Ventilation Without Tracheal Intubation

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I read with great interest the article by Bhandari et al,1_{who discuss the}

feasibility of nasal intermittent positive pressure ventilation (NIPPV) to support premature infants. Their article brings forward a modality for respiratory support of premature infants that is less invasive than mechanical ventilation (MV). Although it is important to demonstrate that the avoidance of intubation and the use of NIPPV can result in less morbidity, it is important to recognize that avoidance of unneeded intermittent ventilation, whether via nasal prongs or an endotracheal tube, could be more beneﬁcial. The use of NIPPV can be used as a second line of support to premature infants who do not respond pos-itively to less-invasive treatments.

Years ago, MV was used as the ﬁrst-line, and maybe the only available, option for respiratory support of premature infants with hyaline mem-brane disease.2 _{Although MV has been widely used, research has}

shown a clear association between MV and lung injury, also known as ventilator-induced lung injury (VILI). Two major components account for lung injury in ventilated infants: tracheal intubation and the me-chanical force on the lung during ventilation.

Tracheal intubation is a traumatic and painful procedure that a pre-mature infant can experience during his or her hospital stay. It is often performed without adequate pain management3_{and may be}

accompa-nied by signiﬁcant hemodynamic instabilities.4_{Once the tube is in the}

trachea, it inevitably serves as a bridge between the sterile lower respiratory system of the infant and the nonsterile outside world. We recently demonstrated that within a few days, colonization of the tra-chea with bacteria occurs in⬎80% of intubated infants.5_These

bacte-ria will ignite the inﬂammatory process, which can lead to lung injury and bronchopulmonary dysplasia.6_{In addition, the ciliary movement of}

the cells lining the trachea is now compromised and cannot clear the mucus because of the mechanical obstruction by the tube. Secretions will accumulate in the dependent part of the lungs, causing alveoli in these areas to become full of secretions without any aeration, whereas other areas become overinﬂated from the increased tidal volume that they receive. Added to these drawbacks is the high resistance to air ﬂow via the endotracheal tube, which is narrower and longer than our natural airways. This increased resistance will result in increased work of breathing. This increased work is a major obstacle for ventila-tion, even in a healthy individual. I still remember Dr Theodore Kollobow at the National Institutes of Health, who used to “treat” his visitors by offering them an endotracheal tube to place in their mouth and breathe through. Everybody will get tachypnea, begin to sweat, and feel tired within minutes. This simple exercise demonstrates the impact of intubation on ventilation in a normal healthy adult lung. What will be the effect of this exercise on a newborn with immature lungs?

The mechanical force during ventilation produces VILI via 4 pathways: barotrauma, volutrauma, atelectrauma, and biotrauma.7_Barotrauma

CONTRIBUTORS:Hany Aly, MD

Department of Newborn Services, George Washington University Hospital and Children’s National Medical Center, Washington, DC

ABBREVIATIONS

NIPPV—nasal intermittent positive pressure ventilation MV—mechanical ventilation

VILI—ventilator-induced lung injury CPAP— continuous positive airway pressure www.pediatrics.org/cgi/doi/10.1542/peds.2009-0256 doi:10.1542/peds.2009-0256

Accepted for publication Mar 30, 2009

Address correspondence to Hany Aly, MD, George Washington University Hospital, Department of Newborn Services, 900 23rd St NW, Suite G2092, Washington, DC 20037. E-mail: haly@mfa. gwu.edu

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causes air leaks when ventilating with a relatively high positive pressure.8

Vo-lutrauma causes overdistention of the alveoli.9_{Atelectrauma can cause}

atel-ectasis of the alveoli when using low pressure.10_{This type of injury can}

re-sult from the repeated opening and closing of lung units. Biotrauma indi-cates a mechanotransduction or con-version of the physical force on the trachea and alveoli receptors into ac-tivation of the intracellular inﬂamma-tory pathway, leading to capillary leaks and increased lung ﬂuids.11_This

mech-anism is responsible for increased neutrophils, hydrogen peroxide, inter-leukins, tumor necrosis factor, throm-boxane B₂, and the platelet-activating factor in tracheal aspirate after MV.12,13 _{Intubated animals supported}

with continuous positive airway pres-sure (CPAP), instead of the intermit-tent pressure, have demonstrated a signiﬁcantly reduced inﬂammatory response.12

Injury induced by MV does not stop at the lung; it has been shown to extend to dif-ferent body organs. Multisystem organ failure and death have been observed with MV.9,14 _{Different mechanisms can}

explain the systemic damage caused by MV. It is recognized that inﬂammatory mediators produced from VILI can mi-grate easily via the bloodstream. The pul-monary vasculature is also a major res-ervoir for marginated neutrophils and can harbor almost one third of all neu-trophils outside the bone marrow. Fluc-tuation and redistribution of blood ﬂow to different organs as a result of ventila-tor pressure on cardiac output is an-other contributing factor in systemic damage. Finally, the translocation of bac-teria from inside the alveolar space to systemic circulation can occur. This has been reproduced experimentally by us-ing high transpulmonary pressure and low expiratory pressure.14,15 _In

prema-ture infants, there is a strong associa-tion between MV and brain injury. In a

recent cohort study that was conducted by the National Institute for Child Health and Development, it was recognized that, for extremely low birth weight infants, each 10 days of MV was associated with a 20% increased risk for cerebral palsy.16_{Such association remained}

sig-niﬁcant even after controlling for possi-ble confounding factors such as intra-ventricular hemorrhage, gestational age, and sepsis. Several mechanisms that can explain the association of cere-bral palsy and MV have been proposed (Table 1).17_{Because of this ﬁnding,}

neo-natal units try to avoid combining tra-cheal intubation and MV and use nasal CPAP instead.

The use of nasal CPAP in premature in-fants prevents alveoli from collapsing and increases the functional residual ca-pacity. It also stents the airways, im-proves the compliance, and, therefore, reduces the efforts of breathing.18_CPAP

conserves surfactant by avoiding the in-ﬂammatory component of VILI and the accumulation of mucus when the tra-chea is intubated. Apart from these “acute” effects of CPAP, the extended use of CPAP is associated with stimulation of the lung units to grow.19_{This makes CPAP}

both a corrective and supportive ther-apy. It allows premature lungs to grow while helping the process of gas ex-change. Multiple neonatal units that al-low extended use of CPAP have reported better outcomes and a reduced inci-dence of bronchopulmonary dyspla-sia20,21_{; whereas when CPAP was weaned}

off prematurely and replaced with nasal cannula, the advantageous effects of CPAP were not appreciable.22_{Infants for}

whom CPAP fails are exposed to intuba-tion and MV, but ventilaintuba-tion without tra-cheal intubation can be a less-invasive approach. This approach is known as na-sal NIPPV.

The concept of ventilation without intu-bation, NIPPV, has been practiced for a long time. Mouth-to-mouth resuscitation is actually a type of NIPPV. NIPPV’s major advantage is that it avoids tracheal intu-bation for infants who are not stable on CPAP or for whom CPAP is expected to fail. It has the ﬂexibility of alternating the mode of support to and from CPAP with-out repeated extubation/intubation at-tempts. In this capacity, NIPPV avoids 1 of the 2 “bad” components of VILI. In addi-tion, the pressure delivered by NIPPV is limited by unavoidable air leakage at the interface between the device and the na-res, or via the oropharynx if the infant’s mouth is open, and downward into the esophagus. NIPPV, therefore, may modify or put a ceiling on ventilation pressures that reach the distal alveoli. Despite these advantages, it is still a mode of de-livering positive pressure ventilation. It is a less-invasive approach than classic ventilation, but it theoretically can have similar adverse effects.

We learned from the past that unnec-essary escalation of intervention im-poses more complications and, as a result, is associated with worse

out-TABLE 1 Proposed Mechanisms That Link MV With Cerebral Palsy and Other Neurodevelopmental Risks

1. Fluctuation of cerebral blood ﬂow: MV is associated with a cascade of increased intrathoracic pressure, impedance of venous return and decreased cardiac preload, decreased cardiac output, and compromised cerebral perfusion

2. Fluctuation of the arterial carbon dioxide tension during ventilation 3. Exposure to sedative medications that are often used during MV 4. Systemic inﬂammation secondary to VILI

5. Other neurodevelopmental risks

a. Frequent sleep interruption and discomfort during tracheal suctioning, heel stick, and blood draws b. Exposure to noise related to ventilator alarms

c. Loss of self-regulatory behaviors that control stress and delayed oral readiness to feed d. Maternal deprivation resulting from physical limitation

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comes during the care of premature infants.23 _{In addition to the effects}

of intermittent pressure discussed, there are also the effects of other as-sociated practices. For example, to ad-just ventilator settings while on NIPPV, blood gases need to be monitored closely, often with the use of indwelling umbilical and arterial lines. These lines are a source for bloodstream in-fections and frequent blood sampling with subsequent transfusions. There-fore, NIPPV is an excellent option when

used in the capacity as a substitute for intubation and MV. However, when used in an infant who could be man-aged adequately by a less-invasive method such as CPAP, it is an unneces-sary escalation of care.

To date, there is no physiologic reason to support the use of NIPPV in infants who can otherwise be managed with CPAP. Instead, I advocate the use of NIPPV in infants for whom CPAP is likely to fail. These infants, once hemody-namically stabilized on NIPPV, can then

of this commentary is to focus our re-search on the use of NIPPV in the right direction, that is, evaluating the out-comes of infants managed with NIPPV as a second-line strategy. NIPPV can also enhance the practice of early ex-tubation in premature infants sup-ported by MV. We know that there is not a single magic bullet that can be used for the respiratory support of premature infants. Instead of trying different tools as an all-or-none modal-ity, we can introduce these tools in a practical algorithm to enhance cur-rent practices (Fig 1). Neonatal man-agement is an art of deciding when and why to use 1 tool over another. The idea that 1 method will work for all infants at all times is unrealistic. Let us stay simple and less invasive and focus our trials on protocols that have a basis in physiology, that are supported by the best available evidence, and can be translated into better clinical practice.

ACKNOWLEDGMENT

I thank Inderjeet Sandhu for help with editing this communication.

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Nasal CPAP

NIPPV

St

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Deterior

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Deterior

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Extu

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Deterior

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Significant apnea and bradycardiaa

FIGURE 1

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DOI: 10.1542/peds.2009-0256 originally published online July 27, 2009;

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Ventilation Without Tracheal Intubation

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