealants are human derived factors that are designed to
0.45% normal saline. They concluded that the infiltration of         reproduce the final steps of the physiologic coagulation
this solution decreased intraoperative bleeding and decreased       cascade of a stable fibrin clot [43,44]. Besides hemostatic
postoperative pain. Furthermore, four out of the five studies        properties fibrin sealant have adhesive properties that can be
that describe blood conserving protocols utilize epinephrine        utilized during skin grafts and flap procedures [45]. Drake and
tumescence as part of the protocol [22–24,30].                      Wong compared the hemostatic effect of a patient derived
                                                                    fibrin sealant against thrombin (100 U/ml) on the donor sites of
3.4.    Thrombin                                                    46 patients [46]. They determined the time to hemostasis to be
                                                                    less with the fibrin sealant (31 s) versus thrombin (58 s,
Topical thrombin as a hemostatic agent is commonly used on a        P = 0.0012). Achauer et al. conducted a study on 10 patients
variety of surgeries [31]. Thrombin is a clotting factor that       with half of the donor site sprayed with thrombin and plasma
converts fibrinogen into fibrin that is the foundation of a blood     placebo while the other half was sprayed with thrombin and
clot. Typically the thrombin is applied directly to the wound via   fibrin glue [47]. They found no difference in blood loss between
a spray system or in combination with an absorbable gelatin or      the two areas. Both Greenhalgh et al. and Nervi et al. compared
collagen sponge. Historically, thrombin (bThrombin) has been        the effects of hemostasis of fibrin sealant versus no fibrin
derived from bovine plasma via different purification processes.     sealant on donor wounds [48,49]. Greenhalgh et al. felt that
Currently, human plasma (hThrombin) derived and human               bleeding at the donor sites were well controlled with the fibrin
recombinant thrombin (rThrombin) products are available [32].       sealant as demonstrated by surgeon estimates [48]. However,
burns 37 (2011) 559–565                                                       563


the treatment failed to demonstrate benefit on semi quantita-          pediatric patients [54]. The protocol consisted of debridement
tive measurements. On the contrary, Nervi et al. demonstrated         of full thickness burns with electrocautery and partial
a reduction in the mean time to hemostasis of approximately           thickness burns with dermabrasion. All donor sites were
200 s with the use of fibrin sealants (fibrin 193 Æ 131 s, control      subcutaneously injected with a solution of epinephrine and
392 Æ 153 s, P < 0.001) [49]. The use of fibrin sealants is not        saline. No more than 10 mg/kg of epinephrine was adminis-
described in the four studies that describe a blood conserving        tered subcutaneously at one time. However, staggered injec-
protocol.                                                             tions were utilized that often resulted in total dose of
                                                                      epinephrine being greater than 10 mg/kg. Additionally, all
3.6.    Electrocautery                                                debrided or harvested surgical sites were treated with
                                                                      epinephrine solution soaked pads. Following this protocol
Most of the studies describe the use of electrocautery as an          they report an average blood loss per percent TBSA treated to
adjunct to achieve hemostasis. However, Mitsukawa et al.              be 17 ml.
describes a novel use for an electrocautery attachment to                 Cartotto et al. compared the results of a comprehensive
assist with hemostasis during large burn area excisions [50].         intraoperative blood conservation strategy and its effects on
They attached a smoke aspiration tip to the electrocautery.           blood loss and wound outcome to a historical cohort [22]. The
Instead of utilizing the aspiration tip to aspirate they used it as   blood conservation technique was as follows: Donor sites
a conduit to expel air. This stream of air cleared blood and fluid     were infiltrated subcutaneously with a 1:500,000 adrenaline
from the tip allowing for improved visualization and electro-         solution. After the grafts were harvested the sites were
cautery function. Compared to regular electrocautery this new         dressed with epinephrine (1:33,333) soaked pads. Burn
device reduced the duration of surgery by 10% and the amount          wounds on limbs where tangentially excised under tourni-
of blood loss by 14% for a 30% TBSA burn.                             quet control. After completion of excision, the wounds were
                                                                      dressed with epinephrine (1:33,333) soaked pads and a firm
3.7.    Systemic therapies                                            circumferential wrapping was performed for full 10 min
                                                                      prior to deflating the tourniquet. After deflation of the
Three studies discuss the use of systemic therapies to assist         tourniquet major bleeding was cauterized and the extremity
with hemostasis in burn surgery [51–53]. Terlipressin is an           rewrapped with epinephrine soaked pads for another 5 min.
analogue of vasopressin used as a vasoactive drug in the              When the tourniquet could not be utilized the wound
management of hypotension. It has been found to be effective          received subcutaneous infiltration with epinephrine solu-
when norepinephrine does not help. Mzezewa et al. describes           tion (1:500,000) prior to excision. After the excision was
the results of a randomized trial comparing the use of                completed the wound was dressed with epinephrine
terlipressin or placebo on 51 patients undergoing early               (1:33,333) soaked pads. Final hemostasis was achieved using
excision and grafting of burns between 10 and 20% TBSA                serial application of the epinephrine pads and electrocau-
[53]. Use of other hemostatic adjuncts where not described. In        tery. Utilizing this blood conserving protocol, the estimated
this study the medication was given intravenously at a dose of        blood loss was reduced from 211 Æ 166 ml per %TBSA excised
20 m/kg body weight and repeated every 4 h for 24 h. Following        and grafted in the historical group to 123 Æ 106 ml in the
this protocol, terlipressin reduced blood loss on average 21%         protocol driven group (P = 0.02). Furthermore, the intra-
compared to placebo.                                                  operative transfusion requirement was reduced from
    Johansson et al. described a technique of utilizing recom-        3.3 Æ 3.1 units per case, in the historical group, to 0.1 Æ 0.3
binant factor VIIa (rFVIIa) at a dose of 100 mg/kg on 4 patients      units per case in the protocol driven group (P < 0.001). Also
undergoing major wound excision that developed periopera-             they reported no compromise on wound outcome and graft
tive uncontrollable bleeding [51]. They report hemostasis             take with the new protocol.
within 15 min of administering the drug and no adverse                    Sheridan and Szyfelbein compared blood use between two
effects with the treatment. In a subsequent study, Johansson          matched groups of 392 pediatric patients who where managed
et al. conducted a single centre, randomized, double blind,           during the calendar years of 1982–1985 and 1992–1995 (blood
placebo controlled trial on 18 consecutive patients [52]. The         conserving protocol) [23]. Three groups were analyzed:
patients were randomized to receive either placebo or 40 mg/kg        children with 10–24%, 25–49% and 50–100% TBSA. The
dose of rFVIIa at the time of skin incision and a second dose of      techniques for intraoperative blood conservation included:
placebo or rFVIIa (40 mg/kg) 90 min later. They demonstrated a        clear preparation of excision plan, performing all extremity
decease in the total number of units of blood components              excisions under tourniquet, and wrapping the extremity in a
transfused per patient compared to placebo (0.9 versus 2.2,           hemostatic dressing prior to tourniquet deflation, conducting
P = 0.0013). Furthermore, they demonstrated a decrease in             all fascial excision under electrocautery, performing all
fresh frozen plasma units and platelet units transfused               tangential excisions as early as possible, executing all torso
utilizing this protocol.                                              tangential excision after subcutaneous epinephrine injection,
                                                                      and maintaining patient euthermic. They demonstrated a
3.8.    Blood conserving protocols                                    reduction in the use of PRBC’s in the 10–24% TBSA from
                                                                      1.9 Æ 0.2 units per child to 0.2 Æ 0.1 units per child (P < 0.001),
Five studies directly address the implementation of multiple          in the 25–49% TBSA from 6.9 Æ 1.1 to 2.5 Æ 0.6 units per child
hemostatic techniques as a blood conserving protocol to               (P < 0.001), and in the 50–100% TBSA 49.5 Æ 10.3 to 10 Æ 1.7
decrease requirements for blood component transfusion                 units per child (P < 0.001) with the implementation of the
[21,23,24,54]. Losee et al. described a protocol followed on 23       blood conserving protocol.
564                                                  burns 37 (2011) 559–565



    Gomez et al. performed a retrospective review of the            variability on the surgical techniques in the use and
requirement of blood products in 30 randomly selected adult         concentration of tumescence, thrombin, fibrin, epinephrine
patients with more than 10% TBSA burns, who had an                  and systemic hemostatic agents. Unfortunately, a clear
operation [24]. The patients were stratified into 2 groups.          conclusion as to the best hemostatic agent cannot be made.
Group 1 consisted of 15 patients that received treatment with           However, as demonstrated by the studies comparing blood
implementation of a blood conserving protocol. Group 2              conserving protocols that the best option is not a single agent
consisted of 15 patients receiving the traditional surgical         but a fusion of techniques. These studies demonstrate that
technique. The traditional surgical technique involved use of       diligent implementation of blood conserving protocols can
epinephrine-thrombin (1 ml of 1:1000 epinephrine, 10,000 U of       decrease blood component requirements in burn surgery.
thrombin in 1 l saline) soaked gauze compresses for 10 min,
and electrocautery on the remaining bleeding points until
hemostasis was achieved. The blood conserving protocol              Conflict of interest
involved the use of tourniquets for extremity harvesting and
excisions,     subcutaneous       infiltration    of  epinephrine    The author(s) declare that there are no conflicts of interest in
(1:1,000,000) solution of donor and burn sites, use of epineph-     the writing of this manuscript.
rine (1:1000) soaked wraps, and the use of electrocautery for
remaining bleeding areas. They demonstrated a decrease in
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Hemostasia

  • 1. burns 37 (2011) 559–565 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/burns Review Hemostasis in burn surgery—A review Jose P. Sterling a, David M. Heimbach b,* a University of Texas, Southwestern Medical School, Dallas, TX, United States b University of Washington, Seattle Washington, USA article info abstract Article history: Over the past 30 years, techniques of early excision and grafting along with enhancement of Accepted 29 June 2010 critical care have significantly improved survival following burn injury. Despite these advancements, large volume blood loss associated with surgical intervention continues Keywords: to be a challenging aspect of burn surgery. This review article will examine the methods of Thermal injury limiting blood loss during surgical procedures. Burns Published by Elsevier Ltd and ISBI Burn surgery Burn excision Blood transfusion Tourniquets Epinephrine Thrombin Fibrin sealant Electrocautery Terlipressin Blood conservation Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560 2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560 2.1. Literature search strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560 2.2. Inclusion criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560 2.3. Data extraction and synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560 3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561 3.1. Description of included studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561 3.2. Tourniquets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561 3.3. Epinephrine tumescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 3.4. Thrombin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 3.5. Fibrin sealant. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 3.6. Electrocautery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563 * Corresponding author. Tel.: +1 206 779 9600. E-mail address: heimbach@u.washington.edu (D.M. Heimbach). 0305-4179/$36.00 . Published by Elsevier Ltd and ISBI doi:10.1016/j.burns.2010.06.010
  • 2. 560 burns 37 (2011) 559–565 3.7. Systemic therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563 3.8. Blood conserving protocols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 4.1. Study limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 1. Introduction Boolean search terms, from the establishment of the database until Jan 2010. Searches were conducted without Over the past 30 years, techniques of early excision and grafting language restriction. The bibliographies of all retrieved along with enhancement of critical care have significantly articles were then manually searched for relevant missed improved survival following severe burn. Despite these advance- articles. The search terms were: ‘‘‘‘haemostasis’’[All Fields] ments, large volume blood loss associated with surgical OR ‘‘hemostasis’’[MeSH Terms] OR ‘‘hemostasis’’[All Fields]) intervention continues to be a challenging aspect of burn surgery. AND (‘‘burns’’[MeSH Terms] OR ‘‘burns’’[All Fields] OR Traditionally, blood was transfused when the hemoglobin ‘‘burn’’[All Fields]) AND (‘‘surgery’’[Subheading] OR ‘‘surger- levels fell bellow 10 mg/dl. This originated from the fear of the y’’[All Fields] OR ‘‘surgical procedures, operative’’[MeSH deleterious effects of anemia on oxygen consumption, cardiac Terms] OR (‘‘surgical’’[All Fields] AND ‘‘procedures’’[All function and tissue perfusion [1,2]. However, such liberal use Fields] AND ‘‘operative’’[All Fields]) OR ‘‘operative surgical of blood has come under question. procedures’’[All Fields] OR ‘‘surgery’’[All Fields] OR ‘‘general Multiple studies questioned the harmful effects of blood surgery’’[MeSH Terms] OR (‘‘general’’[All Fields] AND ‘‘sur- component transfusion. Blood component transfusions can be gery’’[All Fields]) OR ‘‘general surgery’’[All Fields]) AND associated with transfusion related acute lung injury, infec- (‘‘hemorrhage’’[MeSH Terms] OR ‘‘hemorrhage’’[All Fields] tion, immunomodulation, age of the transfused component, OR (‘‘blood’’[All Fields] AND ‘‘loss’’[All Fields]) OR ‘‘blood multi organ dysfunction, acute respiratory syndrome and loss’’[All Fields]’’. increase in mortality [3–7]. Due to the risks associated with blood component transfusion, restrictive transfusion prac- 2.2. Inclusion criteria tices are recommended for both adult and pediatric patients [7–10]. Furthermore, this has been extrapolated and demon- All articles reporting efficacy and/or outcome with the use of strated in the burn patient [4,5,11]. hemostatic techniques and/or agents in humans during burn Unfortunately, the surgical treatment of burn patients is surgery were included. Individual case reports were excluded. associated with substantial blood loss [12–16]. Multiple hemo- The techniques were used for the management of excised static techniques have been proposed for this problem. To wounds and/or donor sites in adults and children. A flowchart address this issue, a review of the hemostatic techniques was of the search results is provided in Fig. 1. The two reviewers undertaken and we present here the findings for assessment. independently applied the inclusion criteria and any differ- ences were resolved through discussion. 2. Methods 2.3. Data extraction and synthesis 2.1. Literature search strategies Data was extracted by the researchers, to determine interven- tion, management of burn and/or management of donor site, A systematic search was conducted of Ovid MEDLINE, number of patients, age (pediatric or adult), and result of EMBASE, Cochrane Library, CINAHL, and PubMed using intervention. [()TD$FIG] Fig. 1 – Flowchart of search results.
  • 3. burns 37 (2011) 559–565 561 Table 1 – Included studies. Study ref. Type of study Site Intervention N Type of Range of (patients) patients % TBSA [17] Comparative Burn Tourniquet versus No Tourniquet 10 All 3–31 [18] Descriptive Burn Tourniquet + Topical Epinephrine 52a NS <12 [19] Descriptive Burn Tourniquet + Thrombin 17 All 0.5–15 [20] Comparative Burn Epinephrine Tumescence or Tourniquet versus 44 Adult >5% Historical Controls [25] Descriptive Burn/donor Epinephrine/Bupivicaine Tumescence 29 Pediatric 1–12 [26] Descriptive Burn Epinephrine Tumescence 10 Adult 5–50% [29] Comparative Burn/donor Epinephrine Tumescence + Thrombin 20 Adult 14–52% versus 0.45% NS + Thrombin [27] Comparative Burn/donor Topical/Tumescence Epinephrine + Thrombin 42 Pediatric 11–66% versus 0.45% NS + Thrombin [28] Comparative Donor Epinephrine/Lidocaine Tumescence + Topical 56 All 10–51% Epinephrine versus 0.45% NS Tumescence + Topical Epinephrine [38] Descriptive Burn Thrombin 72 All 1–4% [33] Comparative Donor Topical Epinephrine versus Thrombin 32 All NS [37] Comparative Donor Topical Phenylephrine versus Thrombin 24 NS NS [35] Comparative Donor Thrombin versus Bovine collagen sheet 20 NS NS [36] Comparative Donor Thrombin Ointment versus Thrombin Solution 11 All NS [46] Comparative Donor Thrombin versus Fibrin Sealant 46 Adult NS [49] Comparative Donor Fibrin Sealant versus No Fibrin Sealant 61 All 2–8%b [48] Comparative Donor Fibrin Sealant versus No Fibrin Sealant 47 All <15% [47] Comparative Donor Thrombin + Fibrin versus Thrombin + Placebo 10 NS NS [50] Comparative Burn Electrocautery knife with air spray versus No air spray 6 NS 10–30% [53] Comparative Systemic Terlipressin versus Placebo 51 All 10–20% [51] Descriptive Systemic rFVIIa 4 All 50–72% [52] Comparative Systemic rFVIIa versus No rFVIIa 18 Adult 12–60% [30] Descriptive Blood Conserving Protocol 23 Pediatric 1–55% [21] Comparative Blood Conserving Protocol 2461 NS 1–>40% [22] Comparative Blood Conserving Protocol 35 Adult 1–36% [23] Comparative Blood Conserving Protocol 392 Pediatric 10–>50% [24] Comparative Blood Conserving Protocol 30 Adult 8–46% NS: not stated. a Upper extremities. b Donor percent total body area. 3. Results However, as part of their intraoperative protocol the wounds in both groups were sprayed with thrombin solution and 3.1. Description of included studies wrapped with epinephrine soaked gauze. Three other studies described the use and benefit of A total of 27 studies were included (see Table 1.) From the tourniquets in the treatment of burns [18–20]. Smoot included studies 8 are descriptive and 19 are comparative described the use of intermittent release and rapid reinflation hemostatic interventions. Specifically, 5 studies compared the of the tourniquet to allow for assessment of tissue viability implementation of blood conserving protocols at single [18]. This method was used in combination with epinephrine institutions. Most studies discussed the use of subcutaneous soaks and compression wraps. Similarly, Sawada and and topical agents to assist in hemostasis. However, 3 studies Yotsuyanagi described the use of a tourniquet and spraying discussed the use of systemic pharmacoactive agents to assist the wound with thrombin prior to, and after, removal of the with hemostasis. tourniquet along with pressure bandages [19]. Djurickovic et al. described the use of a tourniquet during tangential 3.2. Tourniquets excision of the extremity [20]. After completion of the excision the tourniquet was deflated to evaluate areas of O’Mara et al. directly studied the value of tourniquet inadequate excision and then reinflated. After reinflation, application without exsanguination of the limb prior to areas of major bleeding where coagulated and meshed tourniquet inflation to improve visualization of viable tissue autograft was then placed along with cotton gauze dressing during excision [17]. In this study they found that blood loss and elastic bandages. Furthermore, four out of the five studies per area excised was less with tourniquet control that describe blood conserving protocols include tourniquets (0.10 Æ 0.29 cc/cm2) versus no tourniquet (0.32 Æ 0.56 cc/cm2) as part of the hemostatic protocol [21–24]. It was felt by these (P = 0.04). Additionally they demonstrated similar graft take authors that the use of tourniquet is an important adjunct to between the two groups (98.2% versus 96.8%) (P > 0.1). limit bleeding.
  • 4. 562 burns 37 (2011) 559–565 3.3. Epinephrine tumescence Four studies compared the hemostatic efficacy of thrombin (bThrombin) versus other products [33–36]. Brezel et al. Three articles described the technique of epinephrine subcu- compared the visual amount of blood loss form donor sites taneous infiltration as a hemostatic agent [20,25,26]. Djur- on 32 patients that were treated with thrombin (100 U/ml) or ickovic et al. described the use of 1:1,000,000 epinephrine epinephrine solution (1:200,000) [33]. They demonstrated a solution infiltrated to the burn in 23 patients [20]. They superior hemostatic effect from the epinephrine treated donor estimated a 3.42 Æ 0.39% blood volume loss per 1% body site. Caucci et al. compared the hemostatic effect of surface area excised. Fujita et al. preoperatively marked the phenylephrine (1:20,000) versus thrombin (100 U/ml) on the burn wound of 10 consecutive patients with a 5 Â 5 cm square donor sites of 24 patients [37]. They demonstrated a superior grid using crystal violet [26]. This grid was used a guide to hemostatic effect with phenylephrine compared to thrombin inject 20 ml of a dilute epinephrine solution (1 mg/l) per when comparing blood absorbed in a paper filter disk covering square. They felt that this provided an aide and safeguard to the donor site after treatment with the agents (P < 0.005). the amount of epinephrine used with the tumescent tech- Prasad et al. compared thrombin versus a bovine collagen nique. Beausang et al. reported on 29 pediatric patients in dressing on the donor sites of 21 patients [35]. Although, they which the donor sites and burn wounds were infiltrated with a did not describe the concentration of the thrombin spray, they 1:500,000 epinephrine with bupivicane [25]. Bupivicane (0.25% did demonstrated superior hemostatic control with the spray plain) was added to the solution at a 3 mg per kg body weight thrombin. Mean blood loss with thrombin (5.25 Æ 8.68 ml) concentration. They reported no adverse effects and a versus collagen (8.24 Æ 13.54 ml) (P = 0.057). Sawada et al. decrease of postoperative pain with this technique. compared the use of thrombin ointment versus thrombin Three articles compared the use of epinephrine tumes- solution on the donor sites of 11 patients [36]. They created the cence to determine effect on hemostasis [27–29]. Barret et al. ointment by mixing 10,000 units of powdered thrombin with compared the use of topical and subcutaneous epinephrine on 10 g of petroleum jelly based gentamicin ointment. Again, this a cohort of 42 pediatric patients [27]. Half of these patients study did not describe the concentration of the thrombin received topical epinephrine (1:10,000 sprayed and 1:200,000 solution. However, the mean bleeding time with the thrombin compresses) to the excised wound and donor sites and ointment (11.5 s) was less than that of the thrombin solution subcutaneous infusion (1:300,000) to scalp donor sites only. (25.5 s, P < 0.01). The other half of patients followed the same protocol using One study described the efficacy of the recombinant 0.45% normal saline solution. Additionally, both groups human Thrombin (rThrombin) as a hemostatic agent in burn received topical thrombin (1000 units/ml) to the excised surgery. Greenhalgh et al. conducted a single-arm, open label wounds and donor sites. They found no difference in the study of rThrombin (1000 U/ml) on the burn wounds of 72 amount of bleeding per square centimeter excised patients after excision [38]. Hemostasis at 20 min was (0.48 Æ 0.12 ml/cm2 versus 0.51 Æ 0.15 ml/cm2, P = 0.681) be- achieved in 91.5% of the patients. Further application of tween the two groups. Robertson et al. compared the results of rThrombin ensued hemostasis in all but 4 patients. Also, they 20 patients (26 operations) using epinephrine (1 mg/ml) demonstrated a low rate of anti-rThrombin antibody forma- tumescence at the excision and donor sites to 10 patients tion (1.6%) without associated human thrombin neutraliza- (11 operations) [29]. Also, topical thrombin spray was utilized tion, a concern that originated from the use of bThrombin [39– in both groups. They demonstrated almost a 70% reduction in 42]. Furthermore, one out of the four studies that describe a blood loss per unit area excised in the tumescent group blood conserving protocol utilize thrombin in their protocol (0.37 Æ 0.2 ml/cm2 versus 1.15 Æ 0.28 ml/cm2, P 0.0001). [21]. Gacto et al. performed a prospective, randomized, controlled, blinded trial of 56 patients [28]. Both groups received 3.5. Fibrin sealant subcutaneous infiltration at donor sites with either epineph- rine (1:500,000) solution with added lidocaine (5%, w/v) or with Fibrin sealants are human derived factors that are designed to 0.45% normal saline. They concluded that the infiltration of reproduce the final steps of the physiologic coagulation this solution decreased intraoperative bleeding and decreased cascade of a stable fibrin clot [43,44]. Besides hemostatic postoperative pain. Furthermore, four out of the five studies properties fibrin sealant have adhesive properties that can be that describe blood conserving protocols utilize epinephrine utilized during skin grafts and flap procedures [45]. Drake and tumescence as part of the protocol [22–24,30]. Wong compared the hemostatic effect of a patient derived fibrin sealant against thrombin (100 U/ml) on the donor sites of 3.4. Thrombin 46 patients [46]. They determined the time to hemostasis to be less with the fibrin sealant (31 s) versus thrombin (58 s, Topical thrombin as a hemostatic agent is commonly used on a P = 0.0012). Achauer et al. conducted a study on 10 patients variety of surgeries [31]. Thrombin is a clotting factor that with half of the donor site sprayed with thrombin and plasma converts fibrinogen into fibrin that is the foundation of a blood placebo while the other half was sprayed with thrombin and clot. Typically the thrombin is applied directly to the wound via fibrin glue [47]. They found no difference in blood loss between a spray system or in combination with an absorbable gelatin or the two areas. Both Greenhalgh et al. and Nervi et al. compared collagen sponge. Historically, thrombin (bThrombin) has been the effects of hemostasis of fibrin sealant versus no fibrin derived from bovine plasma via different purification processes. sealant on donor wounds [48,49]. Greenhalgh et al. felt that Currently, human plasma (hThrombin) derived and human bleeding at the donor sites were well controlled with the fibrin recombinant thrombin (rThrombin) products are available [32]. sealant as demonstrated by surgeon estimates [48]. However,
  • 5. burns 37 (2011) 559–565 563 the treatment failed to demonstrate benefit on semi quantita- pediatric patients [54]. The protocol consisted of debridement tive measurements. On the contrary, Nervi et al. demonstrated of full thickness burns with electrocautery and partial a reduction in the mean time to hemostasis of approximately thickness burns with dermabrasion. All donor sites were 200 s with the use of fibrin sealants (fibrin 193 Æ 131 s, control subcutaneously injected with a solution of epinephrine and 392 Æ 153 s, P < 0.001) [49]. The use of fibrin sealants is not saline. No more than 10 mg/kg of epinephrine was adminis- described in the four studies that describe a blood conserving tered subcutaneously at one time. However, staggered injec- protocol. tions were utilized that often resulted in total dose of epinephrine being greater than 10 mg/kg. Additionally, all 3.6. Electrocautery debrided or harvested surgical sites were treated with epinephrine solution soaked pads. Following this protocol Most of the studies describe the use of electrocautery as an they report an average blood loss per percent TBSA treated to adjunct to achieve hemostasis. However, Mitsukawa et al. be 17 ml. describes a novel use for an electrocautery attachment to Cartotto et al. compared the results of a comprehensive assist with hemostasis during large burn area excisions [50]. intraoperative blood conservation strategy and its effects on They attached a smoke aspiration tip to the electrocautery. blood loss and wound outcome to a historical cohort [22]. The Instead of utilizing the aspiration tip to aspirate they used it as blood conservation technique was as follows: Donor sites a conduit to expel air. This stream of air cleared blood and fluid were infiltrated subcutaneously with a 1:500,000 adrenaline from the tip allowing for improved visualization and electro- solution. After the grafts were harvested the sites were cautery function. Compared to regular electrocautery this new dressed with epinephrine (1:33,333) soaked pads. Burn device reduced the duration of surgery by 10% and the amount wounds on limbs where tangentially excised under tourni- of blood loss by 14% for a 30% TBSA burn. quet control. After completion of excision, the wounds were dressed with epinephrine (1:33,333) soaked pads and a firm 3.7. Systemic therapies circumferential wrapping was performed for full 10 min prior to deflating the tourniquet. After deflation of the Three studies discuss the use of systemic therapies to assist tourniquet major bleeding was cauterized and the extremity with hemostasis in burn surgery [51–53]. Terlipressin is an rewrapped with epinephrine soaked pads for another 5 min. analogue of vasopressin used as a vasoactive drug in the When the tourniquet could not be utilized the wound management of hypotension. It has been found to be effective received subcutaneous infiltration with epinephrine solu- when norepinephrine does not help. Mzezewa et al. describes tion (1:500,000) prior to excision. After the excision was the results of a randomized trial comparing the use of completed the wound was dressed with epinephrine terlipressin or placebo on 51 patients undergoing early (1:33,333) soaked pads. Final hemostasis was achieved using excision and grafting of burns between 10 and 20% TBSA serial application of the epinephrine pads and electrocau- [53]. Use of other hemostatic adjuncts where not described. In tery. Utilizing this blood conserving protocol, the estimated this study the medication was given intravenously at a dose of blood loss was reduced from 211 Æ 166 ml per %TBSA excised 20 m/kg body weight and repeated every 4 h for 24 h. Following and grafted in the historical group to 123 Æ 106 ml in the this protocol, terlipressin reduced blood loss on average 21% protocol driven group (P = 0.02). Furthermore, the intra- compared to placebo. operative transfusion requirement was reduced from Johansson et al. described a technique of utilizing recom- 3.3 Æ 3.1 units per case, in the historical group, to 0.1 Æ 0.3 binant factor VIIa (rFVIIa) at a dose of 100 mg/kg on 4 patients units per case in the protocol driven group (P < 0.001). Also undergoing major wound excision that developed periopera- they reported no compromise on wound outcome and graft tive uncontrollable bleeding [51]. They report hemostasis take with the new protocol. within 15 min of administering the drug and no adverse Sheridan and Szyfelbein compared blood use between two effects with the treatment. In a subsequent study, Johansson matched groups of 392 pediatric patients who where managed et al. conducted a single centre, randomized, double blind, during the calendar years of 1982–1985 and 1992–1995 (blood placebo controlled trial on 18 consecutive patients [52]. The conserving protocol) [23]. Three groups were analyzed: patients were randomized to receive either placebo or 40 mg/kg children with 10–24%, 25–49% and 50–100% TBSA. The dose of rFVIIa at the time of skin incision and a second dose of techniques for intraoperative blood conservation included: placebo or rFVIIa (40 mg/kg) 90 min later. They demonstrated a clear preparation of excision plan, performing all extremity decease in the total number of units of blood components excisions under tourniquet, and wrapping the extremity in a transfused per patient compared to placebo (0.9 versus 2.2, hemostatic dressing prior to tourniquet deflation, conducting P = 0.0013). Furthermore, they demonstrated a decrease in all fascial excision under electrocautery, performing all fresh frozen plasma units and platelet units transfused tangential excisions as early as possible, executing all torso utilizing this protocol. tangential excision after subcutaneous epinephrine injection, and maintaining patient euthermic. They demonstrated a 3.8. Blood conserving protocols reduction in the use of PRBC’s in the 10–24% TBSA from 1.9 Æ 0.2 units per child to 0.2 Æ 0.1 units per child (P < 0.001), Five studies directly address the implementation of multiple in the 25–49% TBSA from 6.9 Æ 1.1 to 2.5 Æ 0.6 units per child hemostatic techniques as a blood conserving protocol to (P < 0.001), and in the 50–100% TBSA 49.5 Æ 10.3 to 10 Æ 1.7 decrease requirements for blood component transfusion units per child (P < 0.001) with the implementation of the [21,23,24,54]. Losee et al. described a protocol followed on 23 blood conserving protocol.
  • 6. 564 burns 37 (2011) 559–565 Gomez et al. performed a retrospective review of the variability on the surgical techniques in the use and requirement of blood products in 30 randomly selected adult concentration of tumescence, thrombin, fibrin, epinephrine patients with more than 10% TBSA burns, who had an and systemic hemostatic agents. Unfortunately, a clear operation [24]. The patients were stratified into 2 groups. conclusion as to the best hemostatic agent cannot be made. Group 1 consisted of 15 patients that received treatment with However, as demonstrated by the studies comparing blood implementation of a blood conserving protocol. Group 2 conserving protocols that the best option is not a single agent consisted of 15 patients receiving the traditional surgical but a fusion of techniques. These studies demonstrate that technique. The traditional surgical technique involved use of diligent implementation of blood conserving protocols can epinephrine-thrombin (1 ml of 1:1000 epinephrine, 10,000 U of decrease blood component requirements in burn surgery. thrombin in 1 l saline) soaked gauze compresses for 10 min, and electrocautery on the remaining bleeding points until hemostasis was achieved. The blood conserving protocol Conflict of interest involved the use of tourniquets for extremity harvesting and excisions, subcutaneous infiltration of epinephrine The author(s) declare that there are no conflicts of interest in (1:1,000,000) solution of donor and burn sites, use of epineph- the writing of this manuscript. rine (1:1000) soaked wraps, and the use of electrocautery for remaining bleeding areas. They demonstrated a decrease in references the total blood volume transfused 6293 Æ 5141 to 3147 Æ 4585 ml (P = 0.031) utilizing the blood conserving protocol. Furthermore, they demonstrated a decrease in the mean blood units transfused intraoperatively per patient from [1] Spence RK, Cernaianu AC, Carson J, DelRossi AJ. Transfusion in surgery. Curr Probl Surg 1993;30:1112–80. 8.9 Æ 8 to 4.7 Æ 7.8 units (P = 0.026). This trend was also noted [2] Harvey JS, Watkins G, Sherman R. Emergent burn care. with other blood component transfusions. Southern Med J 1984;77:204–14. O’Mara et al. performed an analysis of 3 year periods before [3] Rutan RL, Bjarnason DL, Desai MH, Herndon DN. Incidence and after initiation of a blood conserving protocol [21]. In the of HIV seroconversion in paediatric burn patients. Burns early period after excision and harvesting, the sites where 1992;18:216–9. covered with epinephrine and/or thrombin soaked gauze. [4] Graves T, Cioffi W, Mason A, McManus W, Pruit B. Relationship of transfusion and infection in a burn Pressure was applied to all sites for a minimum of 10–15 min. population. J Trauma 1989;29:948–52. 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