Respiratory Function Measurements in Infants Measurement Conditions

Respiratory Function Measurements in infants Measurement Conditions

CONTENTS Resuscitation Equipment lntroduetion Each laboratory or measurement area should have oxygen and Labomtory Conditions resuscitation equipment available, which must be suitable for the Resuscitation equrpmenl infants being tested. A self-inflating resuscitation bag with oxy- Prepamtion of the Entarrt gen, as we![ as a frrnct~oningsuction apparatus and suction Cmheel length catheters, should be omhand. An emergency cart or kii must k feeding immediaIy available. At least one person must be present who Posture is skilled in airway management and pediatric basic life support. Sedation Medical back-up who are skilled in pediatric advanced life sup- Chlorafi Qeri~tiveS Phamacokinetics port or equivalent should be Miableduring all studies on sedated Side effects infants, or whenever measurements on unsedated infants irwolve Repeated sedation equipment (such as a mask or pneumotachograph) at the airway Midmlam Opening. A direct contact line to the pediatric intensive =re unit Assessment and Monitoring of the Sedated Infant would be advantageous. Trained staff should be n attendance Sleep State throughout all measurements. Development of sleep states organization In the intensive or critical care environment a second person Monitoring d sleep states must be present to monitor the infant. Influence of sleep state on functionat residual capacity Any apparatus that comes into contact with the infant must be Summary Recommendations thoroughly sterilized or disinfected been=. MQ& mmmer- cially available equipment currently in use is difficutt €o disman- THIS OFFlCldl STATEMENTOf THE AMERICANTHORACIC tle and sterilize. Appropriate facitfitis and mummust be es- SOCtEn AND THE EUROPEANRESPIRATORY SOCIETY WE tabllshed to ensure there is no compromise on cleaning and ADOPTEDBY THE AnBOARD OF DIRECTORS(FEBRUARY sterilization of equipment used for infant lung function tests. To control the influence of environmental temperature on re- 1995) AND f HE ERS EXECUTIVECOMMITTEE (MAY 1994). spiratory pattern, room tempemre should be maintained Mn 2049C Advanced reom&! intensbeare and imprwed SUMofprema- (air-oonditioning may be required). Even asmalt increase turely bwn infants with ~ryjngdegrees of chronic Zung disease in mytwnperzrture may induce a change in respiratwy frequency (1,2). have focused attention on the usefulness of pulmonary function and pattern Menstudying young infants (especialty those testing in infants and young children. Pulmonary function tests who are preterm), rt is partlcdarly important that the laboratory at pFTs) are usefut in research and clinical practice. Ciassical PFT is maintained an admuate temperature ta prevent bcdy & techniques have Wnmodified and miniaturized for infants, and ing. Whenever possible, the local environment shwld encoumge and innovativemethods have been developed. Whateverttre PFT used, skpby use of dimmed lighting noise reduction. Infants shwid standardimtion of measurement conditi'ons is crucial for the in- never be left unattended, and when measurementsare to k performed on bench-top type surface, side rails must be fitted. hnYs safety, accuracy of the test, and repraducibillty of the data, a especialjy for longitudinat studies and multicenter trials Standardbation of measurement conditions must addmbath fabratory anditions and the infads mewith respect to such PREPARATlON OF MEINFANT factors as feeding. posture, sedation, and sleep state. For most purpses, lung function measurements shwld not be made within 3 wk of an upper ~piratorytract infection, unless LABORATORY CONDITIONS specifically wishing ta study this period. Airway resistme and all related parameters anchange sfgnficantly due to mu& Achiwernent of satisfactory results depends on careful handling swelling and increased secretions (3). and minimal disturbance of the infant. Opportunities for repeat- Regardless of which tests are to be performed, the ptepara- faubmp jOg Or ddaylng measurementsshoufd tion of the infant for lung function tern is genedly similar. ing testing are usually very limited, and it IS therefore advisable Normal wlues for all mpiratory parameters are usually relared to check all equipment before each test. All equipment should to body weight, length, or both (4). Afl infants should therefore be regularly tested for patient safely. be weighed unclothed and their length measured at the time of test, or-a! the neampcssible time the ease of sick ventilated This Sraternent was dweloped by C. Caultier, M. L Rethr, C kardsmore, S. bglad,and L M~~~~ incmjmdon a $te~x/~~Working G~~~ infants. It is importantthat this is accurate to within 0.5 m. A pe on 5tandardiratiOn of Infant Pulmonary Function Tests. eke infant bdiometer and scales should be available in all centew This paper is being aopublished and mghtedwith the Europwn Respim- undertaking such measuremen&. tory ~ovmrrl. Some forms of monitoring, mast conveniently a pub? oximeter, ~m 1 RespirCritkMd Vod 151.pp2058-rOw. 1495 should ke used during all measurements, since wen heahhy in- ATSIERS Statement fants may respond adversely to trigeminal stimulation or airway The most important consideration in all situations is that. un- oedusion (5-7). less asessing the effect of positioning itself, serial rneasumnts The infanfs clothing shwM not restrict respiratory rnovemerrts in any one infant should be made with the baby in the same po- . in any way and should be loosened or rernwed as necessary. sition. . Mest refwence values have been compiled using data mflected Crown-heel length from infants in thesupine or lateral position, and this must be con- ARhwgh it is fundamental to the establishment and use of refer- sidered when assessing resutts from infants measured in d-ffer- ence values and to the interpretationaf pulmonary function results ent positions. In addition to gross trunk position, neck position during disease, measuring of an infant's kleng is rarely described may also influence resuits, and a neutral position should be in detail. An acceptable method (8) is therefore described below. adopted (avoiding Rexion, rotation, or overextension) (20). An ex- Small infants tend to be disturbed by being straightened for ception to this appears To be during the forced expiration maneu- length rneasuremerrts and, consequenfly such measurements are ver, when higher flows may be obtained by extending the neck, usually performed once all lung funetFon tests are completed. A possibly as a result of stabilization of the upper airway (21). In ad- small cotton sheet is placed on the stadiometer before lying the dition, slight alterations in neck position may resolve problems infant on top, as it is hard and cold. Two adults are needed to rnea- such as glottic closure during forced expiration and airwy occlu- sure an infant, who should be placed supine onto the stadiome sion prrrcedures. ter, One adult positions the haws head so that it is touching the To avoid confusion and aid comparisons, R is important that top of the stadiometer. in the midline (as indicated by the central Myposition is recorded at the time of measurement. Ahhough black line on most stadiometers), while at the same time ensur- historically most measurements in infants have been undertaken ing that the baby's trunk is lying flat and not rotated on the bed. wjth the infant in the supine or lateral position, there is an increas- When this has been achieved, the ather adult gently depresses ing tendency to measure intubated neonates in the pmne posi- the infant's knees until the legs are fully extended. The adjusta- tion. Better oxygenation has been found in neonates recovering ble footplate on the stadiometer should be moved up smoothly from respiralory distress syndrome when in the prone position until it rests against the soles of the infanfs feet, the feet being (22,23).However, there are no normative PFT data for prone in- in the midline (as indicated by the central black line). When this fants. has been achieved, the lever is tumedto fix the hotplate and the length read off the counter. This measurement sharld hrepeated at least twice, until two recordings within 05 cm of each other are dined. The infanfs length is reported to one decimal place. The Most term or preterm neonates can be stdiduring natuml sleep fmtplate should always be moved gently to avoid damage to the without sedation. Beyond 1 rno of age, houlfwer, it bmesin- counter. The calibration of the stadiometer shoutd be checked at creasingly difficuk la dc so. Sleep deprivation, even if brief, sig- least weekly, using a purpsernade steel rod of known length. nifiwntly disrupts sleep patterns and increases cenlral and crb- At themetime, the minimum counter readiy should Ise checked structive apneic episodes (24), and is not recommended. against that specified on each stadiwneter. The use and type of sedation wiIl depend on the age and con- As cbhing varies seasonaify and geographi~ily,all weigh& difion of the infant, the reason for the test, and the type of test should be reported as naked weight (8). being performed. The safety of sedative agents has practical and ethical implicatfons, in that these drugs are mrnmonly used for FEEDING diagnostic lung function assessments and for esmblishing reference values in normal irrfane. Currently, the most commonly used Tests tend to be more successful if the infant is M, clean, and sedative agents for PFT are chloral derivatives. Some centets are dry. Providing the infant is Wing enterally, masl workers feel using rnidazolarn. For these sedative agen'ts, current knowledge that it is not necessary to fast the infanf prior taming, even when an phanacokinetics and side effectsare reviewed. performirtg esophageal manometry or partial expiwry flow manewers. However, due consideration should be given to any relevant underlying pathology, paFtieulady esophageal reflux, with CHORAL DERlVAllVES a suitable delay (3 30 min) between feeding and measurements Rharmacoldnetia in such cases. Ahhough pretem infants with chronic Lung disease In vim, chloral hydrate is metabolized vla af-e teductase, aC particularly to desaturation a feed- may be prone oxygen following whol dehydqenase, and aldehyde dehydrogenase to form tri- ing (9),there is only limited widenee that feeding influences pul- chlomethanol WE), the pharmadqically active metabbite. Both monary function t&s in infants (10, ll). chloral hydrate and TCE are sufficiently lipid soluble tomw cells throughout the w.fCE is mainly conjugated with glucuronic acid in the Iirand rmrstly excreted into the urine. If the process Much has been witten about the effect of Myposition on respi- ofconjugation is limited, TCE is transformed by further oxidation ratory mechanics, lung volumes, gas exchange, and ventilation to trichlomacetic acid, which is considered inactive and excreted in infants. in urine in that fwm (25,261. In Europe, trielofos sodium, the phm Although there appears to be little evidence that lung volume phate ester of 5CE (to which tricw sodium is rapidly hydrolyzed) is witiondependent in the recumbent infant(12). mechani~and (26),has also been used for sedation (Ig of triclofos is pharmaco- respiratory pattern do appear to be positiondependent, especially logically equivalent to 660 mg of chloral hydrate 327l). in the anesthetkd infant or one with respiratory disease (72-18). Triclofos sodium results in less gastric irritation and has a less In addition, signals from measurement apparatus may be in- unpleasant taste than chloral hydrate, and is therefare more ac- fluenced by wition. In particular, esophageal pressure ceptable for oral administration in his age group (27,28). changes may- k underestimated in neonates lying prone (19). In adults, after either chloral hydrate or tricldfos adminiem- However, esophageal prwure changes during breathing have tivn, the plasma half-life of TCE ranges 4-3 h (28). Pharmacoki- been found to be similar in lateral and supine positions (16). netics of chloral hydrate have recently benstudled in neonares 2060 AMERICAN IOURNAL OF RESPIRATORY AND CRmCAL CARE MEDICINE VQP 151 1995

and infants (25,26,M). A study of multiple dosing with chloral may be especially prone to apnea after doses > 30 mg-kg-' and hydrate in neonates and infants indicates that TCE is present h should be sedaed with caution during the neonatal period. blood in sign-Wnt concentration up to 120 h after the last dose Healthy infants. A large number of healthy infants have been of chloral hydrate (26). The pharmacokinetim of chloral hydrate tested by different investigators with regard to potential respira- have been studied after a 50 mpkg-' oral dose of chloral hydrate tov side effects of chloral hydrate or triclofos. The ages ranged in critically tll neonates and children (31).The patient population from 4 wk to 2 yr of age, with doses of c-hlod hydrate ranging was divided into three groups: group 1-preterm infants (31-37 50-100 rng-@-I,and tr~clofos75-100 rng+kgl(650). In all these wk); group 2-f ull-term infane; and group 3-talerchild patients. studies, only one dose was administew. There was a small but Contrary to what has been reportd In adufts, chloral hydrate was significant increase in respiratory rate in one study (48), but Turner detectable for many hours after om1 administration In at1 three and colleagues (50) found no significant change in respiratory groups. The plasma half-life for TCE in group 3 (9.67 2 1.72 h rate, despite a small reduction in tidal volume, following sedation. irnean ? SD]) was close to that reported for adults (28),but in In agroup af 10 infants aged 4-19 mo,in whom resufts from paired the less mature subjects it was approximately three (group 2, measurements were successkrlty obtained, the changss in respi- 27.8 = 21.32 h, including one extreme outlier) to four (group 1, ratory rate (+I9breaths-min-I), heart rate (455beats-min4), and 39.8 + 14.27 h) times greater. arterial oxygen saturation (SwJ (-0.68%) were not considered Considerable interindividual variation was reported, especially to beof clinical importance(48). The strength ofthe Hering-Breuer in less mature subjects. f his study indicated that there are major inflation reflex was not influenced by sedation with triclofos SO- developmental differencss in the metabolism and elimination of dium at a dose of 75 mg.kg-' (49). Measurements of functional chloral hydrate. Newborn infants, and especially pretem new- residual capacity (FRC) and maximal (forced) expiratory flow at borns, cannot clear the metabolites of chloral hydrate as effec- FRC (VmaxFRC) were not significantly affected by sedation (50). tively as older individuals. Wheezy infants. A 70-100 mg-kg-' dose of chloral hydrate caused a fall in Saq and a decrease in clinical score of infants Side Effects recowering from acute viral bronchiditis, but not in infa- with Toric doses. Several recent reports, including one from the clinicaliy stable cystic fibrosis (51). American Academy of Pediatrics, have reviewed the potential side Infants who have suffered an apparent IifWmalwing event eHects of sedation in infants and children, with special reference (ALE). When using chloral hydate at a dose of 100 rng.kg-! to chloral hydrate (32-35). Southall and coworkers (unpublished data) noticed that a signifi- Chiorat hydrate intuxication has been reported both in children cant proportion of infants showed moderate baseline hypoxemia. and adub (36). Reported toxicity includes respiratory inwiTckncy Usually, this invalved oxygen desaturation to just below WO,but (37,38),encephalopathy (39),gastric necrosis (40), and cardiac in two infants there were more profound desaturations, including arrhythmia (41-44). in one the need for bag and mask ventilation. Hypnotic doses. The commonly used hypnotic dose is 30-50 Infants with- upper airway ohmdn.Chbral hydrate has been mg.kg-l chloral hydrate. The dose required for complicated lung shown to reduce the activity of upper aitway muscles (521, a fac- function protocols may be greater (up to 100 mg-kg-' chloral hy- tor that may predisp~sethe airway to collapse during sedation, drate, 1'50 mg-kg-' tricfofos). particularly in infants at risk of airway obstruction. This includes The effects of chloral hydrate or tricIofos administmion on re- infmls with craniafacial abnormalities, enlargd tonsils andk3r ade- spiratory control shuld be examined with due ward tothe dose, noids, and those with obstructive sleep apnea. Hershenson and the age of the subject, and the presence of any known disease coworkers (52) reported a near-fatal airway obstruction and re at time of testing. spim?ory arrest shortly &r a repealed dose of 50 rng.W1af chlo- Newbdms at term. Three studies refer to The neon&tal period. ral hydrate in a 3-yrdd child with obstruaiw sleep apnea syn- Comparing 13 undated infants (posteonceptional age [Pw drome. Similarly, Biban and coworkers (53) have repotted nvo 4t8 -t 4.4 wk, of whom sewn were healthy and six prone to ap cases of respiraturyfailure in 2-yrsld children with suspezted ab- nea), with 31 sedated, apnea-pmne infants (PCA 43.0 e 4.0 wk), sinrctive sleep apnea, following single doses of chloral hydrate Leand coworkers (45) did not find a significant direnee in (80 mg+kgcg-l)given before PFT. Thus, elinicar assessment of the the ventilatory C02 response between natural sleep and sleep infant before sedation should include evaluation of any history of induced by one 50 mg-kg-' dose of chloral hydrate. However, blunt- airway obstruction during steep and visual assessment of the up- ing of the GO, response has henreported in two of 22 healthy per airway. Although complicationsafter sedatron are rare, upper full-term babies (gestational age [GAJ38 & 1.3 wk; postnatal age airway problems undiagnosed More PFT emphasize the need fPNA] 39401 h) (46). In those two babies, tachypnea and oxygen for continual monitoring and amilabilrty df resuscitationequipmefi desaturation occurred. This unpredictable side effect of chloral during all PFTs. hydrate in heatthy full-term newborns may be related to the large Cardiac n'sks. Cardiac atrhythmia has been repr?ed in chil- interindividual variation in chloral hydrate pharmacokinetics in the dren receiving hypnotic dases of chloral hydmte. In the case re neonatal period (31) and reinforces the need for oxygen satura- port of Nordenberg and colleagues (459, cardiac arrythrnia oc- tbn monitoring following sedation in all infants. curred in a heakhy 25-yr-old child aWr a large (118 mg.kgl) oral Preterm newhm [nfants. In ventilated preterm infants, dose of chloral hydrate. Silver and Stier (44) report& sinus ar- prolonged administration of chloral hydrate has been used in in- rhythmamlowing oral chloral hydmtesedation in two infan%aged tensive care units (26,31,47). Adverse effects have been reported, 13 and 18 rno being investigated for seizure disorders (dams of such as direct hyperbilirubinemia (47) and prolonged neurcdeprss- 70 and 40 rng-kg-', respectivety). sion (301,both of which may be related to the deEayed clearance Recent experiments in isolated perfused Mi heart shwd of chloral hydrate metabolites in immature newborns. However, that chloral hydrate and TCE In clinically achievable con-- after a single oral dose of 20-50 mg-kg-' of chloral hydrate, no tions are predominantly cardiac depmnts and may produce significant changes in heast rate and respimtory rate were ob- conduction defects (54). served in 19 preterm infants with respiwury distress syndrome finally, investigators should be aware of a publication (26).Preterm rnfants who have suffered perinatal cerebral insults (55) suggesting that chloral hydrate could be a pmelcarcin~ AEIERS Statement

gen in humans. This issue is presently unresolved but is being (65).fn addition, the effect of rnidblam on the nasal rnucosa add- in wmm~by the American Academy of Mimics must b~ clarified since this may influence measurements of re (34). Reviewing the evidence, Steinberg (56) suggests avoiding sistance. both prolonged sedation in neonates and chronic use of large Further studies are required to assess the safety and suitabil- doses. ity of midamtam administered Intfmasally for rapidly sedating infants for PFT before its widespread use can be recommended. Repeated Sedation Infants who are tired fall asleep more quickly following sedation ASSESSMENT AND MONITORING OFMESEDATED INFANT (57).The timing of measurements should therefore be planned As outlined in the guidelines recently published by the American to coincide with the infanfs normal sleeplwalking mutine as far Academy of Pediatrics (33),patient safety with careful monitoring as possible to minimize any need for repeal sedation. by qualified personnel is of utmost imprtance, especially when The subject of repeat sedation (to p-u p) remains mntpauersial. infants are volunteered for research. Presedation assessment Issues to resolve include what dose, if any, should be used, and should include a physical examination, and observation of vital whether there should be a maximum dose limitation within any signs and any other unusual physical findings should be noted. given measurement sessionl24-h period. Infants underdalion must be monitorwl continually with pulse Until further information is available on this subjmt, it is recorn- oxirnetry until they are fully awake. Electmerdiqraphy and other mended that: (I) additional doses of chloral hydrate should not methods of automated monitoring of heart rate, respiratory rate, be given in excess of a total dose of 120 mg-kg-' (or equivalent and oxygen saturation may be used asa supplement. If vital dgns dose for derivatives such as trielofos); (2) a delay of at least f h are not being continuously recorded, these should be measured should be allowed before administeringa *up dose within this at baseline and at frequent intervals thereafter, and recorded on dose limit. the patient's medical record or a flow sheet designed for this The only circumstances under which these recommendations purpose. might be breached is when an infant has vomited all the syrup To avoid unnecessary and potentially dangerous transfer of immediately after adminishation, h which case a repeat haff-dose deeply sedated infants and children, sedation should be ad- might be given. !t should be noted that absorption of chloral hy- ministered at the location at which the test is to be performed. drate can occur across the ml mucous membrane adthat some Infants should not be released home aher sedation until fully rws- absorption may ham taken place even in an infant who has ap able and capable of swallowing (drinking). In addition, parents parently vomited the entire dose. should be advised that the infant may be dmqand unsteady In premature infants no repeat doses should be given within for severaI hours following sedation, and, therefore, should not 48 hrs of sedation for PFT or other tests (such as echocardiogra- be left unattended unless asleep, until the infant has fully remv- phy) (26. 30, 56). ered normal control of bdy movement.

MIDAZOLAM SLEEP nAfE The common effects of kmcdiwin~include sedatbn (M).The impoflanee of considering sleep state in relation to pulrne Midazolam is a water-soluble, short-acting benzodiarepine. it is nary function testing will depend to some extent on the purpose metablid in the liver, less than 1% being excreted in the utine of the investigation, Sleep state may be less important in an as- unchanged. Midazolam has been used for preoperative sedation sessment of lung mechanics in a ventilated infant for clinical pur- by the intravenous, intramuscular, rectal, oral, and nasal mutes poses than in research studies of respiratory control in normal (77, 34 60, 67). Nasal administration has the advantage of rapid infants. Hmr,little is known about the influence of sleep and absorption of the drug directly into the systemic circulation. The slep state on respiration. In some areas, data are conflicting, mak- half-life is similar alter administration by the intravenous and in- ing this an important area of study in its own righl. The age and tranasal rout= (2.4 rs 2.2 h) in children (61). Midazolam has been maturation of the infant has a major influence on patterns of sleep administered nasal1y at doses from 0.1 rng.kg-I (63). The lowest and respiration and must always be cansidered. dbse has been shown to be effective at rapidly sedating children When attempting to record sleep state, several practical issues before the induction of anesthesia (62).No additional $en& was need to be taken into account, includrng time available for the seen from a dose of 0.3 mg.kg*' as compared wirh 0.2 mg.kg-' study, acceptability to parents and infant, possible disruption of (62) to 0.3 rng-kg-' (633. Mean onset time ms7 min. Maximal ef- nursing pmdures, and accessibiltty, e,g., repositioning and fect and peak plasma concentration were obtained in about 10 recalibration of respiratory inductance plethysmograph may not rnin (62,W). No significant difference wasobserved ktween na- be straightforward if the infant is rying within a wholdmdy pie- sal drops and nasal spray administration concerning onset and thysmograph. It is important to be aware that differences in sleep duration of effect. Repea?& doses (0.2 mg-kg-') have been ad- state definition may arise when different criteria or combinations ministered for effective echomrdicgraph sedation (64)-Recwery of signals are used (66,E'), such that the estimated proportion of norma[ activity oceurrd 20-45 min after sedation (64). of active sleep can vary from 4046% in normal infants (69). Available reports do not mention significant respimtory andkr cardiovascular side effects after intranasa! rnidazolam adrninis- Development of Sleep SFates Organization tration. Hmr,consideration needs to given to the following: Using neurophysiologic and behavioral criteria, sleep can be (I) no study has reported the use of intranasal midamlam in En- differentiated into three states in the neonatal perid (active [REM fantsyounger than 5 mo;(2) available repom do not give precise sleep], quiet [NREM sleep], and indeterminate sleep) (66,69). de?ails of the clinical status of the sedated children: (3) Saq may Some workers prefer the term paradoxical sleep to active sleep fall after rnidazolam administration; in one report an 8% fall in (7Q, 7l), and also recognize a further subdivision that they claim w, was ohwedin one infant (64);and (4)systolic and diastolic resembles the awake state exeept brthe absence of awareness. arterial blood pressures have been reported to fall by tO mrn Hg The proportions of a&, quiet, and indeterminate sleep vary with 2062 AMERICAN IOURNAL OF RESPIRATORY AND CRITICAL CARE MEDtClNE VOL 151 1995 age and maturity of the infant and with time of day (72-74). Acth changes in FRC were obervsd , related siVler to sleep state or and quiet sleep can be reqnized in preterm infants of 27 wk regularity of respiration, but na attempt was made to measure rib geonand oEder (75,761, although preterm infants spend a hgh cage and abdominal motion (85). Two studies concerning both proportion of their time in indeterminate sleep (66, 77). A new- pretenn and full-term newborns showed no change in FRC in B born infant fafs asleep in active sleep. After 1 mo of age, the in- lation to change in sleep state, but a fall in FRC mly when rib fant increasingly startsto fall asleep in quiet sleep (69). Wh ad- cage and abdominal motion were 186 out of phase, regardless vancing postnatal age, the proportion of aciive sleep falEs from of sleep state (86, 8T). Discrepancies between these different approximately 50% in the newborn to 2&%% at 6 mo, while the studies may be relatedto the method of measurement. Using hdy proportion of quiet sleep increases (72).The duration of sleep cy- plethysmography, repeat measurements of FRC can be achieved cles is approximately 45 min at 3144 wk GA and 65-70 min at over much shorter time periods than when using helium dilution, 35-43 wk GA (66). Daytime sleep episodes may consist of quiet when time must be atlowed for helium to wash out of the lungs steep only in infants (69,74). Changes in respiration dufirrg sleep between repeal measurements. If there is a rapid recwery in FRC include an increase in the amount of regular respiration (77) and following any reductions during active sleep (82), any sleeprefat& a fall in the amount of rapid eye movement (REM)fassociated ap changes h FRC may !x deteGted by plethysm~graphybut missed nea over the first 12 wk (78). using helium diEution techniques. However, as stated above, the magnitude of changes during plethysrnographic measurements may have 6een overestimated due to poor equilibration of airway Although Ft is impractical for each labmatory to monizar sleep state p?wures during aimmy occlusion in act-We sleep (84). fully during all infant function tssts, it is Important to be aware al It is difficult to resalve these conflicting observations. However, the potential influence of sleep on measurements of lung some reduction in the endexpiratory revet {EEL) is to be expected mechanics. Where newrophysiolqie: monitoring is possible, it is during active sleep, due to the loss of intercostal muscle activity always recommended, since it is easierto quantify and checkthan associaled with periMs of REM during aettve sleep. Further re- behavioral observations and records can always be mxarnined search investigation~looking at the fall in FRC in active sleep at a later date. In the absence of neurophysiolagic monitoring, should consider the density of REM during the perid of mea- behavioral criteria (79) should be noted, including body and eye surement. It is well. documented that expiratory aimow braking movements and the relationship between rib cage and morni- mechanisms are disabled in a& REM sleep in premature in- nal movement. Akhough these observations should not be taken fants. Both Lopes and cowwkefs (81) and Stark and coworkers as conclusive evidence of any given sleep state, they may faclli- (88) have shown that postinspiratory diaphragmatic activity is E tate comparisons between different studies and help explain ap duced in REM. Animal studies have demonst- a substantial parently conflicting data. AcSive sleep is defined clinically by fre- reduction of laryngeal adduetion during expiration in REM steep quent eye, limb, and facia! movements and by irregular respiration (89, 90). Furthermore, recordings of airflow during quiet sleep in with paradoxical rib cage movements. In the preterm newborn. human pwrmneonates show clear widenbe d expiratory brak- clinical characterimtion of sleep state may be dffcult, since the ing, whereas during REM sleep flowvolume curves appear to be preterm infant has periods of paradoxical rib cage movements passive, with no evidence of braking (88). Thus, although the ex- during quiet sleep and synchronous movements during active piratory time constant appears to be shorter in REM sleep in sleep (80). premature infants, expiratory time (El may be longer during quiet Jtis important to note that sleep staging should not be based sleep. In term infants, followed from birth to 4 mo of age, Haddad on respiratory criteria alone, especially when examining the in- and oowwkers (91)have shown the opposite to be true, tE being fluence of sleep state on respiratwy parameters, Inappropriate greafer and respiratory rate slawer during quiet slep compared classification can occur due to the respiratory instability of new- with active sleep at all ages. Either expiratory braking during quiet brninfants and those with respimry disease, in whom abdorni- steep or more rapid respiratory me during active sleep may serve nallrib cage asynchrony artd an unstable respimtory pattern may to maintain an elevated lung volume. Changes in lung wlume with be present even durrng quiet sleep (67). changing sleep state may be more marked in nmnates than older infants, the former showing considerable instability of their EEL of Influence Sleep State on functional Residual Capacfty (MI. The potential influence of actct-versus quiet sleep on the end- For routine practice, whether testing during natural or induced expiratory lung volume, FRC, remains controversial. Two studies sleep, it is recommended that FRC be measured during quiet have assessed changes in FRC in active compared with quiet sleep, when breathing is regular and when rib cage and abdorni- sleep, using inductance plethysmography ro deteet changes in nal motion are in phase. In pminfants and neon- whom antemposterior diameters of both rib cage and abdomen in pre- ifest frequent periods of paradoxical rib cage motion during quiet term infants (M) and attarations in the baseline signal from a re- sleep and a large proportion of active sleep, measurementof FRC spi- jacket in tm in- (82).In Mhstudies, FRC was found when rib cage and abdominal movements are in phase is diffi- to fall slightly during the transition from quiet to active sleep, al- cult. Other indications of quiet or rndeterminate sleep, including though in the healthyterm infants FRC recwered to previous 4ev- the absemof limb and eye mwernents, should be used to time els within 204.0 s (82).Twa Sudies using a body plethpmograph measurements. have reported a significant fall in FRC in aet~vecornpared with quiet sleep in healthy full-term newborns (8384).The mean fall SUMMARY RECOMMENDATIONS in FRC was N% in six intanls and 12% in eight. There may be magic mtherthan purety physiolqie aplanations for these laboratory Conditions differences, including lack of support of the upper airways (84). 1. Envirnmnental temperature 20-2!j0 C. "Fhrestudies haw measured FRC using the hellurn dilution tech- 2. Resuscitation equipment afways available. nique during active and quiet sleep by neuropfiysiologic 3. Full monitoring, including at least pulse mimetry, of vital signs criteria (85-81). In healthy full-tern- newborn, no significant during sedation. ATS/ERS Statement

4. Second person to be responsible for monitoring in intensive ratory rssponses during REM sleep in human infants. Chest98:92-96. meenvironment and during sedated studies on any 'high risk" 8. Cox, L. A. 199Z.RGuidetothe Measurement and kxeswnentof Grnwth in Children. Castternwad. Welwyn Garden Ci.1-54. infants (see below). 9. Singer, L., R. J. Marhn, S. W. Hawklns. L. J. Berrson-Szekdy, T. S. 5. All apparatus (mask.valves, pneumotachographs, connectors, Yamash'rta, and W. A. Carlo. 1992. Oxygen d-turation complicates etc) must be cleanedkterilized as appropriate between each Wing in infants with bronchopulmonary dysplasia after discharge. Fed- 90:380-393. infant. 10. Krauss, A. N., J. Brown, S. Wallman, G. Gmieb, and k M. Auld. 1978. Pulmonary funct~onfollowing feeding in low birth weight infants. Am. Preparation of the Infant, Feeding, and Position J. DD. Child. 132139-142. 1. Defer measurements for 3 wk after onset of upper respimtory 11. Pier-WilmoQ R., J. G. Sh Wk,and W.W. Fox. 1979. Oecreased lung volume after nasogastric feeding of neonates recovering from respira- tract infection. tory diase. J. Pedatr. 95:?19-121. 2. Length and naked weight measured on each occasion (if> f2. Helms, P., M. G. Hutse, and D. J. Hatch. 1982. Lung volume and lung 1 wk apart). mechanics in infancy: lateral or supine posture? Pediafr. Res. 3. Fasting is not usually indicated. 16:-7. 33. Baird, T-M.. and M. R. Neuman. 1991. Effect of infant position on breath 4. Record posture; avoid flexion or rotation of the neck. amplitude measured by tmnsthoradc impedance and strain gauges. 5. Referenm values are available mainly forthe supine position. Pediatr. Prrtmonol. 1052-56. 14. Helrnler, R.. J. Langlois, D. J. Hodel, L D. Nelin, and P. -dhat-an. 2992. Sedation Effect of psitioning on tbbreathing pattern of preterm infants. Arch. Dis. Child. 67:312314. 1. Contraindication for sedation-known upper airway ob 15. Spdstra. A. J. G., and S. Stikasibhanda. 1973. Dynamic preesure vol- stnrction. ume miationship of the lung and lposition in heatthy neonates. Am. 2. High risk infant groups: a) preterm and full-term neonates (G -. Scand. 62976-180. 16. Vandergbem, A., C. S.Beardsmwe, and M. Silverman. 1983. Pwural 44 when wk postconceptional age) even healthy; b) infarrEs pre varianons in pulmonary resistam and dynamic compliance in nep sewing a history of acute life-threatening events; C) infants at nates. Crit. Care Mad. 11:424-427. increased risk of upper airway oMruction; 6)infantswjtt, Lcnown 17. Wagamaft, M. J.. J. G. Shutack, A. S. Mmmjian, J. G. Scfiwarh, T. H. respiratory embamment;and e) infants with hepatic, renal, Shsffer. and W.W. Fox. 1979. Improved oxygenation and lung compliance with pmne positioning of neonates. J. Map.94787-791. or cardiac disorders. High risk infants must be monitored (oxy- 16. Wotfson, M. R.,J. S. Greenspan, K. S. M,J. L. Alien, and T. H. Shaffer. gen saturation, heart rate) after sedation. Overnight hospital- 1332. Effect of wonon thmechanical interactron between the rib imion may need to be arranged for infants who are clinically cage and abdomen In preterm infants. J. Appl. PhysEd. 721032-f 038. 19. Asher, M. I., A. L Coates, J-M Collngs, and J. Mil~eErnll~.1982 Mea- unstable. svrement of pleural prassure in neonates. J. Appl. Physol. 52:491494. 3. Sedate with caution-wheezy irrfants (51). 20. Retferer, F., S.Abbasi, and V. K Bhutani. 1594. Influence of head-neck 4. R~edationshould be avoid&; the total dose of chloral hydrate posture on airflow and pulmonary mechanics in pwtem neonate. Pea& a*. PuImonoI. 17:14%154. should not exceed 120 mg.w (and dose equivalents for related 21. Reed. W.R., J. L Roberts, and B. T. Thach. 1985. Factors influencing drugs, triclofos dium). regional patsncy and amfiguration of the human infant umrairnay. 5. Always advise parents of possible unsteadiness in infants af- J. Appl. Physio. 58:-. ter sedation. 22. Levene, S.. and S. A. McKentlo. 1990. TransFutansous oxygen saturation in sleeping infams: prone and supine. Arch. Dis. CMd. 65:524-526. Steep State 23. McEvoy, C., V. Hewlatt, S. Sardesai, E. Mendoza, and M. Durand. 1992. Prone mitiming decreases epi- d dmturation in infants with 1. Measurements should h made during quiet sleep, asssssed chronic lung diseasa. Errr. Re@. J. 5:158S. by behavioral criteria in the absence of more sophisticated 24. Carwt.E.,C.Gauher.k-M.[YA1~andM.Dehan.1989.EpI.ectsd~ deprivation on respiratory events during sWp In h&hy infants. J. qopl. monitoring. Physb!. 66:115&11 m. 2. Avoid inappropriate dependence on respiratory definitions of 25. -1, D. K. J., K. W. Hlndmarsh, C. A Hall. D. J. M-, and K Snb quiet sleep. ran. 7990. Determination ot chlmal hydrate metablism in Auk and neonate biologlml Rulds &er sing- dnrinktmon. J. Ch-. 528:-1. ~~The Working Gmup wwld like tn Zhank DLbe& (Univer- 26. Reimche, L D., K. Sankaran, K. W. Hindmarsh, G. F. klan, D. K. J. sity of Sasktchwan. Canada) and ttw committee membws of the Joint Gorecki, and L Tan. 1989. Chloral hydrate sedation in newr&tesand ATSIERS Working Grwp on the Star~dardiionof Infant hngFunUim Tm infantr. dinical and phamadogic considerations. Dev. Pharmacol. for auluable mbubons. Glam Grwp Research LM., UK and Glam Sweden Ther. f2:5f-W. RB. generously pmvided financial support for international mllabom~on. 27. Sellers, E. M., M. Long-Sellers, and J. Koch-Wmr. 1978. bmpamtive metabolism of chloral hydrate and triclofa. d Clin. Pharmmmi. 1B: References 45747. 28. Breimer, D. D. 7977. Clinical pharma&neti= of hypnotics. m. Phw- 1. Berterottiere, D., A. M. D'AlW!, M. Dehan, and C. Gaultier. 1990. Effects rnecokht- 293-109. of inmeas in temperature on the breathing pattern in premature 29. Hindmarsh. K. W., D. K. J. Gorecki. K Sank=, and D. J. Mayers. IW?. infants. J. I.v.PW. 13:m. Chloral hydrate administration to neonates: potential toxicotogi~alim 2. 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