Pharmacologic modification to resuscitation fluid after thermal injury--is drotrecogin alfa the answer to arrest burn depth progression?
OBJECTIVE
The addition of drotrecogin alfa (DA), an anti-inflammatory useful in septic shock, to standard burn shock resuscitation fluids will protect burned, injured skin from further injury.


METHODS
Anesthetized animals were subjected to a standardized burn pattern by applying a branding iron to 10 different locations on the back of the rat for 1 seconds to 14 seconds, creating a range of burn depths and severities.


METHODS
Animal burn shock and resuscitation model.


METHODS
Thirty-one male adult Sprague-Dawley rats.


METHODS
Control animals were resuscitated with lactated Ringer's solution (LRS) at 2 mL/kg/percent total body surface area/24 h; experimental animals received LRS plus DA 24 microg/kg/h (LRS + DA).


METHODS
Perfusion to each burned area was assessed using a laser Doppler imaging technology. Punch biopsies at each burned area were stained with hematoxylin and eosin and assessed for burn depth and for inflammation using previously reported measures. Samples from 14 animals were stained for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and caspase-3 (apoptosis markers).


RESULTS
Increasing branding iron contact times worsened perfusion, burn depth, and apoptotic ratios. There was no correlation between inflammatory markers and burn contact time. The addition of DA leads to worse perfusion, deeper burns, worse inflammation, and decreased apoptotic ratios.


CONCLUSIONS
Laser Doppler imaging is a useful technology to assess burn depth. The addition of DA to traditional resuscitation fluids for burn shock is deleterious to the injured, burned skin. Modifying the traditional burn shock resuscitation fluids, although intellectually attractive, needs to be rigorously studied.
Meyerholz
David K
DK
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Piester
Travis L
TL
McNamara
Andrew R
AR
Sokolich
Julio C
JC
Jaskille
Amin D
AD
Orion
Kristine C
KC
Zamba
K D
KD
Light
Timothy D
TD
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002056:Burns / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D004338:Drug Combinations; D020287:In Situ Nick-End Labeling; D007552:Isotonic Solutions / Q000627:therapeutic use*; D008297:Male; D011486:Protein C / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D000077325:Ringer's Lactate; D018608:Ultrasonography, Doppler
D000890:Anti-Infective Agents; D004338:Drug Combinations; D007552:Isotonic Solutions; D011486:Protein C; D011994:Recombinant Proteins; D000077325:Ringer's Lactate; C421124:drotrecogin alfa activated