Using ventilator graphics and mechanics can assist RCPs in determining the effectivness of bronchodilator therapy in premature infants.

It is well documented by pulmonary function tests that premature infants respond to inhaled bronchodilator therapy.1-3 For premature infants receiving mechanical ventilation, bronchodilator therapy may lead to reduced patient work and thus more efficient weaning from the ventilator. As real-time ventilator graphics and mechanics are becoming readily available in many neonatal intensive care settings, they may be a useful tool in determining proper dosing, frequency, and efficacy of bronchodilator therapy.

According to Rau, there are many issues to consider when examining response to bronchodilator agents in premature infants. These include the medication delivery system, medication delivery technique, the medication itself, the pharmacotherapy of the developing lung, and the measuring technique of the drug effect (see Figure 1).

Aerosol Delivery System Aerosol Delivery Techniques Pharmacologic Agent (Dosage)
The Developing Lung
Measure of Drug Effect
Conclusion about Drug Effect
Figure 1. Five variables that interact when examining aerosolized therapy effect in the premature infant. Adapted from Rau J. Respiratory Care. 1991;36:515.

Aerosolized bronchodilator therapy in premature infants is not as well established as in adults and pediatric patients. There are a wide range of delivery systems,4 delivery techniques,3,5,6 and drug dosages that have been studied.1,7 use of an albuterol sulfate MDI with a spacer has been studied with various numbers of actuations.8-11 Nebulized albuterol sulfate has been studied at various doses as well.3,8 Both MDI with spacer and nebulized bronchodilator therapy have been examined during techniques of manually bagging the medication to the patient as well as inline with the ventilator circuit. A disadvantage to manually bagging in the treatment is inconsistent positive end expiratory pressure (PEEP), peak inspiratory pressures, and inspiratory time that can result in either recruitment or de-recruitment of the lung during treatment. This may cause inaccurate assessment of drug effect since recruitment or de-recruitment of the lung causes changes in pulmonary mechanics.

Traditional pulmonary function testing (PFT) may be performed before and after bronchodilator therapy to assess response. Pulmonary function testing in adults involves the maximal maneuvers of inspiration and exhalation. In adults, PFTs are maximal breath maneuvers; in infants on mechanical ventilation, PFTs have become an analysis of passive nonmaximal tidal breaths.1 The following pulmonary mechanics values are examined both pre- and post- treatment: dynamic compliance (Cd), inspiratory and expiratory resistance, peak inspiratory flow (PIF), peak expiratory flow (PEF), and expiratory time constants. In addition to these pulmonary mechanics values, pre and post flow/volume and pressure/volume loop graphics are compared. An assessment of response can be determined if there are marked changes in the pulmonary mechanics as well as notable changes in pre and post flow/volume and pressure/volume loop graphics. PFTs are the gold standard for examining changes in pulmonary mechanics in infants. They are, however, labor intense and also cause brief disruptions in the premature infant’s mechanical ventilation during the testing process. A flow transducer of the PFT device must be placed in the ventilator circuit at the infant’s endotracheal or tracheostomy tube. When testing is complete, the flow transducer is then removed.

In our Special Care Nursery, we commonly use aerosolized bronchodilator therapy on premature infants. We identify infants that exhibit any of the following: wheezing, decreased air movement upon auscultation, decreased respiratory system compliance, increased respiratory system resistance, or observation of intermittent bronchial reactivity. Infants that exhibit these and show response to bronchodilator therapy are treated. We rarely perform traditional PFTs on infants due to the labor- intense nature of this testing and the disruption of the ventilator circuit during the PFT. Assessment during bronchodilator therapy includes the monitoring of vital signs and breath sounds.

Real-time Ventilator Graphics
There is increasing availability of ventilators with real-time graphics and mechanics in many neonatal intensive care units. These readily available graphics and mechanics can be a valuable tool in assessing respiratory mechanics in response to treatments such as inhaled or intravenous bronchodilators, surfactant replacement, inhaled or intravenous steroids, and any other therapy that could affect the infant’s lung mechanics.

The flow/volume and pressure/volume loops allow general observations about response or lack of response to a bronchodilator. The mechanics values allow measurement of the amount of response that occurs. The mechanics values available include: Cd, C20/Cd (compliance during the last 20% of the breath versus the Cd), Rpk (peak inspiratory resistance), and PEF. The Cd will increase if a bronchodilator substantially reduces the airway resistance. The Rpk will be reduced by bronchodilator therapy. The PEF will increase since the infant’s tidal volume will be exhaled more quickly through bronchodilated airways.

Flow/Volume Loops
The flow/volume loop (Figure 2) is best suited to examine airway resistance issues such as obstructive airways, patency of the endotracheal tube, or secretions in the airways. This loop plots flow on the vertical axis and volume on the horizontal axis. The area closest to where the flow and volume axes intercept is where each breath begins. The breath is then

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Figure 2. A schematic flow/volume loop showing potential changes pre- and post-bronchodilator delivery.

plotted as a loop that rotates clockwise. The portion of the loop that is located below the volume axis is the inspiratory phase of the breath. The portion of the breath that is located above the volume axis is the expiratory phase of the breath. The arrows indicate the areas of the flow/volume loop that may change after a bronchodilator is administered. The key indicators of response are increased inspiratory and expiratory flows. Graphically, this makes the flow/volume loop appear taller, as in the post loop in Figure 2. The flow/volume loop is the primary loop to evaluate for response to bronchodilator therapy.

Pressure/Volume Loops
The pressure/volume loop (Figure 3) is best suited to examine dynamic respiratory system compliance. There are two components to dynamic compliance, the compliance of the lung and the airway resistance of the system. The pressure/volume loop plots volume on the vertical axis and plots pressure on the horizontal axis. The area closest to where the volume and pressure axes intersect is where each breath begins. The breath is then plotted as a loop that rotates counterclockwise for a positive pressure breath. The dynamic compliance value relates to the

Figure 3. A schematic pressure/volume loop showing potential changes pre- and post-bronchodilator delivery.

pressure/volume as the calculated slope of the pressure/volume loop. Figure 3 shows a loop before bronchodilator therapy (pre) and after bronchodilator therapy (post). The normal effect of a bronchodilator is a reduction in airway resistance. A reduction in airway resistance may cause an increase in dynamic compliance. If the dynamic compliance has changed as a result of the bronchodilator, the effect will appear similar to that of the pre and post loops in Figure 3. The arrow in the figure shows the direction of the change in the slope of the loop when the dynamic compliance improves after use of a bronchodilator. Although the flow/volume loop is the primary loop to evaluate for response to bronchodilators, the pressure/volume loop may demonstrate response.

Key Tips on Breath Selection
To use ventilator graphics and mechanics, there are some key tips that must be incorporated to effectively assess bronchodilator therapy. The proper selection of breaths to be evaluated is very important. Since we are not using maximal respiratory efforts, there can be significant variability from breath to breath. Key tips in the selection of acceptable breaths are as follows:
• be sure that the infant is not being stimulated and is relatively calm at the time of the assessment;
• assure that the infant is not coughing or in need of suctioning;
• watch a series of breath loops and identify the “characteristic” breath loop appearance; and
• be sure to select a loop that has the identified “characteristic” look and is complete and undistorted.
If you have not chosen a characteristic breath for the infant’s current condition, you will have misrepresented the current respiratory mechanics and graphical loops of the infant. The loops presented in the two cases that follow were selected with the method of selection outlined above.

Case 1
A 610-g, 26-week gestation, mechanically ventilated premature twin was receiving bronchodilator therapy. The pressure/volume and flow/volume loops shown in Figure 4 are from day 16 after birth. The infant was receiving two puffs of albuterol sulfate every 6 hours. The prebronchodilator loop was saved and printed just before the bronchodilator was given. About 20 minutes after the bronchodilator was given, the postbronchodilator loop was saved and printed. The values associated with these loops are shown in Table 1.

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The key factors to notice are the increased peak flows on inspiration and exhalation in the loops (Figure 4) and the change in Rpk and PEF mechanics values. The 17% increase in Cd, 28% reduction in Rpk, and 36% increase in PEF represent a mild to moderate response to the bronchodilator.

Figure 4. An overlay of the pre- and post-bronchodilator loops of Case 1.

Case 2
A 1,250-g, 28-week gestation, mechanically ventilated premature infant was receiving bronchodilator therapy. The pressure/volume and flow/volume loops shown in Figure 5 are from approximately 7 weeks after birth. The infant was receiving 0.25 mL (1.25 mg) of albuterol sulfate every 4 hours. The pre and post loops and mechanics were obtained as previously described. The values associated with these loops are shown in Table 2.

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The key factors to notice are the increased peak flows on inspiration and exhalation in the loops (Figure 5) and the change in Cd, Rpk, and PEF mechanics. The 100% increase in the Cd, the 44% decrease in Rpk, and the 26% increase in the PEF show a more dramatic response to the bronchodilator than in Case 1. Another remarkable feature of the response is the increased tidal volume seen in the flow/volume loop (Figure 5). A reduction of set PIP should be assessed to reduce the chances of volu-trauma due to the dramatic increase in tidal volume.

Figure 5. An overlay of the pre- and postbronchodilator loops of Case 2.

Lack of Response
The two cases presented here both exhibit a level of response to bronchodilator therapy. Infants will be encountered that do not exhibit a response to bronchodilators. There are several factors to consider when there is no response to the bronchodilator. The infant may need bronchodilator therapy, yet the medication is not effectively bronchodilating the airways. Infants in this category may be experiencing desaturations and bradycardias, and have abnormal breath sounds. Considerations for this situation are increasing the dosage, or changing the method of delivery of the bronchodilator. If the infant is not experiencing the symptoms previously described and shows no response to bronchodilators, the infant may not need the bronchodilator. The bronchodilator should be discontinued only after more respiratory assessment to verify lack of response.

Assessment of response to bronchodilators in premature infants with ventilator graphics is not a precise science. It requires very adept respiratory clinicians to verify consistency in the assessment, especially in the selection of the breaths to be examined. This is especially important since we are using nonmaximal respiratory efforts and there may be significant variability between individual breaths. The key to selecting appropriate breaths is assuring that the infant is not being stimulated and is relatively calm. Then be sure that you select a “characteristic” complete loop and not an abnormal loop for the infant. Ventilator graphics and mechanics can be a valuable tool for respiratory care practitioners to use in examining the effectiveness of bronchodilator therapy in premature infants.

John Emberger, RRT, is respiratory clinical manager at Christiana Hospital, Newark, Del.

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