Intensive Care Med (2002) 28:1151–1156 DOI 10.1007/s00134-002-1368-5 EXPERIMENTAL Huibert R. van Genderingen Oxygenation index, an indicator Johannus A. van Vught Jos R. C. Jansen of optimal distending pressure during Elisabeth L. I. M. Duval Dick G. Markhorst high-frequency oscillatory ventilation? Adrian Versprille D.G. Markhorst Received: 5 June 2001 tion) in series, followed by a similar Pediatric Intensive Care Unit, decrease of Paw (deflation). Accepted: 14 May 2002 Department of Pediatrics, Published online: 20 June 2002 Vrije Universiteit Medical Center, Measurements and results: At each © Springer-Verlag 2002 PO Box 7057, 1007 MB Amsterdam, Paw level, the OI and physiological The Netherlands shunt fraction were determined. The This study was supported by SensorMedics. A. Versprille OI reached a minimum of 6.2±1.4 at Pathophysiological Laboratory, Paw 30±4 cmH2O during inflation Department of Pulmonary Diseases, and a minimum of 2.4±0.3 at Paw Erasmus University Rotterdam, 13±2 cmH O during deflation. H.R. van Genderingen (✉) PO Box 1738, 3000 DR Rotterdam, 2 Department of Clinical The Netherlands Pawoptimal was 32±6 cmH2O on the Physics & Informatics, inflation limb and 14±2 cmH2O on Vrije Universiteit Medical Center, the deflation limb. The difference PO Box 7057,1007 MB Amsterdam, The Netherlands Abstract Objective: To test the hy- between the Paw at minimal OI and e-mail: [email protected] pothesis that, during high-frequency Pawoptimal was –1.9±4.2 cmH2O (NS) Tel.: +31-20-4444118 oscillatory ventilation (HFOV) of during inflation and –1.5±1.6 cmH2O Fax: +31-20-4444147 pigs with acute lung injury, the oxy- (p<0.05) during deflation. In 15 out of the 16 comparisons, the differ- J.A. van Vught · D.G. Markhorst genation index (OI = Paw*FIO2*100/ A. Versprille ence in Paw was within one step PaO2) is minimal at the lowest con- Pediatric Intensive Care Unit, tinuous distending pressure (Paw), (±3 cmH O). Conclusion: The mini- Department of Pediatrics, 2 Wilhelmina Children’s Hospital, where the physiological shunt frac- mal OI is indicative for the Paw where oxygenation is optimal during PO Box 80590, 3508 AB Utrecht, tion is below 0.1 (Pawoptimal). The Netherlands Design and setting: Prospective, ob- HFOV in surfactant-depleted pigs. J.R.C. Jansen servational study in a university re- Department of Intensive Care, search laboratory. Subjects: Eight Keywords Acute lung injury · Leiden University Medical Center, Yorkshire pigs weighing 12.0±0.5 kg, High-frequency oscillatory PO Box 9600, 2300 RC Leiden, with lung injury induced by lung la- ventilation · Oxygenation index · The Netherlands vage. Interventions: After initiation Gas exchange E.L.I.M. Duval of HFOV, the pigs were subjected to Pediatric Intensive Care Unit, Department of Pediatrics, a stepwise increase of Paw to obtain Paola Children’s Hospital, Lindendreef 1, under-inflation, optimal inflation and 2020 Antwerp, Belgium over-distension of the lungs (infla- Introduction by a continuous distending pressure (Paw) and the super- imposed small oscillations of air flow provide gas ex- High-frequency oscillatory ventilation (HFOV) is a safe change. The level of Paw applied is a major determinant mode of respiratory support in the treatment of newborn of patient outcome [1, 2]. The optimal Paw is a compro- infants suffering from idiopathic respiratory distress syn- mise between maximal lung recruitment and minimal drome (IRDS) [1]. Atelectatic lung regions are opened over-distension. To determine lung recruitment, CT is 1152 the preferred diagnostic tool [3], but it is not available at mark). Inspiratory and mixed expiratory gases were analyzed the bedside. The gold standard for assessment of pulmo- by a mass spectrometer (Perkin-Elmer, MGA 1100, Pomona, Calif., USA). Q′S/Q′T and physiological dead space (VD/VT) in nary oxygen transfer is the physiological shunt fraction percentage were calculated according to standard formulas (Q′S/Q′T). Its determination, however, requires invasive [10]. The respiratory system compliance was derived according to access for mixed venous sampling not commonly used in the equation (Crs=VT/(Pplat-PEEP) where Pplat is the plateau infants. We investigated the use of the oxygenation index pressure. The oxygenation index (OI) was derived from (OI= Paw*FIO2*100/PaO2). Cardiac output (Q′T) was determined by (OI=Paw*FIO2*100/PaO2) to find the optimal Paw. The use of the thermodilution method. Four determinations were OI combines the goals to maximize arterial oxygenation equally spread over the ventilatory cycle and averaged [11]. Oxy- and minimize Paw and inspired oxygen concentration. gen delivery (DO2) was determined [10]. So far, use of the OI has been proposed to identify in- Next, FIO2 was set at 1.0 and PEEP was set at 2 cmH2O. The fants who require extra corporeal membrane oxygenation lungs were repeatedly lavaged with 35 ml/kg saline until PaO2 was less than 80 mmHg [12]. After lavage, the baseline measure- therapy (ECMO) [4, 5], to predict outcome of ECMO [6] ments were repeated (post-lavage measurements). Next, the ani- and to assess severity of illness in pediatric patients dur- mals were intubated with a 5.5 mm diameter endotracheal tube. ing HFOV [7]. The index has not been validated to opti- HFOV (Sensormedics 3100A, Yorba Linda, Calif.) was applied at mize ventilatory conditions. We hypothesized that the OI 8 Hz, 33% inspiratory time and bias flow 20 l/min. Paw was set 3 cmH2O higher than the mean airway pressure during CMV. reaches a minimum at the Pawoptimal, defined as the low- Pressure amplitude was set (54±6 cmH2O) and maintained con- est Paw where Q′S/Q′T is below 0.1. This criterion is stant. After the experimental procedure described below, the tube adapted from Lachmann’s “open lung concept” [8], was removed, CMV was resumed and the baseline measurements where the optimal ventilatory condition during conven- repeated (end experiment measurements). tional mechanical ventilation (CMV) is defined as the lowest positive end-expiratory pressure (PEEP) to Experimental procedure achieve a fully recruited lung, i.e. a Q′S/Q′T below 0.1 [9]. In the present study, surfactant-deficient piglets were The continuous distending pressure was increased in steps of subjected to a stepwise increase of Paw to obtain under- 3 cmH2O, until PaO2 was more than 450 mmHg or the increase in PaO was less than 50% of the previous step. One more Paw step inflation, optimal inflation and over-distension of the 2 was added before Paw was set at 40 cmH2O (inflation phase). lungs in series, followed by a stepwise decrease of Paw. Then, it was lowered to the value at which the above-mentioned PaO2 criterion was reached. Subsequently, Paw was decreased in steps of 3 cmH2O until PaO2 was less than 80 mmHg (deflation phase). At each Paw level, the following were measured after Methods and materials a 10min stabilization period: blood gases, blood pressures and car- diac output. All experiments were performed according to the Guide for the Care and Use of Laboratory Animals, published by the National Institutes of Health (NIH publication 85–23, revised 1985) and ap- Data analysis proved by the Animal Care Committee of Erasmus University Rotterdam, The Netherlands. The data are presented as means ± SD. Data comparison was made using the Student’s t-test unless stated otherwise. Both during in- flation and deflation, Paw was determined at the minimal OI Surgical preparation (PawminOI) and the lowest Paw was determined where Q′S/Q′T was below 0.1 (Pawoptimal). PawminOI and Pawoptimal were compared us- Anesthesia of eight Yorkshire pigs (12.0±0.5 kg body weight) was ing the Wilcoxon signed rank test (p<0.05). induced with an intraperitoneal injection of sodium pentobarbital (30 mg/kg) and maintained by continuous infusion (8.5 mg/kg per h). After tracheostomy the pigs received a Y-shaped tracheal can- Results nula and were ventilated (CMV) with 10 breaths/min, an FIO2 of 0.21 and PEEP of 5 cmH2O. The inspiratory: expiratory ratio was 1:1, with an inspiratory pause of 0.6 s. Tidal volume Lavage caused a significant increase of Q′S/Q′T and (V =17.1±0.9 ml/kg) was adjusted to obtain normocapnia T VD/VT and decrease of Crs (Table 1), as can be expected (38–45 mmHg). Arterial blood pressure measurement and blood in IRDS. Comparison of the baseline measurements after sampling were performed using an arterial line in the aorta. A pul- monary arterial catheter was used to measure pulmonary arterial lavage and at the end of the experiment revealed only a pressure and blood temperature, and to sample mixed venous significant increase in PaCO2 (Table 1). Figure 1 shows a blood. Fluids (5 ml/kg per h saline) and anesthetics were adminis- typical example of the relationship between Paw and tered through a line in the superior vena cava. The bladder was PaO , Q′ /Q′ and OI. In all animals we found a similar catheterized to avoid urine retention. Spontaneous breathing was 2 S T suppressed with pancuronium bromide (0.3 mg/kg per h). OI pattern: during inflation the OI decreased from 32.0±10.6 towards a minimum of 6.2±1.4 at PawminOI 30±4 cmH2O and subsequently increased to 7.6±1.0 at Measurements and lavage Paw 40 cmH2O; during deflation the OI decreased to a Prior to lavage, baseline measurements were performed (pre- minimum of 2.4±0.3 at PawminOI 13±2 cmH2O and then lavage measurements). Blood gas samples were analyzed with increased to 22.0±18.4 at Paw 9±2 cmH2O. Q′S/Q′T de- ABL3 and OSM2 oximeters (Radiometer, Copenhagen, Den- creased from 0.53±0.10 at Paw 17±2 cmH2O to 0.06±0.03 1153 Table 1 Settings and measurements during conventional mechani- cal ventilation before lavage, after lavage and at the end of the ex- periment.