Pulmonary: NICU Handbook

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Definition

Apnea is a "pause in breathing of longer than 10 to 15 seconds, often associated with bradycardia, cyanosis, or both." (Martin et al). Apnea at UIHC is defined as cessation of breathing for 20 seconds with the above symptoms.

Sequelae

Apnea in premature infants can result in a failure of the mechanisms that protect cerebral blood flow, resulting in ischemia and eventually leukomalacia.

During apneic episodes, in an attempt to protect cerebral blood flowcardiac output is diverted away from the mesenteric arteries resulting in intestinal ischemia and possibly necrotizing enterocolitis (NEC).

Etiology

The most common cause of apnea in the NICU is apnea of prematurity, but first ALWAYS investigate and rule out the following disorders:

• Infection - Sepsis, especially in the first day of life, and nosocomial infections and/or NEC in the first weeks of life
• Neurological - Intraventricular hemorrhage, intracranial hemorrhage, neonatal seizures, perinatal asphyxia, or other pathology which could lead to increased intracranial pressure
• Cardiovascular - Impairment of oxygenation from congestive heart failure and pulmonary edema (PDA, coarctation, etc.), or from shunting (cyanotic heart disease)
• Pulmonary - Impairment of oxygenation and ventilation from lung disease (surfactant deficiency disease, pneumonia, transient tachypnea of the newborn, meconium aspiration, etc.)
• Metabolic - Hypocalcemia, hypoglycemia, hyponatremia or acidosis
• Hematological - Anemia
• Gastrointestinal - NEC or gastroesophageal reflux
• Temperature Regulation - Hypothermia or hyperthermia
• Drugs - Prenatal exposure with transplacental transfer to the neonate of various drugs (narcotics, beta-blockers). Postnatal exposure to sedatives, hypnotics or narcotics.

Pathophysiology

Mechanisms of apnea of prematurity

Central Apnea - A pause in alveolar ventilation due to a lack of diaphragmatic activity. In other words, there is no signal to breathe being transmitted from the CNS to the respiratory muscles. This is due to immaturity of brainstem control of central respiratory drive. The premature infant also manifests an immature response to peripheral vagal stimulation. For example, stimulation of laryngeal receptors in the adult results in coughing. However, stimulation of these same receptors in the premature infant results in apnea. This reflex apnea can be induced by gavage feeds, aggressive pharyngeal suctioning and gastroesophageal reflux.

Obstructive Apnea - A pause in alveolar ventilation due to obstruction of airflow within the upper airway, particularly at the level of the pharynx. The pharynx collapses from negative pressure generated during inspiration, because the muscles responsible for keeping the airway open, the genioglossus and geniohyoid are too weak in the premature infant. Once collapsed, mucosal adhesive forces tend to prevent the reopening of the airway during expiration. Neck flexion will worsen this form of apnea. Excessive secretions in the nasopharynx and hypopharynx may also cause obstructive apnea.

Mixed Apnea - A combination of both types of apnea representing as much as 50% of all episodes.

Surveillance

All newborns less than 34 weeks gestational age, or less than 1800 grams birth weight, should be monitored for both apnea and bradycardia. This is done by applying ECG leads to the chest which are connected to a bedside respiratory and heart rate monitor. An alarm should sound if respiration ceases for more than 20 seconds, or if the heart rate drops below 100 bpm. Bradycardia by itself is often a sign of obstructive apnea. No apnea alarm is sounded because the chest wall is moving even through air flow is absent. Also reflex apnea can lead to bradycardia within 2 seconds of onset, thus setting off the cardiac alarm 10 to 15 seconds ahead of the apnea alarm.

Management

Acute - When the alarm sounds, the infant should immediately be observed for signs of breathing and skin color. If apneic, pale, cyanotic or bradycardic, then tactile stimulation needs to be given. If the infant does not respond, bag and mask ventilation, along with suctioning and airway positioning, may be needed.

Chronic - The management of apnea of prematurity always involves diagnosing and correcting other potential etiologies, before attributing a specific neonate's apnea to prematurity alone. The decision to initiate chronic therapy is based on clinical judgment. Factors to be considered include the frequency and duration of the episodes along with the level of hypoxia and the degree of stimulation needed. Chronic management of apnea of prematurity involves three major therapies:

• Pharmacologic Therapy - The most common drugs used to treat apnea are the methylxanthines:
  Caffeine (1,3,7-trimethylxanthine) and
  Theophylline (1,3-dimethylxanthine)
  • Mechanism of Action - Methylxanthines block adenosine receptors. Adenosine inhibits the respiratory drive, thus by blocking inhibition, the methylxanthines stimulate respiratory neurons resulting in an enhancement of minute ventilation.
  • Dosages - The following is a guide to the initiation of medical therapy. Further dosing should be based on drug levels and clinical response.
  • Caffeine Citrate - 20mg/ml containing the equivalent of 10 mg/ml of caffeine is available for either IV/po use.
    • Loading Dose - 20 mg/kg/dose of caffeine citrate IV/po
    • Maintenance Dose - 5 mg/kg/day of caffeine citrate given QD
    • Plasma Half Life - 37-231 hrs
    • Therapeutic Level - 8-20 ug/ml
    • Toxic Level - >30 ug/ml
  • Theophylline:
    • Loading Dose - 6 mg/kg/dose IV/po
    • Maintenance Dose - 6 mg/kg/day divided Q6H/Q8H/Q12H IV/po
    • Plasma Half Life - 12-64 hrs
    • Therapeutic Level - 6-12 ug/ml
    • Toxic Level - >20 ug/ml
    • Administration - ALWAYS INFUSE SLOWLY over a minimum of 20 minutes. Rapid IV pushes have been associated with SUDDEN DEATH from CARDIAC ARRHYTHMIAS
  • Major side effects - tachycardia, vomiting, feeding intolerance, jitteriness and seizures.
  • Choice of Methylxanthine - This decision depends on the clinical situation and should take into account the following factors. Caffeine has a longer half life (QD dosing) and is less toxic. At UIHC, caffeine is preferred for the routine management of apnea of prematurity. Theophylline is a bronchodilator and in neonates with BPD it offers the advantage of treating both apnea and bronchospasm.
• Continuous Positive Airway Pressure (CPAP) - CPAP is effective in treating both obstructive and mixed apnea, but not central apnea. CPAP is most commonly delivered by nasal prongs or by an endotracheal tube placed in the nasopharynx (see also separate section on CPAP).
  • Mechanism of Action - Proposed mechanisms include alteration of the Hering-Breuer reflex (leading to higher lung volumes which minimize inspiratory duration and thus decrease the potential for airway collapse by prolonging expiratory time). Furthermore, CPAP increases stabilization of the chest wall musculature and decreases activity of the intercostal inspiratory inhibitory reflex. However, the most likely explanation is that CPAP splints the upper airway with positive pressure during both inspiration and expiration, thereby preventing pharyngeal collapse
  • Initial Settings - Use either nasal prongs or a nasopharyngeal tube to deliver a CPAP of 5 cm H20. Further adjustments should be based on clinical response.
  • Side Effects - Barotrauma, nasal irritation, abdominal distention and feeding intolerance. Feeding difficulties can be minimized by switching the patient to continuous drip feeds.
• Intermittent Mandatory Ventilation (IMV) - If significant apnea persists despite using both pharmaco-therapy and CPAP, the infant should be intubated and ventilated. Initial settings need to be clinically adjusted to prevent episodes of desaturation or cyanosis. In order to minimize barotrauma short inspiratory times should be used along with minimal peak inspiratory and expiratory pressures. The infant may need to remain on a minimal rate for a few weeks while the respiratory control system matures.

Conclusion

Apnea of prematurity is one of the most common and frustrating conditions that nurses, physicians and neonates face in the intensive care unit. A calm, rational team approach to this problem is beneficial for all involved.

References

1. Higgins RD, Richter SE, Davis JM: Nasal continuous positive airway pressure facilities extubation of very low birth weight neonates. Pediatr 1991;88:999-1003.
2. Marchal F, Bairam A, Vert P. Neonatal apnea and apneic syndromes. Clin Perinatol 1987;14:509-529.
3. Hodson WA, Truog WE. Special techniques in managing respiratory problems. In: Avery GB, (ed). Neonatology: Pathophysiology and Management of the Newborn. 3rd ed., Philadelphia: JB Lippincott, 1987: 483-484.
4. Martin RJ, Miller MJ, Carlo WA. Pathogenesis of apnea in preterm infants. J Pediatr 1986;109:733-741.
5. Rall TW. Central nervous system stimulants. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 7th ed., New York: Macmillan Publishing Company, 1985: 589-603.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

A technique of airway management that maintains positive intrapulmonary pressure in the lung during spontaneous breathing.

Purpose

The purpose of Nasopharyngeal CPAP is to reduce the morbidity due to barotrauma and subglottic stenosis from having a neonate intubated and mechanically ventilated because of respiratory failure or apnea.

Indications for NPCPAP

Apnea of Prematurity - obstructive and/or mixed apnea.

Respiratory Distress (i.e., tachypnea, and/or retractions) - RDS, TTN and chronic lung disease (CPIP and BPD).

Weaning from the ventilator.

Types of NPCPAP

Nasopharyngeal Tube - an endotracheal tube whose tip is placed in the nasal pharynx.

• Advantages:
  • May be used on any size infant.
  • Minimal risk of nasal septum necrosis.
  • Easy to place infant in any position.
  • Preferred method at UIHC.
• Disadvantages:
  • May become occluded or plugged with secretions despite suctioning
  • Higher resistance to spontaneous breathing.

Nasal Prongs:

• Advantages:
  • Easier to apply (less traumatic).
  • Lower resistance to spontaneous breathing
• Disadvantages:
  • Easily dislodged from nares.
  • Nasal septal necrosis
  • Difficult to position infant.

Complications of NPCPAP

Pneumothorax - minimize incidence by using minimal pressure needed to accomplish aims.

Nasal irritation - mucosal swelling or erosion, excessive nasal dilatation or septal necrosis. Minimize by proper positioning of infant and alternating nares every 5 to 7 days.

Abdominal distention and feeding intolerance - Minimize by using continuous drip feeds along with placement of the infant on the stomach or side. Additionally, the placement of an oral gastric tube to straight drain will minimize accumulation of air in the GI tract

Management

Management of NPCPAP Pressure - set CPAP at 4-7 cm of H2O pressure, use the previous MAP setting that the infant has been at, before extubation, as a guide (usually 5 cm works well of most infants.)

Trouble-shooting while on NPCPAP

Increasing O2 requirement or episodes of desaturation and apnea - "plugged tube." Prevent by routine suctioning,and adequate humidification. If necessary, replace the tube.

Excessive bradycardia with movement - tip of ETT placed in oral rather than nasal pharynx: correct by repositioning tube.

Excessive nasal irritation - move NP tube to the opposite side, change position of infant.

Significant apnea or increasing respiratory acidosis or O2 requirement of 80-100%; NPCPAP failure - intubate and ventilate patient.

Weaning off NPCAP

Oxygen requirement <30%

Decrease CPAP pressure gradually to 4-6 cm and maintain the pressure at this level until tachypnea and retractions have resolved.

If obstructive apnea still occurs after removal of nasal CPAP, you should RESTART the NPCAP and wait until the infant has achieved adequate nutrition with good weight gain and weight is >1000g; if significant apnea reoccurs even on room air, restart NPCPAP and wait a week before weaning off CPAP again.

Placement

Placement of the NPCPAP tube and care of the neonatal patient on NPCPAP EQUIPMENT:

• ETT (2.5mm ID)
• Six Fr suction catheter
• Water soluble lubricant
• Adhesive tape - 3/4 or 1 inch wide
• Hollister spray
• Stethoscope
• EKG monitoring equipment
• O2 source with connecting tube
• Anesthesia bag
• Mask
• Suction source

Procedure

Insertion:

• Prepare equipment:
  • Thread entire suction catheter through ETT until thumb control is located at the end of the ETT adapter.
  • Lubricate tip of ETT with water soluble lubricant.
• Pass suction catheter nasally as if inserting a nasogastric tube to 10-12 cm. (*See procedure for nasogastric tube placement.) This is to allow for increased ease of nasal ETT insertion. Advance lubricated ETT nasally while maintaining placement of suction catheter.
• Depth of placement - Advance ETT to:
  4 cm at naris if weight < 1500 g
  4.5 cm at naris if weight 1500-2000 g
  5 cm at naris if weight > 2000 g
• Remove suction catheter, maintaining placement of ETT tube (now called NP tube).
• Secure tube with hollister spray and adhesive tape using double "H" technique. One piece over bridge of nose and around tube as an in oral intubation. One piece inverted on lip and around tube. This increases the security of the tube and ensures proper placement; minimizing trauma to mucus membranes.
• Connect NP tube to oxygen source per ventilator or anesthesia bag. Per MD order, O2 may be adjusted per oximeter. CPAP setting may be adjusted via blood gas results.
• NPCPAP is usually ordered at between 4-7 cm of pressure. Five cm works well for most infants.
• Suction NP tubes as indicated (see Endotracheal Tubes, Suctioning of). When ventilating using a resuscitation bag, the infant's mouth must be closed or the mask should be applied to face and infant ventilated/oxygenated per mask.

Precautions, considerations, and observations

• Appropriate NP tube size is usually the same or smaller than that required for intubation.
  < 1500 g = 2.5
  1500-2000 g = 3.0
• The above procedure is recommended to increase ease of initial insertion. Subsequent reinsertions may be accomplished the same way or by following procedure for insertion of nasogastric tubes. Placement guidelines should be strictly adhered to in either case.
• A physician's order is required to initiate or discontinue NPCPAP. It is recommended that a physician be present for both initial insertion and final removal of NPCPAP tube.
• An oral/nasogastric tube should be placed to straight drainage to provide gastric decompression.

References

1. Chernick V. Continuous distending pressure in HMD: devices, disadvantages and daring. Pediatrics, 1973;52:114.
2. Gregory GA, Kitterman JA, Phibbs RH, Tooly WH, Hamilton WK. Treatment of the idiopathic respiratory distress syndrome with continuous positive airway pressure. N Engl J Med, 1971;284:1333.
3. Higgins RD, Richter SE, Davis JM: Nasal continuous positive airway pressure facilities extubation of very low birth weight neonates. Pediatr 1991;88:999-1003.
4. Kim EH, Boutwell WC: Successful direct extubation of very low birth weight infants from low intermittent mandatory ventilation rate. Pediatrics, 1987;80:409-414.
5. Martin RJ, Miller MJ, Carlo WA: Pathogenesis of apnea in preterm infants. J Pediatr, 1986;109:733-741.
6. Wung JT, Driscoll JM Jr., Epstein RA, Hyman AI. A new device for CPAP by nasal route. Crit Care Med, 1975;3:76.
7. Kim EH, Boutwell WC. Successful direct extubation of very low birth weight infants from low intermittent mandatory ventilation rate. Pediatrics, 1987;80:409-414.
8. Higgins RD, Richter SE, Davis JM. Nasal continuous positive airway pressure facilitates extubation of very low birth weight neonates. Pediatrics, 1991;88:999-1003.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

RDS

After initial resuscitation and stabilization, the following should be the ventilator settings used:

• Rate: 30-40/minute

• Peak inspiratory pressure (PIP) - determined by adequate chest wall movement.

  • An infant weighing less than 1500 grams: 16-28 cm H2O.
  • An infant weighing greater than 1500 grams: 20-30 cm H2O.

   

• Positive end expiratory pressure (PEEP): 4 cm of H2O OR 5-6 cm if FiO2 > 0.90.
• FiO2: 0.4 to 1.0, depending on the clinical situation.
• Inspiratory time: 0.3-0.5 sec.

After 15 to 30 minutes, check arterial blood gases and pH.

• If the PaO2 or the O2 saturation is below accepted standards, the FiO2 can be raised to a maximum of 1.0. If the PaO2 or O2 saturation is still inadequate, the mean airway pressure can be raised by increasing either the PIP, PEEP, inspiratory time or the rate, leaving inspiratory time constant.
• If the PaCO2 is elevated, the rate or peak inspiratory pressure can be raised.

Arterial blood gases and pH must be checked 15 to 30 minutes after changing any setting of the respirator: rate, peak pressure, or inspiratory time. Changes in FiO2 may be monitored by pulse oximetry or transcutaneous oxygen monitor.

When lowering the respiratory rate without a concomitant decrease in I:E ratio, the inspiratory time can become quite prolonged. The total inspiratory time should not exceed 0.6 second.

When increasing the respiratory rate above 60/minute, the I:E ratio should be 1:1.

Other respiratory conditions

Recommendations for the initial respiratory settings for other neonatal conditions will be found on the following table. The peak pressure used is a reflection of the anticipated compliance of the lung. Subsequent changes in settings will be determined by arterial blood gases and pH values and the clinical course. During the acute phase of the disease process, arterial blood gases and pH MUST be measured 15 to 30 minutes after a change in ventilatory settings.

When placing a neonate on mechanical ventilation, an order is written indicating:

Conventional Mechanical Ventilation

• Mode (IMV or conventional sigh breaths when using HFV)
• Rate (breaths per minute)
• FiO2
• Inspiratory time (seconds) or I:E ratio
• Peak inspiratory pressure (cm H2O)
• PEEP (cm H2O)

High Frequency Ventilation (HFV)

• Frequency (HZ)
• Amplitude or power
• PEEP or MAP (cm H2O)

Synchronized Intermittent Mandatory Ventilation (SIMV)

• Rate (use up to 40 bpm when on Servo 300, up to 60 on Star Synch)
• PC (pressure control); set a peak pressure, Based on adequate chest wall movement
• PS (pressure support); number of cm H2O pressure above the PEEP, usually start at a PS = (PIP-PEEP)/2, minimal PS = 4-6 cm
• VC (Volume Control) set a tidal volume usually 5-7 cc/kg for premature infnats and 7-10 cc/kg for term infants:

Any change in the above parameters must be written as an order.

See the following Use of Mechanical Ventilation in the Neonate table for details.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Suggested Initial Respirator Settings

(1) Inspiratory Time--All neonates should have aninspiratory time of 0.3 to 0.5 seconds and an expiratory time not less than 0.5 seconds unless the rate exceeds 60/minute. At rates above 60, use equal inspiratory and expiratory times (I:E=1:1).

(2) Confirmation of correct PIP should always be determined by appropriate chest wall excursion.

* Adjust FiO₂ as indicated to maintain oxygen saturation 85%-95% (PaO2 50-70mm Hg).

** Because of the risk of right to left shunting (PFC), the FiO₂ in this condition is adjusted to maintain the oxygen saturation greater than 95% (PaO2 > 80mm Hg) in term infants.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

 Introduction

The use of surfactant replacement therapy has helped to decrease neonatal mortality from respiratory distress syndrome (RDS), but the incidence of pulmonary interstitial emphysema (PIE) and bronchopulmonary dysplasia (BPD) in ventilated neonates (700-1350 grams) is still relatively high (PIE 20-25%, BPD 15-19%; U.S. Exosurf Pediatric Study Group 1990). Thus new therapies involving alternative methods of managing respiratory failure are currently being utilized. One of these new therapies is high frequency ventilation.

High frequency ventilation (HFV)

HFV is a new technique of ventilation that uses respiratory rates that greatly exceed the rate of normal breathing. There are three principal types of HFV:

1. High frequency positive pressure ventilation (HPPV, rate 60-150/minute); 
2. High frequency jet ventilation (HFJV, rate 240-660); 
3. High frequency oscillatory ventilation (HFOV, rate 300-900/minute). 

The advantage of high frequency ventilation as compared to conventional positive pressure ventilation is its ability to promote gas exchange while using tidal volumes that are less than dead space. The ability of HFV to maintain oxygenation and ventilation while using minimal tidal volumes allow us to minimize barotrauma and thus reduce the morbidity associated with the ventilator management of RDS.

Infrasonics infant star

High-Frequency Ventilator: We previously used the Infrasonics Infant Star ventilator at a frequency of 15 Hz (900 breaths/minute) in premature infants who develop PIE while on conventional mechanical ventilation. The Infant Star is a flow interrupter, not a true oscillator, but its physiological effects and advantages are similar to those of true oscillators. While on Infant Star, one observes rapid vibration of the infant's chest wall instead of the normal chest wall excursion that is seen with conventional ventilation. 

The Infant Star is used for the treatment of pulmonary air leaks, primarily pulmonary interstitial emphysema (PIE) and pneumothorax. HFV with the Infant Star allows gas exchange to occur even while the lung is atelectatic, thus the size of the air leak is diminished, allowing for more rapid resolution of air leak syndromes. Thus, by decreasing the severity of PIE, HFV should allow us to minimize the mortality and morbidity (BPD) associated with barotrauma.

Gas exchange

During conventional mechanical ventilation or spontaneous respiration, gas exchange occurs because of bulk transport (convective flow) of the O2 and CO2 molecules from the central or conducting airways to the peripheral airways. The volume of inhaled gas must exceed the volume of dead space. 

Gas exchange during HFV

Theories on why ventilation can still occur when using tidal volumes that are less that dead space: 

• Augmented Diffusion; 
• Bulk Axial Flow; 
• Interregional Gas Mixing (Pendelluft); 
• Axial and Radial Augmented Dispersion (Taylor Dispersion); 
• Convective Dispersion. 

Indications for HFV

• BAROTRAUMA - pulmonary airleaks. 

  • PNEUMOTHORAX 
  • PULMONARY INTERSTITIAL EMPHYSEMA (PIE) 

   

• Respiratory failure unresponsive to conventional ventilation (compassionate use). 

HFV settings

(Infrasonics INFANT STAR High-Frequency Ventilator) - Consult with Staff Neonatologist before instituting high frequency ventilation. 

• FREQUENCY: 15 Hz (900 "breaths per minute") 
• AMPLITUDE: a rough representation of the volume of gas flow in each high frequency pulse or "breath." Adjust the amplitude until you achieve vigorous chest wall vibrations, usually occurs at an amplitude of 20-30. If conventional rate is greater than 60, decrease rate to 40 and increase PEEP by 1 to 2 cm, before adjusting the amplitude. This will give the patient adequate expiratory time for the assessment of vibrations. 
• MAP: Adjust by decreasing conventional rate (by 5 bpm) while increasing PEEP (by 1 cm H2O) until conventional rate is 4 breaths per minute ("sighs") and the MAP becomes approximately equal to the PEEP. IT IS VERY IMPORTANT TO KEEP MAP CONSTANT DURING THE CONVERSION TO HFV TO PREVENT EXCESSIVE ATELECTASIS AND LOSS OF OXYGENATION. The goal being a MAP equal to or slightly (1-3 cm) below the previous MAP. 
• IMV RATE (sighs): The conventional or "sigh" breaths should be similar to the previous settings in terms of PIP, however the inspiratory time should be 0.4 - 0.6 seconds. 
• PEAK PRESSURE (sighs): The PIP is usually set at a pressure equal to MAP +6 cm. 

Blood gas management

• Inadequate oxygenation (low PO2): Manage by increasing the FiO2, increasing the MAP by increasing the PEEP (i.e. PO2 is directly proportional to MAP or by decreasing atelectasis by manually ventilating the infant with an anesthesia bag and then adjusting the "sigh" breaths by increasing either the rate, inspiratory time or PIP of the conventional breaths).

  • IMPORTANT: If oxygenation is lost during weaning when Peepwas decreased, manually "bag" the infant back up to restore lung volumes and reset Peep at 2-3 cm above the previous value. Once adequate oxygenation has been reestablished weaning can begin again, but proceed more slowly with changes in Peep. 

   

• Inadequate ventilation (high PCO2): Manage by increasing the AMPLITUDE (i.e., PCO2 is inversely proportional to AMPLITUDE).

Complications of HFOV

• ATELECTASIS: treat by increasing the rate or PIP of the conventional breaths ("sighs"); 
• INCREASED MOBILIZATION OF SECRETIONS: treat by increasing frequency of suctioning of ETT as needed; 
• HYPOTENSION: treat by lowering MAP by decreasing PEEP, if other methods such as volume and positive inotropic agents have been inadequate. 

Weaning

• Reduce the amplitude of the oscillations by 3 units per change (Q1-2h) until the PCO2 rises. After a change in AMPLITUDE, always observe the chest wall to confirm that it is still vibrating, if vibrations have ceased the AMPLITUDE is too low and thus should be reset at the previous setting. A minimal AMPLITUDE tends to occur around 12-14 units.
• Once oxygenation is adequate (FIO2 less than 0.70) slowly lower the MAP by decreasing the PEEP by 1 cm H2O per change (Q4-8h). Minimal HFOV settings tend to be reached around a MAP of 7 cm with an O2 requirement that is less than 40%. At this point depending on the patient, you can remain on the HFOV while the patient grows, you can convert the patient back to convention ventilation at a low respiratory rate (usually 15-20 bpm), or you can extubate the patient to Nasal CPAP.
   
• Management Strategies with High Frequency Ventilation in Neonates Using the SensorMedics 3100A High Frequency Oscillatory Ventilator
• Management Strategies with High Frequency Ventilation in Neonates Using the Infant Star 950 High Frequency Ventilator
• Management Strategies with High Frequency Jet Ventilation

References

1. Boynton BR et al. High-frequency ventilation in newborn infants. J Intensive Care Med, 1986;1:257-269.
2. Bryan AC, Froese AB. Reflections on the HIFI Trial. Pediatr, 87:565-567;1991.
3. Clark RH, Gerstmann DR, Null Jr DM, De Lemos RA. High-frequency oscillatory ventilation reduces the incidence of severe chronic lung disease in respiratory distress syndrome. Am Rev Respir Dis 141:A686;1990.
4. Courtney SE, HIFO Study Group. High frequency oscillation strategy decreases incidence of air leak syndrome in infants with severe respiratory distress syndrome. Pediatr Res 29:312A;1991.
5. Frantz ID III. Newer methods for treatment of respiratory distress. In: The Micropremie: The Next Frontier. Report of the 99th Ross Conference on Pediatric Research. Columbus, OH: Ross Laboratories: 29-35;1990.
6. Frantz ID III et al. High-frequency ventilation in premature infants with lung disease: Adequate gas exchange at low tracheal pressure. Pediatrics, 1983;71:483-488.
7. Gaylord MS et al. High-frequency ventilation in the treatment of infants weighing less than 1500 grams with pulmonary interstitial emphysema: A pilot study. Pediatrics, 1987;79:915-921.
8. Gerstmann DR, de Lemos RA, Clark RH: High-frequency ventilation: Issues of strategy. Clin Perinatol 18:563-580;1991.
9. Wetzel RC, Gioia FR. High frequency ventilation. Pediatrics Clin North Am, 1987;34:15-38.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Bunnell Life Pulse HFJV - 2020

The Bunnell Life Pulse (www.bunl.com) is a flow interrupter that uses a pinch valve to generate a stream of high frequency pulses. These rapid pulses of fresh gas generate the tidal volumes, which allow ventilation to occur primarily from flow streaming (Taylor Dispersion), which allows ventilation to occur even with below dead space tidal volumes. The gas is squirted into the lungs at a very high velocity, which produces flow streaming, sending gas via laminar and transitional flow down the core of the bronchial tree minimizing the effect of dead space.

A conventional ventilator is always run in tandem with the jet to generate the PEEP and sigh breaths. Expiration on HFJV is passive from elastic recoil. A special ET adapter is used during HFJV. This adapter has a jet port through which the High Frequency Jet pulses are introduced and a pressure monitoring port for determining the delivered pressures.

Initial HFJV settings

First Intention Use in Extremely Premature Infants

 For use in premature infants < 28 weeks Gestation or < 1000 grams. Primary goal of this approach is to minimize mechanical injury from air trapping and/or hyperinflation.

Initial settings

1. Initial Jet Rate for First Intention Use:

   < 24 weeks GA or < 600 grams	300 BPM (I:E of 1:9)
   24-26 weeks GA or 600-1000 grams	360 BPM (I:E of 1:7)
   > 27 weeks GA or > 1000 grams	420 BPM (I:E of 1:6)

    

2. If PIE begins to develop also drop rate from 360 to 300 to 240.
3. I.T. leave fixed at 20 milliseconds (0.02 sec) to minimize risk of air trapping.
4. Initial PEEP start at 5 cm to avoid hyperinflation, can increase as needed if still poorly aerated and requiring FiO2 > 0.40 after surfactant therapy.
5. Initial PIP start at 22-24 cm with visible jet vibrations of the chest wall and adjust based on pCO2 goals.
6. 1st Intention start with no sighs.

Sigh Breaths 

Use for Premature Infants < 27 weeks gestation, generated by the conventional in-line ventilator:

1. Use as an ongoing alveolar recruitment strategy especially for “wandering”/ focal/ patchy atelectasis.
2. Initial rate 4 with I.T of 0.4 with PIP set at 6-10 cm above the PEEP, once initiated no need to wean the rate, however if air leaks develop then turn off sighs (rate of 0) until healed.
3. Can increase rate up to 6-12 for alveolar hypoventilation spells which present with significant desaturations < 80% when the infant’s own spontaneous breathing rate slows < 15-20 BPM. The use of this higher rate will decrease the depth and duration of these desaturation spells.

Outcomes with First Intention HFJV (see below reference) 

• Watkins PL, Dagle JM, Bell EF, Colaizy TT. Outcomes at 18 to 22 Months of Corrected Age for Infants Born at 22 to 25 Weeks of Gestation in a Center Practicing Active Management. J Pediatr 2020;217:52-8

Overall Use for Newborns including Rescue, First Intention in Premature Infants ≥ 27 weeks

Rate (frequency) and inspiratory time

1. Initial Rate or Frequency - 420 BPM (7 Hz) is the usual starting frequency for infants (range of 4 - 11 Hz or 240-660 BPM). Start with a rate of 360 BPM (6 Hz) for infants < 1000 grams or < 27 weeks gestation age or when either air leaks or air trapping is a concern. Changes in rate or frequency are rarely made in the hour-to-hour management of blood gases. Frequency is ordered as rate in BPM. Changes are to be made in 60 BPM (1 Hz) increments.
2. I.T. - High Frequency Breath - always use 20 milliseconds (0.02 sec) for the inspiratory time (range 20-34 milliseconds). The I.T. should never be increased above 20 milliseconds (0.02 sec) without Neonatal staff approval. Any increase in I.T. will greatly increase the risk of air trapping and pneumothorax.
3. I:E ratio - The I:E ratio is dependent on the frequency. Higher frequencies increase the risk of gas trapping. At 20 milliseconds IT and at 11 Hz (660 BPM), the I:E ratio is 1:3.5 while at 7 Hz (420 BPM) the I:E ratio is 1:6. The longest I:E ratio is at 4 Hz (240 BPM) – 1:12.

4. Decreased Frequency (4 - 6 Hz) (240-360 BPM) is used:

   1. To treat air leaks: PIE, pneumothorax.
   2. To avoid hypocarbia from excessive ventilation when at minimum delta P (PIP-PEEP), which is a PIP of 3 - 6 cm above the PEEP.
   3. To minimize inadvertent air trapping, which can be detected when the PEEP measured by the jet exceeds the PEEP set on the conventional ventilator by > 1.5 - 2 cm. Always monitor both PEEP values.

    

5. Increased Frequency (from 8 Hz up to 11 Hz) (480-660 BPM) is used:

   1. To increase alveolar ventilation when the patient has severe hypercarbia despite increased PIP, when there is no evidence of air trapping.
   2. To improve oxygenation by increasing lung volume from decreased expiratory time (i.e., shorter I:E ratio), leading to increased lung recruitment (warning: this maneuver will increase the risk of air leaks).
   3. To decrease the delta P needed and thus minimize the delivered TV in micro-preemies when air trapping is not a concern.

    

PIP (peak inspiratory pressure)

The jet functions as a pressure limited ventilator. Thus, you set the PIP that you want the jet to achieve. The difference between the PIP ordered and the PEEP is the delta P, which represents the volume of gas generated by each high frequency pulse during the opening of the pinch valve (maximum generated volume occurs with a PIP of 50 cm with a minimum PEEP and an IT of 34 milliseconds). Thus, an increase in PIP will increase delta P and improve ventilation and a decrease in PIP will decrease delta P and decrease ventilation.

1. Tidal volume: The TV delivered is attenuated by the following: circuit tubing, humidifier, ET tube diameter and length (FLOW is proportional to r⁴/L), the patient’s airways and compliance. The TV delivered is proportional to the delta P (PIP-PEEP).

2. Initial PIP Settings: Range (8 - 50 cm H2O)

   1. If converting from conventional ventilation, set PIP on the HFJV to a value that is 2-4 cm > PIP on conventional ventilation. If not ventilating well set PIP on the Jet 4 > than the PIP on the conventional ventilator. If starting a patient < 27 weeks gestation on first intention HFJV to minimize volutrama then start with PIP in the low 20's, PEEP 5 and a rate of 360 (22-24 cm JET PIP) with visible jet vibrations of the chest wall and then titrate based on the PCO2 goals, oxygenation and chest radiographs.
   2. If converting from Star HFV or 3100A HFV, then set PIP approximately 1- 2 cm below the measured PIP that is generated by the HFV amplitude, which is measured by monitoring the patient with the jet using the pressure monitoring port of the ET tube adaptor while they are still on HFV (Star or 3100A) prior to conversion. If not ventilating or oxygenating well set PIP on the Jet equal to the measured PIP generated by the amplitude of the high frequency oscillatory ventilator.
   3. Check gases Q15-20 min, and titrate the PIP based on PaCO2 until stable (e.g., RDS - PaCO2: 45 - 60).
   4. Alveolar Ventilation (Ve) on HFJV is proportional to the delta P, which is primarily determined by the PIP.

    

3. Management of PaCO2 (Alveolar Ventilation (Ve) on HFJV):
   During HFJV, Ve =(Vt)² x frequency as compared to CMV in which Ve = Vt x Rate
   Thus, PaCO2 is primarily regulated by changes in PIP or delta P (PIP-PEEP), not rate or frequency! Delta P is primarily regulated via changes in PIP. See table below for rough guidelines on adjusting the PIP.

   1. To change PaCO2 ± 2 - 4 mm Hg adjust PIP by 1-2 cm H2O
   2. To change PaCO2 ± 5 - 9 mm Hg adjust PIP by 3-4 cm H2O
   3. To change PaCO2 ± 10 - 14 mm Hg adjust PIP by 5-6 cm H2O
   4. Always check a blood gas 15-20 minutes after any change in PIP.

    

PEEP and sigh breaths

The PEEP on HFJV is set by using the conventional ventilator that is in-line with the jet. Oxygenation on HFJV is directly proportional to MAP which is similar to CMV; however, with HFJV, the MAP should be generated primarily by PEEP with a contribution from the PIP. The greater the delta P, the larger the contribution of the PIP to the MAP. During HFJV; MAP should primarily be determined by PEEP to avoid excessive use of PIP, thus minimizing barotrauma, volutrauma, and hypocarbia.

1. CONVERSION TO HFJV:

   1. Initial PEEP Settings: Initial PEEP should be 2 - 4 cm below the MAP on either CMV or HFV. IMPORTANT POINT - After converting to the Jet, the MAP on the Jet should equal the MAP on either the CMV or the HFV prior to conversion. After conversion, if Jet MAP is > 2 cm above the CMV/HFV MAP before conversion, then decrease PEEP 1 cm at a time until the MAP on the jet is equal to the MAP before conversion or stop at a MAP 1 cm higher if there is a need to improve oxygenation. If starting the patient immediately on HFJV, use a PEEP of 8 cm and then titrate based on X-ray findings and ability to oxygenate. If starting the patient immediately on HFJV, use a PEEP of 5-6 cm and then titrate based on X-ray findings and ability to oxygenate.
   2. Initial PIP: If converting from Star HFV or 3100A HFV, then set PIP 1- 2 cm below the measured PIP that is generated by the HFV amplitude, which can be measured by monitoring the patient with the jet while they are still on HFV (Star or 3100A) prior to conversion. If converting from conventional ventilation, set PIP on the HFJV to a value that is 2 cm < PIP on conventional ventilation.
   3. Sigh Breaths: When converting from CMV to HFJV, place the Jet in-line with the patient remaining on their conventional settings and then activate the Jet settings (420 bpm, 0.02 sec IT, PIP as previously determined), then increase PEEP by 1 cm while decreasing both conventional rate by 5 bpm and conventional PIP by 2 cm H2O on the conventional ventilator in order to keep MAP constant during the conversion. Keep decreasing rate quickly and increasing PEEP while decreasing conventional PIP until rate of CMV is 3- 4 bpm (sighs) and MAP becomes equal to PEEP. Or in stable patients, just switch the patient directly from conventional ventilation to the previously determined Jet settings After conversion, the PIP of the conventional sigh breaths should be about 6 cm above the PEEP.
   4. It is very important to keep MAP constant during the conversion to HFJV to avoid excessive atelectasis and concomitant loss of oxygenation.
   5. Obtain a CXR 45-60 min after converting to the jet. Follow CXR closely to assess for appropriate lung volume (around 9 ribs)
   6. Gases: Check a gas within 15-20 min after converting to the jet and adjust appropriately.

    

2. Management of ABGs - Oxygenation and Ventilation: Oxygenation is directly proportional to PEEP and MAP – see multiple scenarios below:

   1. Oxygenation Inadequate - If below optimal lung volume and if FiO2 0.6 - 0.7, increase PEEP by 1 - 2 cm H2O. If FiO2 is 1.0, increase by 2 - 4 cm H2. When increasing PEEP, also increase the PIP by the same amount to keep tidal volume constant. Can also increase the PIP, IT or rate of the sigh breaths to improve alveolar recruitment.
   2. Oxygenation Inadequate and CO2 Adequate - If CO2 is acceptable but not oxygenating, increase MAP but keep TV or delta P constant. Thus, when increasing PEEP, also increase the PIP by the same amount (1 and 1 cm H2O or 2 and 2 cm H2O for both PIP and PEEP).
   3. Oxygenation Inadequate and CO2 Too Low – Increase PEEP (1-2 cm) but keep PIP constant. This increases MAP, while decreasing the delta P, thus improving oxygenation while decreasing the TV.
   4. Oxygenation Inadequate and CO2 Too High – Increase both MAP and delta P by increasing PIP until CO2 is acceptable. If the oxygenation is still inadequate with an acceptable CO2, then increase both PIP and PEEP by the same amount to keep TV constant.
   5. Oxygenation Too Good and CO2 Too Low – Decrease PIP until CO2 is appropriate. If oxygenation is still too good with an over-inflated chest X-ray, start decreasing both PIP and PEEP by the same amount to decrease MAP while keeping a constant delta P.
   6. Oxygenation Adequate and CO2 Too Low – Wean delta P by decreasing PIP but increase PEEP as necessary to keep MAP constant. This decreases TV but keeps MAP constant, thus preventing atelectasis with loss of oxygenation.
   7. Oxygenation Too Good and CO2 Adequate — If CO2 is acceptable but FiO2 is too low or CXR over-inflated, then wean MAP by keeping TV (delta P) constant by decreasing both PIP and PEEP by the same amount (1 and 1 cm H2O or 2 and 2 cm H2O).
   8. Sigh Breaths - Conventional IMV breaths used for recruitment of alveoli to improve oxygenation without need for excessive PEEP. Normal settings: Rate = 3 - 4, I.T. = 0.4 - 0.6 sec., PIP = PEEP + 6 cm H2O (minimal adequate PIP). If sigh PIP is higher than jet PIP, then jet will pause. If sigh PIP is less than jet PIP, then jet breaths will be superimposed over IMV breath.
   9. Warning: Oxygenation is directly proportional to PEEP (MAP) unless lung is over-inflated. If the lung is over-inflated, may need to decrease PEEP to improve oxygenation and ventilation.

    

Management strategies

Always place Jet on standby to suction or to give surfactant.

RDS

1. Surfactant Replacement Therapy - Give surfactant then switch to HFJV.
2. If already on to HFJV place jet on standby and then bag in the surfactant.
3. Wean delta P by decreasing PIP to keep PaCO2 45 - 60 mm Hg.
4. Wean FiO2 until ≤ 0.50 then decrease MAP by decreasing PEEP and PIP as necessary.
5. The lower the FiO2, the more frequently the PEEP and PIP need to be weaned to avoid over-inflation. Minimal PEEP 3 - 6 cm H2O with FiO2 ≤ 0.40 and appropriate lung inflation on CXR.

Airleaks: Pulmonary interstitial emphysema (PIE) or pneumothorax

1. Minimize the number and intensity of IMV breaths. Thus, decrease sigh rate to 3 or use no sighs by setting the IMV rate to 0.
2. Permissive Hypercarbia - Decrease delta P to keep PaCO2 55 - 70 mm Hg, by decreasing PIP.
3. Decrease Rate (Frequency) - Because of the fixed I.T. (0.02 sec) decreasing the frequency will increase the expiratory time, thus minimizing air trapping (e.g., 7 Hz (420 BPM) - I:E ratio = 1:6, 6 Hz (360 BPM) - I:E ratio = 1:7, 4 Hz (240 BPM) - I:E ratio= 1:12).
4. Decrease MAP by decreasing both PIP and PEEP — Transiently tolerate increased FiO2 requirements (0.5 - 0.75) in order to heal severe PIE.

BPD

1. The goal is to minimize barotrauma, volutrauma, atelectatrauma, biotrauma, and oxygen toxicity.
2. Minimize delta P by decreasing PIP to keep PaCO2 adequate (e.g., 50 - 70 mm Hg).
3. Increase PEEP as necessary to keep FiO2 ≤ 0.40 - 0.50 with minimum PIP and allow the patient to “self-wean by outgrowing the ventilator.”
4. Decrease PIP and PEEP by 1 cm H2O every 3-7 days once FiO2 remains < 0.40 - 0.45 after each change.

Weaning

Oxygenation

Once oxygenation is adequate and the patient is ready to be weaned, follow these steps:

1. Only wean FiO2 until ≤ 0.50, unless over-inflated.
2. Once FiO2 ≤ 0.50 and CO2 are acceptable, decrease PEEP and PIP by 1 cm H2O Q4 - 8h, if FiO2 ≤ 0.30 - 0.35, decrease PEEP and PIP by 1 - 2 cm H2O Q2 - 4h to avoid over-inflation.
3. Also decrease PIP of conventional sigh breaths at the same time and by the same amount that you decrease the PEEP (e.g., PIP 16 and PEEP 10 to PIP 15 and PEEP 9).
4. Minimal PEEP or MAP ranges from 3 - 7 cm H2O with FiO2 ≤ 0.40. Minimal Jet PIP < 20 cm H2O. At this point one can convert to IMV at low rates (15 - 20 BPM), or remain on HFJV while the patient matures (anti-apnea settings) and grows, or extubate to NPCPAP if ready.

Ventilation

1. Reduce Jet PIP (delta P) at least 1-2 cm H2O per change whenever PaCO2 decreases below threshold, until minimal PIP (< 20) is reached, with a delta P < 10.
2. If PaCO2 is still too low (< 35 mm Hg) on minimal PIP and minimal delta P (3 cm), and if the infant is not ready for extubation, decrease frequency to 5 Hz (300 bpm) and then to 4 Hz (240 bpm) to decrease alveolar ventilation.

Extubation

Patients are usually ready for a trial of extubation with NPCPAP when they meet the following respiratory support criteria:

1. RDS: PEEP or MAP ≤ 7 - 8 cm H2O with FiO2 ≤ 0.35 and Jet PIP (< 20 and delta P < 10). Extubate to a NPCPAP of 6 - 8 cm H2O.
2. BPD: PEEP or MAP ≤ 10 - 12 cm H2O with FiO2 ≤ 0.45 and Jet PIP (< 20-22 and delta P < 10-12) extubate to a NPCPAP of 8 - 10 cm H2O.

Complications associated with HFJV

1. ATELECTASIS – increase the PEEP, or increase the PIP, I.T., or the rate of the sigh breaths from 3 - 6.
2. HYPOTENSION- decrease PEEP and PIP to decrease MAP, or decrease frequency to minimize air trapping.
3. OVERINFLATION- decrease PEEP and PIP, or decrease frequency.
4. APNEA- Increase delta P (PIP), increase sighs to 4 – 6 BPM, or consider converting to conventional ventilation. HFJV is not an optimal mode for the management of apnea.

Alarms

1. Servo Pressure – Represents the amount of gas flow or tidal volume delivered by the ventilator to achieve the PIP ordered. Maximum servo pressure is 22 PSI.

   1. Increase in servo pressure – Causes: Compliance has improved, thus a larger TV is being delivered for the same PIP. Check a blood gas and prepare to wean since the patient is improving, or there may be a leak around the ETT (common in premature infants) or a leak in the circuit requiring an increase in flow to compensate (check circuit).
   2. Decrease in servo pressure – Causes: Plugged or obstructed tube, pneumothorax, right main stem intubation, or worsening lung disease. This worsening of compliance means that it takes very little TV or flow to reach the set PIP. Patient may need suctioning or chest x-ray.

    

High Frequency Jet Ventilator Guidelines (PDFs):

• High Frequency Jet Ventilation in ELBW infants-Iowa Approach
• Jet Ventilation Guidelines 2021
• Basic Management Strategies Table

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

SensorMedics 3100A Oscillatory Ventilator

The SensorMedica 3100A is a true high frequency oscillator with a diaphragmatically-sealed piston driver.  It is theoretically capable of ventilating patients up to 35 kg.  Tidal volume (TV) typically delivered ≈ 1.5-3.0 cc/kg (TV<dead space).  It is an extremetly efficient ventilator secondary to an active expiratory phase, but it is not capable of delivering sigh breaths for alveolar recruitment.

Initial settings

Frequency

 Initial settings:

10 Hz (600 BPM) for term infants ( > 2.5 kg)

12 Hz (720 BPM) for premature infants (1.5 -  ≤ 2.5 kg)

14 Hz (840 BPM) for preterm infants ( 1.0 - < 1.5 kg)

15 Hz (900 BPM) for preterm infants < 1.0 kg

8 Hz (480 BPM) for children between 6-10 kg

6 Hz (360 BPM) for children > 10 kg (consider 4 or 5 Hz if not ventilating)

Lower frequencies will increase absolute IT and often will improve oxygenation via increased alveolar recruitment as well as significantly improve ventilation through increased tidal volume delivery.

If not ventilating at the initial starting frequency on a Power/Amplitude/Delta P that clearly results in good chest wall vibrations then decrease the frequency by 2 Hz, at a time, to significantly increase the delivered TV.  Remember during HFOV, alveolar ventilation (Ve) ≈ (TV)²F as compared to conventional ventilation where Ve ≈ TV(R).

Inspiratory time (I.T.)

Set initially at 33% 

Power/Amplitude/Delta P

A rough representation of the volume of gas generated by each high frequency wave.  Power range (1.0 - 10.0). Oscillatory Pressure/Delta P/Amplitude range (0-90 cm) H₂O. Maximum true volume of gas generated by the piston is 365 cc.  Maximum amplitude (delta P/pressure wave) or tidal volume delivered is highly variable and is highly attenuated by the ETT and the tracheobronchial tree before reaching the alveolus. Thus the delivered TV depends on the following factors: circuit tubing (compliance, length and diameter), humidifier (resistance and compliance - water level), ET tube diameter and length (FLOW is directly proportional to r4/l, where r = radius of airway and l = length of airway), the patient's airways and compliance.

1. Initial Setting for POWER/Amplitude:

• 1.5 - 2.0 (delta P 15-20 cm) for wt  <2.0 kg
• 2.0 - 2.5 (delta P 20-25 cm) for wt 2.0-2.5 kg
• 2.5 - 3.5 (delta P 25-35 cm) for wt 2.5-3.5 kg
• 3.5 - 5.0 (delta P 35-45 cm) for wt 3.5-5.0 kg
• 6.0 (delta P 60 cm) for wt 5.0-7.5 kg, 7.0 (delta P 70 cm) if wt ≥  7.5 kg.

Chest wall needs to be vibrating.  If not vibrating, increase power.

* Check ABG's every 15-20 min until PaCO₂ ≈ 40-60 or within target range, i.e., titrate Power/Amplitude setting based on PaCO₂ desired.  Many HFOV centers have you order amplitude or delta P (∆P) to regulate ventilation instead of power.  Since amplitude or delta P is a measured value, we have decided that the Power setting is a more reliable and consistent way of adjusting this ventilator and thus we order changes in power in order to regulate ventilation by changing the distance the piston travels but either approach is completely valid.

2) Alveolar ventilation is directly proportional to POWER (Ampltiude or delta P), therefore the level of PaCO₂ is inversely proportional to the power/amplitude/delta P.

3) During HFOV, alveolar ventilation (Ve) ≈ (TV)²f as compared to conventional ventilation where Ve ≈ TV(R).  Thus we primarily adjust the power (amplitude/delta P) to change the delivered tidal volume in order to manipulate ventilation.

4)  Management of ABG's (Ventilation - Ve) Guidelines:

a)  Change POWER by 0.2-0.3 to change CO₂ ± 2-4 mm Hg or amplitude/delta P by 2-3 cm H₂O

b)  Change POWER by 0.4-0.7 to change CO₂ ± 5-9 mm Hg or amplitude/delta P by 4-7 cm H₂O

c)  Change POWER by 0.8-1.0 to change CO₂ ± 10-15 mm Hg or amplitude/delta P by 8-10 cm H₂O

d) Warning - It is extremely important to normalize PaCO₂ rapidly by weaning Power/amplitude/delta P in order to avoid volutrauma from excessive tidal volumes.  Thus check ABG's frequently (Q15-20 min) and decrease POWER/amplitude/delta P accordingly until PaCO₂ ≥ 35.  PaCO₂ < 35 mm Hg correlates with an increased risk of pneumothorax.  Thus to minimize the risk of volutrauma, it is important to minimize the amount of delivered TV by regulating the POWER/Amplitude/Delta P needed in conjunction with the optimal frequency based both on patient size and the pathophysiology of the lung disease being treated to maintain balance between shear force and effective ventilation.

e)  If PaCO₂ still remains elevated at high POWER setting (>7.0), decrease FREQUENCY by 2 Hz every 15-20 min until maximum tidal volume is reached (4 Hz at a POWER of 10.0).  The lower frequency leads to a longer absolute I.T. which results in a larger tidal volume of gas displaced towards the infant.  This increased TV leads to increased alveolar ventilation (on HFOV, Ve ≈ (TV)²f).

5)  Manual Ventilation:  Hand bagging while on the SensorMedics Ventilator should be minimized secondary to the risk of barotrauma due to shear force injury from higher TV and possible hyperinflation. Oxygen desaturation can also occur from loss of MAP leading to alveolar derecruitement.  Suctioning should be performed using just the ventilator breaths alone (an inline suctioning adapter is optimal).  If bagging has to be done, the PIP while bagging if possible should be 8-10 cm above the MAP and a PEEP of 6-8 cm should be maintained as tolerated.

MAP

Oxygenation on HFOV is directly proportional to MAP which is similar to conventional ventilation, however with the SensorMedics HFOV the MAP is directly ordered and generated.  Thus during HFOV:MAP ordered = MAP delivered.

1.  Initial Settings:

a)  Neonates - Initial MAP should be 2-4 cm above the MAP on CMV.

b)  Infants/Children - Initial MAP should be 4-6 cm above the MAP on CMV.

c)  If starting immediately on HFOV use a MAP of ≈ 8-10 cm in neonates and 15-18 cm in infants/children.

 2.  Management of ABG's (Oxygenation a MAP):

a)  If not oxygenating adequately at initial MAP (10-18 cm) obtain CXR to assess lung volume.  If lung is not hyperinflated (flattened diaphragm) or is below optimal lung volume ≈ 9 ribs then increase MAP by 1-2 cm every 20-30 min until adequate oxygenation is achieved or lung starts to become overinflated (e.g. FiO₂ 0.6-0.7 increase by 1-2 cm, FiO₂ 1.0 increase by 2-4 cm per change).

b)  Maximum potential MAP = 38-43 cm

c) Warning - If oxygenating adequately, but the lung is hyperinflated immediately decrease MAP by 1-2 cm every 1-2 h until lung volumes return to normal. If the lung is allowed to remain hyperinflated for prolonged periods of time the risk of barotrauma increases.

d) If not oxygenating with lung becoming hyperinflated, you can decrease frequency as a way to increase I.T. to improve alveolar recruitment while keeping I:E ratio constant.

Management strategies

The SensorMedics HFOV is used for premature infants, term infants or young children with respiratory failure not responsive to conventional ventilation or first intention therapy for premature infants with RDS. 

Term infant with severe respiratory failure (PPHN, MAS, GBS pneumonia, RDS)

Start at a frequency of 10 Hz and a Power of 3.0 to 5.0 (amplitude/delta P 35-45 cm).  Initial MAP 4 cm above MAP while on CMV.  Check CXR 1-2 hrs after converting to HFOV, then adjust MAP to achieve optimal lung volume (9 ribs expanded with improved aeration).  If not oxygenating, increase MAP by 1-2 cm every hour until oxygenation improves.  Adjust Power/Amplitude/delta P to keep PaCO2 45-55. Consider decreasing frequency to 8 Hz and then to 6 Hz if ventilation and oxygenation remain problematic. This will increase TV to improve ventilation and absolute IT to help to improve oxygenation via alveolar recruitment.

Airleaks

Pneumothorax or PIE - The goal is to minimize both tidal volume and shear force/peak pressure generated by a given TV at a set MAP.  Transiently tolerate increased FiO₂ requirements (0.6 - 1.0) by reducing MAP as tolerated in order to minimize overdistention from excessive MAP.  Practice permissive hypercarbia and accept higher PaCO₂'s to minimize the delivered TV.  Increase  FREQUENCY up to 12, 14 or 15 Hz in order to minimize both absolure I.T. and delivered TV in order to heal the airleak. Decrease I.T. to 30%. It is better to be on a higher frequency with a concurrent higher level of amplitude to maintain the same level of PaCO₂ then a lower frequency with lower amplitude.  Since the actual delivered TV to the lung will be less and the leak will heal more rapidly with the higher rather than lower frequency.

Reference: Ellsbury DL, Klein JM and JL Segar, Optimization of high-frequency oscillatory ventilation for the treatment of experimental pneumothorax. Crit Care Med 2002; 30:1131-1135.

ARDS

C.   Goal is to minimize volutrauma, shear force and oxygen toxicity.  Use the minimum POWER possible at the appropriate FREQUENCY in order to keep PaCO2 adequate (e.g. 55-70 mm Hg).  Increase MAP as high as necessary to keep FiO2≤1.0.  Also decrease frequency to increase absolute I.T. to improve oxygenation.

RDS

C.   Give surfactant replacement therapy using manual bagging.  Start with frequency of 12-15 Hz depending on EGA/birth weight and I.T. of 33%.  Use initial MAP of 8-10 cm or 2 cm above MAP on conventional ventilation. Obtain chest radiograph and adjust MAP to obtain 9 rib expansion with improving FiO2. Wean FiO2 until <0.40 then MAP as tolerated to avoid overinflation. Wean power/amplitude/delta P to keep PaCO2 45-60 mmHg.  Follow blood gases q30-60 min after SRT until stable and wean power/amplitude/delta P frequently to avoid hypocarbia (PaCO2< 40 mm Hg).

Rescue therapy for premature infant with RDS

To be used for premature neonates who can’t ventilate on high conventional or on excessively high HFJV settings or who require a MAP ≥ 20 cm to achieve oxygenation while on HFJV.  Use initial frequency of 10-12 Hz, Power of 3.0 - 4.0 (delta P 30-40 cm H2O), MAP 2-4 cm above MAP on HFJV or 4 cm above the MAP on conventional ventilation.

BPD (evolving):

Goal is to minimize volutrauma, barotrauma (shear force), atelectatrauma, biotrauma and oxygen toxicity.  Minimize the power/amplitude/delta P to keep PaCO₂ adequate (e.g., 50-70 mmHg).  Increase MAP as necessary to keep FiO₂ <0.50-0.60 if possible avoiding hyperinflation leading to increased PVR.  Use I.T. of 33%.  Use frequency range of 10-15 Hz: use lower frequencies if having difficulty with ventilation and/or oxygenation, use higher frequencies with I.T. of 30% if having problems with PIE.

Other potential indications

CHF/Pulmonary Edema, Hypoplastic Lungs, anascara, hydrops fetalis and so forth …

Not beneficial for asthma

Increased risk of air trapping with severe reactive airway disease.

Weaning

Oxygenation

Once oxygenation is adequate and the patient is ready to be weaned follow these steps:

1) First wean FiO₂ until ≤ 0.60 unless hyperinflated. During active changes in compliance (e.g., surfactant replacement, aggressive diuresis, …) may need to follow chest radiographs as frequently as every 8-12 hours to evaluate lung expansion to avoid hyperinflation leading to decreased cardiac output from impaired venous return with loss of preload or development of pneumothorax. Always wean MAP if hyperinflation is developing. Aim for 9 rib expansion.

2) Once FiO₂ ≤ 0.60 or hyperinflated, decrease MAP by 1 cm Q4-8h; if OXYGENATION is lost during weaning then increase MAP by 2-4 cm to restore lung volumes and begin weaning again, but proceed more slowly with decreases in MAP.

3)  Minimal MAP ≈ 8-16 cm with FiO₂ ≤0.40-0.50, at this point one can convert to conventional ventilation or remain on HFOV while the patient continues to heal (e.g., MAP of 8-12 cm ≤ 5 kg).

Ventilation

Reduce POWER by 0.2-0.3 units per change (amplitude/delta P 2-3 cm H₂O) whenever PaCO₂ decreases below threshold (e.g., < 45 mm Hg) until minimal POWER/amplitude/delta P is reached (power <1.5-2.0, delta P < 15-20 cm H₂O) depending on the size of the patient.  If frequency is below the standard frequency for the patient's weight, then considering weaning by increasing frequency back to baseline which will also decrease the tidal volume, then decrease power/amplitude/delta P as described above.

Potential complications associated with HFOV

Hyperinflation

Can lead to increased pulmonary vascular resistance and air leaks, decrease MAP

Secretions

Increase suctioning (inline suctioning is optimal to minimize loss of lung recruitment

Hypotension

Quickly lower MAP, and rule out other causes [e.g., pneumothorax, sepsis, dehydration, cardiac dysfunction (LV or RV) etc …]

Air leaks

Decrease MAP to minimize over distention and increase frequency to decrease delivered tidal volume

Hypocarbia

Wean ventilation and follow pCO₂ closely until level is appropriate

EFFECTS OF CHANGING FREQUENCY ON VENTILATION USING THE SENSORMEDICS HIGH FREQUENC OSCILLATORY VENTILATOR.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed  

Infrasonics Infant Star Ventilator -- A flow interrupter which functions like an oscillator with a negative pressure phase generated by a Venturi effect. Normally used for premature infants < 2.5 kg. Theoretically delivers a tidal volume of 1.5 - 3.0 cc/kg in a 2 kg infant with normal compliance.

Initial HFV settings

Frequency

12-15 Hz (900 BPM) is the usual starting frequency in a premature infant with RDS (range used of 6 - 15 Hz). Changes in frequency are rarely made in the hour-to-hour management of ABGs. A frequency > 15 Hz may worsen ventilation.

1. I.T.: The inspiration time for the High Frequency breath is fixed at 18 msec (0.018 sec), therefore the I:E ratio is dependent on the frequency. At 15 Hz, I:E is 1:3 while at 6 Hz I:E is 1:8.
2. Decreased Frequency (6 - 12 Hz) is used:
   1. To treat air leaks: PIE, pneumothorax.
   2. To avoid hypocarbia from excessive ventilation when at minimum amplitude.
   3. To minimize inadvertent air trapping. 
3. Increased Frequency (from 6 Hz up to 15 Hz)
   1. To increase alveolar ventilation when the patient remains hypercarbic despite increasing amplitude.
   2. To improve oxygenation by increasing lung volume from decreased expiratory time (i.e., shorter I:E ratio). 

Amplitude

A rough representation of the volume of gas generated by each high frequency pulse through the proportioning valves (maximum generated volume with all 10 valves open is 36 cc). THIS IS NOT THE TIDAL VOLUME DELIVERED!

1. Tidal volume delivered is attenuated by the following: circuit tubing, humidifier (e.g., water level), ET tube diameter and length (FLOW is proportional to r⁴/L), the patient's airways and compliance. Thus, the theoretically delivered tidal volume is on the order of 1.5 cc/kg in a 2 kg infant.
2. Initial Amplitude Settings: Range (approx 11 - 51 cm H₂O)
   1. Adjust amplitude until you see vigorous chest wall vibrations (amp = 24 - 34 cm H₂O) then titrate based on PaCO₂ (e.g., RDS PaCO₂:45 - 60).
   2. Alveolar Ventilation (Ve) on HFV is directly proportional to the Amplitude.
   3. Amplitude Drift: If the amplitude (a measured value) is drifting from ordered values, it is usually due to a change in the compliance of the system (i.e., the infant is improving, secretions in the ET tube or the water level in the humidifier is low). 
3. Management of PaCO₂ (Ventilation on HFV):

• During HFOV: Alveolar Ventilation (Ve) = (Vt)² x freq as compared to CMV where Ve = Vt x Rate
• Thus, PaCO₂ is primarily regulated during HFV by changes in amplitude, not frequency! See table below for guidelines on adjusting the amplitude (minimal AMP change is 3 cm H₂O).
  • To change PaCO₂ ± 2 - 4 mm Hg increase or decrease AMP by approx 3 cm H₂O
  • To change PaCO₂ ± 5 - 9 mm Hg increase or decrease AMP by approx 6 cm H₂O
  • To change PaCO₂ ± 10 - 14 mm Hg increase or decrease AMP by approx 9 cm H₂O

PEEP or MAP

Oxygenation on HFV is directly proportional to MAP which is similar to CMV; however, with HFV almost all of the MAP is generated by PEEP. Thus, during HFV: MAP = PEEP.

1. Initial PEEP settings: Initial PEEP should be equal to or slightly (1 cm) above the MAP on CMV. If starting immediately on HFV use a PEEP/MAP of 10-12 cm for RDS or 7-9 cm for more compliant cases (i.e. after surfactant replacement). When converting from CMV to HFV increase PEEP by 1 cm while decreasing rate by 5 bpm in order to keep MAP constant during the conversion. Keep decreasng rate and increasing PEEP until rate of CMV is 4 bpm (sighs) and MAP becomes equal to PEEP. It is very important to keep MAP constant during the conversion to HFV to avoid excessive atelectasis and concomitant loss of oxygenation.
2.  
   • Follow CXR closely to assess for appropriate lung volume (approx 9 - 10 ribs)!
3. Management of ABGs (Oxygenation): Oxygenation is directly proportional to PEEP or MAP
   • Oxygenation inadequate -- if below optimal lung volume increase PEEP by 2 - 4 cm H₂O (e.g., if FiO₂ 0.6 - 0.7 increase by 1-2 cm H₂O, if FiO₂ 1.0 increase by 2-4 cm H₂O), use sigh breaths or generate manual sighs by bagging.
   • Sighs -- Conventional IMV breaths used for recruitment of alveoli to improve oxygenation without need for excessive PEEP. Normal settings: Rate = 1 - 4, I.T. = 0.4 - 0.6 sec., PIP = PEEP + 6 cm H₂O (minimal adequate PIP).
   • Warning: Oxygenation is directly proportional to PEEP (MAP) unless lung is overinflated. If hyperinflated, may need to decrease PEEP to improve oxygenation. 

Management strategies

RDS

1. Surfactant Replacement Therapy -- give surfactant then switch to HFV.
2. Conversion to HFV:
   • Set frequency to 15 Hz.
   • Increase amplitude over 1-3 min until you achieve vigorous chest wall vibrations which usually occurs at an amplitude of 24-34. However, if conventional rate is > 60, decrease rate to 40 and increase PEEP by 1 - 2 cm, before adjusting the amplitude. This will give the patient adequate expiratory time for the assessment of vibrations.
   • Keep MAP constant during the conversion to HFV to avoid excessive atelectasis and concomitant loss of oxygenation.
   • Use a stepwise process to set MAP: Thus, adjust MAP by decreasing conventional rate (by 5 bpm) while increasing PEEP (by 1 cm H₂O) until conventional rate is 4 breaths per minute ("sighs") and the MAP becomes approximately equal to the PEEP. IT IS VERY IMPORTANT TO KEEP MAP CONSTANT DURING THE CONVERSION TO HFV TO PREVENT EXCESSIVE ATELECTASIS AND LOSS OF OXYGENATION. The goal being a MAP equal to or slightly (1 cm) above the previous MAP.
   • Wean amplitude to keep PaCO₂ 45 - 60 mm Hg.
   • Wean FiO₂ until < 0.50 then PEEP, unless overinflated.
   • The lower the FiO₂, the more frequently the PEEP needs to be weaned to avoid overinflation. Minimal PEEP 3 - 6 cm H₂O with FiO₂ < 0.40 and appropriate lung inflation on CXR.
   • In infants <1000 grams, once FiO₂ < 0.40 and amplitude < 20, start to decrease frequency to minimize risk of inadvertent air trapping. 

Airleaks: Pulmonary Interstitial Emphysema (PIE) or Pneumothorax

1. Minimize the number and intensity of IMV breaths. Thus decrease sighs (decrease PIP, decrease IT, decrease rate) or use no sighs, and set IMV rate to 0.
2. Permissive Hypercarbia -- Decrease AMPLITUDE to keep PaCO₂ 55 - 70 mm Hg.
3. Decrease Frequency -- Because of the fixed I.T. decreasing the frequency will increase the expiratory time, thus minimizing air trapping (e.g., at 10 Hz the I:E ratio is 1:5; at 6 Hz the I:E ratio is 1:8; at 4 Hz the I:E ratio is 1:13).
4. Decrease PEEP -- Transiently tolerate increased FiO₂ requirements (0.5 - 0.75) in order to heal severe PIE. 

BPD

1. The goal is to minimize barotrauma, volutrauma, and oxygen toxicity.
2. Minimize AMPLITUDE to keep PaCO₂ adequate (e.g., 50 - 70 mm Hg).
3. Increase PEEP as necessary to keep FiO₂ < 0.40 - 0.50 with minimum PIP and allow the patient to "self-wean by outgrowing the ventilator."
4. Decrease PEEP by 1 cm H₂O every 4-7 days once FiO₂ remains < 0.40 - 0.45 after each change. 

Weaning

Oxygenation

Once oxygenation is adequate and the patient is ready to be weaned, follow these steps:

1. Only wean FiO₂ until < 0.50, unless overinflated.
2. Once FiO₂ < 0.50, decrease PEEP by 1 cm H₂O Q4 - 8h, if FiO₂ < 0.30 - 0.35, decrease PEEP by 1 - 2 cm H₂O Q2 - 4h to avoid overinflation.
3. Also decrease PIP of Sigh breaths at the same time and by the same amount that you decrease the PEEP (e.g., PIP 16 and PEEP 10 to PIP 15 and PEEP 9).
4. Minimal PEEP or MAP approximately 3 - 7 cm H₂O with FiO₂ < 0.40. At this point one can convert to conventional ventilation at low rates (approximately 15 - 20 bpm), or remain on HFV while the patient matures (anti-apnea settings) and grows, or extubate to NPCPAP if ready.

Ventilation

1. Reduce AMPLITUDE by at least 3 cm H₂O per change whenever PaCO₂ decreases below threshold, until minimal AMPLITUDE (11-13) is reached.
2. Always observe chest wall after a decrease in AMPLITUDE to confirm vibrations, if vibrations have ceased the AMPLITUDE is too low and should be readjusted to previous settings.
3. If PaCO₂ is still too low (< 35 mm Hg) on minimal amplitude, and the infant is not ready for extubation, decrease frequency to 10 Hz and then to 6 Hz to decrease alveolar ventilation.

Extubation

Patients are usually ready for a trial of extubation with NPCPAP when they meet the following respiratory support criteria:

1. RDS: PEEP or MAP < 7 - 8 cm H₂O with FiO₂ < 0.35 extubate to a NPCPAP of 6 - 8 cm H₂O.
2. BPD: PEEP or MAP < 10 - 12 cm H₂O with FiO₂ < 0.45 extubate to a NPCPAP of 8 - 10 cm H₂O.
3. Mechanical support required for ventilation is minimal (see table below).

Complications associated with HFV

A. ATELECTASIS - increase PEEP, or increase the PIP, I.T., or rate of the sigh breaths (0-4).

B. SECRETIONS- Suction more frequently.

C. HYPOTENSION- decrease PEEP to decrease MAP to improve venous return if low BP is due to hyperinflation.

D. OVERINFLATION- decrease PEEP and decrease PIP if using sighs to decrease MAP.

E. APNEA- Increase amplitude or frequency, increase sighs to 4-6 BPM, or consider converting to conventional ventilation. HFV is not an optimal mode for the management of apnea.

• Effects of Changing Frequency on Ventilation using the Infant Star High Frequency Ventilator
• Representative Figures Demonstrating the Effects of Management Strategies using the Infant Start High Frequency Ventilator

Jonathan M. Klein, MD, Julie Lindower, MD
Peer Review Status: Internally Peer Reviewed 4/18/12

Resuscitation in the delivery room (see Neonatal resuscitation flowchart). 

Use of Medications in the delivery room (see section on Neonatal resuscitation medications).

Term infants who have required aggressive resuscitation in the delivery room (birth asphyxia, meconium aspiration, etc.) are at risk of developing persistent pulmonary hypertension of the newborn (PFC) and initially should be closely observed with continuous pulse oximetry for signs of respiratory decompensation and/or right to left shunting, before slowly decreasing their supplemental oxygen while maintaining saturations > 94%.

Reference for Neonatal Resuscitation Guidelines:  Circulation 2010;122:S909-S919. Pediatrics 2010;126:e1400-e1413.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

 Meconium staining of amniotic fluid occurs in 11-22% of all deliveries. Meconium aspiration syndrome occurs in approximately 2% of these deliveries (1). Release of meconium into the amniotic fluid is usually the result of in utero hypoxia and/or fetal distress. If meconium is passed more than 4 hours before delivery, the infant's skin will be meconium stained. The distressed fetus will make reflex gasping movements and aspirate meconium stained fluid into the tracheo-bronchial tree. After the first breath, the infant will deposit the aspirated meconium stained fluid further down the bronchial tree and therefore cause a mechanical blockage of alveoli and small airways with a resultant ball-valve type obstruction. An infant born via breech presentation will often pass meconium prior to delivery, even without fetal distress. 

Treatment in the delivery room

A. Thin Meconium -

1. The infant's oro- and nasopharynx should be suctioned by the obstetrician prior to delivery of the shoulders. 

2. In a clinically well-appearing newborn, visualization of the larynx and intubation should not be necessary. 

3. In a depressed newborn, intubate and suction first, then proceed with the resuscitation.

B. Thick Meconium - 

1. The infant's oro- and nasopharynx should be suctioned by the obstetrician prior to delivery of the shoulders. 

2. Following suctioning of the oro- and nasopharynx by the obstetrician, the infant's oro- and nasopharynx should be immediately suctioned by the pediatrician followed by endotracheal intubation and suctioning of any meconium that is present below the cords. In a clinically well-appearing, vigorously crying newborn without meconium at the level of the vocal cords, intubation may not be necessary.

3. Visualize the cords via direct laryngoscopy and remove as much of the meconium from below the cords as possible. Do not apply suction to the tube by your mouth. Use an adapter connecting the endotracheal tube directly to wall suction, with the pressure set at 40 to 60 TORR. Repeat the intubation as often as necessary to clear the lower airway of meconium, even if the infant has cried. 

4. Following suctioning, ventilate the infant as necessary. 

5. Keep the infant warm and dry to prevent hypothermia and shunting. Continue to monitor the infant's heart and respiratory rates. 

6. After the infant has been stable for a least five minutes, the stomach can be aspirated to remove as much of the meconium-stained fluid as possible. 

7. If warranted by the clinical history (fetal distress, depressed infant, etc.), intubation should be performed even if meconium is not seen on the cords. 

Treatment in the nursery

A. The infant should be monitored and observed carefully for signs of respiratory distress, i.e., cyanosis, tachypnea, retractions, and grunting. 

B. Arterial blood gases and pH should be monitored for evidence of either metabolic or respiratory acidosis. 

C. Obtain a chest x-ray to rule out air leak (pneumothorax, pneumomediastinum, or pneumopericardium), secondary to air trapping from ball-valve obstruction. 

D. An infant with a history of meconium aspiration who develops respiratory distressshould be placed in a hood to maintain O2 saturations greater or equal to 99% to prevent episodes of hypoxia and shunting. 

E. Postural drainage should be done as clinically indicated. 

F. Consider intubation and suctioning below the cords in the nursery, since meconium can be removed from the upper airways even after the infant has initiated spontaneous respirations.

G. If the infant experiences persistent respiratory distress after one-half hour of life, antibiotics should be started after first obtaining blood, tracheal aspirate, and CSF cultures. Urine, for Group B Strep Latex, should also be obtained, but antibiotics should not be withheld while waiting for urine. 

H. Monitor the infant for pulmonary hypertension with evidence of right-to-left shunting (See protocol for Treatment of Pulmonary Hypertension). 

Reference

Holtzman R.B., et al. Perinatal management of meconium staining of the amniotic fluid. Clin Perinatol, 1989;16:825-838.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Background

Pulmonary Hypertension may be a primary or secondary cause of hypoxia in the neonate.

The diagnostic evaluation should include

A. Central hematocrit, serum glucose and calcium levels, platelet count

B. Chest x-ray, EKG

C. Hyperoxia (100% oxygen) challenge test

D. Simultaneous pre- and postductal arterial PaO2 or TcPO2

E. Cardiology consult, if indicated for echocardiography to rule out cyanotic congenital heart disease.

Medical management of PPHN

• Minimize Pulmonary Hypertension/Vasoconstriction
  • AVOID: HYPOXIA, HYPOTHERMIA, ACIDOSIS, ANEMIA,
  • HYPOTENSION AND STIMULATION ! 
• Maximize Pulmonary Vasodilatation (Decrease pulmonary vascular resistance)
  • OXYGEN (FiO2 = 1.0)
  • ALKALINIZATION - METABOLIC ALKALOSIS (pH > 7.55) 
• Support Cardiac Output and Blood Pressure
  • VOLUME
  • INOTROPIC AGENTS: Dobutamine, Dopamine and Epinephrine 
• Relieve Pain and Anxiety
  • ANALGESIA: Morphine or Fentanyl
  • SEDATION: Lorazepam, Chloral Hydrate, Phenobarbital, Midazolam and Thorazine
  • PARALYSIS: Pavulon 
• Administer Pulmonary Vasodilating Agents
  • "INHALED NITRIC OXIDE"
  • TOLAZOLINE
  • PROSTAGLANDIN E1 p
  • ISOPROTERENOL 
• Avoid Barotrauma
  • Small tidal volumes with high rates (i.e., HFOV)
  • Avoid hyperventilation (pCO2 ² 30) to minimize barotrauma 

Initial therapeutic guide

A. Correct hypothermia, hyperviscosity and metabolic problems. 

B. 100% oxygen and transient hyperventilation with goal of an arterial pH value greater than 7.55 (1), and PaCO2 of 30-35 mm Hg, and a PaO2 of 55 mm Hg or greater. This may transiently require rapid ventilation with rates of 60 to 80 BPM (I:E = 1:1). However, to avoid barotrauma alkalinize metabolically and then use gentler ventilation (PaCO2 ³ 35 mmHg) with HFOV. 

C. Alkalinization by metabolic means with the use of a bicarbonate infusion (1-2 meq/kg/hr) (2). 

D. Analgesia with morphine infusion (0.1 - 0.2 µg/kg/hr) and sedation with Lorazepam (0.1 - 0.3 mg/kg/dose PRN Q2H) or chloral hydrate (50 mg/kg/dose Q8H-Q12H). Consider transient neuromuscular blockade with Pavulon if infant is "fighting" the ventilator. 

E. Aggressively support blood pressure with appropriate volume and use Dobutamine (10-20 µg/kg/hr) and Dopamine (5-10 µg/kg/min). Consider NO if PaO2 < 70 on 100% O2. 

V. Start Nitric Oxide at 40 ppm as per experimental protocol if PaO2 < 55 mmHg. 

VI. Pharmacologic intervention with Priscoline (Tolazoline) may be indicated if ventilation, correction of acidosis, and treatment of the primary lung disorder do not lower pulmonary arterial pressure. 

A. Tolazoline is an alpha-adrenergic blocking agent. Given IV, the onset of action is within minutes. The biologic half-life is approximately two hours. It is excreted, largely in the unchanged form, by the renal tubules. 

B. Indications for use: 

1. Documented right-to-left shunt, with a PaO2 gradient >20 TORR 

2. ECHO documentation of pulmonary arterial hypertension. 

3. Failure of hyperventilation and metabolic alkalosis as initial therapy. 

4. Tolazoline should NOT be given without consultation with the staff Neonatologist. 

C. Dose: 1.0 mg/kg IV over 10 minutes followed by a constant infusion of 0.5-2.0 mg/kg/hour via a scalp, or an upper extremity, vein. The hourly dose is infused in the same volume of IV fluid that the infant has been previously receiving. 

D. During the infusion, monitor: 

1. Systemic blood pressure; if low, be ready to treat immediately with volume expansion 

2. Urine output

3. Heart rate 

4. Arterial blood gases pre- and postductal 

5. Evidence of GI hemorrhage

6. Platelet count

E. Consider starting Dopamine or Dobutamine at 5-10 ug/kg/min. prior to the use of Tolazoline to support systemic blood pressure.

F. If improvement is documented (an increase in PaO2 of 20 mm Hg, or a decrease in ventilator settings) within two hours, maintain the same dose. If no improvement is documented, slowly increase the dose of Tolazoline by increments of 0.5 mg/kg/hour. If no response is seen in another two hours, discontinue the infusion. 

G. Tolazoline is excreted by the kidney. If the infant is anuric or oliguric, caution must be used when administering this drug. 

Additional pharmacologic therapy

A. Consider the use of other vasoactive drugs such as Isoproterenol, Nitroglycerin, Epinephrine, or PGE1 after consulting with the staff Neonatologist.

References:

1. Perkins R.M. and Anas N.G. Pulmonary hypertension in pediatric patients. J Pediatr 1984;105:511-522.
2. Dwortz A.R., et. al. Survival of infants with persistent pulmonary without extracorporeal membrane oxygenation. Pediatrics 1989;84:1-6.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Definition

• NO or endothelium-derived relaxing factor is produced within endothelial cell from L-arginine by nitric oxide synthase (see Figure).
• NO is a potent vasodilator of vascular smooth muscle and when delivered by the inhalational route is a selective pulmonary vasodilator.

Mechanism of action

• Diffuses rapidly from alveolus to pulmonary vascular smooth muscle
• Stimulates guanylate cyclase activity which increases the concentration of cyclic GMP which causes vasodilation
• Selectively reverses acute pulmonary vasoconstriction caused by hypoxia or thromboxane
• Rapidly inactivated by forming methemoglobin therefore does not cause systemic hypotension

Dosing of NO (see guidelines for use)

• Continuous inhalational agent given through inspiratory limb of the breathing circuit
• Serum half-life is 3-4 seconds
• Theoretical effective range: 5-40 ppm
• Verify inhaled concentration of NO by using inline chemiluminescence

Side effects of NO

• Methemoglobinemia - (NO + Hgb) - NO avidly binds to Hgb, thus Hgb is not available to carry oxygen (see Table)

  • metabolic acidosis - increased dyspnea and tachypnea on exam
  • gray central cyanosis occurs at levels of 10-15% (NL < 2%)
  • blood appears brown even with a high PaO2
  • treatment: 100% O2, methylene blue, exchange transfusion, hyperbaric oxygen

   

• Nitrogen Dioxide (NO2)

  • levels > 3 ppm: cell injury, increased lung fluid
  • normally < 2% of NO level
  • NO2 and H2O -- H2NO3 (nitric acid)

   

• Inhibits platelet aggregation

References

1. Kinsella JP, Neish SR, Ivy DD, et al. Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide. J Pediatr 1993; 123:103-108.
2. Geggel RL. Inhalational nitric oxide: A selective pulmonary vasodilator for treatment of persistent pulmonary hypertension of the newborn. J Pediatr 1993; 123:76-79.
3. Davidson, D. Inhaled nitric oxide (NO) for neonatal pulmonary hypertension. Am Rev Respir Dis 1993; 147:1078-1079.
4. Kinsella JP, Abman SH. Inhalational nitric oxide therapy for persistent pulmonary hypertension of the newborn. Pediatr 1993; 91:997-998.
5. Kinsella JP, Neish SR, Shaffer E, et al. Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992; 340:819-820.
6. Roberts JD, Polaner DM, Lang P, et al. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992; 340:818-819.
7. Fineman JR, Wong J, Soifer SJ. Hyperoxia and alkalosis produce pulmonary vasodilation independent of endolithium-derived nitric oxide in newborn lambs. Pediatr Res 1993; 33:341-346.
8. Rossaint R, Falke KJ, López F, et al. Inhaled nitric oxide for the adult respiratory distress syndrome. New Eng J Med 1993; 328:399-431.
9. Bone RC. A new therapy for the adult respiratory distress syndrome. New Eng J Med 1993; 328:431-432.
10. Kinsella JP, Toews WH, Desmond H, et al. Selective and sustained pulmonary vasodilation with inhalational nitric oxide therapy in a child with idiopathic pulmonary hypertension. J Pediatr 1993; 122:803-806.

 Figure 1. Metabolism of endogenous nitric oxide in the lung. Endogenous NO is produced from L-arginine by nitric oxide synthase (NOS) within endothelial cells. After diffusing into subjacent smooth muscle. NO affects vascular smooth muscle relaxation by interacting with guanylate cyclase (GS) and increasing cyclic guanosine 3'.5-monophosphate (cGMP). (Adapted from Fractacci MD, Frostell CG. Chen TY, et al: Inhaled nitric oxide: A selective pulmonary vasdilator of heparin0-protamine vasoconstriction in sheep. Anesthesiology 75:990-999, 1991; with permission.)

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

The treatment of the Respiratory Distress Syndrome (RDS) is directed at correction of the pathophysiological conditions that exist in this disease process: A) surfactant deficiency, B) hypoxia, C) acidosis, D) pulmonary vasoconstriction, E) atelectasis, and F) shock.

SURFACTANT REPLACEMENT THERAPY (page 64)

Correction of hypoxia with oxygen. Infants requiring increased ambient oxygen concentration, and who are breathing spontaneously, can be placed on NPCPAP. The concentration of inspired oxygen should maintain the infant's arterial oxygen tension at 50-70 mm Hg. If oxygen required is greater than 50%, consider endotracheal intubation with surfactant replacement (see relevant section). Always confirm diagnosis with a chest radiograph.

Nasal pharyngeal CPAP for RDS should start at 6 cm H2O. If the infant is having recurrent apnea, persistent respiratory acidosis (pH less than 7.20) or if the PaO2 is inadequate in 50% or more oxygen with usage of nasal CPAP, the infant should be intubated and treated with surfactant.

Once intubated, the neonate with RDS should be ventilated by a pressure respirator according to the protocol found on page 36. To minimize both barotrauma and BPD, peak inspiratory pressures should be decreased as tolerated to keep the pCO2 between 40 and 60 mm Hg as long as the pH > 7.25. If pCO2 remains above 60 mm Hg, consider increasing the respiratory rate first, then, if necessary, increase PIP.

If barotrauma occurs (PIE or pneumothorax), consider high frequency ventilation (see separate section on HFV). 

To maintain body temperature, the infant is placed in an incubator or on a radiant heater bed. The skin probe is placed on the mid-epigastrium and covered with heat reflecting tape. The servocontroller is set at 36.5°C.

Intravenous fluids (D10W or D5W) are given at an initial rate of 60-80 ml/kg body weight per 24 hours with fluid therapy reassessed every 8-12 hours. Infants with birth weights less than 750g should be given fluids at an initial rate of 80-150 ml/kg per day due to their increased insensible losses and fluid therapy should be reassessed every 6-8 hours. Sodium received as sodium bicarbonate will also have to be taken into consideration when calculating the daily sodium requirement. IT IS IMPERATIVE THAT FLUID THERAPY BE READJUSTED EVERY 8 TO 12 HOURS, BASED ON INTAKE AND OUTPUT, CHANGE IN BODY WEIGHT, SERUM ELECTROLYTE CONCENTRATIONS AND SERUM AND URINE OSMOLALITY DETERMINATIONS. See section on fluid therapy for additional details. 

Metabolic acidosis (pH< 7.20) is corrected by a slow infusion of sodium bicarbonate (0.5 mEq/ml.; 4% solution) through a peripheral IV at the rate of 1 mEq/kg body weight per hour. The formula for calculation of the base deficit is: mEq of NaHCO3 = base excess x 0.6 x body weight in kg. Give one-half of the calculated dose and then recheck pH and pCO2 within one-half hour.

Shock is corrected by use of normal saline or Plasmanate R; the dose is 10 cc/kg infused over 15 to 30 minutes. Normal values for systolic and mean aortic pressures are found on pages 1 and 2. Please note the values for infants <1000 grams. Carefully evaluate the need for correction of low BP based on numbers alone in a premature infant who is otherwise well oxygenated, since acute changes in blood pressure may be an etiologic factor in intracranial hemorrhage.

Oral feedings may be initiated even if the infant is mechanically ventilated, or on nasal-pharyngeal CPAP, however, feedings should not be initiated until the infant's condition is stable. Ultimately, the oral intake should provide 100-120 calories/kg/day (see feeding protocol). 

When the infant is on CPAP or mechanical ventilation, a chest film should be obtained immediately after initiating therapy and subsequently at least once every 24 hours until the infant's condition is stable.

References: 

1. Kraybill EN, et al. Risk factors for Chronic lung disease in infants with birth weights of 751 to 1000 grams. J Pediatr 1989;115:115-120.
2. Van Marter LJ, et al. Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants. J Pediatr 1990;116:942-949.
3. Avery ME, et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987;79:26-30.
4. Carlo WA, Martin RJ. Principles of neonatal assisted ventilation. Pediatr Clin North Am, 1986;33:221-237.
5. Stark AR, Frantz ID. Respiratory distress syndrome. Pediatr Clin North Am, 1986;33:533-544.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Indications

A. Treatment of intubated infants on 30% or more oxygen whose clinical presentation and chest x-ray are consistent with RDS.

B. Prophylactic administration may be considered in infants < 26 weeks EGA.

C. Secondary surfactant dysfunction, inactivation or post surfactant slump.

Etiology of surfactant inactivation or dysfunction: pulmonary hemorrhage, sepsis, pneumonia, meconium aspiration, and post surfactant slump.

Surfactant replacement therapy for RDS - Early rescue therapy should be practiced: First dose needs to be given as soon as diagnosis of RDS is made. RDS in a premature infant is defined as respiratory distress requiring more than 30% oxygen delivered by positive pressure using either Nasal CPAP or an ET Tube with a chest radiograph that has diffuse infiltrates with a ground glass granular appearance with air bronchograms.  Ideally the dose should be given within 1 hr of birth but definitely before 2 hours of age.  A repeat dose should be given within 4 - 12 hours if the patient is still intubated and requiring more than 30 to 40% oxygen.

Prophylactic therapy (before chest radiograph) can be considered in patients with respiratory distress who are intubated and are < 26 weeks gestation.

Subsequent doses are generally withheld if the infant requires less than 30% oxygen. The technical details of administration are discussed in the package insert and in the NICU Nursing Protocols on administration.

Ventilator Management:  A blood gas should be checked within 15 - 20 minutes of the dose and the ventilator settings should be weaned appropriately to minimize the risk of a pneumothorax. A chest radiograph should be checked both 1 hour and 4 - 6 hours after the initial dose to avoid hyperinflation.

Surveillance after administration

The clinical response is unpredictable. Lung compliance usually improves, sometimes quite rapidly. Blood gases should be monitored frequently, and the ventilator should be adjusted to keep the PCO2 above 40. Occasionally, gas exchange deteriorates after surfactant administration, requiring a temporary increase in settings to facilitate spreading or suctioning if the ET tube is becoming obstructed. In either case, close surveillance of chest wall movement and frequent monitoring of blood gases, especially during the first 3 hours after dosing, will minimize the complications of either volutrauma or atelectasis.

References

1. Prophylactic vs Rescue - Dunn et al, Pediatrics 1991;87:377, Kendig et al. N Engl J Med 1991;324:865, Osiris Exosurf Trial - Lancet 1992
2. Surfactant Inactivation – Hall et al, Am Rev Respir Dis, 1992;145:24, Seeger et al, Eur Respir J, 1993:6:971
3. Survanta vs Infasurf - Bloom et al, Pediatrics 1997;100:31
4. Survanta vs Curosurf - Ramanathan et al, Am J Perinatal 2004;21:109
5. Term Infants - Findlay et al, Pediatrics 1996;97:48. Lotze et al, J Pediatr 1998;132:40
6. Post Surfactant Slump - Katz and Klein, Journal of Perinatology 2006;26:414

Edward F. Bell, MD
Peer Review Status: Internally Peer Reviewed

0.2 ml of blood is required for arterial blood gas sampling. If the syringe is heparinized, the heparin should be removed as completely as possible before drawing blood into the syringe; excess heparin left in the syringe decreases the pH value, dilutes the sample, and lowers the PaCO2. Before drawing a sample from an indwelling arterial line, the line should be cleared by withdrawing 1 to 2 ml of blood which is returned immediately thereafter. 

An infant without an arterial line who is not severely ill can have his oxygenation status monitored by continuous pulse oximetry or by transcutaneous PO2 monitoring. Any infant being monitored by capillary blood gas samples should have arterial sticks done periodically to validate the capillary sample results or should have continuous pulse oximetry or transcutaneous PO2 monitoring.

Arterial sticks are sometimes performed in severely ill neonates who do not have an indwelling arterial line. A percutaneous arterial stick can be performed using the temporal or radial artery. The brachial artery may be use in emergency situations. A femoral arterial stick should be avoided if at all possible, as there is an increased incidence of aseptic necrosis of the femoral head when this site is used for sampling. Since many infants shunt through the ductus arteriosus, the arterial site from which the sample is obtained should be noted on the blood gas sample requisition. 

The frequency of sampling is dependent upon the patient's clinical condition. Any changes in ventilator or CPAP setting must be monitored by a blood gas sample within 15-30 minutes. Any acutely ill child in the NICU in an increased ambient oxygen concentration must have at least daily arterial or fingerstick blood gas sampling

Indwelling catheters should not be placed into the temporal or brachial artery.

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Background

Pulse oximeters determine oxygen saturation noninvasively through absorption spectrophotometry. Oxygen delivery to the tissues is a direct function of cardiac output, oxygen capacity (hemoglobin concentration) and the oxygen affinity of the patient's hemoglobin (see Figure 1). In the presence of both normal cardiac output and normal Hgb, measurement of oxygen saturation can be a guide to both oxygen exchange and delivery. 

We tend to keep the oxygen saturation in premature infants between 88% - 95% (higher in term infants). Pulse oximeters are accurate within ±4%, thus a reading of 95% could represent a saturation of 99% with a concomitant PO2 of 160 (see Figure 2). Thus, to avoid hyperoxia, we would decrease the oxygen concentration for saturations greater than or equal to 95%.

Causes for inaccurate readings:

Jaundice - causes falsely decreased values. 

Direct high intensity light - i.e. phototherapy lights - increases inaccuracy, so cover sensor site from lights, or use a phototherapy blanket. 

Impaired perfusion - need good pulsatile blood flow for accurate readings, manage by treating shock. 

Severe hypoxemia - at saturations less than 70% accuracy begins to fall off with the pulse oximeters overestimating the measured value. Manage by directly checking an arterial PaO2, or by using a transcutaneous oxygen monitor 

References:

1. Oski FA, and Delivoria-Papadopoulos M. The red cell, 2, 3-diphosphoglycerate, and tissue oxygen release. J Pediatr, 1970;77:941-956. 
2. Tobin MJ. Respiratory monitoring in the intensive care unit. Am Rev Respir Dis 1988;138:1625-1642. 

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

The TcPCO2 analyzer operates on a principal similar to that of the TcPO2 analyzer. Because of physiologic differences in O2 and CO2 diffusion through the skin and in electrode design, there are significant differences in the actual arterial pCO2 and TcPCO2 reading. 

The electrode will be applied by the nurse to the anterior chest wall or other acceptable site. The site will be changed every four hours to avoid erythema and burns to the infant's skin. The electrode will be calibrated by the blood gas technician and recalibrated every eight hours. 

With the correlation factor used to calibrate the TcPCO2 analyzer, the TcPCO2 reading will closely approximate PaCO2 value. In certain infants, however, there may be a significant difference between the two values. It is therefore necessary to correlate the TcPCO2 reading with three or four PaCO2 samples. 

The lag time for the TcPCO2 analyzer is 90 seconds; i.e., the analyzer will display the TcPCO2 which was present 90 seconds previously. 

V. The nurse will record the TcPCO2 value and electrode temperature on the nurse's notes at least once an hour and when obtaining an arterial blood gas sample. 

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

The TcPCO2 analyzer operates on a principal similar to that of the TcPO2 analyzer. Because of physiologic differences in O2 and CO2 diffusion through the skin and in electrode design, there are significant differences in the actual arterial pCO2 and TcPCO2 reading. 

The electrode will be applied by the nurse to the anterior chest wall or other acceptable site. The site will be changed every four hours to avoid erythema and burns to the infant's skin. The electrode will be calibrated by the blood gas technician and recalibrated every eight hours. 

With the correlation factor used to calibrate the TcPCO2 analyzer, the TcPCO2 reading will closely approximate PaCO2 value. In certain infants, however, there may be a significant difference between the two values. It is therefore necessary to correlate the TcPCO2 reading with three or four PaCO2 samples. 

The lag time for the TcPCO2 analyzer is 90 seconds; i.e., the analyzer will display the TcPCO2 which was present 90 seconds previously. 

V. The nurse will record the TcPCO2 value and electrode temperature on the nurse's notes at least once an hour and when obtaining an arterial blood gas sample. 

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

The transcutaneous PO2 monitor (TCM allows for non-invasive measurement of arterial oxygen tension. The prerequisite for accurate correlation of an arterial PO2 value with a transcutaneous PO2 value is creation of constant local vasodilatation by heating the skin. This causes maximal blood flow in the skin with little or no difference between the PO2 value at the arterial and venous ends of the capillary. 

The transcutaneous PO2 monitor consists of a combined platinum and silver electrode covered by an oxygen-permeable hydrophobic membrane, with a reservoir of phosphate buffer and potassium chloride trapped inside the electrode. A small heating element is located inside the silver anode. The oxygen monitor consists of a TcPO2 channel, for which high and low alarm limits can be set, a temperature display channel and a heat channel. 

The TCM sensor is applied by the nurse to the anterior chest wall or other acceptable site and heated to 44°C. The site will be changed every four hours to avoid erythema and burns to the infant's skin. The electrode will be calibrated by the blood gas technician and recalibrated every eight hours. 

The nurse will record the TCM value on the nurse's notes at least once an hour. When correlating the transcutaneous PO2 with an arterial or capillary blood gas sample, the value from the TCM should be recorded 15 seconds after obtaining the blood sample. 

An order should be written documenting the desired range of transcutaneous oxygen levels for a given patient. The optimal range for most premature infants will be 50 to 70 mm Hg. Higher limits may be appropriate for large preterm or term infants, especially those at risk of pulmonary hypertension. 

If the patient's transcutaneous PO2 stays outside of these limits for more than two to three minutes, the nurse shall increase or decrease the FiO2 by no more than 0.05 until the patient's reading returns to the desired range. 

If a change in FiO2 is required for more than five minutes, the House Officer shall be notified of the change in the infant's condition. The change in FiO2 and response of the infant will be documented in the nurse's notes.