43 HFPPV conventional ventilators with low-compliance tubing not very effective: minute ventilation decreases with high frequencies. When the inspiratory time is less than 3 time constants, the tidal volume will decrease, decreasing minute ventilation. The exact ventilator rate at which this happens depends on the time constant in the baby and the ventilator design. HFJV (e.g. Bunnell Life Pulse HFJV) adequate gas exchange with lower MAP An increased “servo pressure” indicates improving compliance or resistance or an air leak since more driving pressure is required to develop needed delta pressure . A decreasing servo pressure indicates an obstruction or pneumothorax since less driving pressure is required to develop the needed pressure. Larger babies do better with slower rates of 300 bpm while smaller ones: do well with upto 500 bpm. We commonly use 400-450bpm.
Is it common practice to use hyperventilation for PPHN, and are the effects of respiratory alkalosis the same as the effects of metabolic alkalosis?. This is important to know because high frequency ventilation is often used for hyperventilation. These are the results of an observational study in 12 centers participating in the NICHD neonatal research network in 1993 and 1994, before the use of nitric oxide became common. 385 infants were studied. Infants were studied if they were > 34 wks gestation, < 7 days age, and required mechanical ventilation or > 50% oxygen and documented PPHN on Echo or a pre- to post-ductal gradient of > 20 torr. Hyperventilation (defined as a PaCO 2 <35 mm Hg for >12 hours) was used in the treatment of 66% of neonates with wide variation between centers. High frequency ventilation was used in 39%. Of those treated with high frequency, 72% received oscillatory ventilation and 26% received jet ventilation. Inhaled nitric oxide was used in 8% of the cohort. A continuous infusion of alkali was used in 75% of neonates diagnosed with PPHN Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. This study indicates that hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.
Pulmonary hypertension inneonates Dr Varsha Atul Shah
What is the problem?• PPHN / PFC : Persistence of the pattern of fetal circulation postnatally due to a sustained elevation of pulmonary vascular resistance, with right-to-left shunt at the ductus arteriosus or foramen ovale in the absence of structural heart disease• Incidence: About 1 per 1000. Exact incidence unknown in the absence of ICD coding or a “gold standard” for diagnosis• Mortality and Morbidity: Mortality rate of > 50% in the absence of ECMO, and >10-20% with ECMO; >20% severe handicap/intracranial hemorrhage/deafness (Walsh-Sukys M C: Persistent pulmonary hypertension of the newborn. The black box revisited. Clin Perinatol 20: 127-143, 1993)
Causes of PPHN(Geggel RL, Reid LM:The structural basis of PPHN.Clin Perinatol 11:525-549, 1984) PPHN Normal Arterial Number Decreased Arteries e.g. CDH Normal muscularization Increased muscularization Maladaptation due to acute injury Developmental Chronic injury Malform- (commonest) e.g. immaturity with vascular ation Sepsis, Meconium aspiration synd., remodeling asphyxia
Clinical features of PPHN• Usually a term infant, with risk factors of asphyxia, elective C/section without labor, meconium stained fluid, sepsis, diaphragmatic hernia etc. Some infants have no obvious risk factors (idiopathic PPHN).• Cyanosis due to shunting of blood from right to left (pulmonary to systemic circulation) “persistence of fetal circulation”, causing mixing of deoxygenated with oxygenated blood
Clinical features of PPHN• Right to left shunting of blood occurs most often through the ductus arteriosus, and hence saturation will be lower (by 10-15% or more) in legs (+ left upper limb) as compared to right upper limb and head• In some infants, shunting of blood also occurs within the heart at the foramen ovale level, and hence SpO2 is the same in all limbs• Confirmation of the diagnosis is by echocardiogram, which will demonstrate R to L shunting, elevated R sided pressures, and absence of structural heart disease
Current managementConfirm diagnosis of PPHN Correct underlying abnormalities (hypothermia, acidosis, hypocalcemia, hypoglycemia, polycythemia); Oxygen by hood Conservative mechanical ventilation Trial of hyperventilation If low PO2, trial of rescue therapiesMetabolic HFV Surfactant Vasodilators ECMOAlkalosis NO, PGD2, PGI2, Tolazoline, Adenosine
Pathophysiological basisof current management• Mechanical ventilation: Ventilation-Perfusion (V/Q) matching to improve oxygenation respiratory alkalosis to reduce Pulmonary Vascular Resistance (PVR)• Metabolic alkalosis: effect of pH on PVR• Vasodilators: specific relaxation of the pulmonary vasculature. Most experience with Nitric Oxide• ECMO: modified long-term cardio-pulmonary bypass
Other support measures• Cardiac strategies: Support of cardiac output and SVR with dopamine, fluid infusions• Environmental strategies: Sedation with fentanyl or morhphine Avoidance of noise and light stress
Ventilatory management • ventilator management controversial • FiO2 adjusted to maintain PaO2 80-100 to minimize hypoxia-mediated pulmonary vasoconstriction • ventilatory rates and pressures adjusted to maintain mild alkalosis (pH 7.5-7.6), usually combined with bicarbonate infusion • avoid low PaCO2 (<20 mm Hg) to prevent cerebral vasoconstriction
Nursing care of infant withPPHN• Sedation (+ muscle relaxant) initially, wean as condition improves. Too rapid or too slow weaning are both bad.• Minimal stimulation• Close monitoring, esp. SpO2, PaO2, PaCO2. Hourly, shift, or daily ranges and plan essential.• Do not suction unless necessary! (e.g. MAS, thick secretions). Suctioning can cause pain, fighting ventilator, atelectasis, loss of lung volume• Cannot hear heart sounds/breath sounds/bowel sounds when on HFV. Use monitors!
Ventilator settings: PIP • affects MAP (PO2) and VT (PCO2) • PIP required depends largely on compliance of respiratory system • Clinical: gentle rise of chest with breath, similar to spontaneous breath • Minimum effective PIP to be used. No relation to weight or airway resistance • Neonate with PPHN: 15-30 cm H2O. Start low and increase.
Ventilator settings: PEEP • affects MAP (PO2), affects VT (PCO2) depending on position on P-V curve Volume PEEP PIP Pressure • older infants (e.g. BPD) tolerate higher levels of PEEP (6-8 cm H2O) better • RDS: minimum 2-3, maximum 6 cm H2O.
Ventilator settings: Rate • affects minute ventilation (PCO2) • In general, rate ---> PCO2 • Rate changes alone do not alter MAP (with constant I:E ratio) or change PO2 , unless PVR changes with changes in pH • However, if rate --> TE < 3TC --> gas trapping--> decreased VT-- > PCO2 • Minute ventilation plateaus, then falls
Ventilator settings: TI and TE • Need to be 3-5 TC for complete inspiration and expiration (Note: TC exp = TC insp) • Usual ranges: TI sec TE sec RDS 0.2-0.45 0.4-0.6 BPD 0.4-0.8 0.5-1.5 PPHN 0.3-0.8 0.5-1.0 • Chest wall motion / VT may be useful in determining optimal TI and TE
Ventilator settings: I:E ratio• When corrected for the same MAP, changes in I:E ratio do not affect gas exchange as much as changes in PIP or PEEP• Changes in TI or TE do not change VT or PCO2 unless they are too short (< 3 TC)• Reversed I:E ratio: No change in mortality or morbidity noted in studies. Not often used. May improve V/Q matching and PO2 at risk of venous return and gas trapping
Ventilator settings: FiO2 • affects oxygenation directly • with FiO2 <0.6-0.7, risk of oxygen toxicity less than risk of barotrauma • to improve oxygenation, increase FiO2 to 0.7 before increasing MAP • during weaning, once PIP is low enough, reduce FiO2 from 0.7 to 0.4. Maintenance of adequate MAP and V/Q matching may permit a reduction in FiO2
Ventilator settings: Flow • affects pressure waveform • minimal effect on gas exchange as long as sufficient flow used • increased flow--> turbulence • higher flow required if TI short, to maintain TV • flow of 8-10 lpm usually sufficient • change of flow may affect delivery of NO or anesthesia gases
High frequency ventilation HFPPV HFJV HFFI HFOV VT >dead sp > or < ds > or <ds <ds? Exp passive passive passive active Wave- variable triangular triangular sine wave Form Entrai- none possible none none ment Freq. 60-150 60-600 300-900 300-3000 (/min)
High Frequency Ventilation inPPHN• V/Q matching to improve oxygenation• Respiratory alkalosis to reduce PVR• Improved response to inhaled NO• “Rescue” for air leak syndromes
High frequency ventilation • HFPPV conventional ventilators with low-compliance tubing ventilatory rates of 60-150/min not very effective: minute ventilation decreases with high frequencies [If TI < 3 TC, VT decreases.] (Boros et al. Pediatrics 74: 487-492, 1984 ) ventilator and circuit design are not optimal for use at high frequencies
Which is best: HFOV, HFJV,HFFI, HFPPV ?• No good animal or human comparisons; animal studies suggest HFV causes less lung damage than CMV• Many centers now use HFOV for term infants with PPHN, rather than HFFI or HFJV• Not possible to state if one type of HFV is better in human infants
Hyperventilation in PPHN No HV/Alk HV Alk HV+Alk pMortality% 4.4 6.8 9.5 9.8 0.67ECMO% 33.3 13.6 44.6 34.2 0.01Duration 7.8 7.2 7.8 12.6 0.001ventilator (d)Duration O2 (d) 11.1 11.5 11.9 17.5 0.001O2 at 28 d 2.7 2.8 6.8 16.7 0.1(Walsh-Sukys et al. Pediatrics 105:14-20, 2000)
HFV Indications• Usually used as “rescue” therapy for infants not improving/deteriorating on conventional ventilator• Response to HFJV or HFOV may depend on disease pathophysiology: Pneumonia and RDS more likely to respond (70-90%) MAS (50%) and CDH (20%) less likely to respond (Baumgart et al. Pediatrics 89:491, 1992; Paranka et al. Pediatrics 95: 400, 1995; Stewart et al. Eur Respir J 9:1257, 1996)
HFV techniques: HFOV• MAP: start 1-3 cm H2O higher than on IMV: controls V/Q matching and oxygenation• Frequency: 8-12 Hz• Inspiratory time: 33%• Amplitude: sufficient for visible chest motion: main determinant of CO2 elimination• Target ABG: pH 7.45-7.55, PaCO2 30-40, PaO2 80-100, HCO3 26-30
HFV techniques• “High volume strategy” often used Useful in animal models and preterm infants with RDS Assessment of lung volume a problem (chest X-Rays not accurate) Initial MAP 10-20% more than MAP on IMV. Increase MAP in 1-3 cm H2O increments until oxygenation and a/A ratio improve or cardiac compromise occurs FiO2 can then be weaned to 0.3-0.4. As lungs improve, wean MAP slowly (MAP changes may take > 1 hr to affect PaO2). If air leak, wean FiO2 later.
HFV + NO; HFV+Surfactant• The combination of HFOV and NO is more effective than HFOV alone or NO alone• HFV and surfactant prevent lung injury synergistically, combination: prolongs efficacy of surfactant reduces number of surfactant doses reduces pulmonary morbidity
Summary• PPHN is a rare but serious illness in newborn infants• Close monitoring and a staged approach (oxygen by hood IMV HFV / NO ECMO) improve outcomes• Most infants (>85%) now have normal outcomes, except for infants with diaphragmatic hernias.