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Functional Residual Capacity and Compliance of the Respiratory System After Surfactant Treatment in Premature Infants with Severe Respiratory Distress Syndrome

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Functional Residual Capacity and Compliance of the Respiratory System After Surfactant Treatment in Premature Infants with Severe Respiratory Distress Syndrome Eur J Pediatr (2002) 161: 485–490 DOI 10.1007/s00431-002-0989-6 ORIGINAL PAPER Ju¨ rgen Dinger Æ Andreas To¨ pfer Æ Peter Schaller Roland Schwarze Functional residual capacity and compliance of the respiratory system after surfactant treatment in premature infants with severe respiratory distress syndrome Received: 24 September 2001 / Accepted: 25 May 2002 / Published online: 12 July 2002 Ó Springer-Verlag 2002 Abstract To understand the mechanisms behind im- Abbreviations a/A arterial/alveolar tension Æ CRS proved oxygenation after intratrachealsurfactant in- compliance of the respiratory system Æ FRC functional stillation, the immediate and late effects on lung volume residualcapacity Æ RDS respiratory distress syndrome Æ and compliance of the respiratory system (CRS) were SF6 sulphur hexafluoride analysed. Infants received modified porcine surfactant (Curosurf) or modified bovine surfactant (Alveofact). Introduction Measurements of functionalresidualcapacity (FRC) and CRS were successfully performed in 90 ventilated Surfactant replacement rapidly improves gas exchange preterm infants (birth weight 1264±435 g; gestational and results in early improvement in oxygen saturation age 28.2±2.5 weeks) with severe respiratory distress and reduction in mean airway pressure, decreases neo- syndrome. FRC and CRS were measured during me- natal mortality and incidence of pulmonary interstitial chanicalventilationprior to and 1, 3, 6, 24, 48, 72, 96, emphysema and pneumothorax [8, 9, 25, 40, 44]. Despite 120 and 168 h after surfactant replacement. Oxygen- the clinical improvement reports about changes in pul- ation rapidly improved. FRC increased significantly monary mechanics in neonates with respiratory distress from 7.64±1.58 ml/kg to 15.35±3.27 ml/kg (P<0.01) syndrome (RDS) have been less convincing [5, 11, 12, 14, at 1 h after surfactant instillation. CRS remained vir- 19, 23,24]. Many of the proposed physiological mecha- tually unchanged during the first hours after surfactant nisms thought to govern the effect of surfactant on gas replacement and a concomitant decrease in specific exchange remain either unconfirmed or inadequately compliance was seen. Conclusion: the changes in lung characterised in the ventilated human infant. Our un- function following surfactant treatment can only be ex- derstanding of physiological responses to surfactant plained by initial stabilisation of already aerated alveoli treatment in human infants is limited by difficulties in- followed by recruitment of new gas exchange units as volved in assessing pulmonary function, particularly in mechanisms involved in mediating the effect of surfac- the measurement of lung volume. tant on gas exchange. However, since no significant Although there are several studies describing the ef- correlation between changes in functional residual ca- fect of surfactant treatment on the mechanicalproperties pacity and improvement in arterial-to-alveolar oxygen of the lung in human infants [2, 3, 4, 5, 7, 12, 14, 15,31], tension ratio was seen, other effects of surfactant must the results of these studies had to be interpreted without be considered. These include local and/or systemic knowledge of change in lung volume. To our knowledge, changes in haemodynamics. there are only a few reports [11, 16, 19, 20, 24,39] de- scribing the effect of surfactant treatment on lung vol- Keywords Functionalresidualcapacity Æ Gas ume only selective in a small number of mechanically exchange Æ Premature infant Æ Respiratory distress ventilated preterm human infants. syndrome Æ Surfactant To understand the mechanisms behind improved ox- ygenation after intratracheal surfactant instillation, the immediate and longitudinal effects on compliance of the J. Dinger (&) Æ A. To¨ pfer Æ P. Schaller Æ R. Schwarze respiratory system (CRS), functionalresidualcapacity Klinik fu¨ r Kinderheilkunde, Medizinische Fakulta¨ t, (FRC) and gas exchange were systematically analysed. In Technische Universita¨ t Dresden, Fetscherstrasse 74, this report we describe the changes in FRC, CRS and gas 01307 Dresden, Germany E-mail: [email protected] exchange immediately before and 1, 3, 6, 24, 48, 72, 96, Tel.: +49-351-4582341 120 and 168 h after administration of modified porcine Fax: +49-351-4584331 (Curosurf) or bovine (Alveofact) surfactant. 486 settings (PIP, PEEP, inspiratory and expiratory time, FiO2 ) were Patients and methods noted. From information on blood gases and ventilator settings the Patients following indices were calculated: The patient group comprised 90 preterm infants with RDS treated 1. a/A ratio = PaO2/FiO2·(patm–pH20)–PaCO2 where patm = in the neonatalintensive care unit at Dresden University hospital atmospheric pressure and pH2O = water vapour pressure (Table 1). The inclusion criteria for surfactant instillation were [22]. clinical and radiological evidence of RDS, the need for endotrac- 2. Mean airway pressure = (PIP·Ti + PEEP·Te)/(Ti +Te) heal intubation for ventilation and an arterial/alveolar tension (a/ where Ti = inspiratory time and Te = expiratory time [21]. A) ratio of <0.2. The post-natalage at surfactant treatment ranged from 1 to 12 h (mean 2.5 h). None of the infants had a clinically significant infection or patent ductus arteriosus during this study. Pulmonary function testing Written informed parentalconsent was obtained. The study was approved by the hospitalethics committee. FRC was measured with a computerised multiple breath wash in/ washout technique [18,28], using sulphur hexafluoride (SF6), a nontoxic, insoluble tracer gas [27]. This method allows repeated measurements (each wash in/washout sequence takes about 1.5– Surfactant administration 2 min) without interfering with ventilator settings or the inspired oxygen concentration. For measurement, a heated pneumotach- The endotrachealtube was suctioned just prior to administration ograph and a fast mainstream infrared SF6 analyser were placed of surfactant. Modified porcine (Curosurf) or bovine (Alveofact) between the Y-piece of the ventilator circuit and the endotracheal surfactant was given in two separate boluses (initial dose of tube. Any constant flow ventilator can be used. Set-up of mea- 100 mg/kg), each one being injected over 20 s in the right and surement apparatus, measurement process and algorithms for cal- then in the left lateral position. The surfactant was administrated culation of FRC have been described in detail [17, 36, 37,41]. The intratracheally using a special endotracheal tube with a drug mainstream infrared SF6 analyser was built as a prototype by canal. After each administration, hand ventilation was performed Siemens-Elema, Sweden. SF6 concentration during wash in was with a Laerdalbag for 1 min. and then the ventilatorwas re- 0.8%–1%. Accuracy and reproducibility of the FRC measurement connected. Suctioning of the endotrachealtube was avoided for equipment has been tested in a mechanicallungmodel[37]. 4–6 h after completing the surfactant instillation, unless clinically CRS was measured according to the inflation method [17]. Flow indicated. Up to two retreatment doses (100 mg/kg in the was measured using a pneumotachograph [34] inserted between the Curosurf group and 50 mg/kg in the Alveofact group) were endotrachealtube and the ventilatorcircuit. Airway pressure administrated if the a/A ratio remained <0.2. changes were measured from the infant’s side of the pneumotach- ograph using a Validyne pressure transducer. Flow, volume and pressure were recorded simultaneously, compliance was calculated Ventilation and monitoring and displayed immediately by the computer. Measurement of CRS was tested with lung models (copper wool filled bottles) and found to All infants were given the same method of ventilation by a time have an error of +3% [37]. Compliance was related to the FRC on cycled pressure controlled ventilator (Bear Cub Model BP 2001, each occasion to give specific compliance (compliance/FRC). Medical Systems Inc., Riverside, Calif., USA). Ventilation was Measurements of FRC and compliance were made in triplicate under initially started with PEEP of 0.4 kPa and PIP of between 1.6 and steady state conditions 20 min after varying ventilator settings [41]. 2.5 kPa. The usualunit policywas to adjust FiO 2 and mean The coefficient of variation (range with median in parentheses) of airway pressure to maintain arterialoxygen between 6.0 kPa and repeated measurements was 0.29–4.16 (1.65%) for FRC and 0.67–5.2 8.0 kPa. Arterialcarbon dioxide was maintained between 5.0 kPa (2.44%) for compliance. and 8.0 kPa by adjusting PIP and ventilatory rate. The usual sequence employed in winding down the ventilator with improv- ing blood gases was: (1) reduction of FiO2; (2) reduction of Statistics ventilator rate; (3) reduction in PIP. If necessary, the infants were sedated but not paralysed with intravenous midazolam The Student’s t test for paired data was used to analyse differ- (0.2 mg/kg). ences in absolute values of FiO2, FRC, CRS, a/A ratio and Transcutaneous tpCO2, ECG, oxygen saturation and blood compliance/FRC. Regression analysis was used to determine pressure were continuously monitored. In addition to arterial blood whether quantitative changes in a/A ratio were related to changes gases determined for clinical purposes pH, PaCO2 and PaO2 were in FRC. Statisticalsignificance was accepted at P<0.05. Data measured immediately before surfactant instillation and also with are expressed as mean values ± SD when not otherwise indi- every determination of lung mechanics. At the same time respirator cated. Table
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