Clinical Research

High-flow oxygen therapy in acute respiratory failure by Roca O, Riera J, Torres F, & Masclans JR. (Respir Care. 2010: 55(4), 408-13)

Roca and colleagues show evaluated high flow oxygen therapy between a high f low nasal cannula and a oxygen mask in a crossover study design (each patient evaluated both methods. With a sample of twenty adult patients (mean age of 57 years) the high flow cannula resulted in significantly improved in patient tolerability indices including dyspnea (p = 0.001) dry mouth (p < 0.001) and comfort (p < 0.001). Physiologically, the high flow cannula increased arterial oxygen pressure (p < 0.01) and reduced respiratory rate (p < 0.001) without changing PaCO2, compared to the face mask delivery of oxygen. Note: accompanying editorial by Jeffrey Anderson on page 485 of the same issue. The editorial that accompanies this paper provides additional discussion as to the multiple mechanisms of action for high flow nasal cannula.

High Flow Nasal Cannula and Extubation Success in the Premature Infant: a Comparison of Two Modalities by Miller SM, & Dowd SA. J. Perinatology (2010) 30: 805-808.

Miller and Dowd compared the efficacy of the Vapotherm system compared to the Fisher and Paykel system with regard to extubation success. Importantly, this was a pilot study of 40 patients and was therefore not powered to make any conclusions. The authors indicate from the variance data that the study would need 300 patients to make a statistical determination. Despite the lack of power, they showed that the extubation failure rate at 72 hrs was 18% for Fisher & Paykel, while only 9% for Vapotherm. Extubation failure rates for the period up to 7 days was 30% for Fisher & Paykel, and only 27% for Vapotherm. Note that the authors also did a price comparison, and that these data were based on the 2000i unit that was in use at the time. The price comparison data is more favorable for Vapotherm with the newer generation components.

A Preliminary Randomized Controlled Trial to Assess Effectiveness of Nasal High-Flow Oxygen in Intensive Care Patients by Parke, RL, McGuinness, SP & Eccleston, ML. Respir Care 2011; 56(3):265–270.

Parke and colleagues evaluated high flow oxygen therapy between a high flow nasal cannula and a high flow oxygen mask in patients with mild hypoxemic respiratory failure. The high flow cannula resulted in significantly greater therapeutic success than a high flow mask (p = 0.006). Additionally, fewer patients progressed to NIV (10% with cannula versus 30% with mask; p = 0.10), and the nasal cannula group had fewer desaturations (P = 0.009). Seventy-one percent face mask group had at least one desaturation, compared to 42% in the nasal cannula group (P = 0.16). This paper demonstrates the impact on oxygen and CO2 associated with purging the anatomical dead space as opposed to a mask therapy that does not purge the nasopharynx.

Yoder, BA, Stoddard, RA, Li, M, King, J, Dirnberger, DR & Abbasi, S. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics 2013: 131, e1482-90.

Yoder and colleagues conducted a large, multi-center, randomized controlled trial to compare the safety and efficacy of high flow nasal cannula (HFNC) to nasal continuous positive airway pressure (nCPAP) in 432 infants ranging from 28 to 42 wks gestation. The primary outcome in the study was intubation within 72 hrs of applied HFNC / nCPAP, and secondary outcomes included any need for subsequent intubation, adverse events and time on therapy.

The authors reported no differences in intubation (at 72 hrs, p = 0.344; all intubation, p = 0.252). The rate of adverse events, including air leak, was similar between groups in all cases except for nasal trauma, where compared to nCPAP, HFNC infants had reduced nasal trauma (p < 0.05). HFNC infants did remain on non-invasive support therapy for longer than nCPAP infants (median = 4 vs 2 days; p < 0.01), but the authors discuss that this may have been related to an increased preference for HFNC by caregivers. The authors concluded that HFNC appears to have similar efficacy and safety to nCPAP for both post-extubation as well as initial non-invasive support.

This study differs from the two other recent randomized, controlled trials of HFNC vs nCPAP (Collins 2013 and Manley 2013) in that the infants studied here were slightly larger in terms of both weight and gestational age, and the study used three device platforms with comparatively conservative flow rates. However, all three studies agree that HFNC is equivalent to nCPAP in the neonatal populations studied, and that HFNC has significantly better outcomes with respect to decreased nasal trauma. The infants on Vapotherm in the Yoder study did trend toward having better outcomes with respect to less need for intubation, however the study was not powered for this assessment.

A Randomized Controlled Trial to Compare Heated Humidified High-Flow Nasal Cannula with Nasal Continuous Positive Airway Pressure Postextubation in Premature Infants by Collins CL, Holberton JR, Barfield C & Davis PG. J. Pediatr. 2013 162(5): 949-54.

Collins and colleagues compared the efficacy of Vapotherm HFT to CPAP therapy postextubation in 132 infants less than 32 weeks gestation. If extubated to CPAP infants were started at 7-8 cmH2O, if extubated to HFT flow rate was started at 8 L/min. There were no statistical differences in the rate of extubation failure or bronchopulmonary dysplasia between groups or in any gestational age stratification; Although BPD rates were not different, there was a trend for shorter duration of supplemental oxygen use in the HFT infants (p < 0.06). The absolute percentage of infants meeting the criteria for failed extuabtion was less for Vapotherm HFT (22%) than for CPAP (34%). Additionally, HFT resulted in significantly less nasal trauma (p < 0.001), and in fact 12 (20%) of the infants assigned to CPAP were rescued with HFT because of nasal trauma.

This prospective randomized controlled trial of Vapotherm HFT vs CPAP demonstrates that HFT is more effective than CPAP in preterm infants, both greater and less than 28 weeks gestation. This conclusion is based on the trend for less extubation failure, coupled with the significant reduction in costly iatrogenic complications associated with the CPAP nasal interface.

Manley, BJ, Owen, LS, Doyle, LW, Andersen, CC, Cartwright, DW, Pritchard, MA, Donath, SM & Davis, PG. High-flow nasal cannulae in very preterm infants after extubation. N Engl J MEd 2013: 369, 1425-33.

Manley and colleagues evaluated the safety and efficacy of HFNC vs CPAP in preterm infants <32 weeks gestation using a multicenter, non-inferiority study design (n = 303). The primary outcome was treatment failure (re-intubation) within 7 days, and the test conditions were extubation to CPAP starting at 7 cmH2O (either mechanical or bubble) or HFNC starting at 5 to 6 L/min. The data show that 26% of the CPAP babies failed and 34% of the HFNC babies failed, which was determined to be non-inferior although close to the margin of non-inferiority. However, the incidence of nasal trauma was significantly lower for HFNC compared to CPAP (p < 0.01). There were no differences in any other complications; the primary reason for failure in both groups was apnea.

The authors stated that the aim with HFNC was to occlude approximately ½ of the nares, but actual dimensions are not reported and it is questionable as to whether this was possible with the device in use. The flow limits were set based on prong size, given the systems inherent circuit pressure limits, and thus needed to use larger than “premature” prongs to prescribe above 6 L/min. Thus, some of these premature infants may have been fitted with the larger “infant” or “pediatric” prongs.

These data differ from other recent data on HFNC, potentially due to the differences in the delivered therapy, where Dr. Collins and colleagues showed with the Vapotherm device that HFNC had a lower absolute failure percentage compared to CPAP. Also note that in the Collins paper, some infants were removed from CPAP and thrived on HFNC, while this was not an option in the Manley trial.

Kugelman, A, Riskin, A, Said, W, Shoris, I, Mor, F & Bader, D. A Randomized Pilot Study Comparing Heated Humidified High-Flow Nasal Cannulae with NIPPV for RDS. Pediatr Pulmonol 2014: online ahead of press.

Dr. Kugelman and colleagues evaluated the efficacy of Vapotherm HFT against nasal intermittent positive pressure ventilation (NIPPV) as a primary support modality (not following extubation) in preterm infants. They hypothesized that both modalities give a comparable level of support, and studied infants <35 weeks gestation but >1,000g. Vapotherm therapy was administered with flows up to 5 L/min and using Vapotherm nasal prongs (OD 1.5mm or 1.9mm) such that the prongs were no larger than ½ the diameter of the nares. NIPPV is a bi-level pressure support provided to infants via nasal interface, similar to non-invasive ventilation in adults provided by way of a mask. Studies indicate that NIPPV is a higher level of support for infants compared to nasal continuous positive airway pressure (CPAP).

The primary outcome for this trial was the need for intubation (endotracheal ventilation), with secondary outcomes related to clinical features during therapy and relevant clinical outcomes. Among 76 infants with comparable characteristics, 38 in each group, the need for endotracheal intubation was not different (HFT = 29% vs. NIPPV = 34%, p = 0.80). Among infants who were intubated, arterial CO2 tension was higher (64.0 vs. 48.9 mmHg, P = 0.01), and arterial pH was lower (7.21 vs. 7.28, P = 0.04) prior to mechanical ventilation on NIPPV versus HFT, demonstrating a more pronounced ventilation effect for HFT. There was no difference in clinical outcomes including air leak, nasal trauma and development of chronic lung disease. The time to end nasal support was longer for HFT compared to NIPPV (2 vs 4 days; p = 0.006), but with no difference in length of stay.

The authors conclude that HFT may be as effective as NIPPV in preventing endotracheal ventilation, and discuss that HFT and NIPPV have different physiological mechanisms. The authors also discuss that the difference in length of time on nasal support could be related to the perception of the therapy. They state, “Infants on NIPPV are perceived to be “ventilated” and may be weaned more aggressively to avoid nasal trauma and discomfort (a possible bias for the different length of NRS).”

Work of breathing using high-flow nasal cannula in preterm infants by Saslow, JG, Aghai, ZH, Nakhla, TA, Lawrysh, R, Stahl, GE, & Pyon, KH (Journal of Perinatol 2006: 26, 476-80).

Saslow et al evaluate the use of high flow therapy (HFT; Vapotherm 2000i) with respect to breathing effort and airway pressure development. The most intriguing findings in this paper are that HFT up to 5 l/min does not produce more airway pressure than CPAP set to 6 cmH2O. In fact, these authors demonstrate that at 5 l/min airway pressure is significantly less that with a CPAP of 6. Although complex, this finding may have an explanation based on the concepts of gas flow properties where greater flow currents in the nasopharyngeal cavity may actually unload pressure forces to the airways.

Observ. Study of Humidified High-Flow Nasal Cannula Compared with Nasal Cont. Pos. Airway Pressure by Lampland, AL, MD, Plumm, B, Meyers, PA, Worwa, CT & Mammel, MC. (Pediatrics. 2009: 154, 177-182).

Despite the negative conclusion that is based on the false belief that pressure needs to be more substantial, the data show that the patients are quite stable on High Flow Therapy despite lower pressure.

Inadvertent Administration of Positive End-Distending Pressure During Nasal Cannula Flow by Locke, RG, Wolfson, MR, Shaffer, TH, Rubenstein, SD & Greenspan, JS, Pediatrics 1993: 91(1), 135-8.

Locke and colleagues evaluated the use of conventional low flow oxygen cannula on development of airway distending pressure and influence on breathing pattern in neonates. These authors demonstrated that when they used a smaller of two cannulae (2 mm outer diameter) no distending pressure developed and breathing pattern was unaltered, but when they used a larger cannula (3 mm outer diameter) pressure developed and thoracoabdominal synchrony improved proportional to flow. These data have been important in identifying the influence of cannula fit to the development of pressure with nasal cannula use.

High-Flow Oxygen Therapy: Pressure Analysis in a Pediatric Airway Model by Urbano, H; Castillo, J; Lopez-Herce, J; Gallardo, J; Solana, M; Carillo, A. . Resp Care 2012: 57(5), 721-726.

Urbano and colleagues used a pediatric manikin bench model to evaluate HFT against high flow nasal mask or oronasal interface; this manikin model is a much better portrayal if actual airway geometry compared to other bench studies on HFT. Pressures were measured in the airway as well as the device circuit while delivering flows up to 20 L/min. The data confirm that the nasal cannula does not generate significant, or in this case measureable, airway pressured when applied without holding the mouth closed to block up oral pathway for gas flow. However, compared to the mask applications, circuit pressure is increased 30 to 100 fold when the same high flows are administered through the cannula. Thus, although a HFT device must be able to tolerate the high pressures associated with nasal cannula delivery, HFT does not create a marked CPAP effect. In this regard, the authors concluded that the effects seen with HFT must be related to other mechanisms.

High Flow Through a Nasal Cannula and CPAP Effect in a Simulated Infant Model by TA Volsko, K Fedor, J Amadei, & RL Chatburn. Resp Care 2011: 56(12), 1893-1900

Volsko and colleagues used a bench model of the nasopharynx attached to a lung simulator to test the hypothesis that airway pressures generated by HFNC at flows between 2-6Lpm are minimal and clinically unimportant. These authors utilized a lung simulator and attached a capped 22mm adaptor which had holes drilled, using a standardized CPAP sizing template, to simulate the nares of a patient with a closed mouth. The range of expiratory pressures generated by all cannula sizes were 0.04 cmH20 to 1.3 cmH20. The data confirmed that insignificant pressures were generated at these flow rates in a correctly sized cannula, not occluding 50% of the nares.

Effects of Flow on Airway Pressure During Nasal High-Flow Oxygen Therapy by Parke, RL, Eccleston, ML & McGuinness SP. Respir Care 2011; 56(8): 1151-1155.

Parke and colleagues evaluated pressure build in the nasopharynx using the Fisher & Paykel nasal high flow system set at 30, 40 and 50 LPM of flow. These authors found average pressures to be dependent on flow rate and whether the mouth was open or closed. Average pharyngeal pressures were between 1.9 and 3.3 cmH2O with the mouth closed and between 1.0 and 1.7 cmH2O with the mouth open. These data agree with the other published reports that mild pressure does develop, and although it is considered to be a mechanisms of action for HFT, is not of great enough magnitude to be concerning.

Children with respiratory distress treated with high-flow nasal cannula by T Spentzas, N Minarik, A Patters, B Vinson, G Stidham (Journal of Intensive Care Med – Vol 24, 5 Sep/Oct 2009 Pg 323-328).

Spentzas and colleagues demonstrated a improvement in comfort and oxygenation, while reducing ARDS score in pediatric patients receiving HFT. The authors show that mild pressure develops in the nasopharynx (4 +/- 2 cmH2O) and they propose that this may be a mechanism of action for the efficacy of the therapy. This hypothesis is supported with chest x-rays that showed improved aeration or no change in 40 or the 46 patients.

Y-Piece Temperature and Humidification During Mechanical Ventilation by Solomita M, Daroowalla F, LeBlanc DS, & Smaldone GC (Respiratory Care. 2009 54(4): 480-6).

Williams and colleagues describe the shortcomings of heated wire circuit technologies for maintaining humidification during delivery of conditioned breathing gases. Although the emphasis behind this bench protocol is with regard to mechanical ventilation, the study demonstrates that heated wire circuit systems do not accurately maintain humidity of the conditioned gases. The study data show that while heated wire circuits can affect the temperature of the gas at the patient end, these systems allow for substantial water vapor loss within the patient circuit.

What is optimal humidity? by Rankin N (Respir Care Clin N Am. 1998 4(2): 321-8)

Dr. Rankin reviews the factors that determine optimal humidification for respiratory gases. This paper examines the relationship between water content of the inspired gas and mucosal function to determine that the optimal conditioning for inspired gas is 37ºC and 100% relative humidity.

The clinical utility of long-term humidification therapy in chronic airway disease by Rea, H, McAuley, S, Jayaram, L, Garrett, J, (Respiratory Medicine 2010: 104, 525-33)

Rea and colleagues investigated the long-term use of heated-humidified, high flow nasal cannula (HFNC) for humidification therapy in 108 COPD patients randomized to receive their typical care or HFNC for 12 months. Patients on HFNC had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045), increased time to first exacerbation (median 52 versus 27 days; p = 0.0495), and reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p = 0.067) compared with typical care. Additionally, patients on HFNC had improvement in quality of life scores and lung function compared with typical care.

Resuscitation of Preterm Neonates by Using Room Air or 100% Oxygyen by Wang, CL; Anderson, C; Leone, TA; Wade, R; Govindaswami, B & Finer, NN. (Pediatrics. 2008 (121): 1083-1089)

Wang et al identify that the ideal oxygen percentage for use in resuscitation in newborns is between room air (21%) and 100%. Therefore there is a need for oxygen blending in the delivery room.

Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa by Williams R, Rankin N, Smith T, Galler D, & Seakins P (Critical Care Medicine. 1996 24(11):19)

Williams and colleagues review the impact of respiratory gas temperature and humidification on airway mucosal cell function. This report reviews peer-reviewed manuscripts and other valuable information sources to construct a model for optimal gas conditioning and show the effects, both acute and chronic of inadequate gas conditioning. This paper emphasizes the importance of precise respiratory gas warming and absolute humidification to protect airway cell function during respiratory support efforts.

Domicilliary humidification improves lung mucocilliary clearance in patients with bronchiectasis by Hasani, A, Chron Respir Dis 2008: 5, 81-6.

Hasani and colleagues evaluated the impact of delivering humidified respiratory gas by nasal cannula on mucocilliary clearance by assessing retention of labeled tracer particles. They demonstrate that just three hours a day of humidification therapy in patients with bronchiectasis significantly improved clearance. The authors speculate that humidified respiratory gas treatment can be useful in patients with respiratory diseases that hinder the mucocilliary transport process.

Comparing Two Methods of High Flow Delivery by Nasal Cannula Following Extubation by DD Woodhead (Journal of Perinatol 2006: 26,481-5)

Woodhead et al performed a crossover design study showing that when using optimal warming and humidification for nasal gas flows above 1 l/min (i.e., Vapotherm technology), nasal mucosa appeared more normal (p < 0.001) and patients had less pronounced indices of labored respiratory effort (p < 0.05). Additionally, some patients failed on conventional high flow cannula therapy and needed to be rescued to Vapotherm or reintubation; no infants failed on Vapotherm. These findings support Vapotherm’s proposed mechanisms that optimal warming and humidification not only preserves nasal tissue architecture but also have a positive impact on pulmonary mechanics, thus enhancing ease of breathing.

Changes in airway resistance induced by nasal inhalation cold dry, dry, or moist air in normal individuals,Fontanari P, Burnet H, Zattara-Hartmann MC, Jammes Y Journal of Applied Physiology 96,81:1739.

Fontanari et al evaluated the impact of gas conditioning on airway resistance in normal participants through the impact on the receptors in the nasal mucosa. This paper shows breathing warm, humid gas versus cool, dry gas results in a significant improvement in airway resistance. Furthermore, these authors demonstrate that the resistance change is due to stimulation of receptors in the nose because this response is eliminated when mouth breathing or when receptors in the nose are blocked. The results of this study support the proposition that HFT via nasal cannula should be done with optimal temperature and humidification to reduce resistive work of breathing.

An Evaluation of 2 New Devices for Nasal High-Flow Gas Therapy by Waugh JB & Granger WM (Respiratory Care. 2004 49(8): 902-6).

Waugh and Granger describe the ability of the Vapotherm technology to accurately condition breathing gases. This report is an independent bench analysis that demonstrates Vapotherm technology delivers gas to the patient interface that is saturated with water vapor and at precisely controlled temperature at flows up to 40 lpm.

Airway Responsiveness to Low Inspired Gas Temperature in Preterm Neonates by Greenspan, JJ, Wolfson, MR & Shaffer, TH. (Journal of Pediatrics. 1991 118(3):443-445.)

Greenspan et al show that without warming and humidification of breathing gas, there is a statistically significant and clinically relevant adverse effect on dynamic compliance, airway conductance and elastic work of breathing. The implication is that better warming and humidification (to body temperature and saturated with water vapor) of respiratory gases alone can have a substantial impact on respiratory mechanics.

Mechanics and energetics of breathing helium in infants with bronchopulmonary dysplasia. Wolfson MR, Bhutani VK, Shaffer TH, Bowen FW. J Pediatr. 1984;104:752–757.

Wolfson and colleagues investigated the precise changes in airway mechanics associated with heliox breathing in neonates. They confirmed that in spontaneous breathing infants there was a marked reduction in pulmonary resistance associated with heliox breathing that resulted in a significant reduction in resistive work of breathing with no changes in minute ventilation. These authors discus how this reduced efforts and energy expenditure reduces the risk of respiratory muscle fatigue, and subsequently the need for mechanical ventilation.

Heliox attenuates lung inflammation and structural alterations in acute lung injury. Nawab US, Touch SM, Irwin-Sherman T, Blackson TJ, Greenspan JS, Zhu G, Shaffer TH, Wolfson MR. Pediatr Pulmonol.20.

Nawab and colleagues investigated the use of helium-oxygen gas (heliox) as a ventilation medium on lung inflammation indices. These authors showed a dramatic reduction in pulmonary pro-inflammatory mediators when using heliox versus a nitrogen-oxygen mixture, resulting in an improvement in lung morphology. These data indicate that heliox improved the distribution of inspired gas, thereby recruiting more gas exchange units, improving gas exchange efficiency, reducing ventilatory and oxygen requirements, and thereby attenuating lung inflammation.

Growth and Development in a Heliox Incubator Environment: A Long-Term Safety Study. Singhaus CJ, Utidjian LH, Akins RE, Miller TL, Shaffer TH, Touch SM. Neonatology. 2007;91(1):28-35.

Singhaus and colleagues investigated the safety and efficacy associated with growth and development while breathing heliox. Four-day-old rabbit pups were randomized to be raised in air or heliox (21% O2; 79% He) for two weeks. All pups thrived in both environments, achieving expected evelopmental milestones. There were no physiologically significant group differences in weight, growth factors, tissue weight, blood chemistry or muscle enzyme activity.

Heated humidified high-flow nasal cannula: use and a neonatal early extubation protocol by Holleman-Duray, Loyola University, D, Kaupie, D, & Weiss, MG.(Journal of Perinatol 2007: 27, 776-81).

Holleman-Duray et al describe how the use of high flow therapy (HFT; Vapotherm 2000i) support infants post extubation. The patient data, compared to historical control where CPAP was used prior to their adoption of HFT, resulted in extubation from higher ventilator rates (p < 0.01), fewer days on ventilators (p < 0.05). These data support Vapotherms proposed mechanisms of action for HFT with respect to CO2 elimination and improved alveolar oxygen concentrations. In addition, this study showed that incidence of ventilator-associated pneumonia was reduced (p < 0.05), and infants were discharged with greater weights (p < 0.05) despite similar lengths of stay and time to full feeds. The decrease in pneumonia is likely associated with reduction in ventilator time, while the greater discharge weights may be indicative of a reduced respiratory work effort (caloric consumption).

Use of a high-flow oxygen delivery system in a critically ill patient with dementia by Calvano, TP, Sill, JM, Kemp, KR, & Chung, KK. (Respiratory Care 2008: 53(12), 1739-43).

Calvano et al describe how they used High Flow Therapy (HFT; Vapotherm 2000i) to comfort and provide high oxygen fractions to an end-stage multi-lobar pneumonia patient who would not tolerate a mask to receive her prescribed non-invasive ventilation (this patient could not be intubated as per a DNR order). The paper describes how HFT improved not only oxygenation, but also work of breathing, comfort and nutrition. To view paper click here. Use of high flow nasal cannula on a pediatric burn patient with inhalation injury and post-extubation stridor by Byerly FL, Haithcock JA, Buchanan IB, Short KA, Cairns BA, Burns (2006) 32: 121-5 Byerly et al demonstrate and discuss the impact of HFT on a pediatric burn patient in respiratory distress with respect to the mechanisms of action associated with humidification and potentially a mild distending pressure.

The effects of high-flow vs low-flow oxygen on exercise in advanced obstructive airways disease by Chatila, W, Nugent, T, Vance, G, Gaughan, J, & Criner, GJ (CHEST 2004: 126, 1108-15).

Chatila et al showed that adult patients with airflow restriction were able to exercise longer (p < 0.05) on high flow oxygen therapy (HFT; 20 l/min) than on conventional low flow oxygen (< 6 l/min) despite matched FIO2. In addition to the overall longer performance, during HFT patients demonstrated lower dyspnea scores (p < 0.03), improved breathing patterns (RR, RR/Vt; p < 0.05), and lower arterial pressure (p < 0.05) and better oxygenation (p < 0.001). This study supports Vapotherm’s proposed mechanisms of action with respect to improving both oxygen and CO2 composition of alveolar gas by way of dead space elimination. The patients oxygenation indices were reported as significantly improved, plus the improvement in exercise time while demonstrating a lower breathing rate would indicate an effect on CO2 (CO2 was not different despite differences in work). Furthermore, the patients’ Ti/Ttotal was lower (p < 0.05) on HFT which may be indicative of reduced airway resistance.

Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients,Nakos G,Lachana A,Prekates A,Pneumatikos J, Guillaume M, Pappas K, & Tsagaris H Intensive Care Med, 95 21:904

Nakos et al shows that flushing anatomical dead space of the upper airway in humans during spontaneous breathing improves respiratory work indices while reducing blood carbon dioxide.

Research in high flow therapy: Mechanisms of action by Dysart, K, Miller, TL, Wolfson, MR, & Shaffer, TH (Respiratory Medicine. 2009).

Dysart et al summarizes the mechanisms of action behind the efficacy of HFT via nasal cannula. The mechanisms discussed include washout of nasopharyngeal dead space, reduction of inspiratory resistance in the nasopharynx, improvement in airway and lung mechanics, mild distending pressure and a reduction in energy expenditure associated with inspiratory gas conditioning. To view paper click here.

Effect of low flow and high flow oxygen delivery on exercise tolerance and sensation of dyspnea. A study comparing the transtracheal catheter and nasal prongs by Dewan NA & Bell CW (Chest. 1994 105:1).

Dewan and Bell describe the effectiveness of high flow nasal cannula in maintaining oxygenation and work tolerance. This paper shows that high flow oxygen delivery by nasal cannula is more effective at maintaining blood oxygen saturation and work performance than low flow oxygen cannula. Furthermore, the data indicate that high flow nasal cannula therapy is similar in efficacy to transtracheal catheters, which are intended to attenuate the effects of anatomical dead space on breathing efficiency. This paper therefore supports the proposed mechanism of action for high flow nasal cannula related to dead space washout.

Impact on Oxygenation and Ventilation in an Acute Lung Injury Model by Frizzola, M, Miller, TL, Rodriguez, ME, Zhu, Y, Rojas, J, Hesek, A, Stump, A, Shaffer, TH, & Dysart, K. Pediatr Pulmonol. 2010.

Frizzola and colleagues demonstrate that by way of purging anatomical dead space in a piglet model, High Flow Therapy (HFT) results in a ventilation effect that is not matched by CPAP therapy. The study shows that the impact HFT has on blood gas parameters is a function of flow, and not inadvertent pressure development. Moreover, these data demonstrate that cannulae which do not obstruct the nares, as compared to more obstructive cannulae, produce the optimal effect on blood O2 and CO2 at significantly lower flow rates and subsequently lower resulting end-distending pressure development. In simpler terms, the more of the nares that are exposed the greater the degree of flush. Therefore, this validation research for the mechanisms behind the efficacy of HFT provides evidence that HFT should be applied with minimally occlusive nasal prongs, and flow parameters set to optimize anatomical flush, and not administered in a way to promote pressure development.

Numa, AH., & Newth, CJL. Anatomic dead space in infants and children. J. Appl. Physiol. 80(5): 1485-89, 1996.

Numa and Newth demonstrate that extrathoracic dead space volumes in infants are typically 2.5 to 3 fold greater, expressed as volume per unit of body weight, compared to adults. A review of literature shows that adult extrathoracic dead space volume (i.e., anatomic reservoir) is on average 0.8 ml/kg of body weight. In the neonatal / pediatric population, extrathoracic dead space volumes show a significant, inverse relationship with age. Herein, neonates have an extrathoracic dead space volume of around 3 ml/kg, which decreases with age to below 1.5 ml/kg after 2 years of age. Only by six years of age did some of the children studies have an extrathoracic dead space volume similar in relative size to adults.

Using a high-flow respiratory system (Vapotherm®) within a high dependency setting by Price, A, Plowright, C, Makowski, A & Misztal, B, Nurs Crit Care 2008: 13(6), 298-304.

Price and colleagues generically discuss use and tolerance of Vapotherm HFT on various patient populations as a means of delivering humidified supplemental breathing gases. The authors describe some of the perceived mechanisms of action including mild distending pressure and the impact of humidification on mobilizing secretions. Additionally, the authors analyzed data from 72 patients and showed that use of HFT reduced respiratory rate and increased arterial oxygen saturation, while a patient survey revealed that 90% of the patients were satisfied with the therapy.

Nasal and oral flow-volume loops in normal subjects and patients with obstructive sleep apnea by Shepard JW & Burger CD (Am Rev Respir Dis. 1990 142: 1288-93).

Shepard and Burger evaluated the variations in nasopharyngeal flow resistance between inspiratory and expiratory phases of the breathing cycle. This study demonstrates that in normal subjects, inspiratory resistance through the nasopharynx is greater than expiratory resistance as a result of the distensibility of nasopharyngeal tissues. This information supports the concept that HFT via nasal cannula can reduce inspiratory work of breathing by reducing resistance normally associated with the encroachment of nasal tissues secondary to a negative nasopharyngeal pressure.