Combined recombinant human activated protein C and ceftazidime prevent the onset of acute respiratory distress syndrome in severe sepsis

Maybauer, Marc O., Maybauer, Dirk M., Fraser, John F., Westphal, Martin, Szabo, Csaba, Cox, Robert A., Hawkins, Hal K., Traber, Lillian D. and Traber, Daniel L. (2012) Combined recombinant human activated protein C and ceftazidime prevent the onset of acute respiratory distress syndrome in severe sepsis. Shock, 37 2: 170-176. doi:10.1097/SHK.0b013e31823ca8ee


Author Maybauer, Marc O.
Maybauer, Dirk M.
Fraser, John F.
Westphal, Martin
Szabo, Csaba
Cox, Robert A.
Hawkins, Hal K.
Traber, Lillian D.
Traber, Daniel L.
Total Author Count Override 10
Title Combined recombinant human activated protein C and ceftazidime prevent the onset of acute respiratory distress syndrome in severe sepsis
Journal name Shock   Check publisher's open access policy
ISSN 1073-2322
1540-0514
Publication date 2012-02-01
Sub-type Article (original research)
DOI 10.1097/SHK.0b013e31823ca8ee
Volume 37
Issue 2
Start page 170
End page 176
Total pages 7
Place of publication Baltimore, MD, United States
Publisher Lippincott Williams and Wilkins
Collection year 2013
Language eng
Formatted abstract
This experimental animal study investigates the effects of combined recombinant human activated protein C (rhAPC) and ceftazidime on cardiopulmonary function in acute lung injury and severe sepsis. Twenty-one sheep (37± 2 kg) were operatively prepared and randomly allocated to either the sham, control, or treatment group (n = 7 each). Single treatments of rhAPC or ceftazidime were published previously; therefore, control groups were dispensed in the present study, what may be considered a study limitation. Acute lung injury and sepsis were induced according to an established protocol. The sham group received only the vehicle. The sheep were studied in awake state for 24 h and mechanically ventilated. Recombinant human APC (continuous infusion 24 µg/kg per hour) and ceftazidime (3-g bolus at 1 and 13 h) were intravenously administered. The animals were fluid resuscitated with Ringer’s lactate to maintain hematocrit at baseline. Compared with injured controls, the treatment group had a significantly higher PaO2/FIO2 ratio, and the onset of acute respiratory distress syndrome was prevented. The increase in pulmonary microvascular shunt fraction and airway obstruction in bronchi and bronchiole, as well as lung 3-nitrotyrosine, lung myeloperoxidase, cardiac 3-nitrotyrosine, and cardiac malondialdehyde levels, was significantly reduced as compared with controls (P < 0.05 each). Treated sheep had significantly improved hemodynamics as reflected by mean arterial pressure, heart rate, cardiac index, and systemic vascular resistance index (P < 0.05 each). In addition, plasma oncotic pressure and urine output were significantly improved (P < 0.05 each). Combined rhAPC and ceftazidime significantly improved cardiopulmonary function, reduced pulmonary
and cardiac tissue injury, and prevented the onset of acute respiratory distress syndrome in ovine severe sepsis without
obvious adverse effects.
Keyword Airway
hypotension
nitric oxide
3-nitrotyrosine
peroxynitrite
shock
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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