Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock

Marc O. Maybauer, Dirk M. Maybauer, John F. Fraser, Lillian D. Traber, Martin Westphal, Robert A. Cox, Ruksana Huda, Yoshimitsu Y. Nakano, Perenlei Enkhbaatar, Hal K. Hawkins, David Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: To investigate ceftazidime in acute lung injury (ALI) and sepsis. Design and setting: Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. Interventions: Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. Measurements and 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.

Original languageEnglish (US)
Pages (from-to)1219-1227
Number of pages9
JournalIntensive Care Medicine
Volume33
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Smoke Inhalation Injury
Ceftazidime
Septic Shock
Sheep
Hemodynamics
Sepsis
Smoke
Inhalation
Lung Injury
Airway Obstruction
Arterial Pressure
Wounds and Injuries
Heart Rate
Bronchioles
Lung
Acute Lung Injury
Poisons
Bronchi
Nitrites
Nitrates

Keywords

  • 3-Nitrotyrosine
  • Acute lung injury
  • Acute respiratory distress syndrome
  • Airway obstruction
  • Nitric oxide
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Maybauer, M. O., Maybauer, D. M., Fraser, J. F., Traber, L. D., Westphal, M., Cox, R. A., ... Traber, D. L. (2007). Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock. Intensive Care Medicine, 33(7), 1219-1227. https://doi.org/10.1007/s00134-007-0658-3

Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock. / Maybauer, Marc O.; Maybauer, Dirk M.; Fraser, John F.; Traber, Lillian D.; Westphal, Martin; Cox, Robert A.; Huda, Ruksana; Nakano, Yoshimitsu Y.; Enkhbaatar, Perenlei; Hawkins, Hal K.; Herndon, David; Traber, Daniel L.

In: Intensive Care Medicine, Vol. 33, No. 7, 07.2007, p. 1219-1227.

Research output: Contribution to journalArticle

Maybauer, MO, Maybauer, DM, Fraser, JF, Traber, LD, Westphal, M, Cox, RA, Huda, R, Nakano, YY, Enkhbaatar, P, Hawkins, HK, Herndon, D & Traber, DL 2007, 'Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock', Intensive Care Medicine, vol. 33, no. 7, pp. 1219-1227. https://doi.org/10.1007/s00134-007-0658-3
Maybauer, Marc O. ; Maybauer, Dirk M. ; Fraser, John F. ; Traber, Lillian D. ; Westphal, Martin ; Cox, Robert A. ; Huda, Ruksana ; Nakano, Yoshimitsu Y. ; Enkhbaatar, Perenlei ; Hawkins, Hal K. ; Herndon, David ; Traber, Daniel L. / Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock. In: Intensive Care Medicine. 2007 ; Vol. 33, No. 7. pp. 1219-1227.
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abstract = "Objective: To investigate ceftazidime in acute lung injury (ALI) and sepsis. Design and setting: Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. Interventions: Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. Measurements and 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.",
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AU - Maybauer, Dirk M.

AU - Fraser, John F.

AU - Traber, Lillian D.

AU - Westphal, Martin

AU - Cox, Robert A.

AU - Huda, Ruksana

AU - Nakano, Yoshimitsu Y.

AU - Enkhbaatar, Perenlei

AU - Hawkins, Hal K.

AU - Herndon, David

AU - Traber, Daniel L.

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N2 - Objective: To investigate ceftazidime in acute lung injury (ALI) and sepsis. Design and setting: Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. Interventions: Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. Measurements and 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.

AB - Objective: To investigate ceftazidime in acute lung injury (ALI) and sepsis. Design and setting: Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. Interventions: Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. Measurements and 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.

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KW - Acute lung injury

KW - Acute respiratory distress syndrome

KW - Airway obstruction

KW - Nitric oxide

KW - Sepsis

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