Effects of Nasal High Flow on Ventilation in Volunteers, COPD and Idiopathic Pulmonary Fibrosis Patients

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1 Clinicl Investigtions Respirtion 213;85: DOI: /34227 Received: Octoer 27, 211 Accepted fter revision: June 28, 212 Pulished online: Novemer 1, 212 Effects of Nsl High Flow on Ventiltion in Volunteers, COPD nd Idiopthic Pulmonry Firosis Ptients For permitted use only. ANY FURTHER DISTRIBUTION OF THIS ARTICLE REQUIRES WRITTEN PERMISSION FROM S. KARGER AG BASEL AND MAY BE SUBJECT TO A PERMISSION FEE Jens Bräunlich Denise Beyer Dvid Mi Stefn Hmmerschmidt Hns-Jürgen Seyfrth Huert Wirtz Deprtment of Respirtory Medicine, University of Leipzig, Leipzig, Germny Key Words Nsl high flow Tidl volume Hypercpni Idiopthic pulmonry firosis COPD Astrct Bckground: A high flow of ir pplied y lrge ore nsl cnnule hs een suggested to improve symptoms of chronic respirtory insufficiency. In peditric ptients, nsl high-flow () ventiltion ws similrly effective compred to noninvsive ventiltion with fce msk. Ojectives: The im of this study ws to descrie chnges in respirtory prmeters. Methods: We mesured pressure mplitudes during the respirtory cycle nd men pressures in ptients with idiopthic pulmonry firosis (IPF) nd COPD. In order to chieve tidl volume nd minute volume mesurements, we used polysomnogrphy device. Cpillry lood ws tken for lood gs nlysis efore nd fter rething (8 h). Results: led to n increse in pressure mplitude nd men pressure in helthy volunteers nd in ptients with COPD nd IPF in comprison with spontneous rething. In COPD, incresed tidl volume, while no difference in tidl volume ws oserved in ptients with IPF. Interestingly, tidl volume decresed in helthy volunteers. Brething rtes nd minute volumes were reduced in ll groups. Cpillry pco 2 decresed in ptients with IPF nd COPD. Conclusions: resulted in significnt effects on respirtory prmeters in ptients with ostructive nd restrictive pulmonry diseses. The rise in pressure mplitude nd men pressure nd the decrese in rething rte nd minute volume will support inspirtory efforts, helps to increse effectiveness of ventiltion nd will contriute to reduction in the work of rething. A CO 2 wsh-out effect in the upper irwy prt of the ntomicl ded spce my contriute to the eneficil effects of the instrument. Introduction Copyright 212 S. Krger AG, Bsel Noninvsive ventiltion hs ecome min sty of the therpy of respirtory insufficiency in vrious conditions. It is lso pplied in COPD ptients, lthough its efficcy is less well demonstrted in this disese. However, the method is inpplicle to some ptients with poor msk tolernce nd other well-known fctors [1]. Recently, high flow rtes of room ir or room ir/oxygen gs mixtures hve een tried in situtions of sleep pne nd Fx E-Mil krger@krger.com S. Krger AG, Bsel /13/ $38./ Accessile online t: Jens Bräunlich, MD Deprtment of Respirtory Medicine University of Leipzig DE 413 Leipzig (Germny) E-Mil medizin.uni-leipzig.de

2 respirtory insufficiency [2, 3]. These flow rtes (rnge 16 4 liters/min) re tolerle ecuse the ir is wrmed nd humidified nd ecuse nsl cnnuls re designed in order to void creting jet directed to mucosl surfces. Vrious terms hve een used for the new method such s high-flow nsl cnnul, mini-cpap or trnsnsl insuffltion (TNI). The terms nsl high flow () or nsl high-flow ventiltion re the most descriptive nd precise terms from our point of view nd re therefore used in this study. hs een employed in peditric settings with some success [2]. Shoemker et l. [3] compred ventiltor support vi nd vi nsl CPAP. Compred to infnts mnged with, no increse in dverse outcomes were oserved with. Ptient dys on ventiltor were decresed (19.4 down to 9.9 dys) with. Benefits were lso oserved in peditric sleep pne when nsl CPAP ws compred to : episodes of ostructive pne decresed from to events per hour with therpy. The reduction in pne-hypopne index with ws comprle to tht in. A positive irwy pressure during ws suggested to e the predominnt mechnism [4 7]. hs lso een used in ostructive sleep pne [4, 7, 8]. In study y Nilius et l. [8] the respirtory disturnce index decresed from to events per hour in ptients treted with (2 liters/ min). The respirtory disturnce index significntly dropped y 27% in ostructive sleep pne ptients treted with. In this study sugroup, nlysis reveled tht ptients with ostructive hypopne nd rpid eye movement-ssocited events enefited the most [8]. The differences etween nsl low ( liters/ min) nd high flow (2 liters/min) in ptients with COPD were nlyzed y Chtil et l. [9]. These uthors oserved incresed exercise cpcity ( vs min) with improved oxygention using n unloded icycle ergometer (12 min for every flow with 3 min rest etween mesurements) with compred to spontneous rething. Severl groups hve descried elevted end-expirtory pressures with vrious settings [1, 11]. Roc et l. [12] compred n -system with conventionl oxygen ppliction vi msk (3 liters/min vi nsl high flow vs. 15 liters/min vi msk). The group exhiited higher flows following 3 min under ventiltion. This ws ssocited with lesser dyspne, decresed rething rte nd n elevted po 2. Mterils nd Methods Ventiltion For this study, the TNI2s oxy device ws used (TNI medicl AG, Freiurg, Germny). The system is le to provide flow of up to 3 liters/min nd llows the dmixture of oxygen up to 16 liters/min. The ir strem delivered is wrmed nd humidified with some degree of individul regultion of temperture. ws pplied vi nsl prongs with lrger ore outlets (in comprison to regulr oxygen supplementtion with nsl prongs) to ccommodte the intended flow ( fig. 1 ). We used the BiPAP synchrony system when CPAP ws pplied (Philips/Respironics, Andover, Mss., USA). Volunteers nd Ptients The 16 helthy volunteers were yers old ( yers; 6 mles, 1 femles). Tidl volumes were mesured with elstic sensor elts in 12 individuls out of the group of 16 volunteers (4 mles, 6 femles). Ptients with COPD nd idiopthic pulmonry firosis (IPF) were recruited mong the ptients from the respirtory wrds t the university hospitl, Leipzig. Pressure mesurements were completed in 15 ptients with COPD ( yers; 8 mles, 7 femles) nd in 13 ptients with IPF ( yers; 7 mles, 6 femles). Additionl tidl volume mesurements were done in 12 of the ptients with COPD nd in 12 of the ptients with IPF ( yers; 3 mles, 4 femles). Finlly we recruited 8 dditionl ptients with COPD ( yers; 4 mles, 4 femles) nd 8 ptients with IPF ( yers; 3 mles, 5 femles) who suffered from glol respirtory insufficiency with hypercpni. These ptients were used in the pilot tril to investigte pco 2 chnges with therpy. The study ws pproved y the locl ethics committee nd ptients gve their informed consent to prticipte (No ). Mesurement of Airwy Pressure A wter-filled flexile tue (inner dimeter 1 mm, Originl Perfusor -cle type stndrd; B. Brun, Meisungen, Germny), plced in the nsophryngel spce ws used s pressure trnsducer. A pressure trnsformer (Infinity Hemo 4; Dreger Medicl Systems, Lüeck, Germny), n mplifier nd nlogue chrt writer (L2E; Linseis Messgeräte GmH, Sel, Germny) were used to record the signl ( fig. 1 ). Ten reths were recorded ech during spontneous rething, (24 liters/min) nd rething (4 mr; fig. 1 c). These mesurements were done for oth prone nd supine ody positions. For clirtion of the system, pressure detector (GMH3111; Greisinger Electronic GmH, Regenstuf, Germny) ws used. Mesurement of Tidl Volume, Brething Rtes nd Minute Volume A polysomnogrph (Respitrce; Cre Fusion, Höcherg, Germny) ws used to mesure tidl volume. Elstic sensor elts were plced 1 cm elow the jugulr notch nd 1 cm elow the xiphoid process in ll individuls in whom tidl volume mesurements were performed. Susequently, we clirted the device individully for ech volunteer/ptient strting t quiet rething recorded with stndrd lung function equipment (Mster Screen Body; CreFusion GmH, Höcherg, Germny). While mesuring tidl volumes of 1 reths nd simultneously registering the sensor signl, we were le to clirte the sensor elt signl to chnges 32 Respirtion 213;85: Bräunlich/Beyer/Mi/Hmmerschmidt/ Seyfrth/Wirtz

3 in lung volume. Following clirtion, volume mesurements during (2 liters/min) nd spontneous rething were strted. Chest nd dominl excursions were recorded nd volumes were clculted. Mesurement of I-E Rtio Thorcic wll excursions during inspirtion nd expirtion were used to clculte the I-E rtio for ll reths. Color version ville online C p i l l r y p C O 2 Sixteen ptients (8 COPD nd 8 IPF) were identified with little vriility in pco 2 vlues. Cpillry lood gs nlysis ws done in the morning nd fternoon t the hyperemic erloe (Cpsmol; Wörwg Phrm GmH, Bölingen, Germny). The following dy ptients received ventiltion t 2 liters/min. Gs checks were repeted prior to ventiltion (t = ) nd 8 h of rething. S t t i s t i c s Dt were nlyzed using Student s t test (Sigm Plot; Systt Softwre GmH, Ekrth, Germny). A proility level for the null hypothesis (no difference) of 5% or elow (p!.5) ws ccepted for significnce. R e s u l t s Elevtion of Pressure Amplitude nd Men Pressure The pressure mplitude of rething cycles, descriing the difference etween miniml nd mximl pressures during rething ws significntly elevted in helthy volunteers compred to spontneous rething ( fig. 2 ). Similr results were oserved in ptients with COPD ( fig. 2 ) nd IPF ( fig. 2 c). At the sme time, menpressures were lso elevted during ventiltion in helthy volunteers ( fig. 2 d) s well s in COPD ( fig. 2 e) nd in IPF ptients ( fig. 2 f). No differences etween prone nd supine ody position were oserved (dt not shown). We lso compred with therpy, which is supposed to chieve the chosen pressure in the phrynx. The device ws set to 4 mr in order to llow for phryngel pressures within the vicinity of the pressures reched with the device. We relized tht this pressure is lower thn tht chosen for most ptients using, e.g. for ostructive sleep pne. The pressure set t 4 mr ws not chieved in the phrynx, insted, lower vlues were recorded in the nsophryngel spce. A fce msk ws firmly occluded in order to vlidte our experimentl setup in terms of pressure mesurements. The occluded system ws lso set t 4 mr nd this pressure ws recorded. Thus, the system ws le to keep up the set pressure level of 4 mr. c Fig. 1. device with thick nsl prong. Setup for mesurement of pressure chnges, with device (left), mplifier (lower right), Hämoox nd pen recorder (upper right). c Exmple of pressure digrm. SA = rething; TNI = device; pressure mplitude = pek to trough; men pressure increse = shift to the left. Effects of on Ventiltion Respirtion 213;85:

4 1.3 Helthy prone (n = 17) p > COPD prone (n =15) Color version ville online.4 rething rething IPF prone (n = 13) Helthy prone (n = 16) p >.5 c rething d rething/seline COPD prone (n = 15) IPF prone (n = 13) e rething/seline f rething/seline Fig. 2. Chnges in pressure mplitude ( c ) nd men pressure ( d f ) in helthy volunteers, COPD nd IPF ptients. 322 Respirtion 213;85: Bräunlich/Beyer/Mi/Hmmerschmidt/ Seyfrth/Wirtz

5 Tidl volume (%) Helthy COPD p >.5 IPF Color version ville online Tidl Volumes Tidl volumes in helthy volunteers were reduced y ml ( %) during the use of. However, in ptients with COPD tidl volume ws incresed during ventiltion y ml ( 8 18%). In ptients with IPF, however, no chnges in tidl volume were noticed ( fig. 3 ). Brething Rte Brething rtes during rething were reduced in helthy volunteers y pm ( %), in ptients with COPD y pm ( %) nd in IPF ptients y pm ( %; fig. 3 ). These were ll significnt chnges. Brething rte (%) Minute Volum e Minute volumes with ventiltion were similrly reduced in helthy volunteers y liters ( %), in COPD ptients y 1 8 liters ( %) nd lso in IPF ptients y liters ( %; fig. 3 c). Agin ll of these chnges were significnt. I-E Rtio In helthy volunteers, ptients with COPD nd ptients with IPF, the I-E rtio did not differ with versus spontneous rething. Minute volume (%) c Helthy Helthy COPD COPD IPF Fig. 3. Chnges in tidl volume ( ), rething rte ( ) nd minute volume ( c ) in helthy volunteers, COPD nd IPF ptients (n = 12 for ech). IPF C pil l r y p C O 2 Sixteen ptients with chronic respirtory insufficiency due to COPD (n = 8) nd IPF (n = 8) were investigted for chnges in cpillry pco 2 with. During 8 h of spontneous rething none of these ptients showed significnt chnges in pco 2. However, following 8 h of rething (2 liters/min) we oserved significnt fll in pco 2 in ptients with COPD y kp ( %). In ptients with IPF, pco 2 decresed y kp ( %; fig. 4 ). This represents significnt fll in pco 2 in COPD ptients y to kp nd in IPF ptients y to kp. Discussion We investigted the effects of ventiltion on phryngel pressures, tidl volumes, rething rtes nd minute volumes in helthy volunteers s well s in ptients with ostructive s well s restrictive lung disese. In order to compre chnges with to more estlished mens of ventiltor support, ws compred to t 4 mr. Effects of on Ventiltion Respirtion 213;85:

6 Color version ville online pco2 (kp) pco2 (kp) t = t = 8 Time (h) 5.5 t = t = 8 Time (h) Fig. 4. Chnges in pco 2 in ptients with COPD ( ) nd IPF ( ), 2 liters/min (n = 8 for oth). A significnt increse in pressure mplitude nd in men pressure ws oserved in helthy volunteers, in ptients with ostructive nd restrictive lung disese during rething compred with spontneous rething. The effects on pressure descried in this study confirm nd expnd on the results of other uthors who suggested incresed pressure during s n indiction of relief of rething-relted work [7, 12] nd lso oserved flow-dependent increse in phryngel pressure which ws greter with the mouth closed thn with the mouth open. Tidl volume ws oserved to e incresed in ptients with COPD during rething. In contrst, tidl volume ws decresed in helthy volunteers during rething. It is possile tht COPD ptients on support were reenled to hyperventilte in order to compenste for COPD-relted pulmonry deficits. An increse in tidl volume ws lso oserved in ptients with COPD following the initition of NIV [13]. Without ny ventiltory support, severe COPD ptients demonstrte decrese in ventiltion nd concomitnt hypercpni. Ventiltor support provided with ventiltion my thus support the chievement of compenstory hyperventiltion. In contrst to the incresed tidl volume in COPD ptients, we oserved reduction in rething rtes nd lso in minute volumes in ll groups including COPD ptients. Thus the efficiency of rething ppers to e incresed y nd this increse will in turn need less work of rething for given respirtory result. Indeed, n effect on rething efficiency nd rething-relted work might come y one of three fctors: (1) positive pressure support, (2) constnt flushing of the upper respirtory trct with oxygen-enriched ir, or (3) component of trchel gs exchnge rought out y the ir streming over the lryngel opening. Ventiltion is primrily dpted to pco 2 nd more efficient elimintion of pco 2 in the upper irwys my therefore result in reduced ventiltory drive. Thus the rte of rething decreses nd will result in decresed minute volume. Incresed elimintion of CO 2 is the prerequisite for stle pco 2 or even decrese in pco 2 with decrese in minute ventiltion. 324 Respirtion 213;85: Bräunlich/Beyer/Mi/Hmmerschmidt/ Seyfrth/Wirtz

7 This possile explntion ws supported very recently y Frizzol et l. [14]. A more direct mesurement of n increse in trchel pressures with ws descried in n experimentl niml setting. The piglets ventilted in this study following cute lung injury exhiited similr increses in directly mesured trchel pressure. Interestingly, pco 2 decreses were not correlted to trchel pressures ut were correlted to flow rte. Since high-lek nsl prongs led to improved pco 2 in comprison with low-lek nsl prongs it ws suggested tht pco 2 improvement ws more likely to e cused y constnt flushing of the upper respirtory trct thn y trchel pressure. ppers to emerge s n interesting lterntive wy of supporting ventiltion. It is well tolerted nd esy to use. The dditionl effect of n improvement of inspirtory efforts y some increse in trchel pressure nd supporting of inspirtion my depend on the flow chosen. Tolernce of the flow will depend on the extent of humidifiction nd on dequte wrming of the irstrem, which re importnt prerequisites of therpy. However, effects in helthy individuls s well s ptients with COPD nd ptients with IPF re encourging nd lrger studies should expnd on these oservtions. Limittion of the Study Our study is pilot study investigting sic ltertions in ventiltory pttern nd in phryngel pressure with. The numer of volunteers nd ptients in ech group is low. The groups were not ge mtched since pressure differences nd ventiltory responses to rething were thought to e siclly similr, ut n influence of ge cnnot e excluded. The oserved pco 2 differences vry within groups, mening the extent of ventiltory support y cnnot e estimted relily. We did not mesure respirtory muscle ctivity or force nd thus cn merely suggest tht our oservtions re consistent with prtil relief in respirtory muscle lod with. Acknowledgements This study ws supported y equipment from TNI medicl AG. Finncil Disclosure nd Conflicts of Interest Dr. Bräunlich hs received equipment from TNI medicl AG nd trvel funds. All other uthors declre no finncil interests or conflict of interests. References 1 Tsolki V, Pstk C, Kostiks K, Kretsi E, Dimoulis A, Zikiri A, Koutsoker A, Gourgoulinis KI: Noninvsive ventiltion in chronic respirtory filure: effects on qulity of life. Respirtion 211; 81: Sreenn C, Lemke RP, Hudson-Mson A, Osiovich H: High-flow nsl cnnule in the mngement of pne of premturity: comprison with conventionl nsl continuous positive irwy pressure. Peditrics 21; 17: Shoemker MT, Pierce MR, Yoder BA, Di- Geronimo RJ: High flow nsl cnnul versus nsl CPAP for neontl respirtory disese: retrospective study. J Perintol 27; 27: McGinley B, Hlower A, Schwrtz AR, Smith PL, Ptil SP, Schneider H: Effect of high-flow open nsl cnnul system on ostructive sleep pne in children. Peditrics 29; 124: Spence KL, Murphy D, Kilin C, McGonigle R, Kilni RA: High-flow nsl cnnul s device to provide continuous positive irwy pressure in infnts. J Perintol 27; 27: Kuick ZJ, Limuro J, Drnll RA: Heted, humidified high-flow nsl cnnul therpy: yet nother wy to deliver continuous positive irwy pressure? Peditrics 28; 121: McGinley BM, Ptil SP, Kirkness JP, Smith PL, Schwrtz AR, Schneider H: A nsl cnnul cn e used to tret ostructive sleep pne. Am J Respir Crit Cre Med 27; 176: Nilius G, Wessendorf T, Murer J, Stoohs R, Ptil SP, Schuert N, Schneider H: Predictors for treting ostructive sleep pne with n open nsl cnnul system (trnsnsl insuffltion). Chest 21; 137: Chtil W, Nugent T, Vnce G, Gughn J, Criner GJ: The effects of high-flow vs lowflow oxygen on exercise in dvnced ostructive irwys disese. Chest 24; 126: Groves N, Toin A: High flow nsl oxygen genertes positive irwy pressure in dult volunteers. Aust Crit Cre 27; 2: Prke R, McGuinness S, Eccleston M: Nsl high-flow therpy delivers low level positive irwy pressure. Br J Anesth 29; 13: Roc O, Rier J, Torres F, Msclns JR: Highflow oxygen therpy in cute respirtory filure. Respir Cre 21; 55: Schonhofer B, Dellweg D, Suchi S, Kohler D: Exercise endurnce efore nd fter longterm noninvsive ventiltion in ptients with chronic respirtory filure. Respirtion 28; 75: Frizzol M, Miller TL, Rodriguez ME, Zhu Y, Rojs J, Hesek A, Stump A, Shffer TH, Dysrt K: Peditr Pulmonol 211; 46: Effects of on Ventiltion Respirtion 213;85: