2003 10 41 10 Chin J Pediatr October 2003 Vol 41 No. 10 761 (Surf) (NO) (ALI) 33 5 : (C n = 8) NO + Surf (SNO n = 6) (N n = 6) ALI ;N ;NO NO 1 10-6 10 10-6 20 10-6 40 10-6 1 h 30 min ;Surf Surf 100 mg/ kg ;SNO NO Surf 6 h NO C 30 min (PaO 2 / FiO 2 ) (Dynamic Compliance Cdyn) Cdyn SNO Surf NO NO Y NO (1020) 10-6 NO Surf NO ALI Surf NO ; ; Effects of combined surfactant and inhaled nitric oxide in ventilated rabbits with meconium aspiration2 induced acute lung injury HU Xiao2wei ZHU You2rong Lα Yong LAM Li Kuei ZHANG Ling2en SHAO Xiao2mei SUN Bo1 Laboratory of Pediatric Respiratory & Critical Care and Department of Pediatrics Children s Hospital of Fudan University Shanghai 200032 China Abstract Objective To evaluate dose response of inhaled nitric oxide (ino) for surfactant2treated rabbits with meconium aspiration2induced acute lung injury(ali) and hypoxemic respiratory failure ( HRF) and variation of measured ino by continuous NO delivery in pressure support ventilation ( PSV) 1 Methods Adult rabbits (210-315 kg n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment ( n = 6-8). There were 4 groups : Control (C) ; NO ino at 1 10 20 and 40 10-6 each for 60 min at 30 min interval of disconnection ; Surf intratracheal instillation of porcine lung surfactant phospholipids (100 mg/ kg) ; SNO both ino and surfactant as in the NO and Surf groups ; and a normal group (N) which did not undergo meconium aspiration but received sham deliveries of normal saline1 All the animals were treated with PSV for 6 h1 ino levels at different input and sampling sites in the NO and SNO groups were detected by on2line chemiluminescent technique1 The blood gas and lung mechanics were measured during the experiments every 2 h1 Results (1) Meconium aspiration induced ALI and severe HRF ( PaO 2 / FiO 2 < 200 mmhg) and depressed dynamic compliance of respiratory system ( Cdyn) and airway resistance ( Raw) 1 In both Surf and NO groups modestly improved oxygenation was observed1 In the SNO values for PaO 2 / FiO 2 were improved from ( 185 39) mmhg at baseline to ( 301 123) mmhg at 6 h while moderate or transient improvement was observed in both Surf and NO groups1 Cdyn and Raw were only improved for short time in the Surf NO and SNO groups1 ino had a mild response at 1 10-6 to good response at 10 and 20 10-6 but no further improvement occurred at 40 10-6 1 The response of ino in NO group was relatively transient compared to the SNO group1 (2) When ino was connected to the ventilator circuit the connected site should be placed before humidifier to minimize fluctuation of ino concentration and sampling site for ino monitoring should be placed : :200032 ( ) ( ) ( 200003 )
762 2003 10 41 10 Chin J Pediatr October 2003 Vol 41 No. 10 adequately to eliminate artifact1conclusions ino synergistically improved surfactant effects on oxygenation and lung mechanics1 Continuous supply of ino with non2continuous flow ventilator provided stable NO within accepted target range with least variation1 Key words Nitric oxide ; Meconium aspiration ; Pulmonary surfactants (MAS) ml) ; (4) Surf NO ( SNO n = 6) ) : NO Surf ( n = 6) Surf [1 ] (Surf) Surf Surf NO : (1) ( 900C ) : ( PSV) ] ; Surf NO ( PIP) 1530 cmh 2 O (ALI) (CPAP) 2 cmh 2 O (V T ) 68 ml/ NO kg (R) NO 4065 / min PIP R FiO 2 PaCO 2 [3 ] 2001 10 2002 3 3055 mmhg PaO 2 > 60 mmhg(2) Surf () NO : 510 ml/ (kg h) NO 5 % N 4 5 % 2 % 011110g/ (kg h) 1. :33 ; 6 h 210315 kg 41 : (1) : 12 h 2 mg/ kg 15 min ( SC9000 ) (AVL 20 mg/ kg 35 mg/ (kg h) 993 ) (2) :Navigator 315 ( airway mm 22 resistance Raw) G 2. : 30 min 1 2 h 1 25 mg/ ml ] NO SNO NO 34 ml/ kg 3 ; 30 min 51 (ino) : NO ALI : SNO 1 10-6 10 10-6 20 10-6 40 Cdyn 30 % PaO 2 / FiO 2 300 mmhg ] 31 :ALI 30 min Y (D) 4 : (1) (C n = 8) : 3 ml/ kg ; (2) NO ( n = 6) : 3 ml/ kg (MetHb) (A B) NO NO (NO ) 1 (C D) NO 10-6 10 10-6 20 10-6 40 10-6 1 h 30 min ; (3) : Surf [4 ] 100 mg/ kg (40 mg/ 5 min 2 mg/ kg [ (1030g/ (kgh) ] 011 mg/ kg 10-6 1 hno (A) NO (280 Sievers) NO 2 ( gx s) Student2 Newman2Keuls
2003 10 41 10 Chin J Pediatr October 2003 Vol 41 No. 10 763 t ; P < Raw 0105 Surf ino NO 2 %3 % ph PaCO 2 BE B NO C D NO NO (PaO 2 / FiO 2 ) Cdyn Raw ( P > 30 % (1 3) NO 0105) ; PaO 2 / FiO 2 NO 2 (2) Cdyn Raw ( P < 0101) Surf NO C ( P < 0105) N ( P < 0101) SNO Surf NO ( P < 0105 1) Surf () ino Cdyn Raw C 4 h (1) NO NO NO 10 10-6 ino 1 h PaO 2 / FiO 2 ( P < 0105) ;SNO 20 10-6 40 10-6 ino PaO 2 / FiO 2 ( P < 0105) NO NO ino ino : NO (A ) C D 30 % ( P < 0101 1 3) 1 1 000 10-6 NO (A) Y 20 cm (B) ; Y (D) Y (C) NO NO (2) NO Cdyn [5 ] Surf Surf Surf PaO 2 / FiO 2 (mmhg) S N ( n = 6) 1 ( gx s) (h) 0 2 4 6 366 46 152 58 120 47 86 31 84 43 427 53 199 52 224 32 3 245 66 3 158 69 412 41 173 48 216 93 3 200 117 3 132 86 425 23 185 39 224 68 3 314 95 3 3 301 123 3 3 + 414 60 435 68 # 402 42 # 369 37 3 3 + + 356 29 3 3 + + F 21179 281916 181492 141287 121379 Cdyn [ml/ (cm H 2 O kg) ] S N ( n = 6) 1130 0132 0160 0112 0144 0115 0139 0116 0137 0115 1184 0153 0161 0117 0165 0108 0153 0105 0147 0110 1112 0113 0158 0123 0166 0114 0162 0113 3 0152 0109 1140 0112 0157 0119 0172 0122 3 0157 0112 0151 0114 1138 0127 1126 0131 # 1121 0126 # 1119 0131 # 1110 0121 # F 21395 121605 16199 191967 241697 Raw [cmh 2 O/ (L s) ] 5414 1015 7215 1515 7717 2615 9612 2910 10912 3616 4716 2313 6214 1213 5911 1911 5617 519 3 3 6419 1315 3 3 5013 1015 6515 910 6612 1412 6814 1018 3 9211 1511 SNO( n = 6) 4918 615 4916 417 3 3 5419 1513 5313 1418 3 3 5313 1313 3 3 N ( n = 6) 4514 710 5018 1110 3 4611 1314 3 5019 513 3 3 6010 1018 3 3 F 21395 121605 161990 191967 241697 : 3 P < 0105 3 3 P < 0101 ;NO + + + P < 0105 P < 0101 ;Surf P < 0105 P < 0101 ; NO # P < 0101
764 2003 10 41 10 Chin J Pediatr October 2003 Vol 41 No. 10 1 10 20 40 ino( 10-6 ) 2 NO NO 2 ( gx s) NO : 3 P < 0105 n = 6 PaO 2 / FiO 2 (mmhg) SNO NO MetHb( %) SNO 199 52 185 39 018 013 018 014 NO NO 2 ( 10-6 ) 217 52 206 62 118 017 119 019 0 0 224 32 196 50 SNO 265 31 3 257 56 212 017 214 110 0118 0108 0115 0106 214 51 248 47 245 66 302 58 3 214 015 210 018 0125 0105 0132 0112 187 87 237 84 158 69 301 123 3 314 111 310 112 0150 0120 0143 0110 NO ( 10-6 ) 3 NO ( gx s %) A C D B C D 1 1112 416 3415 812 3 3618 715 3 3519 818 3 10 219 116 2410 1112 3 2910 1213 3 2918 1015 3 20 215 117 2218 1313 3 2912 610 3 3019 1110 3 40 116 019 2817 818 3 2911 915 3 2812 818 3 : 3 A C P < 0101 ) NO NO (1020) 10-6 [8 ] NO NO ( > 50 %) NO 900C [9 10 ] PSV (1 A ) NO NO 60 % NO 2 ; Y 20 cm (1 B ) NO 30 % NO NO [6 ] ino Surf NO ( > 30 %) : Surf ino Y (1 D ) NO ; Surf ino Cdyn Raw [7 ] : Surf Y (1 C ) NO ino NO NO (1 10-6 ) NO NO 10 10-6 ino FiO 2 / PaO 2 ino ino ALI NO ( 1 Cleary GM Antunes MJ Ciesielka DA et al. Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration. Pediatrics 1997 100 : 99821003. 2 Sun B Curstedt T Robertson B. Exogenous Surfactant improves ventilation efficiency and alveolar expansion in rats with meconium aspiration. Am J Respir Crit Care Med 1996 154 : 7642770. 3 Francoe M Troncy E Blaise G. Inhaled nitric oxide : technical aspects of administration and monitoring. Crit Care Med 1998 26 : 7822796. 4 Zhu GF Sun B Niu SF et al. Combined surfactant therapy and inhaled nitric oxide in rabbits with oleic acid2induced acute respiratory distress syndrome. Am J Respir Crit Care Med 1998 158 : 4372443. 5 Sun B Curstedt T Song GW et al. Surfactant improves lung function and morphology in newborn rabbits with meconium aspiration. Biol
2003 10 41 10 Chin J Pediatr October 2003 Vol 41 No. 10 765 Neonat 1993 63 : 962104. 6 Huang QW Sun B Gao F et al. Effects of inhaled nitric oxide and high2frequency ventilation in rabbits with meconium aspiration. Biol Neonate 1999 76 : 3742382. 7 Sison C Bry C Sephus J et al. Effects of inhaled nitric oxide and surfactant treatment on lung function and pulmonary hemodynamics in bronchoalveolar lavage2induced respiratory failure. Pediatr Pulmonol 2000 29 : 2022209. 8 Kinsella JP Walsh WF Bose CB et al. Inhaled nitric oxide in premature neonates with severe hypoxemic respiratory failure : a randomised controlled trial. Lancet 1999 354 : 106121065. 9 Imanaka H Hess D Kirmse M et al. Inaccuracies of nitric oxide delivery systems during adult mechanical ventilation. Anesthesiology 1997 86 : 6762688. 10 Clark PL Ekekezie II Kaftan HA et al. Safety and efficacy of nitric oxie in chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2002 86 : F412F45. ( :2003205214) ( : ) 6 3 d 2002 ( + ) G262PD 1 26 4 d 5 g(10 ) ;1 29 : 8 250 U/ L ( 5 000 2 12 000 U/ L) ( ) ; C 3 63310 mg/ L 1 d ( 7801 650 mg/ L) CD 4 4313 % CD 8 2818 % IgG 39 ; IgA IgM ; 1 512 : :T 36 P 130 / min R 24 / min BP 98/ 45 mm Hg (13/ 6 kpa 1 mm Hg = 01133 kpa) ( ) 012 cm 11 d Hb 72 g/ L / 2 6 3 cm 4 cm : 1987 11 ( - ) : (1) ( - ) ( - ) : :1 (1 26 ) :WBC 2913 10 9 / L N 0180 L 0120 RBC 0138 10 12 / L Hb 25 g/ L PLT 427 10 9 / L 01045 ;2 (2 5 ) :WBC 1015 10 9 / L N 0150 L 0150 RBC 2104 10 12 / L Hb 72 g/ L PLT 440 10 9 / L : + + + + + + 25/ HP 25/ HP + + / LP :ph 71113 HCO 3 1116 mmol/ L BE - 1618 mmol/ L : 112 U/ L 145 U/ L 2919mol/ (s L) (1 786 U/ L) 52mol/ L 911mol/ L 4219mol/ L 1.. 1. : MB 6417 U/ L 20 nmol/ (s L) (1 222 U/ L) ; : 13117 mmol/ L 47512mol/ L 2417 1727. : 637000 ( ) ; ( ) : [1 ; (2) ; (3) ] ] 1998. 213. 2.. 6. : 1996. ( :2002208208) ( : )