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Combined Recombinant Human Activated Protein C and Ceftazidime Prevent the Onset of ARDS in Severe Sepsis.
MedLine Citation:
PMID:  22089200     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT: This experimental animal study investigates the effects of combined recombinant human activated protein C (rhAPC) and ceftazidime on cardio-pulmonary 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. ALI and sepsis was induced according to an established protocol. The sham group received only the vehicle. The sheep were studied in awake state for 24h and mechanically ventilated. RhAPC (continous infusion 24 mcg/kg/h) and ceftazidime (3 g bolus at 1h and 13h) was intravenously administered. The animals were fluid resuscitated with Ringer's lactate to maintain hematocrit at baseline. Compared to injured controls, the treatment group had a significantly higher PaO2/FiO2 ratio, and the onset of ARDS was prevented. The increase in pulmonary microvascular shunt fraction, airway obstruction in bronchi and bronchioli, as well lung 3-nitrotyrosine, lung myeloperoxidase, cardiac 3-nitrotyrosine, and cardiac malondialdehyde levels was significantly reduced as compared to 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 ARDS in ovine severe sepsis without obvious side effects.
Authors:
Marc O Maybauer; Dirk M Maybauer; John F Fraser; Martin Westphal; Csaba Szabó; Robert A Cox; Hal K Hawkins; Lillian D Traber; Daniel L Traber
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-15
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  -     ISSN:  1540-0514     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital for Children, 301 University Blvd, Galveston, TX 77555-0591, USA. 2Department of Anaesthesiology and Intensive Care Medicine, Philipps University of Marburg, Baldinger Str. 1, Marburg 35033, Germany. 3Critical Care Research Group, University of Queensland and The Prince Charles Hospital at Brisbane, Rode Road, Chermside 4032, Queensland, Australia. 4Department of Pathology, The University of Texas Medical Branch and Shriners Burns Hospital for Children, 815 Market Street, Galveston, TX 77550-2725, USA.
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