title: Arteriovenous CO2 removal improves survival compared to high frequency percussive and low tidal volume ventilation in a smoke/burn sheep acute respiratory distress syndrome model.
abstract: OBJECTIVES AND SUMMARY BACKGROUND: Low tidal volume ventilation (LTV) has improved survival with acute respiratory distress syndrome (ARDS) by reducing lung stretch associated with volutrauma and barotrauma. Additional strategies to reduce lung stretch include arteriovenous carbon dioxide removal (AVCO2R), and high frequency percussive ventilation (HFPV). We performed a prospective, randomized study comparing these techniques in our clinically relevant LD100 sheep model of ARDS to compare survival, pathology, and inflammation between the 3 ventilator methods.
  
  
  METHODS
  Adult sheep (n = 61) received smoke inhalation (48 breaths) and a 40% third-degree burn. After ARDS developed (Pao2/FiO2 <200), animals were randomized. In experiment 1, animals were killed at 48 hours after randomization. Hemodynamics, pulmonary function, injury scores, myeloperoxidase (MPO) in lung tissues and neutrophils, IL-8 in lung tissues, and apoptosis were evaluated. In experiment 2, the end point was survival to 72 hours after onset of ARDS or end-of-life criteria with extension of the same studies performed in experiment 1.
  
  
  RESULTS
  There were no differences in hemodynamics, but minute ventilation was lower in the AVCO2R group and Paco2 for the HFPV and AVCO2R animals remained lower than LTV. Airway obstruction and injury scores were not different among the 3 ventilation strategies. In experiment 1, lung tissue MPO and IL-8 were not different among the ventilation strategies. However, in experiment 2, lung tissue MPO was significantly lower for AVCO2R-treated animals (AVCO2R < HFPV < LTV). TUNEL staining showed little DNA breakage in neutrophils from experiment 1, but significantly increased breakage in all 3 ventilator strategies in experiment 2. In contrast, AVCO2R tissue neutrophils showed significant apoptosis at 72 hours post-ARDS criteria as measured by nuclear condensation (P < 0.001). Survival 72 hours post-ARDS criteria was highest for AVCO2R (71%) compared with HFPV (55%) and LTV (33%) (AVCO2R vs. LTV, P = 0.05).
  
  
  CONCLUSIONS
  Significantly more animals survived AVCO2R than LTV. In experiment 2, Lung MPO was significantly lower for AVCO2R, compared with LTV (P < 0.05). This finding taken together with the TUNEL and neutrophil apoptosis results, suggested that disposition of neutrophils 72 hours post-ARDS criteria was different among the ventilatory strategies with neutrophils from AVCO2R-treated animals removed chiefly through apoptosis, but in the cases of HFPV and LTV, dying by necrosis in lung tissue.
authors: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA. fschmals@utmb.edu
authors: Frank C
authors: FC
authors: Schmalstieg
authors: Susan E
authors: SE
authors: Keeney
authors: Helen E
authors: HE
authors: Rudloff
authors: Kimberly H
authors: KH
authors: Palkowetz
authors: Manuel
authors: M
authors: Cevallos
authors: Xiaoquin
authors: X
authors: Zhou
authors: Robert A
authors: RA
authors: Cox
authors: Hal K
authors: HK
authors: Hawkins
authors: Daniel L
authors: DL
authors: Traber
authors: Joseph B
authors: JB
authors: Zwischenberger
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D002059:Burns, Inhalation / Q000150:complications*; D002245:Carbon Dioxide / Q000097:blood*; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D016209:Interleukin-8 / Q000378:metabolism; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000628:therapy*; D034561:Sheep, Domestic; D015208:Smoke Inhalation Injury / Q000150:complications*; D015996:Survival Rate; D013990:Tidal Volume
chemical_list: D016209:Interleukin-8; D002245:Carbon Dioxide
references: J Clin Invest. 1998 Feb 15;101(4):890-8
references: 9466984
references: N Engl J Med. 1998 Feb 5;338(6):355-61
references: 9449728
references: Am J Respir Crit Care Med. 1998 Dec;158(6):1831-8
references: 9847275
references: J Burn Care Rehabil. 1999 May-Jun;20(3):232-5
references: 10342478
references: Ann Thorac Surg. 1999 Jul;68(1):181-7
references: 10421138
references: Chest. 1999 Jul;116(1 Suppl):89S-90S
references: 10424608
references: Ann Surg. 1999 Aug;230(2):215-24
references: 10450736
references: Perfusion. 1999 Jul;14(4):299-310
references: 10456785
references: Crit Care Med. 1999 Aug;27(8):1492-8
references: 10470755
references: Circ Res. 1965 May;16:482-8
references: 14289157
references: Am J Respir Crit Care Med. 2005 Jan 15;171(2):147-57
references: 15477499
references: J Biol Chem. 2005 Feb 18;280(7):5843-53
references: 15576378
references: Crit Care Med. 2005 Mar;33(3 Suppl):S175-81
references: 15753725
references: Crit Care Med. 2005 Mar;33(3 Suppl):S241-5
references: 15753734
references: Crit Care Med. 2005 May;33(5):925-9
references: 15891315
references: Am J Respir Crit Care Med. 2005 Jun 15;171(12):1371-7
references: 15695495
references: N Engl J Med. 2006 Apr 27;354(17):1775-86
references: 16641394
references: Blood. 2006 Oct 15;108(8):2821-6
references: 16804110
references: Intensive Care Med. 1999 Sep;25(9):936-41
references: 10501748
references: N Engl J Med. 2000 May 4;342(18):1301-8
references: 10793162
references: Crit Care Med. 2000 May;28(5):1469-76
references: 10834698
references: J Thorac Cardiovasc Surg. 2001 Mar;121(3):542-51
references: 11241090
references: Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1233-41
references: 11350803
references: ASAIO J. 2001 Jul-Aug;47(4):365-71
references: 11482488
references: Intensive Care Med. 2001 Aug;27(8):1340-51
references: 11511947
references: Burns. 2002 Aug;28(5):503-8
references: 12163294
references: J Burn Care Rehabil. 2002 Nov-Dec;23(6):444-8
references: 12432322
references: J Clin Invest. 2002 Dec;110(11):1703-16
references: 12464676
references: Am J Respir Crit Care Med. 2003 Jan 15;167(2):171-9
references: 12406830
references: Clin Sci (Lond). 2003 Mar;104(3):313-21
references: 12605592
references: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):295-302
references: 12936906
references: J Appl Physiol (1985). 2003 Oct;95(4):1385-93
references: 12807894
references: N Engl J Med. 2004 Jul 22;351(4):327-36
references: 15269312
references: J Biol Chem. 2004 Oct 22;279(43):44695-703
references: 15292176
references: J Clin Invest. 1982 Apr;69(4):794-8
references: 7076848
references: Am Rev Respir Dis. 1983 Mar;127(3):290-300
references: 6830052
references: J Appl Physiol (1985). 1987 Jan;62(1):27-33
references: 3558186
references: Surgery. 1988 Aug;104(2):208-15
references: 3400056
references: Am Rev Respir Dis. 1988 Dec;138(6):1480-7
references: 3144216
references: J Trauma. 1989 Mar;29(3):350-4
references: 2926848
references: Intensive Care Med. 1990;16(6):372-7
references: 2246418
references: Circ Shock. 1991 Jan;33(1):48-62
references: 1849056
references: Arch Surg. 1993 Jul;128(7):772-8; discussion 778-80
references: 8317959
references: Ann Surg. 1993 Sep;218(3):328-35; discussion 335-7
references: 8373275
references: Chest. 1993 Dec;104(6):1833-59
references: 8252973
references: Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):311-9
references: 7905767
references: J Appl Physiol (1985). 1994 Feb;76(2):539-44
references: 8175560
references: Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1550-4
references: 7952613
references: J Appl Physiol (1985). 1994 Sep;77(3):1355-65
references: 7836140
references: J Burn Care Rehabil. 1997 Nov-Dec;18(6):531-4
references: 9404988
references: Ann Thorac Surg. 1997 Dec;64(6):1599-604; discussion 1604-5
references: 9436542
references: N Engl J Med. 1998 Feb 5;338(6):347-54
references: 9449727
references: J Clin Invest. 1998 Jun 15;101(12):2900-9
references: 9637725