High  Flow  Nasal  Cannula  Therapy  

T  Townend  Christchurch  Hospital  

Ra9onale  

•  Non-­‐invasive  respiratory  support  •  Delivery  of  prescribed  FiO2  

– ↓air  entrainment  (dilu9on)  •  Humidifica9on  (≥95%)  •  Comfortable  nasal  interface  •  Low-­‐level  CPAP  

•  Easier  applica9on  and  beNer  facial  access  than  nasal  CPAP  

Mechanisms  of  ac9on  

•  Washout  of  nasopharyngeal  deadspace  •  Reduced  WOB  

•  Improved  mechanics  •  Reduced  metabolic  expense  •  Distending  pressure  

       Dysart  et  al,  Respiratory  Medicine  2009;  103:1400-­‐1405  

Applica9ons  

•  High  O2  requirements  or  WOB  •  Need  for  humidifica9on  (secre9ons)  •  Poor  tolerance  of  mask  

 

Paucity  of  evidence  

•  Cochrane  review  2014  – To  determine  whether  HFNC  therapy  is  more  effec9ve  than  other  forms  of  non-­‐invasive  therapy  in  paediatric  pa9ents  who  require  respiratory  support  

– Content  to  1st  April  2013  – No  study  matched  inclusion  criteria  

•  Neonatal  evidence  not  much  beNer  

Neonates  •  Most  studies  have  focused  on  respiratory  support  during  post-­‐

extuba9on  period  in  premature  infants  

•  RCT  of  432  infants  28-­‐42  weeks  gesta9on  comparing  nCPAP  and  HFNC  –  Primary  therapy  or  post-­‐extuba9on  –  Primary  outcome:  need  for  intuba9on  within  72hrs  of  applied  non-­‐invasive  

therapy  

•  No  difference  in:  –  Early  failure  HFNC  vs  nCPAP  –  Subsequent  need  for  any  intuba9on  –  Dura9on  on  oxygen  –  Rates  of  BPD                  

 Bradley  et  al,  Pediatrics  2013;131;e1482  

     

of bronchopulmonary dysplasia (BPD)at 36 weeks’ gestational age for infantsborn at ,32 weeks’ gestation wassimilar between study groups, as wasthe proportion of infants dischargedfrom the hospital on oxygen (Table 4).

After study entry, several potentialadverse outcomes were closely mon-itored. As shown in Table 5, the over-all adverse event rate was similar

between infants randomly assignedto nCPAP compared with HHHFNC.Importantly, the rate of any form of airleak occurring on study mode sup-port was quite low and not differentbetween groups. There were also nodifferences in the occurrence of in-creased apnea or sepsis, frequency ofdelayed intubation, or time to full oralfeedings between study groups. The

only difference in measured adverseoutcomes was a small but statisticallysigni!cant higher rate for any nasaltrauma during nCPAP support (Table 5).

We compared infants successfullymanaged by either study mode withthose with early study failure to de-termine if there were identi!ablecharacteristics that might help to pre-dict early failure. We did not !nd anydifferences in prestudy characteristics(Table 6). Speci!cally, gestational age,birth weight, surfactant therapy, pre-study respiratory support mode, re-spiratory support pressure, and FIO2were similar for infants experiencingearly failure compared with thosesuccessfully managed by either nCPAPor HHHFNC.

Rates for early failure were not signif-icantly different between devices (P =.521): Fisher and Paykel (16 of 143;11%), Vapotherm (4 of 52; 8%), andHudson Comfort-Flo (3 of 17; 18%).Likert scale assessments from thebedside nurse and respiratory thera-pist related to ease of care and patientcomfort revealed no differences be-tween the 2 study modes.

DISCUSSION

In this multicenter randomized trialinvolving neonates $28 weeks’ gesta-tional age undergoing planned non-invasive respiratory support, we foundno signi!cant difference betweenHHHFNC and nCPAP with regard to theprimary outcome of intubation withinthe initial 72 hours of support. In ad-dition, we found no differences be-tween infants randomly assigned tonCPAP compared with HHHFNC forseveral respiratory outcomes, includ-ing duration of oxygen supplementation,diagnosis of BPD, or discharge fromthe hospital on oxygen. Despite con-cerns over unregulated/unmonitoredpressure delivery during HHHFNC sup-port, we found no differences in theoccurrence rate for any form of air

TABLE 2 Demographic Characteristics of Infants Randomly Assigned to nCPAP or HHHFNC

nCPAP (n = 220) HHHFNC (n = 212)

Gestational age, mean 6 SD, wk 33.2 6 3.2 33.5 6 3.6,32 wk, n (%) 75 (34) 75 (35)

Birth weight, mean 6 SD, g 2108 6 782 2201 6 816,2000 g, n (%) 111 (50) 100 (47)

Male, n (%) 137 (62) 137 (65)Antenatal steroids, n (%) 71 (32) 80 (38)Respiratory distress syndrome, n (%) 162 (74) 156 (74)Study start age, median (25%–75%), h 20 (7–54) 24 (8–62)Start age ,7 d, n (%) 201 (91) 194 (92)Prestudy support mode, n (%)Ventilator 145 (66) 146 (69)nCPAP 46 (21) 39 (18)Other (NC, hood O2, room air) 29 (13) 27 (13)

Prestudy surfactant, n (%) 129 (59) 142 (67)Prestudy nitric oxide, n (%) 18 (8) 13 (6)Prestudy caffeine, n (%) 66 (30) 58 (27)

P . .05 for all comparisons.

TABLE 3 Early Respiratory Failure in Infants Managed With nCPAP and in Those Managed WithHHHFNC

nCPAP (n = 220) HHHFNC (n = 212) OR (95% CI)a

Early failure, all 18 (8.2) 23 (10.8) 1.37 (0.71–2.61),32 weeks’ gestational age 5/75 (6.7) 3/75 (4.0) 0.58 (0.13–2.53)Prestudy ventilator 9/145 (6.2) 17/146 (11.6) 1.89 (0.86–4.63)Start age ,7 d 16/201 (8.0) 23/194 (11.9) 1.56 (0.80–3.04)

Data are shown as n (%). Data in rows 3–5 are also shown as number of failures/number of infants (%). CI, con!denceinterval; OR, odds ratio.a Unadjusted.

TABLE 4 Respiratory Support Outcomes Among Infants Randomly Assigned to nCPAP ComparedWith HHHFNC

nCPAP (n = 216) HHHFNC (n = 211) P

Days on study mode 2 (1–4) 4 (2–7) ,.001Delayed use of other study mode, n (%) 31 (14) 19 (9) .096Days ventilated 2 (1–4) 2 (1–5) .476Days any positive pressure support 4 (2–8) 6 (3–11) ,.001Days supplemental O2 8 (5–24) 10 (5–27) .357BPD,a n (%) 12/73 (16) 15/75 (20) .575Home oxygen, n (%) 38 (18) 40 (19) .698Age at discharge 25 (13–47) 25 (14–49) .756

Data are shown as medians (25%–75%) unless otherwise indicated.a Only surviving infants ,32 weeks’ gestational age at birth.

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leak. The outcome results from thisrelatively large randomized trial in-dicate that the use of HHHFNC, as de-scribed in this report, appears to be aseffective and as safe as nCPAP in thispopulation of infants.

The actual approach to “high-!ow”nasal cannula must be carefully con-sidered in evaluating all studies. Someinvestigators have described “high-!ow” in the presence of !ow limited to1 to 2 lpm and in the absence of a well-heated, humidi"ed gas source for !ow.

Flow limitation has been based on ear-lier studies from Locke et al5 andSreenan et al6 suggesting the potentialfor high, unregulated positive airwaypressure. Over the past decade, sys-tems have been designed to allowmuchhigher !ow rates (2–8 lpm for neonatesand up to 50 lpm in adults) accompa-nied by optimal heating (37°C) andhumidi"cation (100%) of the deliveredgas. We, and others, have de"ned thissystem of NC therapy as heated, hu-midi"ed high-!ow nasal cannula or

HHHFNC.19 Recent studies have reportedmuch lower airway pressures usingHHHFNC, both indirectly via pharyngealor esophageal pressure measurementand, in an animal model of neonatalrespiratory distress, directly via intra-tracheal pressure monitor.20–23 Theimportance of the NC interface in thepotential delivery of airway pressureshould not be minimized. In recentneonatal studies, external NC diame-ters were typically limited to ,3 mm.This size appears to be a critical di-mension for neonatal HHHFNC, becauseLocke et al5 demonstrated that highairway pressures were measurablewith a cannula diameter of 3 mm butnot when the cannula was 2 mm in di-ameter. All infants in our study weremanaged with NC having an externaldiameter of ,3 mm, with 95% mea-suring ,2.0 mm.

Several retrospective and observa-tional studies have been publishedsuggestingthatHHHFNCmaybeeffectiveand safe in managing preterm infantswith respiratory dysfunction.8,12–14 Itis important to differentiate "ndingsfrom these reports from those of otherinvestigations in which high-!ow nasalcannula has been applied with the useof inadequately heated/humidi"ed gasat signi"cantly lower !ow rates. Abdel-Hady et al24 reported that weaningfrom nCPAP to high-!ow NC limited to 2lpm was associated with longer dura-tion of oxygen and respiratory supportcompared with infants maintained onnCPAP until weaned directly to roomair. In their study, not only was NC !owrate limited but the gas conditioningmay have been inadequate. Campbellet al25 reported in 40 infants that “HF-CPAP” [high-!ow CPAP], administeredvia standard NC, was less effective atpreventing reintubation than nCPAP.There were limitations in NC !ow rate(range: 1.4–1.7 lpm) and gas condi-tioning similar to those in the Abdel-Hady et al study, and “HF-CPAP”

FIGURE 2Infants randomly assigned to nCPAP (black line) had signi"cantly shorter duration of study supportmode compared with infants randomly assigned to HHHFNC (gray line); P , .01. There were no sig-ni"cant differences between study groups for duration of ventilator support (dotted lines) or time towean to room air (dashed lines) in the 7 days after study entry. RA, room air.

TABLE 5 Occurrence Rates for Secondary Outcomes in the nCPAP Compared With the HHHFNCStudy Group

nCPAP (n = 220) HHHFNC (n = 212)

Any adverse event 46 (21) 52 (25)Air leak 5 (2) 1 (,1)Increased apnea 15 (7) 23 (11)Con"rmed sepsis 7 (3) 7 (3)Con"rmed NEC 4 (2) 2 (1)Reintubation, any 25 (11) 32 (15),72 hours 18 (8) 23 (11),7 days 21 (10) 23 (11)

No nasal trauma 180 (84) 187 (91)*Abdominal distention 17 (8) 21 (10)Days to full oral feedings, median (25%–75%) 17 (8–35) 18 (8–41)Death 4 (2) 1 (,1)

Data are shown as n (%) unless otherwise indicated. *P = .047. NEC, necrotizing enterocolitis.

ARTICLE

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Bradley  et  al,  Pediatrics  2013;131;e1482  

Paediatrics  •  Most  studies  have  focused  on  infants  with  bronchioli9s  •  Efficacy  of  HFNC  yet  to  be  demonstrated  in  other  paediatric  condi9ons  

•  Retrospec9ve  case-­‐control  study,  Brisbane  2011  –  Reduced  intuba9on  rates  in  infants  with  bronchioli9s  when  HFNC  introduced  in  the  PICU  –  No  direct  comparison  with  nasal  CPAP  –  Clinical  effects  need  to  be  reassessed  at  60-­‐90min  as  most  improvement  (in  RR  and  HR)  

will  be  seen  in  this  9me  

•  French  study  2014,  compared  HFNC  and  nCPAP  in  bronchioli9s  –  No  difference  in  LOS,  oxygen  requirement,  RR,  HR  

             

Schibler  et  al.  Intensive  Care  Medicine  2011;  DOI  10.1007/s00134-­‐2177-­‐5  Metge  et  al.  Eur  J  Pediatr  (2014)  173;953-­‐958  

•  HFNC  use  in  PICU  transports  •  Pre-­‐HFNC      7%  NIV          49%  IV  •  Post-­‐HFNC  33%  HFNC    2%  NIV      35%  IV  

 Schlapbach  et  al.  Intensive  Care  Medicine  (2014)  40;  592-­‐599  

Physiological  effect  of  HFNC                        

 Pham  et  al.  Pediatric  Pulmonology  2014  

Outside  PICU?  •  Pilot  study  2014,  Mater  Children’s,  Ward  seing  •  61  infants  

–  <12m,  bronchioli9s,  oxygen  requirement  in  ED  –  HFNC  2L/kg/min,  FiO2  to  keep  sats  >94%  

•  Control  group  low-­‐flow  nasal  O2  

•  Responders  iden9fied  within  60min  

•  HFNC  4  9mes  less  likely  to  require  PICU  admission  

     Mayfield  et  al,  Journal  of  Paediatrics  and  Child  Health  50;  (2014)  373-­‐378  

HFNC  Distending  Pressure  •  Pressure  generated  is  inconsistent  and  unpredictable  

•  Affected  by  mouth  opening  and  size  of  leak  at  nares  

•  Reported  pressures  range  from  2-­‐8  cmH2O  

•  Prospec9ve  study  2013  •  21  infants  <6m,  RSV  bronchioli9s  •  Flow  ≥2L/kg/min  achieved  a  clinically  relevant  mean  pharyngeal  pressure  

≥4cmH2O  –  Associated  with  improved  breathing  paNern  and  rapid  unloading  of  respiratory  muscles  

   

 Milesi  et  al.  Intensive  Care  Medicine  2013  39:1088-­‐1094  

•  Study  of  18  preterm  infants  NICU  Melbourne  – Median  age  34/40  – Catheter  9p  pressure  transducer  in  nasopharynx  

   

     Wilkinson  et  al,  Journal  of  Perinatology  (2008)  28,  42–47    

pressure in infants of a given weight and at a given flow rate(see above). There was some variability between infants in themeasured pharyngeal pressure, particularly at higher flow rates.Previous studies have measured oesophageal pressure and

demonstrated increases in proportion to flow rate when flows ofmore than 1 l min!1 were delivered to infants.2,3 However, there issome difference between the pressures obtained during this studyand those previously measured (Table 1). Locke et al.2 measuredchanges in oesophageal pressure from baseline in preterm infants.They showed large increases in oesophageal pressure atcomparatively low flow rates (1 to 2 l min!1), but only in a subsetof infants in whom larger diameter cannulae were used.3 They did

not assess the relationship between infant weight and oesophagealpressure. Sreenan et al.3 titrated the flow rate of nasal cannulae toachieve the same oesophageal pressure as that measured duringnasal CPAP set at 6 cm H2O. In that study the mean change frombaseline in oesophageal pressure was 4.5 cm H2O, and the flow raterequired was estimated as (0.92" 0.68 wt).3

Considerably lower pressures were measured in a more recentstudy in 18 preterm infants, where flow rates of 3 to 5 l min!1 ledto oesophageal pressures of less than 2 cm H2O.

9 Interestingly inthe same study, the oesophageal pressure in infants receiving nasalCPAP set at 6 cm H2O was only 1.8 cm H2O.

9

Figure 1 Measured pharyngeal pressure at variable flow rate in one infant. Compressed recording in one infant (1.398 kg) over 2 min. The rhythmical fluctuations inpharyngeal pressure are related to infant breathing. During this recording flow was increased from 2 to 4 to 6 l min!1.

Figure 2 Mean pharyngeal pressure (with 95% confidence intervals) recorded atflow rates 2 to 8 l min!1.

Figure 3 Pharyngeal pressure vs flow per kg. Linear regression with 95%confidence interval. Predicted pressure (cm water)# 0.7" 1.1$ F (F# flow perweight in l min!1 kg!1).

Pharyngeal pressure with high-flow NCDJ Wilkinson et al

44

Journal of Perinatology

•  Study  of  18  preterm  infants  NICU  Melbourne  – Median  age  34/40  – Catheter  9p  pressure  transducer  in  nasopharynx  

•  Mouth  leak  may  be  less  important  than  nasal  leak  

       Wilkinson  et  al,  Journal  of  Perinatology  (2008)  28,  42–47    

Contraindica9ons  

•  Maxillofacial  trauma  •  Choanal  atresia  or  nasal  obstruc9on  •  Suspected  base  of  skull  fracture  •  Risk  of  air  leak  

•  Noise?  •  Too  sick  for  HFNC?    

Complica9ons  

•  Case  series  published  2013,  all  with  serious  air  leak  – 2m  RSV  bronchioli9s  – 16y  cerebral  palsy,  post-­‐surgical/extuba9on  – 22m  NAI,  post-­‐extuba9on  

•  Use  is  “off  label”  

 Hegde  and  Prodhan,  Pediatrics  2013;131;e939  

Flow  rate  

•  2L/kg/min  •  Children  >20kg    40-­‐50L/min  •  Adult            40-­‐60L/min  

2L/kg/min?    

             

 Schmalisch  et  al.  BMC  Pediatrics  2005,  5:36    

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>8?3!(!1@!:#./)0&$1234&+$15*$65+$,(*)*(51$/2+/5-&-7

the body weight and in the widely used TB-parameterstPTEF/tE and VPTEF/VT.

The discriminative power of TB parameters between bothpatients groups was investigated by using the ROC analy-sis (Fig. 3). In Table 4 the area under the ROC curve(AUC), the optimal cut-off value for each significantly dif-

ferent TB parameter and the resulting sensitivity and spe-cificity were presented. For the best discriminatingparameters tI and RR the area under the curve was not sta-tistically different. This means that there will not be a largedifference in the diagnostic value of tI compared to themore commonly used parameter RR. The sensitivity ofboth parameters using the optimal cutoff value was the

Table 3: Comparison of TB parameters between both patient groups ordered according to the p-value of the ANOVA (Presented are group means ± SD, statistically significant p-values after Bonferroni correction (p < 0.0028) are printed in bold)

Parameter Healthy neonates (n = 48) CLD infants (n = 48) p-value CLD

tI(s) 0.65 ± 0.14 0.45 ± 0.11 p < 0.0001RR (min-1) 39.2 ± 8.6 55.4 ± 14.2 p < 0.0001(PTIF+PTEF)/VT (s-1) 0.27 ± 0.06 0.37 ± 0.09 p < 0.0001tE (s) 0.98 ± 0.24 0.72 ± 0.22 p < 0.0001VT/tI(mL·s-1·kg-1) 8.9 ± 2.2 11.6 ± 2.8 p < 0.0001V'E(mL·min-1·kg-1) 215 ± 51.7 276 ± 76.8 p < 0.0001TIF 50 (L·min-1·kg-1) 0.75 ± 0.21 0.98 ± 0.26 p < 0.0001PTIF (L·min-1·kg-1) 0.83 ± 0.20 1.05 ± 0.28 p < 0.0001PTEF/tPTEF (L·s-2·kg-1) 2.90 ± 1.68 5.25 ± 3.66 p = 0.0001PTEF (L·min-1·kg-1) 0.64 ± 0.19 0.82 ± 0.29 p = 0.0006tptef (s)*) 0.24 ± 0.09 0.18 ± 0.11 p = 0.001TEF75 (L·min-1·kg-1) 0.60 ± 0.20 0.76 ± 0.29 p = 0.003TEF50 (L·min-1·kg-1) 0.52 ± 0.17 0.66 ± 0.25 p = 0.003TEF25 (L·min-1·kg-1) 0.38 ± 0.11 0.46 ± 0.16 p = 0.006Vptef (mL/kg)*) 1.68 ± 0.52 1.37 ± 0.44 p = 0.006VT (mL·kg-1) 5.57 ± 1.06 5.15 ± 1.35 p = 0.09VPTEF/VT(%)*) 29.4 ± 6.6% 27.2 ± 6.1% p = 0.13tPTEF/tE (%)*) 25.8 ± 9.7% 23.2 ± 7.8% p = 0.20

*)Loops with flow limitations, grunting or other deformations were excluded from the evaluation (6 controls, 8 CLD infants)Abbreviations: tI,E-inspiratory, expiratory time, RR-respiratory rate, PTIF, PTEF-peak tidal inspiratory and expiratory flow, VT-tidal volume, TIF 50-tidal inspiratory flow when 50% of VT is inspired, TEF 75, TEF 50, TEF 25-expiratory flow when 75%, 50% and 25% of tidal volume remains in the lung, V'E-minute ventilation, tPTEF,VPTEF-time and volume to peak tidal expiratory flow

Table 4: ROC analysis of commonly used TB parameters between CLD infants and healthy controls. If the 95% confidence interval (95% CI) of the area under the normalized ROC curve (AUC) include the 0.5 value (no discrimination) than there is no evidence that the TB parameters has the ability to distinguish between the two groups

Parameter AUC with 95%CI Optimal cut-off point Sensitivity Specificity

tI 0.879 (0.808 to 0.950) 0.48 s 70.8% 91.7%RR 0.842 (0.754 to 0.909) 49.1 min-1 70.8% 89.6%VT/tI 0.809 (0.721 to 0.896) 11.1 mL·s-1·kg-1 58.3% 89.6%V'E 0.776 (0.682 to 0.869) 250 mL·min-1·kg-1 64.6% 85.4%PTIF 0.747 (0.649 to 0.845) 0.95 L·min-1·kg-1 62.5% 79.2%PTEF/tPTEF 0.688 (0.582 to 0.794) 4.57 L·s-2·kg-1 52.8% 87.5%PTEF 0.673 (0.566 to 0.780) 0.79 L·min-1·kg-1 45.8% 83.3%TEF25 0.653 (0.544 to 0.762) 0.67 L·min-1·kg-1 43.7% 87.5%VT 0.610 (0.497 to 0.722) - - -VPTEF/VT 0.565 (0.450 – 0.620) - - -tPTEF/tE (%) .552 (0.437 – 0.670) - - -

(Abbreviation see Table 3)

•  2L/kg/min  ensures  flow  higher  than  peak  inspiratory  flow  rate  (SSH)  

•  Alterna9ves:  – 2L/kg/min  up  to  10kg,  plus  0.5L/kg/min  for  each  kg  above  10kg  to  max  50L/min  (RCH)  

– Flow  (L/min)  =  maintenance  fluid  rate  (ml/hr)  /  2  

Op9flow  Junior  

Op9flow  Junior  

Op9flow  Junior  

Op9flow  Junior  

1-­‐4kg  

3-­‐10kg  

10-­‐12.5kg  

Nasal  Prong  sizing  

•  Op9flow  Junior  ≤12.5kg  •  Op9flow  >12.5kg  

Adult  Op9flow  

Prescribing

•  S9pulate  FiO2  and  Flow  Rate  

 

Weaning  (Acute  Paeds)  

•  Titrate  FiO2,  weaning  to  40%  – Then  trial  Low  Flow  oxygen  at  1-­‐2L/min  (wall,  not  mixer)  

 

•  Don’t  wean  flow  ie.  ‘High’  or  ‘Low’  – No  need  to  change  cannula  (Op9flow  Junior)  

Nebulising  via  HFNC  

•  No  paediatric  data  of  effec9veness  

•  In  vitro  study  nebulised  albuterol  via  Vapotherm:  –  3  sizes  cannulae  

•  Adult    5-­‐40L/min  •  Pediatric  3-­‐20L/min  •  Infant    3-­‐8L/min  

–  Inadequate  delivery  to  achieve  a  clinical  response  •  0-­‐2.5%  of  nominal  dose  

–  Delivery  inversely  propor9onal  to  flow  rate  –  Delivery  propor9onal  to  cannula  size  

 Perry  et  al.  Pediatric  CriEcal  Care  Medicine  14(5);e250-­‐e256,  June  2013  

•  Limited  adult  data  suggest  pulmonary  deposi9on  of  aerosol  through  High  Flow  circuit  similar  to  level  obtained  by  direct  inhala9on  from  nebuliser  

               

 Dhand  R.  Journal  of  Aerosol  Medicine  and  Pulmonary  Drug  Delivery  2012;  25(2):  63-­‐78  

 

Ques9ons?