Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock.
OBJECTIVE
To investigate ceftazidime in acute lung injury (ALI) and sepsis.


METHODS
Prospective, randomized, controlled animal study in an investigational ICU at a university hospital.


METHODS
Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol.


RESULTS
Whereas global hemodynamics and oxygenation remained stable in sham animals (no injury, no treatment), the injury contributed to a hypotensive-hyperdynamic circulation in the control group (smoke inhalation and sepsis, no treatment), as indicated by a significant increase in cardiac index) and heart rate and a drop in mean arterial pressure. Treatment with ceftazidime (smoke inhalation and sepsis, treatment group) stabilized cardiac index and heart rate and attenuated the decrease in mean arterial pressure. The deterioration in PaO2/FiO2 ratio and pulmonary shunt fraction (Qs/Qt) was significantly delayed and blunted by ceftazidime. At 24 h after injury a significant increase in airway obstruction scores of bronchi and bronchioles in both injured groups was observed. Ceftazidime significantly reduced airway obstruction vs. control animals. Whereas plasma nitrate/nitrite levels increased similarly in the two injured groups, lung 3-nitrotyrosine content remained at the baseline level in the ceftazidime group.


CONCLUSIONS
In ovine lung injury ceftazidime improves global hemodynamics and oxygenation not only by bacterial clearance but also via reduction in toxic nitrogen species such as 3-nitrotyrosine. Therefore ceftazidime appears as a clinically relevant adjunct in the common setting of sepsis-associated lung injury.
Maybauer
Marc O
MO
Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital, 301 University Blvd., 77555-0833, Galveston, TX, USA. marc.maybauer@uni-ulm.de.|Department of Anesthesiology and Intensive Care, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, University of Ulm, Steinhövelstrasse 9, 89075, Ulm, Germany. marc.maybauer@uni-ulm.de.
Maybauer
Dirk M
DM
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.|Department of Anesthesiology and Intensive Care, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, University of Ulm, Steinhövelstrasse 9, 89075, Ulm, Germany.
Fraser
John F
JF
Royal Children's Hospital Burns Research Group and Prince Charles Hospital, University of Queensland, Brisbane, Australia.
Traber
Lillian D
LD
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Westphal
Martin
M
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.|Department of Anesthesiology and Intensive Care Medicine, University of Münster, Münster, Germany.
Cox
Robert A
RA
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Huda
Ruksana
R
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Nakano
Yoshimitsu Y
YY
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Enkhbaatar
Perenlei
P
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Hawkins
Hal K
HK
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Herndon
David N
DN
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
Traber
Daniel L
DL
Departments of Anesthesiology, Pathology, and Surgery, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, Tex., USA.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002442:Ceftazidime / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008168:Lung / Q000737:chemistry; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D011897:Random Allocation; D012756:Sheep; D012772:Shock, Septic / Q000503:physiopathology*; D015208:Smoke Inhalation Injury / Q000503:physiopathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000900:Anti-Bacterial Agents; D009566:Nitrates; D009573:Nitrites; C002744:3-nitrotyrosine; D014443:Tyrosine; D002442:Ceftazidime