The application of NCPAP in the NICU is expanding in the United States with the potential to be utilized on an even larger percentage of neonates than in the past.
Continuous positive airway pressure (CPAP) was introduced as a treatment for neonatal respiratory distress syndrome (RDS) in the early 1970s.1 Nasal CPAP refers to spontaneous ventilation through the nose with positive pressure applied throughout the respiratory cycle. A continuous pressure applied to the airways restores functional residual capacity (FRC) and reverses the hypoxemia caused by ventilation-perfusion mismatching by recruiting collapsed alveoli. When positive airway pressure is kept constant throughout the respiratory cycle, FRC is more effectively restored.2 An increase in FRC results in an increase in lung compliance and a decrease in the work of breathing. Nasal CPAP appears to stabilize the chest wall and upper airway and to reduce apneas.3 Early application of CPAP might also preserve surfactant.4 A premature neonate can have difficulty maintaining FRC and upper-airway patency. The chest wall is soft and flexible, and it may not be capable of holding open the lung. The neonate also has a reduced potential for lung expansion due to horizontal ribs and a flatter diaphragm. Premature infants may have inadequate surfactant, predisposing their lungs to collapse, and they also lack the fat layer in the neck that helps to stabilize the airways of older infants.5
Surfactant therapy and antenatal steroids enhance absolute lung volume in the neonate. Before these therapies were widely available in the United States, the mortality rate for RDS in infants of very low birth weight (VLBW), defined as less than 1.5 kg, had decreased from 80% to 100% in the 1960s to 20% by the1980s.6 An additional 50% drop in mortality has occurred with the use of antenatal steroids and postnatal surfactant, resulting in a survival rate today of approximately 90%.6 One of the primary goals today in neonatal medicine is to decrease pulmonary injury and avoid chronic lung disease (CLD) while preserving brain function. Some of the factors contributing to CLD are oxygen therapy and the damage caused by mechanical ventilation. In some countries, and within individual neonatal intensive care units (NICUs) where nasal CPAP has been used as an alternative to mechanical ventilation or neonates have been rapidly weaned to nasal CPAP, a lower incidence of CLD has been reported.6
A group generates recommendations for practice based on analysis of a thorough review of the literature. It concluded that nasal CPAP is effective in preventing failure of extubation and reducing oxygen use at 28 days of life in preterm infants following a period of endotracheal intubation and [intermittent positive-pressure ventilation (IPPV)].3 The studies that evaluated nasopharyngeal CPAP showed more adverse events (apnea, respiratory acidosis, and compromised oxygenation) than for short prongs and suggested a clear advantage for short-prong delivery, but nasopharyngeal CPAP still improved outcomes at 28 days. The recommending group also evaluated the use of endotracheal-tube CPAP prior to the removal of the tube versus direct extubation and recommended that preterm infants no longer requiring endotracheal intubation and IPPV should be directly extubated without a trial of [endotracheal-tube] CPAP.7
Many different devices have been developed and used to deliver CPAP to the neonate, including face masks, head boxes with seals, negative-pressure boxes, and endotracheal tubes. Currently, nasal cannulae, nasal prongs in conjunction with a conventional continuous-flow mechanical ventilator, and new variable-flow nasal CPAP generators are the primary devices being used in NICUs in the United States. All these devices have advantages, disadvantages, and attendant difficulties. Some of the problems of delivering nasal CPAP with these devices include difficulty in obtaining a seal and maintaining pressure, the fact that tubes can become blocked and prevent pressure from being delivered to the lungs, nasal trauma and breakdown, and increased work of breathing due to the design of the device.
Nasal cannulae are primarily used to deliver supplemental oxygen. The advantages of using nasal cannulae as nasal CPAP devices are that they are low in cost, easy to set up, readily available, and well tolerated by neonates. Unlike conventional nasal CPAP devices, however, nasal cannulae do not have a mechanism to monitor or regulate the generation of excessive positive airway pressure. The American Association for Respiratory Care,8 in its clinical practice guidelines, recommends continuous proximal airway pressure monitoring. In a study by Locke et al9 investigating the effects on neonatal pulmonary mechanics of high-flow nasal cannulae (HFNC) having flows of 0.5 to 2 L/min, the investigators quantified the pressure created by this device. In this study, 13 preterm infants with a postconception age of 30±4 weeks were studied at a postnatal age of 28±19 days and a weight of 1.59 kg±667 g. No distending pressure was generated with the 0.2-cm (outer diameter) infant nasal cannula with flow rates of up to 2 L/min, whereas the 0.3-cm (outer diameter) pediatric cannula generated a mean pressure of 9.8 cm H2O at a flow rate of 2 L/min. There was no correlation between diameter of the nares and generated end-distending pressure. The size of the cannula in relationship to the size of the neonates entire nasal passage is what determined positive-pressure delivery. The authors theorized that it is, therefore, still possible to deliver CPAP using the infant cannula in certain neonates. It was the conclusion of this study that using a nasal cannula to deliver CPAP is inherently unsafe.9 Of equal concern would be a possible lack of CPAP delivery due to the cannula size selected.
A second study of 40 preterm infants weighing less than 2 kg, conducted by et al,10 investigated the amount of flow required to provide nasal CPAP at 6 cm H2O and assessed the effectiveness of HFNC. The HFNC was compared to nasal CPAP using short prongs and a ventilator in the management of apnea of prematurity.
It was the conclusion of this study that the flow required to generate a positive distending pressure varied with the patients weight and was represented by this equation:
(x=weight in kg)
The authors stated, however, that the nasal cannulas structure, the flow of gas through it, and the anatomy of the neonates airway also determined the pressure generated. Unfortunately, the size of the nasal cannulae used in this study was not indicated in the published report. In a study period of 6 hours for each device, the investigators found no differences in the number of apneas, bradycardias, or desaturations, and they concluded that the HFNC device was as effective in the management of apnea of prematurity as the traditional ventilator nasal CPAP device. A longer study period might have yielded different results, as the neonates on HFNC might still have been experiencing benefits from their previous 6 hours of nasal CPAP. As the authors did not perform any measurements of pulmonary mechanics or work of breathing, they did not recommend the use of HFNC as a method of respiratory support in the neonate.
Recently, Courtney et al11 compared the changes in lung volume and breathing pattern seen in patients using the devices currently employed for nasal CPAP in the investigators NICU. One of these devices was a 1.5-mm (internal diameter) nasal cannula modified to attach, via endotracheal-tube adapter, to a conventional infant ventilator in the CPAP mode. The CPAP level was controlled by the mechanical ventilator and a flow rate of 6 L/min was maintained. The nasal cannula recruited volume as well as the nasal prongs did, but the neonates respiratory rate and oxygen requirement increased significantly. Based on the inability of Locke et al9 to generate a distending pressure with a similar-size nasal cannula using flow rates of up to 2 L/min, Courtney et al11 concluded that flow rates have to be very high to provide distending pressure through a nasal cannula. The work of breathing is probably also increased with HFNC, and its use to provide nasal CPAP was not recommended. The authors also questioned the use of the nasal cannula to provide oxygen in the preterm neonate due to the design of the nasal cannula base, which covers much of the nares and may obstruct expiration.
Besides the lack of evidence for clinical effectiveness, there are other concerns related to the use of nasal cannulae as nasal CPAP devices. There are no compensatory mechanisms for the loss of positive pressure through an open mouth, it is difficult to provide optimal humidity, and there is a potential for neonatal heat loss. Large volumes of air passing the nasal mucosa can cause increased nasal resistance, nasal congestion, a dry nose and mouth, a sore throat, and a bleeding nose.12 Other symptoms such as headache, chest discomfort, and infections of the nose, throat, and sinuses may also occur, and the mucociliary transport system is slowed.13 To avoid the dangers of mucosal drying in a healthy adult, it is necessary to deliver at least 30.6 mg/L of humidity.14 This need may explain why bubble humidifiers, which deliver only 1.6 to 7.4 mg/L of moisture to air, have had limited success in reducing symptoms.15 The heat lost from the respiratory tract depends on the temperature of the inspired gases and the ventilation rate. For a 1-kg infant, total body temperature can be lowered by 0.72°C per hour. If clinicians humidify the gases using a heated humidifier, no respiratory heat loss will occur, and secretion clearance from the lungs will be maximized.16 More research studies need to be done exploring the clinical effectiveness of nasal-cannula CPAP, as well as investigating the possible negative consequences of delivering cool, poorly humidified gases to the neonate. None of the three studies of the effects of HFNC recommend its use as a nasal CPAP device in the NICU.9-11
For the past 30 years, nasal CPAP has been primarily delivered to the neonate using some sort of nasal mask, prong, or endotracheal tube connected to a conventional mechanical ventilator. One of the advantages of using traditional ventilators is that they are already available in many NICUs. The same circuit can be used, and head gear and nose pieces are relatively inexpensive. Modern ventilators, however, are expensive to acquire and costly to maintain. In our NICU, 25% of the time, the ventilator is being used as a CPAP device. Maintenance hours are being accumulated when the device is being used for CPAP. In addition, its use for CPAP can make a ventilator, possibly much needed, unavailable.
The failure of nasal CPAP is seen primarily in the VLBW neonate. Several reasons for failure are not device related; these include apnea, inability to generate an opening pressure, and the use of excessive pressure. Some failures are device related. Klausner et al17 noted that earlier research had found increasing respiratory work to be an important factor in the failure of CPAP therapy. For the VLBW neonate, prongs of a very small diameter are used. There is much concern about the potential for increased resistance to airflow and imposed work of breathing from the use of these devices. To obtain positive pressure with ventilator CPAP, a resistance must be applied to the expiratory limb of the circuit. To achieve higher pressures, flow must be increased, and this can make it increasingly difficult for the patient to exhale. This type of system can also cause very large variability in pressure during inhalation and exhalation.17 If the flow is set too low to meet the neonates inspiratory demands, then the neonate may become agitated. Short nasal prongs can be difficult to fit and hard to keep fastened. They can become blocked when placed against the nares. Leaks through the nose and mouth can make it difficult to maintain pressure, and prongs that are too large or that are fastened too tightly can cause tissue breakdown. Long prongs, although easier to keep secured, can have a resistance two to three times that of short prongs,18 greatly increasing the work of breathing. They are also prone to occlusion by secretions, and when attached to a ventilator for CPAP, they may not elicit an alarm when occluded. In 1979, Goldman et al19 reported an almost 100% increase in work of breathing during nasal CPAP due to the nasal CPAP device itself. Flow resistance through the nasal attachment was the primary explanation. Leaks through the mouth and nose are almost unavoidable during clinical use. In most ventilator systems, flow will increase in an attempt to maintain the preset pressure. The resulting increase of flow will further increase the resistance of the system, with further impedance to breathing. The inability to maintain a constant pressure can also cause hypoxemia. The combined effects of hypoxemia and increased work of breathing may increase energy expenditures, cause metabolic acidosis, and lead to mechanical ventilation of the neonate.17,20 The anatomy of the normal neonate predisposes him or her to low lung volume, with a tendency toward atelectasis and decreased gas exchange. RDS aggravates this problem; the effectiveness of nasal CPAP, as a therapy for this disease process, revolves around its ability to maintain lung volume and thereby minimize the work of breathing. The preterm neonate is likely to fail at spontaneous breathing with minor increases in work of breathing. The treatment itself should not push the neonate into respiratory failure.
The new variable-flow nasal CPAP devices generate CPAP at the airway, unlike continuous-flow CPAP devices. They use the Bernoulli effect and dual injector jets directed toward each nasal passage to maintain a constant pressure. If the infant needs more flow, the Venturi action of the jets will entrain additional flow. The infant can exhale without added work because the expiratory flow is shunted out the expiratory outlet that is open to ambient air. Continuous positive pressure is maintained throughout the respiratory cycle by residual gas pressure. Due to improved design, the nasal prongs used can be of a much larger diameter than traditional prongs. They are made of a thin, soft material that flares out during inspiration, increasing the internal diameter and decreasing the leaking around them. There are no mechanical valves used, and the intranasal airway pressure can be continuously monitored.
Two laboratory studies have been published comparing a variable-flow device with a continuous-flow device. Moa et al21 demonstrated, in a lung model, a more constant and stable mean airway pressure, a lower flow resistance, and the variable-flow device to be less affected by leakage. Klausner et al17 used a simulated breathing apparatus and compared work of breathing for traditional nasal prongs and a variable-flow device. Using a prong size that is appropriate for a VLBW neonate, the investigators demonstrated that the imposed work of breathing for the variable-flow device was only one-fourth of that for the continuous-flow device. To determine whether lung volumes and breathing patterns differ among devices, Courtney et al11 compared the variable flow device with the continuous-flow device and with the modified nasal cannula. Thirty-two premature infants receiving CPAP for apnea or mild respiratory distress (mean gestational age: 29±2 weeks) were studied using all three devices in random order. Compared to the other two continuous-flow devices, the variable-flow device provided significantly greater overall lung recruitment.
Three randomized clinical trials have been published demonstrating a clear clinical advantage for a variable-flow nasal CPAP device. Sun and Tien22 randomized neonates of less than 30 weeks gestation who had RDS and were mechanically ventilated to either a variable-flow device or conventional CPAP on extubation. The failure rate, after 7 days, was 16% for the new device, versus 54% for the conventional device. In a two-center randomized trial,23 neonates weighing 1.25 kg or less were randomized, on extubation, to prophylactic variable-flow nasal CPAP or conventional nasopharyngeal CPAP. Their mean gestational age was 26.2 weeks. Of the 48 infants randomized to variable-flow nasal CPAP, 30 were successfully extubated. Only 18 of the 45 infants randomized to nasopharyngeal CPAP were successfully extubated. Neonates were enrolled in a crossover arm of the study24 using the alternate device if they were not successfully extubated with the first device. Of the 38 infants who crossed, 28 were extubated with the variable-flow device and only 10 were extubated with nasopharyngeal CPAP; when the entire group was evaluated, 58 were extubated with the variable-flow device and 28 were extubated with nasopharyngeal CPAP.
The application of nasal CPAP in the NICU is expanding in the United States, and it has the potential to be used by an even larger percentage of neonates than in the past. Exciting research is being done evaluating the value of early CPAP application (as well as on CPAP as an alternative to prolonged mechanical ventilation). Smaller infants are arriving in the NICU today than 30 years ago. These VLBW infants provide a new set of challenges. The devices needed to care for these infants must be developed and evaluated in the clinical arena. Established NICU devices such as the nasal cannula may become valuable tools in the treatment of apnea of prematurity. Unfortunately, the use of the HFNC has proliferated without clinical evidence that it is a safe and effective therapy. The most widely used nasal CPAP device, the continuous-flow ventilator with nasal prongs, has many design and practical difficulties that limit its effectiveness for the VLBW neonate. New variable-flow generators show promise that they may decrease the work of breathing, enhance lung recruitment in the VLBW infant, and prevent extubation failure. A large, multicenter randomized trial comparing the mostly widely used nasal CPAP devices should be undertaken to determine whether the nasal CPAP device does, in fact, make a difference.
Melissa K. Brown, RRT, is an NICU clinical specialist, Sharp Mary Birch Hospital for Women, San Diego.
1. Gregory GA, Kitterman JA, Phibbs RH, et al. Treatment of idiopathic respiratory distress syndrome with continuous positive airway pressure. N Engl J Med. 1971;284:1333-1337.
2. Claris O, Salle BL, Lapillonne A, et al. Nasal continuous positive airway pressure in the treatment of neonatal respiratory distress syndrome. Arch Pediatr. 1996;3:452-456.
3. Davis PG, Henderson-Smart DJ. Nasal continuous positive airway pressure immediately after extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev. 2000;2:CD000143.
4. Kamper J. Early nasal continuous positive airway pressure and minimal handling in the treatment of very-low-birth-weight infants. Biol Neonate. 1999;76:S22-S28.
5. Morley C. Continuous distending pressure. Arch Dis Child Fetal Neonatal Ed. 1999;81:F152-F156.
6. Hutchinson AA. Advances in nasal continuous positive airway pressure (NCPAP). Validation of an improved design. Neonatal Intensive Care. 1999;12:16-18.
7. Davis PG, Henderson-Smart DJ. Extubation from low-rate intermittent positive airway pressure versus extubation after a trial of endotracheal continuous positive airway pressure in intubated preterm infants. Cochrane Database Syst Rev. 2000;2:CD001078.
8. AARC Clinical Practice Guideline. Application of continuous positive airway pressure to neonates via nasal prongs or nasopharyngeal tube. Respir Care. 1994;39:817-823.
9. Locke R, Wolfson M, Shaffer T, et al. Inadvertent administration of positive end-distending pressure during nasal cannula flow. Pediatrics. 1993;91:135-138.
10. Screenan C, Lemke RP, Hudson-Mason A, et al. High-flow nasal cannulae in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure. Pediatrics. 2001;107:1081-1083.
11. Courtney SE, Kee PH, Saslow JG, et al. Lung recruitment and breathing pattern during variable versus continuous flow nasal continuous positive airway pressure in premature infants: an evaluation of three devices. Pediatrics. 2001;107:304-308.
12. Richards G, Cistulli P, Ungar R, et al. Mouth leak with nasal continuous positive airway pressure increases airway resistance. Am J Respir Crit Care Med. 1996;154:182-186.
13. Estey R. Subjective effects of dry vs humidified low flow oxygen. Respir Care. 1980;24:1143-1144.
14. Dery R. Water balance of the respiratory tract during ventilation with a gas mixture saturated at body temperature. Can Anaesth Soc J. 1973;20:719-727.
15. Darin J, Broadwell J, MacDonell R. An evaluation of water vapor output from four brands of unheated prefilled bubble humidifiers. Respir Care. 1982;27:41-50.
16. Varene P, Ferrus L, Manier G, et al. Heat and respiratory exchanges: comparison mouth and nose breathing in humans. Clin Physiol. 1986;6:405-414.
17. Klausner JF, Lee AY, Hutchison AA. Decreased imposed work with a new nasal continuous positive airway pressure device. Pediatr Pulmonol. 1996;22:188-194.
18. Czervinske M, Durbin CG, Gal TJ. Resistance to gas flow across 14 CPAP devices for newborns. Respir Care. 1986;31:18-21.
19. Goldman SL, Brady JP, Dumpit FM. Increased work of breathing associated with nasal prongs. Pediatrics. 1979;64:160-164.
20. Cats BP. Nasal prongs and work of breathing. Pediatrics. 1980;65:1195-1196.
21. Moa G, Nilsson K, Zetterstrom H, et al. A new device for administration of nasal continuous positive airway pressure in the newborn: an experimental study. Crit Care Med. 1988;16:1238-1242.
22. Sun CS, Tien HC. Randomized controlled trial of two methods of nasal CPAP: flow driver versus conventional CPAP. Pediatr Res. 1999;45:322A/1898.
23. Roukema H, OBrien K, Nesbitt K, et al. A randomized controlled trial of Infant Flow continuous positive airway pressure versus nasopharyngeal CPAP in the extubation of babies <1250 grams. Pediatr Res. 1999;45:318A/1874.
24. Roukema H, OBrien K, Nesbitt K, et al. A crossover trial of infant flow continuous positive airway pressure versus nasopharyngeal CPAP in the extubation of babies <1250 grams. Pediatr Res. 1999;45:317A/1873.