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01-07-2007 | Experimental

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

Authors: 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 N. Herndon, Daniel L. Traber

Published in: Intensive Care Medicine | Issue 7/2007

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.

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310CrossRefPubMed

Shirani KZ, Pruitt BA Jr, Mason AD Jr (1987) The influence of inhalation injury and pneumonia on burn mortality. Ann Surg 205:82–87CrossRefPubMedPubMedCentral

Maybauer MO, Maybauer DM, Herndon DN (2006) Incidence and outcomes of acute lung injury. N Engl J Med 26:416–417

Murakami K, Bjertnaes LJ, Schmalstieg FC, McGuire R, Cox RA, Hawkins HK, Herndon DN, Traber LD, Traber DL (2002) A novel animal model of sepsis after acute lung injury in sheep. Crit Care Med 30:2083–2090CrossRefPubMed

Maybauer MO, Maybauer DM, Traber LD, Westphal M, Enkhbaatar P, Morita N, Jodoin J, Heggers J, Herndon DN, Traber DL (2005) Gentamicin improves hemodynamics in ovine septic shock following smoke inhalation injury. Shock 24:226–231CrossRefPubMed

Boselli E, Breilh D, Rimmele T, Poupelin JC, Saux MC, Chassard D, Allaouchiche B (2004) Plasma and lung concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumonia. Intensive Care Med 30:989–991CrossRefPubMed

Tonnellier M, Ferrari F, Goldstein I, Sartorius A, Marquette CH, Rouby JJ (2005) Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia. Anesthesiology 102:995–1000CrossRefPubMed

Girardi C, Tonellier M, Goldstein I, Sartorius A, Wallet F, Rouby JJ (2006) Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia. Intensive Care Med (in press)

Andrews P, Azoulay E, Antonelli M, Brochard L, Brun-Buisson C, Dobb G, Fagon JY, Gerlach H, Groeneveld J, Mancebo J, Metnitz P, Nava S, Pugin J, Pinsky M, Radermacher P, Richard C, Tasker R (2006) Year in review in intensive care medicine, 2005. II. Infection and sepsis, ventilator-associated pneumonia, ethics, haematology and haemostasis, ICU organisation and scoring, brain injury. Intensive Care Med 32:380–390CrossRefPubMed

10.

Andrews P, Azoulay E, Antonelli M, Brochard L, Brun-Buisson C, De Backer D, Dobb G, Fagon JY, Gerlach H, Groeneveld J, Mancebo J, Metnitz P, Nava S, Pugin J, Pinsky M, Radermacher P, Richard C, Tasker R (2006) Year in review in intensive care medicine. 2005. I. Acute respiratory failure and acute lung injury, ventilation, hemodynamics, education, renal failure. Intensive Care Med 32:207–216CrossRefPubMed

11.

Richard P, Le Floch R, Chamoux C, Pannier M, Espaze E, Richet H (1994) Pseudomonas aeruginosa outbreak in a burn unit: role of antimicrobials in the emergence of multiple resistant strains. J Infect Dis 170:377–383CrossRefPubMed

12.

Edgeworth JD, Treacher DF, Eykyn SJ (1999) A 25-year study of nosocomial bacteremia in an adult intensive care unit. Crit Care Med 27:1421–1428CrossRefPubMed

13.

Shawar RM, MacLeod DL, Garber RL, Burns JL, Stapp JR, Clausen CR, Tanaka SK (1999) Activities of tobramycin and six other antibiotics against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 43:2877–2880PubMedPubMedCentral

14.

Conway SP, Brownlee KG, Denton M, Peckham DG (2003) Antibiotic treatment of multidrug-resistant organisms in cystic fibrosis. Am J Respir Med 2:321–332CrossRefPubMed

15.

Maybauer DM, Maybauer MO, Fraser JF, Traber LD, Traber DL (2005) Ceftazidime improves hemodynamic outcome in an ovine model of septic shock following smoke inhalation trauma. Anesthesiology 103, abstract 251

16.

Maybauer MO, Maybauer DM, Fraser JF, Traber LD, Cox RA, Hawkins HK, Westphal M, Enkhbaatar P, Nakano YY, Branski L, Parish L, Herndon DN, Traber DL (2006) Ceftazidime reduces airway obstruction in ovine smoke inhalation injury and sepsis. Shock 26(Suppl 1):8CrossRef

17.

Maybauer DM, Maybauer MO, Fraser JF, Traber LD, Enkhbaatar P, Westphal M, Murakami K, Nakano YY, Traber DL (2005) Ceftazidime improves oxygenation by reduction of lung tissue 3-nitrotyrosine content in ovine septic shock following acute lung injury. Infection 33(Suppl 1):31-Abstract-51

18.

Maybauer DM, Salsbury JR, Westphal M, Maybauer MO, Salzman AL, Szabo C, Westphal-Varghese BB, Traber LD, Traber DL (2004) The ATP-sensitive potassium-channel inhibitor glibenclamide improves outcome in an ovine model of hemorrhagic shock. Shock 22:387–391CrossRefPubMed

19.

Maybauer MO, Maybauer DM, Fraser JF, Traber LD, Westphal M, Enkhbaatar P, Cox RA, Huda R, Hawkins HK, Morita N, Murakami K, Mizutani A, Herndon DN, Traber DL (2006) Recombinant human activated protein C improves pulmonary function in ovine acute lung injury following smoke inhalation injury and sepsis. Crit Care Med 34:2432–2438CrossRefPubMed

20.

Maybauer DM, Maybauer MO, Traber LD, Westphal M, Nakano YY, Enkhbaatar P, Morita N, Herndon DN, Traber DL (2006) Effects of severe smoke inhalation injury and septic shock on global hemodynamics and microvascular blood flow in sheep. Shock 26:489–495CrossRefPubMed

21.

Shimoda K, Murakami K, Enkhbaatar P, Traber LD, Cox RA, Hawkins HK, Schmalstieg FC, Komjati K, Mabley JG, Szabo C, Salzman AL, Traber DL (2003) Effect of poly (ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep. Am J Physiol Lung Cell Mol Physiol 285:L240–L249CrossRefPubMed

22.

Pearce ML, Yamashita J, Beazell J (1965) Measurement of pulmonary edema. Circ Res 16:482–488CrossRefPubMed

23.

Cox RA, Burke AS, Soejima K, Murakami K, Katahira J, Traber LD, Herndon DN, Schmalstieg FC, Traber DL, Hawkins HK (2003) Airway obstruction in sheep with burn and smoke inhalation injuries. Am J Respir Cell Mol Biol 29:295–302CrossRefPubMed

24.

Rue LW, III, Cioffi WG, Mason AD Jr, McManus WF, Pruitt BA Jr (1995) The risk of pneumonia in thermally injured patients requiring ventilatory support. J Burn Care Rehabil 16:262–268CrossRefPubMed

25.

Vidaur L, Gualis B, Rodriguez A, Ramirez R, Sabdiumenge A, Sirgo G, Diaz E, Rello J (2005) Clinical resolution in patients with suspicion of ventilator-associated pneumonia: a cohort study comparing patients with and without acute respiratory distress syndrome. Crit Care Med 33:1248–1253CrossRefPubMed

26.

Shorr AF, Sherner JH, Jackson WL, Kollef MH (2005) Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis. Crit Care Med 33:46–53CrossRefPubMed

27.

Hutchinson GR, Parker S, Pryor JA, Duncan-Skingle F, Hoffman PN, Hodson ME, Kaufmann ME, Pitt TL (1996) Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram-negative bacteria in patients with cystic fibrosis. J Clin Microbiol 34:584–587PubMedPubMedCentral

28.

Bone RC, Sprung CL, Sibbald WJ (1992) Definitions for sepsis and organ failure. Crit Care Med 20:724–726CrossRefPubMed

29.

Kirikae T, Kirikae F, Saito S, Tominaga K, Uemura Y, Yokochi T, Nakano M (1998) Biological characterization of endotoxins released from antibiotic-treated Pseudomonas aeruginosa and Escherichia coli. Antimicrob Agents Chemother 42:1015–1021PubMedPubMedCentral

30.

Gressier B, Brunet C, Dine T, Luyckx M, Ballester L, Cazin M, Cazin JC (1998) In vitro activity of aminioglycosides on the respiratory burst response in human polymorphnuclear neutrophils. Methods Find Exp Clin Pharmacol 20:819–824CrossRefPubMed

31.

Szabo C (1996) The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6:79–88CrossRefPubMed

32.

Barth E, Radermacher P, Szabo C (2006) The world according to poly (ADP-ribose) polymerase (PARP)-update 2006. Intensive Care Med 32:1470–1474CrossRefPubMed

33.

Asfar P, Hauser B, Radermacher P, Matejovic M (2006) Catecholamines and vasopressin during critical illness. Crit Care Clin 22:131CrossRefPubMed

34.

Cantin A, Woods DE (1993) Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro. J Clin Invest 91:38–45CrossRefPubMedPubMedCentral

35.

Healy DP, Silverman PA, Neely AN, Holder IA, Babcock GE (2002) Effect of antibiotics on polymorphonuclear neutrophil apoptosis. Pharmacotherapy 22:578–585CrossRefPubMed

36.

Carreer R, Deby-Dupont G, Deby C, Jadoul L, Mathy M (1998) Oxidant-scavenging activities of beta-lactam agents. Eur J Clin Microbiol Infect Dis 17:43–46CrossRefPubMed

37.

Mouithys-Mickalad A, Mathy-Hartert M, Du G, Sluse F, Deby C, Lamy M, Deby-Dupont G (2002) Oxygen consumption and electron spin resonance studies of free radical production by alveolar cells exposed to anoxia: inhibiting effects of the antibiotic ceftazidime. Redox Rep 7:85–94CrossRefPubMed

38.

Traber DL, Maybauer MO, Maybauer DM, Westphal M, Traber LD (2005) Inhalational and acute lung injury. Shock 24(Suppl 1):82–87CrossRefPubMed

39.

Foucaud P, Borel B, Charara O, Nathanson S, Petitprez P, Pin I (2002) [Anti-Pseudomonas aerosol therapy in cystic fibrosis: improvement with tobramycin]. Rev Pneumol Clin 58:131–138PubMed

40.

Bone HG, Sakurai H, Schenarts PJ, Traber LD, Traber DL (2002) Effects of manganese superoxide dismutase, when given after inhalation injury has been established. Crit Care Med 30:856–860CrossRefPubMed

41.

Maybauer MO, Maybauer DM, Herndon DN, Traber DL (2006) The role of superoxide dismutase in systemic inflammation. Shock 25:206–207CrossRefPubMed

Title: Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock
Authors: 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 N. Herndon
Daniel L. Traber
Publication date: 01-07-2007
Publisher: Springer Berlin Heidelberg
Published in: Intensive Care Medicine / Issue 7/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0658-3

At a glance: The STEP trials

Springer Medicine

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

Abstract

Objective

Design and setting

Interventions

Measurements and results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Design and setting

Interventions

Measurements and results

Conclusions

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