Introduction

The cells in our bodies need a constant supply of oxygen to function. Carbon dioxide is produced by cells and must be continuously eliminated. The alveoli are ventilated with atmospheric gas allowing transfer of gas between the alveoli and the blood. The blood then transports gas to and from the the tissues and cells where respiration takes place. At any point in this chain of gas exchange, pathophysiology may occur whereby hypoxia and hypercarbia result.

see also Respiratory Care in the Neonate and Adjuncts in Respiratory Care

Content in this topic is referenced in SCORE Lung Physiology, Pathophysiology, Ventilators, and Pneumonia overview

Basic Science

What are the mechanics of the lung?

Three pressures are important in ventilation - atmospheric pressure, intra-alveolar pressure and intrapleural pressure. Atmospheric pressure is the pressure exerted by the weight of the gas in the atmosphere with a reference measurement of 760 mm Hg at sea level. Intra-alveolar pressure is the pressure exerted by a gas on the alveoli and typically equilibrates with atmospheric pressure. Intrapleural pressure is the pressure that is exerted within the pleural space and may be less than, equal to or greater than atmospheric pressure.

Under normal physiologic conditions the thoracic wall and the lungs move in conjunction with each other. Inspiration is an active process that depends on muscle contraction. When the phrenic nerve activates the diaphragm, the normally dome shaped muscle contracts and flattens. When the external intercostal muscles contract, the ribs are lifted and the chest wall moves out. These two movements expand the volume of the chest. An increase in the volume of the chest generates subatmospheric intra-alveolar pressure and air enters the lung until the intra-alveolar pressure equalizes with the atmospheric pressure.

Expiration is a passive process brought about by the relaxation of the diaphragm and the intercostal muscles. During expiration, the chest wall and lungs recoil to their preinspiratory positions. The lung recoils during expiration due to the elastic connective tissue in the lungs and alveolar surface tension. Recoil causes the intra-alveolar pressure to rise and air begins to leave the lungs. Passive expiration will continue until intra-alveolar pressure becomes equal to atmospheric pressure. This is also the point where the lung recoil is equal to the tendency for the chest wall to re-expand.

Gas exchange occurs across the alveolar membrane and the capillaries underlying the membrane. The alveolar surface and the adjacent capillaries are only one cell layer thick; therefore, gas exchange occurs across very thin endothelial and epithelial surfaces [1].

How is carbon dioxide eliminated?

Carbon dioxide (CO2) is produced by cells as a product of metabolism and enters the venous blood for elimination through the lungs. CO2 travels through the blood stream in three forms - protein bound (hemoglobin), chemically modified or dissolved in plasma. CO2 bound by hemoglobin accounts for about twenty to thirty percent of CO2 in the venous blood. CO2 reversibly binds with the free amino termini of the hemoglobin molecule. Chemically modified CO2 occurs when CO2 combines with water to form carbonic acid and is catalyzed by the carbonic anhydrase enzyme in red blood cells. Carbonic acid dissociates into free hydrogen ion and bicarbonate. The free hydrogen ions appear to be absorbed by hemoglobin and may promote enhanced oxygen unloading at the cellular level (i.e. Bohr effect). Five to ten percent of carbon dioxide is transported in the blood in simple dissolved form.

The exchange of CO2 between the alveoli and the blood occurs by simple diffusion. Diffusion is a passive process whereby gas is transferred from a region of high partial pressure of the gas to a region with a lower partial pressure. The concentration of CO2 is higher in the blood compared to the air in the alveolar sacs. CO2 in the blood rapidly equilibrates with the CO2 in the alveolar space and is efficiently eliminated as the blood moves through the alveolar capillaries. Normally, the gas exchange of CO2 in the lung is perfusion limited based on the blood flow rate.

What are the dynamics of oxygen transfer?

Under normal circumstances, the partial pressure of oxygen in the blood equilibrates with the partial pressure of oxygen in the alveolar space early in its course through the pulmonary capillaries. Thus, like CO2, oxygen gas exchange is perfusion limited in a normal, healthy lung and can only be enhanced by increasing pulmonary blood flow.

In several instances, however, oxygen transfer can be diffusion limited; that is, there is incomplete equilibration of oxygen during the transit of blood through the capillaries. During heavy exercise, augmentation in cardiac output results in an increase in blood flow rate through the alveolar capillaries. As a result, the partial pressure of oxygen may not equilibrate between the alveoli and blood as the blood courses through the capillaries. Diffusion limitation can also occur at normal pulmonary blood flow rates in disease states where there is alveolar thickening (e.g. pulmonary edema).

Oxygen is transported within the blood in two forms - dissolved and bound to hemoglobin. Oxygen bound to hemoglobin accounts for 97% of transported oxygen. Oxygen rich arterial blood unloads oxygen at the tissue and cellular level. The primary factor determining whether oxygen is loaded or unloaded onto hemoglobin is the surrounding partial pressure of oxygen. The relationship between the partial pressure of oxygen and the percent of hemoglobin molecules bound to oxygen is demonstrated by the oxygen hemoglobin dissociation curve. The oxygen hemoglobin dissociation curve was derived empirically by placing human blood in an oxygen free environment, gradually increasing the partial pressure of oxygen and then measuring the percent saturation of oxygen bound to hemoglobin [2]. The curve is nonlinear. The saturation of hemoglobin changes substantially when the partial pressure of oxygen ranges between 20 to 60 mm Hg but tends to plateau at oxygen partial pressures above 80 mm Hg. There are factors that favor the release of oxygen from hemoglobin molecules. These factors shift the O2 dissociation curve to the right and include hyperthermia, decreased pH, increased 2,3-diphosphoglycerol (2,3-DPG), and increased CO2.2,3-DPG levels are higher in conditions of hypoxemia (lung disease, higher altitude) and anemia.

oxyhemoglobin dissociation

Oxyhemoglobin dissociation curve. P50 for O2 dissociation is a partial pressure of 26 to 27 mm Hg.

The Haldane effect describes a phenomenon by which the binding of oxygen to hemoglobin displaces carbon dioxide. Two mechanisms are responsible for this. First, when oxygen is bound to hemoglobin, the affinity of hemoglobin for CO2 is decreased thereby facilitating the release of CO2. Second, the binding of oxygen makes the hemoglobin molecule more acidic thereby releasing more hydrogen ions. This phenomenon drives the carbonic acid equilibrium towards water and carbon dioxide and facilitates CO2 elimination.

see Respiratory Care in the Neonate Embryology for a discussion of fetal hemaglobin.

What are the physics of the pediatric airway?

The pediatric airway has unique characteristics that must be considered in order to optimize delivery of gas to the lungs. A child’s trachea is small and its length is short. Hagen-Poiseuille’s Law describes the flow of gas through a cylinder.

Hagen-Poiseuille’s Law

Although flow occurs easily in short pediatric airways since the radius is proportional to the fourth power to the resistance, the size of the airway lumen is the most important factor in determining flow. Practically speaking, consider an infant with a 4 mm airway that is decreased by 2 mm due to inflammation. Although the absolute diameter is only decreased by fifty percent, the flow decreases by more than ninety percent (24=16 versus 44= 256). In contrast, an adult with an 8 mm airway that decreases by 2 mm experiences a diameter reduction of 25% and a flow reduction of 69%.

Another factor that can influence the flow of gas (fluid) the Reynold’s number (Re). Re is a dimensionless number that expresses the ratio of inertial forces to viscous forces for given flow conditions. The Reynolds number is an important parameter that describes whether flow conditions lead to laminar or turbulent flow.

Re = (ρVL)/μ

where ρ is the fluid density, V is the fluid velocity, L is the linear dimension, and μ is the fluid viscosity. A Re of less than or equal to 2,000 leads to laminar flow while an Re of 4,000 or greater signifies turbulent flow.

Helium is less dense than nitrogen and slightly more viscous thereby increasing the chance for laminar flow. This is why heliox (helium and oxygen mixture) is useful in upper airway problems such as croup. Conversely, heliox does not work in status asthmaticus since the level of obstruction is at the subsegmental bronchi.

see Anatomy

Pathophysiology

What are the causes of poor oxygenation?

Hypoxemia, or poor oxygenation of the arterial blood, can be caused by many factors. These include global hypoventilation, diffusion disequilibrium, pulmonary shunt and ventilation/perfusion mismatch.

Hypoventilation can cause hypoxemia. Alveolar PO2 is the resulting balance between the oxygen delivered from the airways into the alveoli and oxygen removed through the alveolar capillaries. With decreased breathing or hypoventilation, hypoxemia ensues accompanied by an increase in paCO2 or end tidal CO2. In newborns, an immature nervous system can lead to apnea in response to different stimuli such as pain, sepsis, or medications such as narcotics. Hypoxemia is treated by increasing ventilation through stimulation (manual stimulation, positive flow of oxygen, caffeine) or positive pressure ventilation depending on the situation. Hypoxemia from hypoventilation can be reversed by increasing the fraction of inspired oxygen (FiO2).

Diffusion disequilibrium occurs when there is a thickening of the interface through which oxygen diffuses from the alveoli to the blood in the pulmonary capillaries. Pulmonary edema, interstitial diseases of the lung and alveolar capillary dysplasia are examples of disease processes whereby the primary case of hypoxemia is impaired gas diffusion.

Pulmonary shunting is a physiological condition that occurs when the alveoli of the lung receive normal blood flow, but ventilation of the lung fails to supply the perfused region. In this situation the ventilation to perfusion ratio, or the ratio of air reaching the alveoli to blood perfusing the lung, is zero (V/Q = 0). For example, atelectasis, pulmonary aspiration or pneumonia impairs the alveolar air space but the alveolar unit may be still perfused. Shunt fraction is the percentage of blood pumped from the heart that is not completely oxygenated. A small amount of shunt is normal but this is rarely over four percent. Conditions such as pneumonia, atelectasis, airway foreign bodies, or pulmonary contusion increase the shunt fraction. Consider a patient with a foreign body blocking the right main stem bronchus. Half of the pulmonary blood flow is directed to the right lung where the gas in the alveolar segments has a very low partial pressure of oxygen. The blood returning from the right lung is poorly oxygenated and mixes with the oxygenated blood from in the left lung. As a result, the blood returning to the left atrium and left ventricle has a low pO2. Even breathing 100% oxygen will not fully oxygenate the blood in this situation.

Ventilation/perfusion (V/Q) mismatch is the most common cause of hypoxemia. To understand V/Q mismatch, one should recall that pulmonary venous pressures are 20 to 30 mm Hg on average. With such low pressures, gravity can affect pulmonary blood flow significantly, with less blood flow in the apex of the lungs and more blood flow to the inferior most segments. The ventilation perfusion ratio is therefore higher in the superior regions of the lung and lower in the basal regions. Dead space ventilation occurs normally in the central airways and is typically about thirty percent of the ventilated volume. Dead space ventilation increases when the gas ventilates alveoli which are not perfused. In this case, the V/Q ratio approaches infinity. Consider a patient with a massive pulmonary embolus. Despite the fact that the partial pressure of oxygen in the alveoli can be maximized, the blood does not come in contact with the alveoli due to the mechanical blockage caused by the embolus. When V/Q mismatch is not severe, hypoxemia can be remedied to some extent by increasing the FiO2.

Hypoxic pulmonary vasoconstriction is a physiologic phenomenon in which pulmonary arteries constrict during hypoxia without hypercapnia. This response redirects blood flow to alveolar units with higher oxygen content. Constriction allows redistribution of blood flow to areas of the lung with better ventilation. This improves V/Q mismatch. Hypoxic pulmonary vasocontriction can be inhibited by increased CO2, hypocapnea, acidosis, alkalosis and positive end expiratory pressure.

What causes poor mixed venous oxygen saturation?

In a state of equilibrium, oxygen (O2) demand equals O2 consumption, which is the amount of oxygen used for aerobic metabolism. Under normal aerobic conditions, O2 delivery (DO2) is three to four times that which is consumed by the body; oxygen delivery does not limit the amount of oxygen consumed. In a critically ill patient, the delivery of oxygen may be an important factor for oxygen consumption.

Mixed venous oxygen saturation (SvO2) is the measurement of oxygen saturation in the pulmonary artery. When compared to arterial oxygen saturation, SvO2 gives an indication of the amount of oxygen delivered in relationship to the amount consumed. Mixed venous oxygen saturation should be differentiated from central venous oxygen saturation monitoring (ScvO2) because ScvO2 does not account for blood returned from the coronary sinus and is typically higher than the true mixed venous oxygen saturation. ScvO2 is more practically obtained from blood in the superior vena cava since pulmonary artery catheters are not commonly placed. Inferior vena cava measurements are highly variable and should not be used to approximate SvO2. ScvO2 has been utilized to guide early goal directed therapy for adult sepsis with good outcomes. (see Surgical Infection) A normal SvO2 is 65 to 75%, with lower values (less than 65%) signifying a reduction in the ratio of oxygen delivery to oxygen consumption. When SvO2 approaches fifty percent, there is a 2:1 ratio of oxygen delivery to consumption. In this case, oxygen consumption is close to being dependent on oxygen delivery; in other words, when the SvO2 is below fifty percent, oxygen consumption decreases directly in relationship to oxygen delivery. When the SvO2 is over eighty percent it may signify inappropriate tissue unloading of oxygen as seen in some forms of septic shock or in the presence of arteriovenous shunts.

Abnormalities in mixed venous saturation may be due to poor oxygen delivery, high oxygen demand, or a combination of both.

How do you optimize oxygen delivery?

Oxygen delivery is the product of cardiac output (CO) and arterial oxygen content. During the process of metabolism oxygen consumption is expressed as the volume of oxygen consumed per minute (VO2) and ranges 100 to 200 cc/m2/min in the homeostatic state while the oxygen delivery (DO2) is generally 4 fold higher (500 to 600 cc/m2/min).

Optimizing oxygen delivery is generally achieved more easily than altering oxygen demand. Identifying the factors that can lead to optimization of oxygen delivery can be accomplished by breaking down the components of the DO2 equation.

DO2= cardiac output (bound O2 + dissolved O2)

DO2= cardiac output [(1.34 x Hgb x O2 sat) + (pO2 x 0.003) ]

Therefore, the three elements that primarily determine oxygen delivery are cardiac output, hemoglobin content and oxygen saturation. The dissolved pO2 plays a smaller role, since its contribution is multiplied by a factor of 0.003. As a result, enhancing DO2 may be best accomplished by blood transfusion, increasing SaO2 and optimizing cardiac output (CO). The latter requires manipulation of the components of cardiac output:

CO = heart rate x stroke volume

Stroke volume is affected by preload (volume status), afterload (systemic vascular resistance) and contractility (inotropic characteristics).

Preload is simply the volume that the heart sees. The volume that the right heart receives is the same as that of the left heart. The volume of blood that the right heart receives correlates to the central venous pressure which normally ranges from 5 to 8 cm H2O. Optimizing preload generally requires the expansion of intravascular volume with crystalloid or blood products depending on the clinical need.

Afterload refers to the resistance of the vascular bed that receives flow from the heart, also known as the systemic vascular resistance. In septic shock, bacteria and host characteristics contribute to decreased vascular tone leading to decreased afterload. In this context, increasing afterload is accomplished by vasoactive medications such as norepinephrine. Importantly, one must ensure that the patient has adequate preload before using medications to augment afterload.

Cardiac contractility refers to the force by which the heart ejects blood. Preload, as dictated by the Frank Starling curve, is responsible for part of cardiac contractility. Contractility can also be affected by inherent cardiac muscle weakness due to ischemia, trauma, postoperative dysfunction, and electrolyte or hormonal dysfunction (e.g. hypocalcemia, hypothyroidism). Contractility can be augmented by myotropic agents such as dobutamine (β2 adrenergic), epinephrine (β1 and β2), and milrinone (increased cyclic adenosine monophosphate). (see also Cardiovascular Physiology and Shock)

Decreasing oxygen consumption (VO2) requires paying attention to the patient’s metabolic state. Normothermia should be achieved. Decreasing the work of breathing, ablating seizures, providing sedation and treating hyperdynamic states such as sepsis and thyrotoxicosis are helpful in modulating oxygen consumption.

How do the cardiovascular and respiratory systems interact?

When manipulating parameters of oxygen delivery, one should also pay close attention to the cardiovascular and respiratory systems as a whole. The heart and lungs interact so closely that to only consider one system can cause detriment to the patient.

The right atrium fills from the superior vena cava (SVC) and the inferior vena cava (IVC). In the normal circumstance, the right atrium (RA) is passively filled with blood and this filling is augmented by the negative intrathoracic pressure. Therefore, positive pressure ventilation (PPV) decreases RV preload by decreasing the gradient between the SVC/IVC and the RA. An increase in the mean airway pressure (MAP) further decreases the pressure gradient between the systemic venous system and the RA. In addition, increases in MAP may translate to an increase in pulmonary vascular resistance (PVR).

The left ventricle (LV) is also affected by PPV. The effects of positive pressure on the LV preload are directly related to the preload delivered to the right heart from the systemic venous system. Therefore, PPV and higher MAP can decrease LV preload. Interestingly, however, PPV can also decrease LV afterload. The positive intrathoracic pressure adds to the total pressure generated by the LV to maintain systemic blood pressure. For example, in a spontaneously breathing patient with a baseline thoracic pressure (P thorax) of -10, the LV has to generate a pressure of 110 to obtain a systemic pressure of 100. If the patient is mechanically ventilated with a MAP of 10, the heart has to generate a pressure of only 90 to reach a systemic pressure of 100.

The dominant effect of PPV on lung and cardiac mechanics is mediated through the MAP. The effects due to phasic changes between inspiration and expiration are minor.

Pulmonary vascular resistance is also modulated by lung volume. When there is atelectasis the geometry of pulmonary vessels may increase PVR. However, when the lungs are over distended, pulmonary vessels may be compressed by the distended alveoli increasing PVR. As a result, both atelectasis and over distension can increase PVR. Hypoxia, respiratory alkalosis and metabolic alkalosis can also increase PVR. It is the change in pH and not the paCO2 that modulates PVR [3].

Assessment

What is the role of pulse oximetry?

Pulse oximetry provides an instantaneous and continuous noninvasive method of monitoring hemoglobin saturation. The basic principle is based on the fact that hemoglobin exhibits different absorbance and transmittance characteristics for specific wavelengths of light depending on its level of oxygenation. Transmittance is a measure of how much light passes through a substance as defined by the equation

T = I/Io,

where T is the transmittance or percent transmitted light, I is the transmitted light and Io is the incident light. Absorbance is defined by the equation

A = log10 (1/T)

where A is absorbance and T is transmittance. Therefore, absorbance is inversely related to transmittance. If all the light passes through a solution without any absorption then absorbance is zero and percent transmittance is 100%. If all the light is absorbed, then percent transmittance is zero and absorption is infinite.

Within a pulse oximeter, there is an electronic processor and two small light emitting devices (LED) with a photodiode facing the LEDs. One LED emits red light at a wavelength of 660 nm while the other emits infrared light both of which are transmitted through the tissues. The absorption of wavelengths differs between oxygenated and deoxygenated hemoglobin with oxygenated hemoglobin absorbing more infrared light and deoxygenated blood absorbing more red light. This ratio is used to calculate the percentage of oxygenated hemoglobin (oxygen saturation). The addition of two more wavelengths of light within the pulse oximeter has improved its accuracy. This results in absolute values that reliably lie within two percent of blood gas measurements and can accurately report total hemoglobin, methemoglobin, and carboxyhemoglobin concentrations on a continuous basis. The ability of the pulse oximeter to function may be diminished by bright ambient light, peripheral vasoconstriction, and nail polish.

Measurement of oxygen saturation is standard of care in all aspects of medicine including anesthesia, surgery and critical care. It allows ready evaluation of interventions. Evaluation of the waveform during continuous pulse oximetry is valuable in monitoring cardiac output. Beat to beat variation of the waves often indicates a relative hypovolemic state [4][5].

What is the role of noninvasive CO2 monitoring?

While capnometry and capnography are often used synonymously, capnometery refers to continuous monitoring of expired CO2 while capnography refers to the continuous graphic recording of expired CO2. End tidal CO2 levels reflect alveolar CO2 concentration and, because of the extreme diffusability of CO2, also represent paCO2.

End tidal CO2 (ETCO2) monitoring is very helpful in clinical practice. During intubation the presence of CO2 in the endotracheal tube is an indication of correct placement. Disappearance of ETCO2 may signify extubation or complete cessation of pulmonary blood flow such as seen in cardiac arrest or massive pulmonary embolus. ETCO2 waveforms can be analyzed to assess lung compliance, bronchospasm and response to ventilator weaning. One of the earliest indications of malignant hyperthermia is an abrupt and sustained rise in ETCO2.

How are blood gases analyzed?

The arterial blood gas consists of four components: pH, paO2, pCO2 and bicarbonate (HCO3). pH, paCO2 and HCO3 are interrelated by the Henderson-Hasselbach equation

[H+] = 24 paCO2 / [HCO3]

The paCO2 typically increases 0.5 to 1.0 kPa for each mEq/L increase in serum bicarbonate.

There are several ways to interpret blood gases such as Fencl-Stewart’s strong ion difference and base excess analysis. This six step method [6] is straightforward and simple.

1. Assess the internal consistency of the Henderson-Hasselbach equation. The table below approximates the relationship between the pH and [H+].

pH and H+

pH

Approximate [H+] (mmol/L)

7.00

100

7.07

89

7.10

79

7.15

71

7.20

63

7.25

56

7.35

45

7.40

40

7.45

35

7.50

32

7.55

28

7.66

25

7.65

22

2. Analyze if there is alkalemia or acidemia. A pH greater than 7.45 signifies alkalemia and pH less than 7.35 signifies acidemia. If there is alkalemia or acidemia this is typically the primary disorder.

3. Assess whether the disturbance is primarily respiratory or metabolic. Analyze the relationship between pH and pCO2. In primary respiratory disorders pH and pCO2 change in opposite directions. In primary metabolic disorders, pH and pCO2 change in the same direction.

4. Analyze whether there is a compensatory mechanism for a primary disturbance. A primary metabolic acidosis typically elicits compensatory respiratory alkalosis (i.e. decrease in paCO2).

5. If a metabolic acidosis exists, calculate the anion gap. The anion gap is the difference between the measured cations and the measured anions. A normal anion gap is 12.

Specifically, the anion gap (AG) is calculated as

AG= Na + (Cl + HCO3) + 2

Several clinical situations exist that can lead to an increase in anion gap. The mnemonic most frequently used to identify potential causes of high anion gap acidosis is MUDPILES - methanol, uremia, diabetes, propylene glycol, isopropyl alcohol, lactic acidosis, ethanol and salicylates. Other causes include alcohol abuse, iron, isoniazid and cyanide.

6. If there is a high anion gap, assess the relationship between the increase in the anion gap and the decrease in [HCO3].

Assess the ratio of the change in the anion gap (∆AG) to the change in [HCO3-] (∆[HCO3-]): ∆AG/∆[HCO3-]

If ∆AG/∆[HCO3-] equals 1.0 - 2.0 then a noncomplicated anion gap metabolic acidosis is present.

If ∆AG/∆[HCO3-] is less than 1.0 then a concurrent nonanion gap metabolic acidosis is likely to be present.

If ∆AG/∆[HCO3-] is greater than 2.0 then a concurrent metabolic alkalosis is likely to be present.

Anatomy

What are the different elements of the pediatric airway and lung?

Most cardiac arrests in newborns and children are respiratory in origin. Several critical anatomic features should be considered when controlling a child’s airway. Children are obligate nose breathers the nose accounts for one third to one half of all resistance to flow of air.

Children have large tongues relative to their oral cavities and the tongue can easily occlude the palate. In addition, the larynx is cephalad (located at the region of C2 and C3) compared to adults where the larynx is located at C4 to C5. The airway in a child is funnel shaped with the most narrowed portion being the circular cricoid cartilage. By comparison, adults have a trapezoid shaped laryngeal apex. The cricoid cartilage remains the narrowest point of the pediatric airway until eight to ten years of age after which the vocal cords become the narrowest portion. A child’s epiglottis is long, narrow and omega-shaped. A child has a relatively large head compared to an adult. Placing a roll under the shoulder may align the oral, pharyngeal and laryngeal openings for optimal visualization of the cords and successful intubation.

Air enters the system through the nose and then passes through the pharynx, larynx, trachea, and right and left mainstem bronchi before reaching the segmental bronchi of each lobe. The right bronchus comes off the trachea at a less acute angle than the left. Consequently, airway foreign bodies are more often lodged in the right bronchus and specifically the right lower lobe bronchus.

The right upper lobe is divided into the apical, anterior and posterior segments. The right middle lobe is divided into the lateral and medial segments. The right lower lobe is divided into superior, lateral, medial, anterior and posterior segments. The left upper lobe is divided into anterior, apical, and posterior, medial and lateral lingular segments. The lower lobe is comprised of superior, anterior medial, lateral, and posterior segments. Each subsegmental bronchus gives rise to smaller and smaller bronchioles. Overlying the terminal bronchioles are alveoli - the ultimate location of gas exchange.

bronchopulmonary segments

The bronchopulmonary segments of the lung are shown here. (from http://intranet.tdmu.edu.te.ua…)

Medical Treatment

How is a child’s airway controlled and intubated?

Most infants and children who lose their spontaneous ability to breathe can have their respiration augmented by bag mask ventilation (BMV). Any obstruction (including salivary secretions, vomitus or foreign material) should be recognized and removed. The tongue can also obstruct the airway especially when the child is sedated or nonresponsive. A jaw thrust or placement of the child in a sniffing position creates the optimal alignment for BMV and intubation. Peripheral oxygen saturation should be monitored to assure the success of BMV. It is easy to distend the child’s stomach during this maneuver. Gastric distention can lead to bradycardia and, therefore, the stomach should have a nasogastric or orogastric tube placed to suction.

When considering intubation one should examine the airway carefully. This assessment should start with an external examination. In an awake child (e.g. prior to an elective intubation for a surgical procedure) this includes a mouth opening assessment to see whether the pharynx can be seen (Mallampati exam), measurement of hyomental distance (at least three finger breadths) and thyrohyoid distance (at least two finger breadths) and relative neck mobility.

Mallampati classification

From: Amantea SL, Piva, JP, Rodrigues MI.[ Rapid airway access]. J Pediatr (Rio J). 2003 Nov;79 Suppl 2:S127-38. PMID 14647709

The child should be preoxygenated with BMV and 100% oxygen prior to intubation. The heart rate and peripheral oxygen saturation should be monitored continuously. A suction apparatus, endotracheal tube and laryngoscope should be readily available. When needed, a rapid sequence intubation may be used. The Sellick maneuver (which refers to the gentle pressure on the cricoid cartilage to avoid aspiration of gastric contents) may be performed before the administration of an induction agent that consists of a sedative and a rapidly acting neuromuscular relaxing agent. This maneuver is employed in patients who are thought to have a full stomach such as trauma patients, patients requiring emergent operations who have eaten recently (typically two hours for clear liquids and eight hours for solid food) or patients with intestinal obstruction. When intubating, noncuffed endotracheal tubes are generally used for children less than eight years of age to avoid the development of subglottic stenosis. However, cuffed endotracheal tubes (e.g. microcuff) may be appropriate in anticipation of the need for high ventilator pressures (e.g. in the setting of acute lung injury). A straight Miller blade is used to lift the floppy epiglottis allowing direct visualization of the cords.

laryngoscope blades

Blades used in direct laryngoscopy. A Mac blade (top) is more useful in older children while a Miller blade allows more optimal visualization in infants and young children.

After intubation, breath sounds should be checked in both lung fields and the stomach. Importantly, CO2 should be noted inthe exhaled breath on either the end tidal CO2 monitor or by a colorimetic CO2 detector. Finally, a chest radiograph should confirm the placement of the endotracheal tube with its tip located one vertebral space below the clavicle when the chin is visible on the film.

Children have disproportionately active parasymphathetic tone and may become bradycardic while their airway is being secured. This may require the use of atropine prior to intubation - especially in neonates and young infants.

The size of the endotracheal tube is estimated using a variety of means including the size of the child’s small finger, the diameter of the nare, or the formula

(N/4)+4 where N is the age of the child in years.

Cricothyroidotomy is contraindicated in children due to the potential for significant damage to the airway. Various sources list the lower age limit for cricothyroidotomy from five to twelve years. The Pediatric Advanced Life Support guidelines [7] define the pediatric airway as age less than eight years. The most conservative approach is to use twelve years as the cutoff for cricothyroidotomy. A needle cricothyroidotomy can be used in dire circumstance but a more durable airway should be established immediately since CO2 elimination is suboptimal during ventilation by needle cricothyroidotomy.

The American Society of Anesthesiologists has published practice guidelines for dealing with the patient with a difficult airway[8]. It is always recommended to have the most experienced provider secure the airway of a difficult to intubate patient. The preparation prior to intubation should include a history and physical examination when possible, preoxygenation by mask and adjunct medications for sedation and muscle relaxation when appropriate.

There are multiple reasons why a patient may have a difficult airway. These include poor visualization of the cords, recent operation in the head and neck area, local trauma and other clinical situations. Interventions to secure a difficult airway may include the use of supraglottic airways such as the laryngeal mask airway, video assisted laryngoscopy, the use of intubating stylets or tube changers, fiberoptic guided intubation and lighted stylets or wands. Video assisted laryngoscopy (i.e. glidescopes) have been shown to improve laryngeal views and increase the frequency of successful intubation. However, size considerations make its use limited in very small infants. When using flexible bronchoscopy the endotracheal tube is placed over the scope. The cords are visualized and the flexible bronchoscope is placed into the trachea. Subsequently, the endotracheal tube is slid through the cords into the trachea and the bronchoscope is carefully withdrawn.

The American Society of Anesthesiologists recommends having a complete plan when dealing with patients with a difficult airway. Is awake intubation possible? Although the success rate of awake intubation may be as high as eighty percent, awake intubations are not well tolerated in young children. There should be a contingency plan in case intubation is unsuccessful. Is there a more experienced provider available? Should a noninvasive airway or an invasive airway be performed? Should spontaneous breathing continue or neuromuscular blockade be instituted? Each patient and clinical scenario will have different immediate and long term goals. Thus, the approach should be individualized.

How does a conventional ventilator work?

Modern ventilators have circuits that have constant gas flow going from the inspiratory to the expiratory limb. Patient initiated breaths are detected by either a change in the flow (more sensitive with less patient effort required) or by pressure changes in the ventilator circuit (less sensitive with more patient effort required).

With conventional ventilation, each positive pressure breath is generated by the ventilator and airflow is delivered at a specific rate via an endotracheal tube.

A ventilator breath is a full cycle consisting of inspiration with positive inspiratory flow and passive expiration with negative inspiratory flow. A breath delivered by the ventilator can be classified according to three factors

  • the trigger or the mechanism that initiates the breath
  • the targeted variable, control or limit for the delivered breath
  • the variable that terminates or cycles the breath

ventilator breath

Components of a ventilator breath. 1 - trigger is either initiated by the ventilator or the patient, 2 - limit (what controls the breath) pressure versus volume, 3 - cycle (how the breath is terminated, time versus flow). (figure courtesy of Martin Wakeham MD)

Triggering refers to the start of the breath. The traditional trigger is time where breaths are delivered by the ventilator at set time intervals without regard for patient effort. Time triggered breaths can lead to patient ventilator asynchrony, air trapping and an increased work of breathing. For this reason, time triggered ventilation is rarely used. Some modes of ventilation detect patient respiratory effort as the trigger for breath initiation. Patient triggered ventilation can occur with four methods: pressure, flow, volume or shape signal changes. The goal of patient triggered breaths is to make the ventilator as sensitive as possible to patient effort. Patient efforts are detected by the ventilator by a decrease in pressure or flow within the circuit. Pressure triggered breaths requires the patient to decrease airway pressure from the end expiratory level to a threshold pressure sensitivity setting on the ventilator. Pressure sensitivity settings vary from from 0.5 in infants to 1 to 2 cm H2O in adults. Flow triggered breaths require flow changes in the ventilator circuit beyond some predetermined threshold (flow sensitivity). Flow sensitivity settings are typically 0.2 L/min for infants, 1 L/min for adolescents and 2 L/min for adult patients.

Once a breath is initiated, the ventilator assists with the breathing by using either volume or pressure limits or controls (these terms are used interchangeably). The tidal volume (TV) refers to the size of each breath delivered by the ventilator. The breath delivered is defined by the maximum volume (volume control, VC) or the peak pressure (pressure control, PC) delivered with each inspiration. Since volume and pressure are related by the lung compliance (compliance = ∆V / ∆P), when volume is kept constant (volume control ventilation) the pressure required to deliver that volume varies depending on the lung compliance. Similarly, when pressure is held constant (pressure control ventilation) the volume delivered may vary from breath to breath. The flow with which gas is delivered and the resistance of the system are factors that can affect the ventilating volume or pressure delivered as well as the shape of the pressure/volume inspiratory wave. Volume and pressure are the most common limits or controls of a ventilator delivered breath.

pressure vs volume control ventilation

In pressure control ventilation, the pressure is limited such that the volume changes depending on the lung compliance. In volume ventilation, the delivered tidal volume remains the same, and pressure with which the breath is delivered changes when compliance. (figure Courtesy of Martin Wakeham MD)

Cycle refers to the determinant that ends the breath. Like the initiation of the breath, the termination of the breath can be determined by the machine or by the patient. Typically, PC breaths are time-cycled, that is the expiration begins after a preset inspiratory time (ITime) or inspiratory:expiratory ratio (I:E) is reached. With VC, expiration usually begins after a certain tidal volume (VT) is reached and, thus, the breaths are volume-cycled. Another alternative is for the patient to determine when the breath should terminate. This approach of patient-determined cycling is called pressure or volume "support": the breath usually stops when the inspiratory flow decreases to a small percentage of peak inspiratory flow and, thus, is flow-cycled. The ventilator senses that the patient is about to terminate his or her own breath and cycles the breath into expiration prior to reaching a zero flow state.

When initiating conventional mechanical ventilation several determinants need to be considered. These factors include the ventilator mode, rate, tidal volume or peak inspiratory pressure (PIP), FiO2, and positive end expiratory pressure (PEEP).

What are the modes of conventional mechanical ventilation?

Based on who or what initiates the delivered breath one can choose a mandatory mode, support mode, or combination of both. The different modes of ventilation are typically based on the triggering mechanism.

With the first four modes (see below), the limit of the breath can be determined by volume or pressure. When VC is utilized, expiration starts after the full TV is delivered (volume-cycled). In PC, expiration begins after a preset inspiratory time is reached (time-cycled) or according to the preset I:E ratio.

Controlled Mandatory Ventilation (CMV)

The ventilator initiates and delivers a set of mandatory breaths at equal intervals (based on a set respiratory rate) regardless of the patient effort. Patient initiated breaths are ignored by the ventilator.

Intermittent Mandatory Ventilation(IMV)

Similar to CMV, the ventilator delivers a set number of mandatory breaths. The difference from CMV is that the patient is able to breathe from a gas flow system between the mandatory breaths. The size of the patient’s breaths depend on the patient effort since they are not supported by the ventilator at all. Since breaths are delivered independent of patient effort, significant asynchrony can result.

Assist Control (AC)

AC is a mode in which all spontaneous breaths that exceed the trigger sensitivity result in the delivery of a fully assisted mechanical breath (assist) synchronous to the patient’s inspiratory effort. If the patient fails to breathe or cannot trigger the ventilator, a mandatory breath will be provided at the desired interval. However, the timing mechanism resets after each mechanically delivered breath. For the patient initiated breaths, the ventilator delivers the same level of support as the mandatory ones.

Synchronized Intermittent Mandatory Ventilation (SIMV) +/- Pressure Support (PS)

It is similar to IMV, but the ventilator synchronizes the mandatory breaths with the patient effort. For example, if the RR is set at twelve breaths/min, the ventilator would wait up to five seconds in order to detect a patient effort; if an effort is detected at any time during that period, a fully supported breath is delivered in synchrony with that effort. If no effort is detected, a fully supported breath is delivered. Again, similar to IMV, the patient is able to breathe above the set rate. The level of ventilator support during these spontaneous breaths could be set from none to a level (by choosing the SIMV/PS mode) that equals the support received during the mandatory breaths. During SIMV without the addition of pressure-support, however, any spontaneous breaths beyond the mandatory rate are not assisted by the ventilator. That spontaneous breaths are not supported is one of the disadvantages of this mode, along with concern for patient asynchrony.

Pressure Support Ventilation (PSV)

As a sole mode of ventilatory support (not an adjunct to SIMV), PSV is a pressure limited, flow cycled mode of ventilation that decreases the work of breathing by providing flow during inspiration for patient triggered breaths [9]. In this modality, the patient triggers each breath by a decrease in pressure or decrease in flow within the circuit and the ventilator typically delivers inspiratory pressure until the inspiratory flow decreases to about 25% of its peak value. Flow triggering may be superior to pressure triggering in PSV mode. The pressure limit during PSV can be adjusted to provide fully supported breaths (pressure sufficient to deliver a full tidal volume breath) or partially supported breaths. It is a comfortable mode that is good for weaning since gradually lowering the pressure limit allows the patient to use his or her own muscles gradually for breathing. However, it is not good for prolonged full ventilatory support, patients with central apnea or in patients that require high airway pressures.

What are additional settings on the ventilator?

Pressure Support (PS)

Positive pressure is delivered by the ventilator in order to overcome the resistance of the endotracheal tube and the ventilator circuit tubing during inspiration. The narrow endotracheal tube and the long tubing from the ventilator absorbs a significant amount of the flow delivered. PS decreases the work of breathing by providing flow during inspiration. It can also be adjusted by increasing the flow until the intended tidal volume is delivered to the patient.

Inspiratory Time (ITime)

Inspiratory time refers to the period of time during the breath that is occupied by inspiration. Generally, ITime is age dependent, being shorter in infants and small children (0.4 to 0.7 second) than in adolescents (0.8 to 1 second). Increasing ITime increases MAP and, as a result, oxygenation. If the expiratory phase becomes too short, CO2 elimination may be compromised and auto PEEP may occur because of incomplete expiration (air trapping).

Positive End Expiratory Pressure (PEEP)

Setting the PEEP regulates the pressure at the end of the expiratory phase and this is a mechanism to control the patient’s functional residual capacity (FRC). The goal should be to maintain FRC above closing capacity: the volume at which the smallest airways start to collapse during expiration. PEEP should rarely be set below four to five cm H2O (good starting point) and should be titrated up based on the oxygen requirements. Other than increasing the FiO2, because increases in PEEP directly augment the MAP, increasing the PEEP is the most effective way to increase oxygenation. However, since PEEP is transmitted through the chest cavity, a very high PEEP can increase intrathoracic pressure and decrease cardiac preload.

Continuous Positive Airway Pressure (CPAP)

In this mode of ventilation, a constant PEEP is set without an associated respiratory rate. No mandatory breaths are delivered and all breaths must be triggered and performed by the patient. The clinician can choose the level of PEEP and, thus, the support provided. Most ventilators have a backup rate in case the patient becomes apneic while on this mode.

How are ventilator waveforms interpreted?

Ventilator graphics create waveforms that demonstrate the interactions between the ventilator and the patient, allowing users to evaluate and optimize the ventilator. Waveforms describe the patient’s lung status including compliance and airway resistance. Waveforms also enable the interpretation of the synchrony between the patient and ventilator to optimize ventilatory support.

There are two types of waveforms:

  1. Scalar waveforms plot pressure, volume, or flow on the y-axis against time on the x-axis.
  2. Loop waveforms plot pressure or flow (y axis) against volume (x axis).

Scalar waveforms

There are three shapes of scalar waveforms:

  1. Square - represents a constant parameter (e.g., pressure in Pressure Control Mode increases to a set pressure during inspiration and returns to the set PEEP during expiration)
  2. Ramp - represents a variable parameter that can be accelerating or decelerating and varies with lung characteristics
  3. Sine - typically seen with spontaneous, unsupported breaths.

The ventilator screen usually shows three different types of graphic scalar waveforms—pressure, flow, and volume.

scalar ventilator waveforms

Medium blue—inspiratory phase, dark blue—expiratory phase, lightest blue—inspiratory hold. Note that in the pressure modes, flow waveforms are able to distinguish pressure limited control modes (time cycled) versus support modes. With control modes, inspiratory flow returns to baseline before expiration, but with support modes inspiratory flow does not return to baseline. (figure courtesy of Charles S. Williams RRT, AE-C)

Pressure Waveforms

In volume modes, the pressure waveform is ramp shaped for the ventilator initiated breaths. Adding an inspiratory hold to the end of inspiration creates a small plateau to the waveform which allows one to see the static (versus the dynamic) airway pressure (Pplat). Peak inspiratory pressure (PIP) is higher when compared to the Pplat since the PIP is measured during active ventilator inspiration while Pplat is measured under static conditions when inspiration is complete and airway pressure has come to equilibrium.

pressure waveform

The components of the pressure waveform. 1 - peak inspiratory pressure (PIP), 2 - plateau pressure (Pplat), A - airway resistance, B - alveolar distending pressure. The entire area under the curve represents the mean airway pressure (MAP). (figure courtesy of Charles S. Williams RRT, AE-C)

When a patient initiates a breath, there is a negative deflection to the baseline. Ventilator initiated breaths start the inspiration at baseline.

ventilator versus patient triggered

Pressure waveform demonstrates whether the trigger (beginning of the wave) is ventilator generated (first wave, no deflection in pressure that would indicate inhalation) or patient generated (second wave, designated by the negative deflection ofpressure of inspiratory effort). (figure courtesy of Charles S. Williams RRT, AE-C)

An increase in airway resistance increases PIP, but keeps Pplat the same.

increase in airway resistance

When there is an increase in airway resistance, PIP increases, but Pplat remains the same. (figure courtesy of Charles S. Williams, RRT AE-C)

A decrease in compliance results in a higher PIP and Pplat (more pressure to get the same volume). To determine whether there is air trapping, apply an expiratory hold and see whether the waveform rises above baseline.

air trapping

When an expiratory hold is applied, the pressure wave shifts above the baseline. Set PEEP is the value from pressure from the x axis to the start of inhalation (blue line). Auto PEEP is the value above the blue line. (figure courtesy of Charles S. Williams RRT, AE-C)

In pressure modes, the shape of the pressure wave is a square shape because the pressure is constant and is a set parameter.

Flow Waveforms

In volume modes, the flow wave is square shaped. This is because in traditional volume control the flow delivery quickly accelerates at the beginning of inspiration, but is then held at a set constant through inspiration resulting in a square shaped waveform and a slower inflation of the lung. Some ventilators will allow selection of a variable flow pattern in volume control. For instance, a decelerating flow pattern may allow the delivery of the same tidal volume at a lower peak pressure compared to constant flow: the PIP approaches Pplat toward the end of inspiration with decelerating flow.

In pressure modes, the flow waveform will have a decelerating ramp pattern. The inspiratory phase in pressure ventilation has a rapid acceleration of flow during the onset of ventilation and achieves the peak pressure and target volume early in the phase of inspiration. A decelerating flow pattern is thereby generated. With this pattern, pressure and volume are "front-loaded" which may have the advantage of recruiting lung and enhancing oxygenation.

flow waveform

During volume ventilation, flow is constant during inhalation until the desired volume is reached. Flow then goes to zero as exhalation is a passive process of negative flow. With pressure ventilation, flow is highest in the beginning of the inhalation until the PIP is reached then flow decreases. (figure courtesy of Charles S. Williams RRT, AE-C)

Flow waveforms are helpful in determining the presence of air trapping as the expiratory flow does not return to baseline before the start of the next breath. In patients with a short ITime or disease states such as asthma, where expiratory flow is limited, expiration may be incomplete at the time that the next breath is triggered. As a result, "air trapping" may occur. A response to bronchodilator therapy is shown with resulting improved peak expiratory flow (deeper negative inflection) and a shorter time to return to baseline at expiration.

auto PEEP

Auto PEEP can be determined using flow waveforms when the waveform does not return to baseline before the next breath. (figure courtesy of Charles S. Williams RRT, AE-C)

Flow waveforms also help distinguish between pressure limited modes, which are time cycled, and support modes, which are flow cycled. With pressure limited, time cycled modes, inspiratory flow typically approaches zero or baseline before expiration. However, with support modes the ventilator cycles into expiration when the flow decreases to a set fraction of peak flow (e.g. 25%). As a result, inspiratory flow is positive at the time that expiration is initiated.

ventilator versus supported breath

In pressure limited ventilation, control mode (time cycled) waveforms return to baseline. In contrast, those with pressure support modes (flow limited) the flow does not return to baseline. (figure courtesy of Charles S. Williams RRT, AE-C)

When using time cycled control modes, if there is a substantial segment of time at baseline (zero flow state) before expiration starts, it is likely that the inspiratory phase is too long.

Volume Waveforms

Volume waveforms have the appearance of mountain peaks both in pressure control or volume control ventilation. A plateau at the top of the peak signals an inspiratory hold.

volume waveform

Volume waveforms usually look like a peak. An inspiratory hold is a plateau at the end of the inspiration. The volume wave returns to baseline on expiration. (figure courtesy of Charles S. Williams RRT, AE-C)

Volume waveforms are most commonly used to assess for the presence of air trapping or leaks. With air trapping, the expiratory phase does not return to baseline before the next inspiration is triggered. With leaks, the volume returned is less than that inspired even with an adequate ITime.

volume waveform: airtrapping

Air trapping or system leak. The expiratory phase does not return to baseline before the next inspiration. Dotted line represents normal waveform. (figure courtesy of Charles S. Williams RRT, AE-C)

Loop Waveforms

Pressure/volume loops demonstrate the changes in pressure (x axis) and volume (y axis) during a single mechanically delivered breath. The loop begins at volume = 0 and pressure = PEEP. The inspiratory phase curves upward and the expiratory phase curves downward because dynamic pressures are being measured. Spontaneous breaths go clockwise and positive pressure breaths go counterclockwise. A line is drawn in the middle of the loop and the area above the line represents expiratory resistance and the area below the line identifies the inspiratory resistance. The pressure-volume relationship at the top of the loop represents the "dynamic" compliance since airway pressures may, at that point, not be in equilibrium. Thus, the compliance is being measured at PIP rather than Pplat.

presssure-volume loop

Spontaneous breaths go clockwise. Ventilator breaths go counterclockwise. The bottom of the loop is the PEEP. The area to the right of the line drawn in the middle of the loop represents inspiratory resistance (red) and the area to the left (blue) is the expiratory resistance (blue) . When the red area becomes bigger (hysteresis) it signals higher inspiratory resistance such as a kinked endotracheal tube, patient biting the tube or secretions in the tube. When the blue area gets bigger, it demonstrates higher expiratory resistance such as bronchospasms. The upper point of the curve is the dynamic compliance of the lung. (figure courtesy of Charles S. Williams RRT, AE-C)

In pressure control (PC) ventilation, the loop is more square shaped because when the pressure limit is reached the inspiratory loop travels straight upward.

pressure control ventilation

During pressure control ventilation, once the PIP is reached, the pressure remains the same, creating a square shaped loop. (figure courtesy of Charles S. Williams RRT, AE-C)

If beaking occurs at the end of the inspiratory curve, it signals increased pressure with little volume change or over distension. In this case, the PIP should be decreased.

overdistension

An example of “beaking”. PIP should be decreased. (figure courtesy of Charles S. Williams, RRT, AE-C)

A lung with decreased compliance has a pressure-volume loop that is flatter (increased pressure with lower volume). Better compliance creates a taller curve with increases in pressure corresponding to higher volumes.

change in compliance

Increased compliance shows a pressure-volume loop towards the left (higher volume for less pressure). Decreased compliance is demonstrated by lower volumes achieved by higher pressures, thus a flatter pressure volume curve. (figure courtesy of Charles S. Williams RRT, AE-C)

If the expiratory phase of the pressure-volume loop does not return to baseline it suggests a leak in the system or air trapping.

A flow volume loop plots volume on the x-axis and flow on the y-axis. Inspiration is above the horizontal line and expiration is below. The shape of the inspiratory portion of the curve matches the flow waveform. The shape of the expiratory flow represents passive exhalation. Thus, a flow volume loop for a volume controlled breath has a square waveform while a pressure control breath has a decelerating shape. Spontaneous breaths look circular. Flow volume curves look similar to pulmonary function tests. They are useful in determining peak inspiratory and expiratory flows.

flow volume loop

Inspiration is above the x axis and the expiration is below the y axis. The shape of the inspiration curve matches the flow waveform. The expiratory portion represents passive exhalation. (figure courtesy of Charles S. Williams, RRT, AE-C)

When the exhalation phase does not come down to baseline there is an air leak or air trapping. In airway obstruction states, such as asthma, reduced peak flow and scooping of the inspiratory flow are seen.

airway obstruction

Airway obstruction is signaled by reduced peak flow and scooping on exhalation. (figure courtesy of Charles S. Williams RRT, AE-C)

What are the advanced modes of mechanical ventilation?

Pressure regulated volume control (PRVC) is a hybrid mode of mandatory ventilation that combines pressure and volume control/limited ventilation. A preset TV and frequency (minute ventilation) is delivered with a pressure limit. A decelerating flow pattern allows the TV to be obtained at the lowest peak pressure. The preset TV is achieved with a different pressure by breath to breath regulation based on the previous breath and accounting for lung compliance and airway resistance. This mode can be used in a controlled or SIMV mode.

pressure regulated volume control

A preset VT and frequency (minute ventilation) is delivered with a pressure limit and at the lowest possible pressure by a changing (adapting) decelerating flow. The preset VT is achieved with a different pressure by breath to breath regulation.

For the PRVC mode, the following ventilator settings are typically determined: minimum respiratory rate, target tidal volume, upper pressure limit, FiO2, inspiratory time or I:E ratio, rise time, and PEEP. Inspiratory rise time determines speed of rise of flow (volume control mode) or pressure (pressure control and pressure regulated volume control modes). It should be about five percent of Itime. A short rise time is uncomfortable for the patient while a long rise time may fail to deliver the full breath.

PRVC is advantageous for the patient because the pressure used to deliver a breath is automatically adjusted for changes in lung compliance and airway resistance within a set range. Therefore, the delivered tidal volume is guaranteed, but volutrauma is limited. The pressure delivered is dependent on the tidal volume achieved on the last breath, allowing breath to breath modulation of pressure. It is less suitable for patients with asthma and chronic obstructive pulmonary disease. PRVC may fail to provide programmed TV, since the ventilator may sense a higher airway pressure, ultimately leading to hypoventilation of the patient.

Airway pressure release ventilation (APRV) [10] is a time triggered, pressure-limited, and time-cycled mode. This mode of ventilation can be thought of as giving a patient two different levels of CPAP. A high continuous pressure (Phigh) is delivered for a long duration (T high) which then is "released" to a lower pressure (Plow) for a shorter duration (Tlow). The clinician/operator sets “high” and “low” pressures and a release time. The length of time at “high” pressure is generally greater than the length of time at “low” pressure. “Releasing” to the lower pressure allows lung volumes to decrease to FRC, thereby providing ventilation. Spontaneous breathing is allowed (with or without pressure support) during inflation and deflation phases.

airway pressure release ventilation

A high continuous pressure (Phigh) is delivered for a long duration (T high) then falls to a lower pressure (Plow) for a shorter duration (Tlow). The clinician adjusts the high and low pressures with release time. Releasing to the lower pressure allows lung volume to decrease to FRC alllowing ventilation.

Conceptually, APRV maximizes alveolar recruitment by keeping the lung inflated for extended periods of time with high CPAP. The "driving pressure" is the pressure difference between Phigh and Plow. The size of the tidal volume is related to both the driving pressure and the compliance. The transition from Phigh to Plow deflates the lungs and eliminates CO2. Thigh and Tlow determine the frequency of inflations and deflations.

The potential benefits of APRV include improved alveolar recruitment and oxygenation. Some observational studies show decreased peak airway pressure, improved alveolar recruitment, increased ventilation of the dependent lung zones, and improved oxygenation. However, no improvement in mortality has been reported. In severe obstructive disease, APRV could lead to hyperinflation and barotrauma [11].

Biphasic ventilation (i.e. Bi-Vent, BiLevel, BiPhasic, BiPAP and DuoPAP) is similar to APRV except that time at Plow is longer during biphasic ventilation allowing more spontaneous breaths to occur during this period.

In adaptive support ventilation mode the ventilator automatically adjusts respiratory rate and inspiratory pressure to achieve a desired minute ventilation based on the patient’s respiratory mechanics. The clinician sets a desired minute ventilation and a patient weight (for estimating anatomic dead space). The ventilator calculates an expiratory time from the flow volume loop and determines the respiratory rate that minimizes work of inspiration at a given minute ventilation. Breaths are pressure-controlled and there is pressure support for triggered breaths to achieve a desired respiratory rate. As respiratory mechanics change the rate and tidal volume pattern is automatically adjusted to maintain this optimal pattern.

Volume support (VS, i.e. automatic pressure ventilation) is designed for spontaneously breathing patients who need only partial ventilatory support. In the VS mode, the patient triggers each breath. Clinicians select a target tidal volume and the ventilator makes automatic adjustments in pressure support as long as the patient’s TV reaches the minimum TV prescribed. If the patient is able to breathe without support, the ventilator monitors spontaneous breathing and volumes achieved. If ventilatory support is needed, the ventilator automatically adapts the inspiratory pressure support level to the lowest appropriate pressure support level. The lowest appropriate level is based on automatic monitoring by the ventilator of the mechanical properties of the lungs and thorax and the preset tidal volume and minute volumes. In VS the inspiratory pressure is constant and the inspiratory flow is decelerating. The patient determines the rate and inspiratory time.

Inverting the inspiratory to expiratory ratio (I:E ratio, I>E) is used to potentially improve oxygenation in a patient who is already receiving optimal PEEP and FiO2. It can be used with volume-limited or pressure-limited mechanical ventilation.

In pressure-limited ventilation, the I:E ratio is simply increased. In volume-limited ventilation with a "ramp" waveform, the peak inspiratory flow rate is decreased until I exceeds E. In volume-limited ventilation a pause is added to the end of inspiration in order to increase the overall inspiratory time until I exceeds E.

When the inspiratory time is increased the expiratory phase may be limited. It is imperative to ensure that the patient is able to eliminate CO2. In addition, one must be cautious of auto PEEP whereby the full inhaled volume is not eliminated causing hyperinflation.

What is the role of high frequency oscillatory and jet ventilation?

High frequency ventilation (HFV) is based on the open lung concept - keeping the lung inflated for extended periods of time to maximize alveolar recruitment. HFV uses very high breathing frequencies (120 to 900 breaths/min) coupled with very small tidal volumes (less than 1 mL/kg) to provide gas exchange in the lungs. These breaths can be delivered by oscillators or jets. Jets inject high frequency pulses of gas into the airways at rates between 100 to 600 breaths per minute.

In high frequency oscillatory ventilation (HFOV), both inspiration and expiration are active processes, in contradistinction to the passive exhalation that occurs in conventional ventilation. Conceptually, in HFOV, a relatively high mean airway pressure (MAP) keeps the lung open or inflated. Frequent, small breaths are cycled or oscillated around this MAP to deliver oxygen and remove carbon dioxide. To increase oxygenation, MAP and FiO2 are the parameters that can be adjusted. Secondarily, alveolar recruitment strategies such as hand ventilating may improve oxygenation as well. To affect ventilation, the amplitude (i.e. power, ΔP) and frequency of breaths (1 Hertz = 60 breaths per minute) are adjusted. Other strategies to facilitate CO2 removal are deflating a cuffed tube (allowing CO2 to escape along the tracheal walls) and decreasing Itime.

In HFOV, MAP is typically set at 2 to 4 cm H2O above the level on conventional ventilation in neonates or 6 to 8 cm H2O higher than conventional ventilatory MAP in older infants and children. When starting HFOV, MAP in infants should be 8 to 10 cm H2O and 15 to 18 in children. Frequency is started at approximately 12 Hz in premature infants, 10 Hz in term infants, 8 Hz in children weighing up to 10 kg and 6 Hz in children greater than 10 kg in weight. Power is started at 4. Itime is set at about 33% [12].

When using HFOV, one must look at the patient for the chest wiggle to determine the adequacy of ventilation. With an adequate MAP a should show lung expansion to the ninth or tenth ribs.

When weaning oxygenation support on HFOV, FiO2 is weaned first when there is good chest expansion and then MAP is weaned by 1 to 2 cm. To wean ventilatory support, the amplitude is typically weaned before the frequency.

Very small alveolar tidal volumes minimize cyclical overdistention and derecruitment. HFV maintains the alveoli open at a relatively constant airway pressure and thus may prevent atelectrauma and barotrauma. Conceptually, HFV improves ventilation/perfusion (V/Q) matching by ensuring uniform aeration of the lung.

high frequency oscillatory ventilation

The waveforms depicting the key variables that are controlled during high frequency oscillation as compared to conventional ventilation are depicted in the next figure.

HFOV versus conventional ventilation

The y axis on the left demonstrates changes in airway pressure seen with HFOV and the y axis on the right depicts changes in peak airway pressure with conventional ventilation. The tracheal pressure becomes negative at peak expiration, making expiration an active process. As amplitude increases, delivered minute ventilation increases. A background tracing of pressure versus time using a respiratory rate of 12 and inspiratory to expiratory ratio of 1:3 with conventional ventilation is presented for comparison.

The most common indications for HFOV are a failure of conventional mechanical ventilation and a need to decrease peak inspiratory pressure. Some surgeons find HFOV useful in thoracoscopic surgery [13] High frequency jet ventilation (HFJV) is typically used for bronchopleural fistulas or conditions with significant air leaks.

What is neurally advanced ventilatory assist?

Neurally advanced ventilatory assist (NAVA) is an innovative approach to ventilation which relies on the the detection and quantification of the electrical activity of the diaphragm to initiate and to proportionally assist each breath [14]. Theoretically this mode has the advantage of better patient and ventilator synchrony. NAVA requires the insertion of a specialized nasogastric tube which contains a set of electrodes that recognize the electromyographic activity of the diaphragm (Edi) and transmits this activity to a ventilator. The signals are digitally amplified and processed. For each breath the waveform with the highest Edi value is termed the Edi peak. The Edi peak is the neural inspiratory effort that dictates the size and duration of each breath. The lowest Edi value (Edi low) is the baseline tone of the diaphragm. Edi low is likened to PEEP in that it keeps alveoli from collapsing. The Edi trigger is set to detect the patient desire for a breath.

The NAVA level is a proportional factor that converts the Edi signal into a pressure. Its units are cm H2O/mV. The airway pressure above PEEP (i.e. PIP) is determined by multiplying the Edi by the NAVA level thus providing breath to breath tailoring of patient support. The peak pressure is determined every 60 milliseconds and increases as long as the Edi increases. Thus, the NAVA level is continually adjusted based on the neural feedback.

When a patient is placed on NAVA, the same PIP that was effective for the patient while on conventional ventilation should be used as the initial target. Initially, the NAVA level is set at 0.5 to 1. The Edi peak is observed and if it is high (.15 to 20) and/or significant retractions are observed the NAVA level is increased by 0.2 to 0.5. Typically, when the NAVA level is increased, it results in an increase in PIP, mean airway pressure and tidal volume while the Edi peak remains constant until a break point in the NAVA level is identified. At that point the PIP has reached a sufficient point such that patient desire and Edi peak decrease. If the NAVA level is increased beyond the break point, the respiratory drive and, therefore, the Edi will decrease further. The NAVA level can be titrated as the pulmonary pathology changes much like any ventilator support parameter.

There are normative data available on Edi in populations including preterm infants and neonates. If a patient’s Edi is higher than normal this indicates that the patient is working too hard and higher ventilatory support (higher NAVA) may be needed. Conversely, a low Edi may signal lack of spontaneous respiratory drive and a decreased need for ventilatory support.

An important consideration is the proper positioning of the esophageal probe in order to capture the Edi accurately. Indeed, misplacement of the esophageal probe places the ventilator in back up mode. Other ventilator parameters which are set while on NAVA include PEEP (with a goal of Edi min less than 3), apnea limit (usually about five seconds), back up settings (rate, PIP, Itime), upper pressure limit (start 10 mm above usual PIP) and Edi trigger (default is 0. 5 mcV) [15].

What is the role of inhaled nitric oxide?

Nitric oxide is produced by many cells in the body including the vascular endothelium and is important in mediation of vascular tone. Inhaled nitric oxide (iNO) results in preferential pulmonary vasodilation and decreased pulmonary vascular resistance. iNO within the alveoli diffuses into the capillaries and then the smooth muscle of pulmonary vessels where it activates guanylate cyclase which converts guanine triphosphate (GTP) to cGMP. cGMP results in smooth muscle relaxation. iNO is scavenged by hemoglobin so that the vasodilatory effect is limited to the pulmonary vascular bed.

The unit of iNO delivered is expressed in parts per million (ppm). Concentrations greater than 20 ppm have not been shown to provide additive beneficial effects.

iNO is used to help manage persistent pulmonary hypertension in neonates and children. It is administered most commonly to patients on the ventilator, but other routes are possible. The iNO/nitrogen mixture is introduced into the ventilator tubing close to the patient to decrease the formation of nitrogen dioxide.

iNO administration impairs endogenous NO production. Since the abrupt discontinuation of iNO can result in rebound pulmonary hypertension, iNO should be weaned gradually.

iNO is utilized in patients with pulmonary hypertension such as diaphragmatic hernia, meconium aspiration, and persistent pulmonary hypertension of the newborn[16]. A 2011 Cochrane Review of inhaled iNO in premature infants with respiratory distress syndrome show no significant effects in death, development of bronchopulmonary dysplasia or intraventricular hemorrhage (incidence or severity) with the use of iNO compared to conventional therapy [15][17]. The use of iNO in newborns with diaphragmatic hernia is widespread [18]. However, data show that iNO use in diaphragmatic hernia does not increase survival or decrease the need for extracorporeal life support (ECMO)[17][19].

In contrast, in term and near term neonates with hypoxemic respiratory failure, multicenter randomized clinical studies subsequently confirmed that iNO therapy reduces mortality and the need for ECMO [19][20]. In fact, inhaled NO therapy has been approved by the FDA for clinical use in term/near term newborn infants (greater than 34 wks gestation) with hypoxic respiratory failure and PPHN since 2000 [21].

Recent reviews show that in children and adults with acute respiratory distress syndrome and acute lung injury, although the use of iNO led to a transient improvement in oxygenation its use did not reduce mortality and may potentially be harmful [22][23].

What is the role of prone positioning?

Prone positioning refers to mechanical ventilation while the patient is lying prone. It has been used to improve oxygenation in patients who require mechanical ventilatory support for the management of ARDS. Although the mechanism is largely unknown several hypotheses exist. When a patient with edematous, sick lungs lays supine, the weight of the lungs results in atelectasis of the posterior lung fields and inflation of the anterior lung fields.

prone positioning in ARDS

Effects on lung densities of supine positioning at a) end expiration and at b) end inspiration and prone positioning at c) end expiration and d) end inspiration. At end expiration, densities moved from dorsal to ventral regions. At end inspiration, ventilation is improved in the prone compared to supine position. (rom Pelosi P, Brazzi L, Gattinoti L. Prone positioning in acute respiratory distress syndrome. Eur Respir J 2003)

In addition, because of the effects of gravity, pulmonary blood flows preferentially to the atelectatic, posterior aspects of the lung leading to a V/Q mismatch. Prone positioning may equalize the distribution of ventilation and perfusion within the lung units by redistributing the pulmonary blood flow and the regional tendency toward inflation or collapse. Prone positioning may also potentially reduce lung injury by minimizing the stress and strain on the alveoli by equalizing the inflation across segments.

In adults, meta-analyses and randomized controlled trials have shown that prone positioning, when performed early and for a prolonged time, decreases 28 and 90 day mortality [24]. A 2013 Cochrane review found that prone positioning only slightly improved oxygenation in infants, but a sustained and clinically relevant improvement was not observed [25].

What is the role of permissive hypercapnea?

Mechanical ventilation can potentiate or cause ventilator associated lung injury (VALI). Permissive hypercapnea is a strategy that accepts hypoventilation and elevated carbon dioxide blood levels to avoid the detrimental effects of baro- and volutrauma.

Advances in the understanding of the biology of hypercapnia have suggested that hypercapnic acidosis may modulate lung inflammation and tissue injury as well as systemic organ injury. For example, hypercapnic acidosis may play a role in lung protection in endotoxin-mediated lung injury and pulmonary apoptosis in the setting of ischemia and reperfusion injury. These protective effects have also been demonstrated in the ex vivo hepatocyte and in neuronal cell models. Likewise, hypercapnic acidosis has been shown to exert cardioprotective effects in ex vivo and canine models. However, there are no clinical data evaluating the effectiveness of hypercapnia per se independent of ventilator strategy in acute lung injury states [26].

In infants, permissive hypercapnia is employed as a part of gentle ventilation strategies in patients with diaphragmatic hernia and respiratory failure of other etiologies. Caution should be exercised in shock states given the potential for exacerbating systemic acidosis and hemodynamic compromise. Additionally, hypercapnia should be avoided in clinical situations where increased intracranial pressure is a possibility. The level of acidosis generally tolerated is about 7.2 to 7.25. If necessary, buffering pH with bicarbonate is used to treat the acidosis.

Medical Decision Making

What are the indications for mechanical ventilation?

The decision to place a patient on mechanical positive pressure ventilation is based on several parameters including an assessment of the symptoms and signs of respiratory failure, laboratory tests, such as blood gases, and physiologic parameters (pulse rate, respiratory rate, pulse oximetry, measurement of pulmonary mechanics). The indications for mechanical ventilation can be divided into primary pulmonary or nonpulmonary causes of respiratory failure.

Primary lung disease can be at the airway, alveolar or interstitial level but, in most cases, multiple levels of the lung unit are affected. These disease processes include bronchiolitis, asthma, pneumonia and interstitial fibrosis.

There are many causes of nonpulmonary respiratory failure. Extrinsic pressure on the lungs such as in tension pneumothorax or hemothorax can cause lung dysfunction. Cardiac failure can cause both acute and chronic pulmonary compromise. Neuromuscular dysfunction such as amylotropic lateral sclerosis or spinal muscular atrophy can also result in respiratory failure due to weakness. Sepsis, shock, and other disease states require mechanical ventilation as supportive therapy while the underlying cause is being treated. In cases where patients cannot initiate or maintain spontaneous breathing, such as in a comatose patient, mechanical ventilation is necessary for airway protection and ventilatory support. Mechanical ventilation is also an important adjunct in the management of traumatic brain injury since prevention of hypercapnia helps to avoid exacerbation of elevated intracranial pressure.

What is the decision making process around ventilation approach and techniques?

There is no ventilation approach that has been demonstrated to be better than others. Therefore, the physician should use the ventilator modality and settings that would optimally support the patient without causing ventilator associated lung injury. In a spontaneously breathing patient, the use of a synchronized modality may result in more patient comfort and earlier weaning. Similarly, the use of patient initiated breaths alone would be inappropriate in an obtunded, apneic patient who cannot generate spontaneous respiration.

Pressure control ventilation is more commonly used in infants and young children but recent data have shown that volume ventilation can be successful and even protective from lung injury in small babies [14].

High frequency oscillatory ventilation is a modality used when conventional ventilator techniques are unable to deliver adequate gas exchange at settings that are not harmful to the lung. High frequency jet ventilation is most often used when there are sustained leaks in the respiratory system.

How are the initial ventilator settings chosen?

  1. Select a mode based on the desired triggering mechanism (see Medical Treatment). The mode chosen is dependent mainly on the clinical scenario.

Is the patient requiring mandatory breaths due to muscle relaxation or heavy sedation such that time is the best trigger? If so, intermittent mandatory ventilation, in which a set of prescribed mandatory breaths are provided with gas flow available should any spontaneous breaths occur, may be the best option.

Is the patient instead able to trigger the breath? If so, options include (from the most to the least synchronous support) assist control in which every patient initiated breath is met with a full breath from the ventilator, pressure support ventilation which provides preset, but varied, levels of support for each patient initiated breathand synchronized intermittent mandatory ventilation which allows the patient to trigger mandatory breaths but which does not support additional spontaneous breaths.

  1. Select the method of limiting the delivered breath size. In infants and children, pressure controlled breaths are traditionally utilized due to concerns of ventilator associated lung injury. However, volume control ventilation has been increasingly used even in the preterm population [14]. Volume control ventilation is preferred in some centers for postcardiotomy patients.

For patients on volume control or pressure regulated volume control, the desired tidal volume (TV) is set between 4 and 6 mL/kg in children in order to minimize ventilator associated lung injury and 5 and 7 mL/kg in adults. In these modes, the peak inspiratory pressure (PIP) becomes a dependent variable and will depend on the chosen TV, Itime (shorter Itime results in higher PIP), PEEP and lung compliance.

For patients on pressure control, the peak inspiratory pressure (PIP) is chosen in order to achieve the desired TV. The PIP is the sum of inspiratory pressure and PEEP. A range of 20 to 24 is a good starting point and should be titrated in order to achieve adequate chest rise and the desired TV. In this mode, the TV is the dependent variable and will be affected by the settings for PIP, Itime and lung compliance. A longer Itime generally results in a larger TV.

  1. Select the FiO2. In respiratory failure, it is reasonable to start at 1.0 and decrease to the lowest level needed to achieve adequate oxygenation. An FiO2 of 0.6 or less is targeted to minimize oxygen toxicity. Other parameters may need to be manipulated to reach this goal including PEEP and Itime.
  1. Select the respiratory rate (RR). Start with a RR that is physiologically normal based on the patient’s age. Newborns would generally have a backup rate of 30 to 40 breaths per minute, infants and small children a rate of 20 to 30/min and adolescents a rate of 12 to 16/min. A high RR may decrease the exhalation time for each breath leading to autoPEEP.
  1. Select the amount of positive end expiratory pressure (PEEP). Start with 5 mm Hg. If oxygenation is problematic, PEEP may be increased in increments of 1 to 2 mm Hg.

What should prompt adjustment of the ventilation parameters?

Ventilation parameters are adjusted in response to the patient’s condition and changes in respiratory status. Poor oxygenation (low pulse oximetry readings, low O2 saturation, low paO2) and poor ventilation (high ETCO2, paCO2) should warrant changes in ventilator support. The mode of ventilation may be altered to compensate for changes in the clinical status including changes in hemodynamic state, neurologic status, or lung compliance.

Oxygenation is related primarily to the mean airway pressure (MAP) and the percent of inspired oxygen (FiO2). Problems with oxygenation (e.g reduced O2 saturation or paO2) may require increases in the MAP. The MAP is the average pressure of the airway throughout the respiratory cycle. On PC mode it depends on the PEEP, Itime, PIP and RR; on VC and PRVC it depends on the PEEP, Itime, TV and RR. As stated above, the most effective way to increase the MAP (in any mode) is to increase the PEEP. However, increasing PEEP can increase dead space and adversely affect cardiac output.

PaCO2 is inversely related to the minute ventilation (minute ventilation equals RR x TV); therefore changes on the RR or on the TV will affect the PaCO2 in the opposite direction.

The patient’s respiratory and overall status will dictate the level of support required. For example, a patient who cannot initiate a breath due to severe brain injury would require full mechanical support. A child who is fighting the ventilator may benefit from a synchronized modality. A patient whose lungs are recovering from injury may require PRVC mode to recruit healthy lung units while respecting the differential compliance that the lungs may acquire with time.

If the patient requires very high level of support (PIP greater than 26) the physician may consider whether HFOV is a better way to achieve gas exchange.

How are patients weaned from mechanical ventilation?

Several parameters are considered when weaning patients from mechanical ventilation. First, the initial indication for support (airway protection, sepsis, cardiovascular failure) is an important factor since the ability to wean will depend on the patient’s recovery from the primary insult. Additional consideration is given to the patient’s level of consciousness (somnolent, hypopneic), fluid status and overall hemodynamic status.

If the patient requires ventilator support for primary respiratory pathophysiology, then weaning would be determined by the normalization of lung function. While radiographic changes may persist for significant periods of time despite clinical improvement, a recent chest radiograph should be interrogated for evidence of volume loss, interstitial edema, pleural effusion and air space disease as these findings may predict weaning failure. Importantly, patient level criteria for weaning should include presence of spontaneous ventilation, intact airway reflexes and manageable respiratory secretions.

The most common method of weaning involves gradually decreasing the support of the ventilator by utilizing the oxygen saturation and arterial blood gas analysis for guidance. If the PaO2 and arterial O2 saturation are improving, then FiO2 and/or PEEP may be reduced to meet predetermined goals for these parameters. Improvement in PaCO2 indicates that minute ventilation can be decreased. On IMV or SIMV, weaning occurs by decreasing the respiratory rate. Pressure support (PS) is often combined with IMV or SIMV during weaning - initially being set to deliver a high level of support during spontaneous breaths, then gradually decreasing the support as weaning continues. In volume support ventilation (VSV or automatic pressure support ventilation) the ventilator is guaranteed to deliver a certain volume of breath. As compliance improves, the amount of pressure support required to deliver the same volume of breath decreases. Extubation occurs when the ventilator support is minimal.

Another approach to weaning is to perform an extubation readiness trial (ERT) daily. ERT is a formal trial of spontaneous breathing with variable pressure assist, continuous positive airway pressure of less than 5 cm H2O, or the addition of a T piece (zero end expiratory pressure). Advocates of this method believe that ERT should be performed even with the patient on moderate ventilator settings. The duration of ERT is variable but should be no more than two hours. There are no criteria that have been proven to be universally successful in predicting whether extubation will be successful, but several indices have been described to gauge readiness. Clinical criteria during an ERT which suggest that extubation will not be successful include diaphoresis, tachychardia (an increase in heart rate over baseline by greater than forty beats per minute), arrhythmias, perceived respiratory distress (nasal flaring, use of accessory muscles) or apnea. During the trial, a greater than five percent decrease in oxygen saturation or a greater than 10 mm Hg increase in end tidal CO2 suggests the patient’s continued need for ventilator support. At the end of the trial, an arterial blood gas is analyzed for changes in pH and paO2. ERT’s have been effective in individual institutions. The results have not been uniform, however, but there is evidence to suggest that physician assessment of the patient’s readiness using the criteria listed above leads to a 91% successful extubation rate [27]. It should be recognized, however, that reliable and reproducible methods of assessing readiness for weaning and predicting successful extubation in children have not been well developed [28].

The criteria for extubation are even less well defined in the neonatal and infant population. The predominant data on ventilatory weaning in newborns exist in infants with chronic lung disease and bronchopulmonary dysplasia. Indices of weaning and successful extubation cannot be utilized uniformly among all newborns since the pathophysiology in acute conditions differs considerably from that associated with chronic lung disease. Not surprisingly there are wide disparities in weaning practices amongst neonatologists - sometimes even within the same intensive care unit. With regard to the best mode of weaning, there is no strong evidence to support any one method. In fact, there are reports that weaning while on high flow oscillatory ventilation is a valid approach in certain populations [29].

Very limited data exist on the utility of weaning protocols in newborns and there are no consensus guidelines on how weaning should be undertaken. Similarly, spontaneous breathing trials and/or extubation readiness trials in newborns have been studied to identify potential predictors of successful extubation such as spontaneous minute ventilation, changes in heart rate, and oxygen saturation. Although initial results at predicting successful extubation appeared promising, further research is still required to identify the best predictive tools for successful weaning [28].

Several adjuncts have been used to increase the chances for successful extubation. In preterm infants, caffeine is used to decrease the apnea rate. Since upper airway obstruction is the most common reason for extubation failure in infants and children, modalities to decrease airway swelling are also utilized. For example, the absence of a leak around the endotracheal tube during application of an airway pressure of 20 cm H2O suggests upper airway edema. Agents to decrease airway swelling include parenteral periextubation steroids and nebulized racemic epinephrine. Furthermore, heliox may aid the delivery of inhaled oxygen (by increasing laminar flow) through a narrow upper airway in patients with postextubation stridor as long as FiO2 requirements are not above 0.40.

Extubation failure rates range between two and twenty percent in pediatric patients. Interestingly, extubation failure is not correlated with duration of time on the ventilator.

What should be done following a failed extubation?

If a patient requires reintubation after a planned extubation, the physician should consider reasons why the failure occurred. Upper airway obstruction is the most common cause of a failed extubation in the pediatric population. The use of steroids, racemic epinephrine or heliox should be considered.

Has the patient been deconditioned during the hospitalization and would muscle conditioning be helpful?

Is the patient being fed with the proper ratio of calories, protein and fat to yield a respiratory quotient that does not yield too much CO2? The respiratory quotient describes the ratio of CO2 produced / O2 consumed while food is metabolized. The RQ of carbohydrates is 1, protein 0.8 and fat 0.6. As an energy substrate, fat produces less CO2 when consumed compared to carbohydrates. In a patient who requires higher ventilator support to remove CO2, changing the composition of nutritional support to produce less CO2 (more fat relative to carbohydrates) may help with weaning.

Would the patient benefit from noninvasive modes of ventilation (such as CPAP, BiPAP, or NAVA)? Are there other diagnostic modalities required such as axial imaging of the airway and lungs or lung biopsy? Does the child have life threatening gastroesophageal reflux?

There are certain patients where controlled extubation in the operating room is the safest approach. Patients who required mechanical ventilation postoperatively for complex laryngotracheal reconstruction may benefit from extubation in the operating room. Infants and children who have failed several trials of extubation at the bedside should have a directed examination of the airway by nasopharyngoscopy, laryngoscopy or bronchoscopy to help determine the reason for extubation failure. Some diagnoses that may contribute to extubation failures include vocal cord weakness, laryngeal pathology, subglottic stenosis, anomalies of the great vessels, tracheomalacia and bronchomalacia. Flexible bronchoscopy with bronchoalveolar lavage may reveal possible infectious processes.

A tracheostomy should be considered after optimization of all the pertinent systems when the patient continues to be dependent on the ventilator. This decision is typically made in a multidisciplinary fashion with input from the neonatologist or intensivist, pulmonology, otolaryngology, the primary care physician and the patient’s parents or guardians.

What is the best way to troubleshoot problems with ventilator adjustment and gas exchange?

Troubleshooting problems in a mechanically ventilated patient requires a physician at the bedside. The patient should be examined. The DOPE mnemonic can be applied quickly

Is the ETT displaced or kinked?

Is the ETT obstructed?

Is there a pneumothorax?

Is there equipment malfunction?

Is the patient comfortable? Struggling? How does the patient sound? Does the patient need to be suctioned? Are there bilateral breath sounds? Is there adequate chest rise? Does the patient have wheezing or rales? Is there good peripheral perfusion?

A quick assessment of the vital signs is imperative. Check that there is a functioning pulse oximetry, an end tidal CO2 monitor and other noninvasive tissue monitoring. Obtain a blood gas or chest radiograph if the situation dictates.

Look at the ventilator. What is the plateau pressure? What is the expired tidal volume? What do the waveforms tell you? (PIP; expired TV; alarms, etc)

When in doubt, disconnect the patient from the ventilator and begin bag mask ventilation. Ensure you are bagging with 100% O2. This eliminates the ventilator circuit as the source of the problem. Bagging by hand can also help you gauge the patient’s pulmonary compliance.

Consider if the ventilator settings are the most optimal for the patient and the situation? Is this the right mode? Is the underlying process getting worse? Is there a new problem? Is there an air leak? Does the patient need to be more sedated? Is the patient ready to be extubated?

Consider problems with interaction between the patient and the ventilator. Does the ventilator recognize the patient’s respiratory efforts (trigger)? Does the ventilator meet the patient’s demands? Is the ventilator interfering with the patient’s spontaneous breaths?

One should also recognize that the physician’s short term expectations may often have to be modified to achieve long term benefits. For instance, one may need to accept a higher paCO2 in order to limit TV or PIP and minimize barotrauma or volutrauma. Permissive hypoxemia (paO2 in the 55 to 65 range and saturation in the 88 to 90%) may be necessary to maintain the FiO2 less than 0.6 and to limit PEEP.

How is inhaled nitric oxide used?

Initiation

Controversy exists regarding the timing of initiation and starting dose of inhaled nitric oxide (iNO) in pulmonary hypertension. An oxygenation index (OI) of 25 is associated typically associated with a fifty percent risk of requiring extracorporeal life support (ECMO) or mortality but an earlier initiation of iNO in patients with OI of 15 to 25 did not reduce the need for ECMO but may have a tendency to reduce the risk of progression to severe hypoxemic respiratory failure in newborns [30]. An OI of 20 is usually utilized as a good clinical indicator for starting iNO in pulmonary hypertension.

Dosing

The ideal starting dose for iNO is 20 ppm with effective doses between 5 and 20 ppm. Doses greater than 20 ppm do not increase the efficacy and are associated with more adverse effects such as systemic hypotension and elevated methemoglobin (greater than seven percent) and nitrogen dioxide (NO2) (greater than 3 ppm). Typical initial dose of iNO is 20 ppm when the OI is approximately twenty. A complete response to iNO is defined as an increase in the PaO2/ FiO2 ratio of greater than 20 mm Hg. At two and eight hours after iNO initiation, methemoglobin levels are monitored and then once a day until iNO is complete. High inspired oxygen and high mean iNO dose are risk factors for elevated methemoglobin in term infants .

Weaning

iNO requires gradual weaning because abrupt cessation can cause rebound vasoconstriction and resultant pulmonary hypertension. Weaning in steps from 20 ppm gradually over a period of time before its discontinuation has been shown to prevent the rebound effect [31]. If there is oxygenation response, FiO2 is first weaned below 0.6 and then iNO is weaned only if PaO2 can be maintained greater then 60 mm Hg (or preductal SpO2 greater than 90%) for sixty minutes (60-60-60 rule of weaning iNO). Often iNO is weaned at a rate of 5 ppm every four hours. Once the iNO dose is 5 ppm, gradual weaning by 1 ppm every four hours is performed. Continuing iNO in the absence of a response or not weaning iNO or extremely slow weaning can potentially lead to suppression of endogenous nitric oxide synthetase [32][33].

iNO is a very expensive therapy and its use should be warranted by its clinical efficacy on an individual level.

In summary, a simple guideline is that iNO is initiated if OI is 20 at a dose of 20 ppm. A complete response to iNO is defined as an increase in paO2/ FiO2 ratio of greater than 20 mmHg. (20-20-20 rule for initiating iNO). iNO is weaned when the percetnage of inspired oxygen is less than 60%, paO2 is maintained greater than or equal to 60 mmHg for 60 minutes (60-60-60 rule for weaning iNO).

Complications

How does the ventilator induce lung injury?

Ventilator induced lung injury (VILI) or ventilator associated lung injury (VALI) can be seen with all types of positive pressure ventilation. Excess volume leading to alveolar overdistention appears to be primarily responsible for VALI/VILI.

Volutrauma results in physiologic, radiologic and histologic changes that are similar to acute respiratory distress syndrome. In fact, the ARDSNet trial recommends limiting tidal volumes to 5 to 7 mL/kg in order to protect the lung from VALI[34].

Barotrauma and atelectrauma (repetitive alveolar collapse and re-expansion) have also been implicated in VALI. Although high peak inspiratory pressures (PIP) and peak plateau (Pplat) pressure play a role, the absolute transpulmonary pressure, or the difference in pressure between the alveolus and the pleural space, may be more directly responsible for over distension and injury.

On a tissue and cellular level, the lung injury caused by positive pressure ventilation has been ascribed to surfactant inactivation (i.e. epithelial injury) which leads to increases in surface tension and pulmonary capillary permeability as well as the activation of inflammatory cells and cytokine release (endothelial injury).

To prevent VILI/VALI aim for a Pplat less than 30 cm H20, TV of 5 to 7 ml/kg, FiO2 less than 0.6 and optimize PEEP in order to decrease over distension and under distension of lung segments [35].

What is ventilator associated pneumonia?

Ventilator associated pneumonia (VAP) is currently defined by the Centers for Disease Control (CDC) as a pneumonia that develops when the patient has been on mechanical ventilation for greater than two calendar days, with the day of ventilator placement being day one and is still on the mechanical ventilator or has been extubated for less than one day [36]. In critically ill children it is the second most common hospital associated infection and accounts for approximately twenty percent of hospital associated infections in pediatric intensive care units [37]. The risk factors for VAP include genetic syndromes (Odds Ratio =2.04; 95% CI: 1.08-3.86), steroids (OR =1.87; 95% CI: 1.07-3.27), reintubation or self extubation (OR=3.16; 95% CI: 2.10-4.74), bloodstream infection (OR =4.42; 95% CI: 2.12-9.22), prior antibiotic therapy (OR=2.89; 95% CI: 1.41-5.94) and bronchoscopy (OR =4.48; 95% CI: 2.31-8.71) [38].

In neonates, VAP risk factors are related to length of stay in the neonatal intensive care unit (OR=23.45), reintubation (OR=9.18), enteral feeding (OR=5.59), mechanical ventilation (OR=4.04), transfusion (OR=3.32), low birth weight (OR=3.16), prematurity (OR=2.66), parenteral nutrition (OR=2.30), bronchopulmonary dysplasia (OR=2.21) and tracheal intubation (OR=1.12) [39].

The CDC has listed very specific guidelines that include clinical, radiologic, and microbiologic criteria defining VAP. These criteria are age-, patient-(i.e. immunocompromised vs immunocompetent) and organism-specific. There are no specific criteria defining VAP for neonates.

Most studies have proposed a bundle whereby several measures are applied to decrease the incidence of VAP. There are four recommended elements for VAP prevention: at least once daily assessment for readiness to extubate (SHEA Quality of Evidence Grade II pediatric, Grade III neonates), elevation of the head of bed 30 to 45 degrees (Grade III pediatric and neonates), oral hygiene every twelve hours (Grade II pediatrics, no evidence in neonates), minimizing disruption of the ventilator circuit (Grade II pediatric, Grade III neonates) anas care giver hand washing. The circuit should be examined for condensation or contamination at least every eight hours with subsequent drainage of condensation and changing of visibly soiled circuits. Routine changing of the circuit when there is no contamination is discouraged [40][41]. There are data in adults suggesting that routine subglottic drainage of secretions may help prevent VAP [40].

The predominant pathogens in VAP are gram negative bacteria. Current Infectious Diseases Society of America guidelines call for obtaining a lower respiratory tract sample for culture if VAP is suspected. Empiric antibiotic therapy is started immediately. In a patient with a low risk for multiple drug resistance (MDR) pathogens the recommended initial antibiotics include ceftriaxone, fluoroquinolones, ampicillin sulbactam, or ertapenem [37].

If a patient has been intubated for greater than five days or has high risk factors for multidrug resistant pathogens, then the antibiotics started should cover multiple drug resistant organisms including Pseudomonas aerigunosa and methicillin resistant Staphylococcus aureaus. Antibiotics are given for 48 to 72 hours and changed based on culture results [42].

Research and Future Directions

see Extracorporeal Life Support Research and Future Directions

Perspectives and Commentary

To submit comments about this topic please contact the editors at NaT@eapsa.org.

Additional Resources

APSA Handbook of Pediatric Surgical Critical Care

APSA Critical Care Syllabus

Discussion Questions and Cases

To submit interesting cases which display thoughtful patient management please contact the editors at NaT@eapsa.org.

Additonal questions are in SCORE Lung Physiology, Pathophysiology, Ventilators, and Pneumonia conference prep

References

  1. www.pathwaymedicine.org
  2. Collins JA et al: Relating oxygen partial pressure, saturation and content: the haemoglobin-oxygen dissociation curve. Breathe (Sheff) 11:194, 2015  [PMID:26632351]
  3. Bronicki RA, Anas NG: Cardiopulmonary interaction. Pediatr Crit Care Med 10:313, 2009  [PMID:19307810]
  4. Fouzas S, Priftis KN, Anthracopoulos MB: Pulse oximetry in pediatric practice. Pediatrics 128:740, 2011  [PMID:21930554]
  5. Pizov R et al: Arterial and plethysmographic waveform analysis in anesthetized patients with hypovolemia. Anesthesiology 113:83, 2010  [PMID:20526193]
  6. www.thoracic.org/professionals/.../abgs.php
  7. Pediatric Advanced Life Support Provider Manual, Chameides L, Samson RA, Schexnayder SM, Hazinski MF (Eds), American Heart Association, Dallas 2012
  8. Apfelbaum JL et al: Practice guidelines for management of the difficult airway: an updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 118:251, 2013  [PMID:23364566]
  9. Hess DR: Ventilator waveforms and the physiology of pressure support ventilation. Respir Care 50:166, 2005  [PMID:15691390]
  10. González M et al: Airway pressure release ventilation versus assist-control ventilation: a comparative propensity score and international cohort study. Intensive Care Med 36:817, 2010  [PMID:20229042]
  11. Seymour CW et al: Airway pressure release and biphasic intermittent positive airway pressure ventilation: are they ready for prime time? J Trauma 62:1298, 2007  [PMID:17495742]
  12. Stawicki SP, Goyal M, Sarani B: High-frequency oscillatory ventilation (HFOV) and airway pressure release ventilation (APRV): a practical guide. J Intensive Care Med 24:215, 2009 Jul-Aug  [PMID:19617228]
  13. Mortellaro VE et al: The use of high-frequency oscillating ventilation to facilitate stability during neonatal thoracoscopic operations. J Laparoendosc Adv Surg Tech A 21:877, 2011  [PMID:21859342]
  14. Arca MJ, Uhing M, Wakeham M: Current concepts in acute respiratory support for neonates and children. Semin Pediatr Surg 24:2, 2015  [PMID:25639802]
  15. Barrington KJ, Finer N: Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev  [PMID:21154346]
  16. Pediatric Acute Lung Injury Consensus Conference Group: Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 16:428, 2015  [PMID:25647235]
  17. Clark RH et al: Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med 342:469, 2000  [PMID:10675427]
  18. Campbell BT et al: Inhaled Nitric Oxide Use in Neonates With Congenital Diaphragmatic Hernia. Pediatrics Jul 14  [PMID:25022736]
  19. Neonatal Inhaled Nitric Oxide Study Group: Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 336:597, 1997  [PMID:9036320]
  20. Roberts JD et al: Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med 336:605, 1997  [PMID:9032045]
  21. Peliowski A, Canadian Paediatric Society, Fetus and Newborn Committee: Inhaled nitric oxide use in newborns. Paediatr Child Health 17:95, 2012  [PMID:23372402]
  22. Afshari A et al: Inhaled nitric oxide for acute respiratory distress syndrome and acute lung injury in adults and children: a systematic review with meta-analysis and trial sequential analysis. Anesth Analg 112:1411, 2011  [PMID:21372277]
  23. Afshari A et al: Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults. Cochrane Database Syst Rev  [PMID:20614430]
  24. Galiatsou E et al: Prone position augments recruitment and prevents alveolar overinflation in acute lung injury. Am J Respir Crit Care Med 174:187, 2006  [PMID:16645177]
  25. Balaguer A et al: Infant position in neonates receiving mechanical ventilation. Cochrane Database Syst Rev 3:, 2013  [PMID:23543520]
  26. O'Croinin D et al: Bench-to-bedside review: Permissive hypercapnia. Crit Care 9:51, 2005  [PMID:15693984]
  27. Bancalari E, Claure N: Strategies to accelerate weaning from respiratory support. Early Hum Dev 89 Suppl 1:S4, 2013  [PMID:23809348]
  28. Blackwood B et al: Protocolized versus non-protocolized weaning for reducing the duration of invasive mechanical ventilation in critically ill paediatric patients. Cochrane Database Syst Rev 7:, 2013  [PMID:23900725]
  29. Seller L et al: Weaning to extubation directly from high-frequency oscillatory ventilation in an infant with cystic lung disease and persistent air leak: a strategy for lung protection. Respir Care 46:263, 2001  [PMID:11262553]
  30. Konduri GG et al: A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Pediatrics 113:559, 2004  [PMID:14993550]
  31. Sokol GM et al: Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide. Pediatr Pulmonol 32:14, 2001  [PMID:11416871]
  32. Sheehy AM, Burson MA, Black SM: Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. Am J Physiol 274:L833, 1998  [PMID:9612300]
  33. Black SM et al: Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension. Am J Physiol 277:H1849, 1999  [PMID:10564139]
  34. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342:1301, 2000  [PMID:10793162]
  35. Haitsma JJ: Physiology of mechanical ventilation. Crit Care Clin 23:117, 2007  [PMID:17368160]
  36. www.cdc.gov/HAI/vap/vap.html
  37. Chang I, Schibler A: Ventilator Associated Pneumonia in Children. Paediatr Respir Rev Sep 25  [PMID:26527358]
  38. Liu B et al: Risk factors of ventilator-associated pneumonia in pediatric intensive care unit: a systematic review and meta-analysis. J Thorac Dis 5:525, 2013  [PMID:23991312]
  39. Tan B et al: Risk factors for ventilator-associated pneumonia in the neonatal intensive care unit: a meta-analysis of observational studies. Eur J Pediatr 173:427, 2014  [PMID:24522325]
  40. Wang F et al: Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials. J Trauma Acute Care Surg 72:1276, 2012  [PMID:22673255]
  41. Yokoe DS et al: A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates. Infect Control Hosp Epidemiol 35:967, 2014  [PMID:25026611]
  42. www.cdc.gov/nhsn/PDFs/pscManual/6pscVAPcurrent.pdf
  43. Abman SH et al: Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society. Circulation 132:2037, 2015  [PMID:26534956]
  44. Agrons GA et al: From the archives of the AFIP: Lung disease in premature neonates: radiologic-pathologic correlation. Radiographics 25:1047, 2005 Jul-Aug  [PMID:16009823]
  45. Amantéa SL et al: [Rapid airway access]. J Pediatr (Rio J) 79 Suppl 2:S127, 2003  [PMID:14647709]
  46. Anderson M et al: Deposition in asthmatics of particles inhaled in air or in helium-oxygen. Am Rev Respir Dis 147:524, 1993  [PMID:8442582]
  47. Barach AL: RARE GASES NOT ESSENTIAL TO LIFE. Science 80:593, 1934  [PMID:17798415]
  48. Bjornson C et al: Nebulized epinephrine for croup in children. Cochrane Database Syst Rev 10:, 2013  [PMID:24114291]
  49. Chaves GS et al: Chest physiotherapy for pneumonia in children. Cochrane Database Syst Rev 9:, 2013  [PMID:24057988]
  50. Cheng KC et al: Methylprednisolone reduces the rates of postextubation stridor and reintubation associated with attenuated cytokine responses in critically ill patients. Minerva Anestesiol 77:503, 2011  [PMID:21540805]
  51. Deakins K, Chatburn RL: A comparison of intrapulmonary percussive ventilation and conventional chest physiotherapy for the treatment of atelectasis in the pediatric patient. Respir Care 47:1162, 2002  [PMID:12354335]
  52. Duncan PG: Efficacy of helium--oxygen mixtures in the management of severe viral and post-intubation croup. Can Anaesth Soc J 26:206, 1979  [PMID:466564]
  53. El Shahed AI et al: Surfactant for meconium aspiration syndrome in term and late preterm infants. Cochrane Database Syst Rev 12:, 2014  [PMID:25504256]
  54. Fernandes RM et al: The Cochrane Library and safety of systemic corticosteroids for acute respiratory conditions in children: an overview of reviews. Evid Based Child Health 9:733, 2014  [PMID:25236311]
  55. François B et al: 12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial. Lancet 369:1083, 2007  [PMID:17398307]
  56. Gluck EH, Onorato DJ, Castriotta R: Helium-oxygen mixtures in intubated patients with status asthmaticus and respiratory acidosis. Chest 98:693, 1990  [PMID:2118449]
  57. Gupta VK, Cheifetz IM: Heliox administration in the pediatric intensive care unit: an evidence-based review. Pediatr Crit Care Med 6:204, 2005  [PMID:15730610]
  58. Hollman G et al: Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis. Crit Care Med 26:1731, 1998  [PMID:9781732]
  59. Hough JL et al: Chest physiotherapy for reducing respiratory morbidity in infants requiring ventilatory support. Cochrane Database Syst Rev  [PMID:18646156]
  60. Hutchings FA, Hilliard TN, Davis PJ: Heated humidified high-flow nasal cannula therapy in children. Arch Dis Child 100:571, 2015  [PMID:25452315]
  61. Jansaithong J: The use of dexamethasone in the prevention of postextubation stridor in pediatric patients in PICU/NICU settings: an analytical review. J Soc Pediatr Nurs 6:182, 2001 Oct-Dec  [PMID:11777331]
  62. Kelly M et al: Heated humidification versus heat and moisture exchangers for ventilated adults and children. Cochrane Database Syst Rev  [PMID:20393939]
  63. Kemper KJ et al: Helium-oxygen mixture in the treatment of postextubation stridor in pediatric trauma patients. Crit Care Med 19:356, 1991  [PMID:1999097]
  64. Lakshminrusimha S, Keszler M: Persistent Pulmonary Hypertension of the Newborn. Neoreviews 16:e680, 2015  [PMID:26783388]
  65. Lee CH, Peng MJ, Wu CL: Dexamethasone to prevent postextubation airway obstruction in adults: a prospective, randomized, double-blind, placebo-controlled study. Crit Care 11:, 2007  [PMID:17605780]
  66. Lumb AB, Slinger P: Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications. Anesthesiology 122:932, 2015  [PMID:25587641]
  67. Mandelberg A, Amirav I: Hypertonic saline or high volume normal saline for viral bronchiolitis: mechanisms and rationale. Pediatr Pulmonol 45:36, 2010  [PMID:20014350]
  68. McDonough AK, Curtis JR, Saag KG: The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol 20:131, 2008  [PMID:18349741]
  69. Myers TR: Positive expiratory pressure and oscillatory positive expiratory pressure therapies. Respir Care 52:1308, 2007  [PMID:17894901]
  70. Myers TR, American Association for Respiratory Care (AARC): AARC Clinical Practice Guideline: selection of an oxygen delivery device for neonatal and pediatric patients--2002 revision & update. Respir Care 47:707, 2002  [PMID:12078654]
  71. Papamoschou D: Theoretical validation of the respiratory benefits of helium-oxygen mixtures. Respir Physiol 99:183, 1995  [PMID:7740207]
  72. Pelosi P, Brazzi L, Gattinoni L: Prone position in acute respiratory distress syndrome. Eur Respir J 20:1017, 2002  [PMID:12412699]
  73. Plioplys AV, Lewis S, Kasnicka I: Pulmonary vest therapy in pediatric long-term care. J Am Med Dir Assoc 3:318, 2002 Sep-Oct  [PMID:12807620]
  74. Racz GB: Humidification in a semiopen system for infant anesthesia. Anesth Analg 50:995, 1971 Nov-Dec  [PMID:5166916]
  75. Respiratory Physiology, The Essentials, Tenth Edition. West JB, Luks AM, Lippincott, Williams and Wilkins.
  76. Rimensberger PC, Cheifetz IM, Pediatric Acute Lung Injury Consensus Conference Group: Ventilatory support in children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 16:S51, 2015  [PMID:26035364]
  77. Rowe BH et al: Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev  [PMID:17636617]
  78. Russell KF et al: Glucocorticoids for croup. Cochrane Database Syst Rev  [PMID:21249651]
  79. Sassoon CSh: Triggering of the ventilator in patient-ventilator interactions. Respir Care 56:39, 2011  [PMID:21235837]
  80. Soll RF: Inhaled nitric oxide for respiratory failure in preterm infants. Neonatology 102:251, 2012  [PMID:22907671]
  81. Sontag MK et al: Lessons learned from a randomized trial of airway secretion clearance techniques in cystic fibrosis. Pediatr Pulmonol 45:291, 2010  [PMID:20146387]
  82. Strickland SL et al: AARC clinical practice guideline: effectiveness of nonpharmacologic airway clearance therapies in hospitalized patients. Respir Care 58:2187, 2013  [PMID:24222709]
  83. Sweet DG, Halliday HL, Speer CP: Surfactant therapy for neonatal respiratory distress syndrome in 2013. J Matern Fetal Neonatal Med 26 Suppl 2:27, 2013  [PMID:24059549]
  84. Tamburro RF, Kneyber MC, Pediatric Acute Lung Injury Consensus Conference Group: Pulmonary specific ancillary treatment for pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 16:S61, 2015  [PMID:26035366]
  85. Terregino CA et al: The effect of heliox on croup: a pilot study. Acad Emerg Med 5:1130, 1998  [PMID:9835482]
  86. Verma RP et al: Risk factors and clinical outcomes of pulmonary interstitial emphysema in extremely low birth weight infants. J Perinatol 26:197, 2006  [PMID:16493434]
  87. Vitaliti G et al: Noninvasive ventilation in pediatric emergency care: a literature review and description of our experience. Expert Rev Respir Med 7:545, 2013  [PMID:24138696]
  88. Waisman Y et al: Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). Pediatrics 89:302, 1992  [PMID:1734400]
  89. Walsh BK et al: AARC Clinical Practice Guideline. Surfactant replacement therapy: 2013. Respir Care 58:367, 2013  [PMID:23359726]
  90. Wolfson MR et al: Mechanics and energetics of breathing helium in infants with bronchopulmonary dysplasia. J Pediatr 104:752, 1984  [PMID:6546945]
  91. Yen Ha TK et al: Atelectatic children treated with intrapulmonary percussive ventilation via a face mask: clinical trial and literature overview. Pediatr Int 49:502, 2007  [PMID:17587276]
  92. Zhang L et al: Nebulized Hypertonic Saline for Acute Bronchiolitis: A Systematic Review. Pediatrics 136:687, 2015  [PMID:26416925]

Respiratory Care is a sample topic from the Pediatric Surgery NaT.

To view other topics, please or purchase a subscription.

APSA Pediatric Surgery Library combines Pediatric Surgery Not a Textbook (NaT) with APSA ExPERT, a powerful platform for earning MOC CME credits -- all powered by Unbound Medicine. Learn more.

Last updated: August 1, 2018

Citation

* When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Respiratory Care ID - 829020 Y1 - 2018/08/01/ PB - Pediatric Surgery NaT UR - https://www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829020/all/Respiratory_Care ER -