Novel Strategies in NICU and PICU for the Child Who is Really Difficult to Ventilate

Transcription

1 Novel Strategies in NICU and PICU for the Child Who is Really Difficult to Ventilate Larry C. Lands, MD, PhD Professor of Pediatrics, McGill University Director, Pediatric Respiratory Medicine Montreal Children s Hospital-McGill University Health Centre Introduction The majority of patients who require mechanical support can be treated with a variety of standard techniques, and will successfully wean.(1) However, no matter what the underlying pathophyisiology, there will always be a subset of patients who require extra attention to detail and alternative approaches to allow for successful resolution of their disease, without suffering complications induced by medical management. There are two principles to always keep in mind. The first is the need for an assessment of the problem and the goals of support. In your assessment of the patient, you need to discern whether the patient is having primarily problems to oxygenate, ventilate or both. You then need to consider what could be the underlying pathophysiology leading to the problem. Finally, you must decide on, and clearly elaborate, the goals that you wish to achieve over the ensuing period of time. The second principle is to match the ventilatory and supportive strategy to the respiratory condition.(2) This is important whether you are reading the literature on respiratory support, or deciding at the bedside amongst your choices for support. Some strategies are best suited for certain conditions and unhelpful, if not deleterious, for other conditions. You must also appreciate that many of the ventilatory techniques regularly employed have not been formally tested in randomized controlled trials in pediatric patients, but are either extrapolated from the adult experience, or based on small case series.(3) Newer approaches to mechanical ventilation include non-invasive ventilation, high frequency oscillatory ventilation, and airway pressure release ventilation. There are also a variety of adjuvant therapies, including surfactant and nitric oxide. Assessment of Patient Needs Before deciding on whether a change in strategy is needed, it is vital to assess the current status of the patient, and the evolution of the patient to that point. Physical exam is important to get a sense of the efficacy of air entry, the appropriateness of the respiratory rate, and the partitioning of the duty cycle between inspiratory and expiratory times. Frankly, the best physical assessment comes during a session of manual ventilation. Using a bagging system that has a pressure manometer, with the patient on a cardiopulmonary monitor tracking oxygen saturation, heart rate and blood pressure, (and potentially inline endtidal PCO 2 ) you can handbag the patient while observing chest wall movement and auscultating the chest. This provides a multi-modal assessment of ventilation (visual, tactile, and aural) and an assessment of cardiopulmonary interaction. This can be quite helpful in deciding and adjusting the ventilatory parameters.

2 Most ventilators now are equipped with a variety of monitoring screens that should be assessed. In particular, the Flow-Time profile and the Pressure-Volume loop should be reviewed. The Flow-Time profile is particularly useful in assessing whether exhalation has finished within the set expiratory time. If expiratory flow has not stopped before the onset of the next inhalation, then there will be retention of gas in the lungs leading to inadvertent Positive End-Expiratory Pressure (PEEP). This PEEP is inadvertent as it is in excess of the PEEP that was set. PEEP may potentially impede cardiac output. A normal heart can withstand a PEEP of 8 cm H 2 O within a normal lung. However, in the situation of significant cardiac impairment (either functional or post-surgical), the heart may not be able to withstand a PEEP of 8 cm H 2 O. For example, it should be noted that an insufficient right heart output characterizes many congenital heart diseases. On the pulmonary side, for PEEP to be a factor, it must be transmitted to the interstitium. A chest radiograph showing a white lung means that air is not getting to the alveolus, and therefore the pressure is not being transmitted to the interstitium. In spontaneously breathing patients, excessive PEEP will increase the elastic work of breathing to an unacceptable level causing patient distress and fatigue. The magnitude of inadvertent PEEP can be directly measured on most of the current ventilators, as long as the patient is quiet, by invoking an end-expiratory pause and letting the system (ventilator plus patient) come to a standstill. In patients with demonstrated inadvertent PEEP, the set PEEP should be no greater than 2 cm H 2 O below the measured PEEP of the system, and this should be reassessed regularly. The Pressure-Volume loop is useful for assessing the relative importance of respiratory system compliance and resistance, and the critical pressure that must be delivered before the lung volume begins to increase. This will aid in determining a ventilatory strategy. When assessing the Pressure-Volume loop and its shape and position, it should also be recalled that the area subtended by the inspiratory portion on the Pressure-Volume loop represents the elastic work of breathing. If the Pressure-Volume loop is narrow, but at a low angle, then there is a problem with low compliance. This pattern would typically be seen in adult or infant respiratory distress syndrome. If the loop is wide, then it is a problem with resistance, as seen in patients with asthma. If the inspiratory loop has a knee or lower inflection point, then there is a critical pressure that must be reached before lung volume will increase. From work on adult patients, setting the PEEP at 2 cm H 2 O below the lower inflection point can be useful in situations of Acute Respiratory Distress Syndrome (ARDS), particularly if the strategy is coupled with a low (6-8 ml/kg) tidal volume. Noninvasive Ventilation Noninvasive respiratory support can be used in both neonates and older children. This can be done as either Continuous Positive Airway Pressure (CPAP) or using phasic increases in pressure, with both a pressure-supported inspiration, and a positive endexpiratory pressure. There are several devices and delivery systems for providing CPAP and noninvasive ventilatory support.(4)cpap can be delivered by single or bilateral nasal prongs, longer nasal prongs, or an endotracheal tube placed in the pharynx. For neonates, generally bilateral prongs work better than unilateral ones. Older nasal masks that are

3 held in place by a headstrap were associated cerebellar hemorrhage in newborns, attributed to the direct distorting pressure on the soft deformable skull. Newer masks require less pressure to hold them in place, but their safety profile is still being determined. Synchronized noninvasive ventilation allows the patient to spontaneously breathe using a pattern of their choice. The patient can also participate in adjusting the settings in a dynamic fashion that is difficult to achieve with ventilation through an endotracheal tube. Avoiding intubation often lessens the time of support and decreases the risk of lower respiratory tract infection. It must be recognized that a common cause of death is ventilator associated pneumonia, so that noninvasive ventilation can positively impact mortality. Noninvasive ventilation has been used in children in need of support for hypoxic or ventilatory failure from a variety of causes. It can help with lung volume recruitment, increased MAP and FRC, thus improving oxygenation. With improved oxygenation and gas exchange, noninvasive ventilation can be particularly helpful in avoiding intubation in situations of respiratory muscle weakness or fatigue. There is not a large reported pediatric experience with noninvasive ventilation. One crossover study in newborns with respiratory distress showed that noninvasive ventilation resulted in less work of breathing than CPAP.(5) Another open-label pilot study found that noninvasive ventilation could be used instead of conventional ventilation, following rescue endotracheal administration of surfactant for mild respiratory distress.(6) Support for patients with status asthmaticus deserves particular mention. There are several advantages to using noninvasive ventilation in this particular case. In status asthmaticus, the prolonged expiratory phase leads to airtrapping through dynamic hyperinflation, resulting in autopeep. The airtrapping, and resultant autopeep, increases the inspiratory eleastic work of breathing and leads to dyspnea. Dyspnea promotes faster respiratory rates, further worsening dynamic hyperinflation, which can lead to muscular fatigue. By providing inspiratory support, the inspiratory elastic work of breathing is reduced. This will decrease the degree of dyspnea, and often lead to reduced respiratory rates. Reducing the respiratory rate leaves more time for exhalation, thus diminishing the autopeep to a tolerable level. Two case series have been reported in children, one with 3 patients and one with 83 patients.(7;8)while there is limited detail, the majority of patients tolerated, and improved, on noninvasive ventilation. High Frequency Ventilation High frequency ventilation includes both jet ventilation and oscillatory ventilation. Most studies in recent years have used oscillatory ventilation. This technique uses small volumes (typically less than the anatomical deadspace) and frequencies of 8 to 15 Hz (cycles per second) or 480 to 900 breaths per minute. Due to technical difficulties in being able to generate an oscillating pressure waveform that can be transmitted to large patients, much of the experience has been with neonates. Recent technological advances have made it possible to now use this strategy in children, adolescents, and adults.(9) Generally, spontaneous breathing is suppressed with sedation, as high frequency ventilation works best when there is no spontaneous breathing.

4 This technique is best used in situations of hypoxemia, especially when volume recruitment is required, while limiting lung injury. There are have many trials in newborns with respiratory distress.(10;11) Other uses have been in patients with ARDS, pneumonia and lung consolidation, and patients with airleak. In newborns with persistent pulmonary hypertension, high frequency oscillation combined with inhaled nitric oxide can be useful.(12) However, high frequency ventilation can be difficult to use in situations of significant airway secretions. With secretions, the vibrations cannot reach the alveoli or are dampened by the secretions. This ventilatory technique may also push and keep secretions more peripherally. High frequency ventilation has been used as both initial and rescue therapy. In newborns with respiratory distress, the more recent use of protective lung strategies seems to have limited the advantages of high frequency ventilation seen in earlier studies.(11) There are a few small studies suggesting that early use may limit the inflammatory response associated with mechanical ventilation.(13) Airway Pressure Release Ventilation This is a variant on high volume ventilation, where a high level of CPAP is maintained, interspersed with brief releases of pressure.(14) It has been used in situations of hypoxic respiratory failure requiring lung volume recruitment, such as ARDS in adults. Unlike high frequency ventilation, spontaneous ventilation is allowed, and less sedation is needed. If high frequency ventilation is not available, this may be a reasonable alternative. The mode consists of maintaining a high level of CPAP for seconds followed by a release time long enough to allow expiratory flow to fall to 50-75% of its initial value ( sec in children). The release time relates to the time constant (τ) of the respiratory system, which is equal to the product of respiratory resistance and compliance. The initial high CPAP is set equal to the plateau pressure during conventional ventilation. The low pressure is often set at zero. Adjuvant Therapies There are a variety of adjuvant therapies that can truly enhance the response to assisted respiration.(15)one adjuvant therapy that has not worked in children is prone positioning for acute lung injury.(16) Surfactant Surfactant replacement therapy has become standard practice for infants with the respiratory distress syndrome. There has not been any benefit demonstrated for surfactant replacement therapy with adults with ARDS.(17)However, a trial in patients aged 1 week to 21 years (26% less than 12 months of age) demonstrated improvements in oxygenation, although the time to extubation was not shortened.(18) There are a variety of surfactant formulations, both natural and synthetic, that have been developed. There is evidence suggesting that newer generation synthetic

5 surfactants might result in better outcomes.(19)delivery by aerosol, thus avoiding the need to intubate for delivery, is also in development.(20) There have been several trials conducted in children with meconium aspiration. As reviewed by the Cochrane Collaboration, surfactant replacement therapy can reduce the severity of illness and decrease the risk of respiratory failure requiring extra corporal membrane oxygenation (ECMO).(21) Inhaled Nitric Oxide There has been significant controversy over the use of inhaled nitric oxide in newborns.(22-24) Much of this is due to variable results coupled with the therapy being expensive and requiring monitoring. As with the other therapies discussed, it is important to note the type of patients being studied, as this appears to be an important determining factor for outcome. A further issue is the lack of agreement on the effective dose. Doses from 2 to 80 ppm have been used. Animal work suggests little advantage in exceeding 5 ppm, but many clinicians will use 20 ppm and wean from there.(25) The Cochrane Collaboration systematic review for hypoxemic term and near-term infants found that inhaled nitric oxide improved outcome by reducing the need for Extracoporeal Membrane Oxygenation (ECMO).(22) It did not appear to be helpful in cases of congenital diaphragmatic hernia. Combined inhaled nitric oxide with high frequency ventilation may be helpful in respiratory distress syndrome or meconium aspiration.(12) Subsequent to the recent Cochrane Collaboration systematic review suggesting no benefit of inhaled nitric oxide for premature infants (23), two other studies have been published suggesting that inhaled nitric oxide may be beneficial in selected groups of premature infants.(24)ballard and colleagues found that nitric oxide started between 7 and 14 days of life in preterm infants who were on a ventilator at 7 days of age were less likely to subsequently develop Bronchopulmonary Dysplasia.(26)Interestingly, if therapy began after 14 days, there was no beneficial effect. Kinsella and colleagues looked at the effect of nitric oxide at 5 PPM started within the first 48 hours of life in preterm infants weighing less than 1250 gm.(27) For infants weighing between 1000 and 1250 gm, there was a reduced incidence of Bronchopulmonary Dysplasia. The incidence of brain injury was reduced in infants less than 1000 gm. Sedatives, Anaesthetic and Other Agents Certain medications, in addition to their effects on sedation or neuromuscular blockade, can have additional benefits in patients with status asthmaticus. Ketamine can have a bronchodilating effect through vagolytic and direct smooth muscle relaxant effects.(28)isoflurane is an inhalational anaesthetic agent with bronchodilating properties, although the mechanism for this is unclear. There are several case reports and a cse series in children.(29) It requires the use of a ventilator equipped for the delivery of anaesthetic agents. The onset of effect appears to be rapid. Hypotension requiring pressors commonly occurred. The patient treated for the longest period had transient encephalopathy. In nonintubated children in the emergency room, intravenous magnesium appears to decrease the need for hospitalization.(30) The limited number of studies and range of doses used leaves many questions unanswered. The combination of inhaled magnesium sulphate with salbutamol in severe asthma requires more study.

6 Conclusion All patients requiring respiratory support need to be evaluated to ascertain the underlying pathphysiology and determine the goals of support. Applying physiological principals will allow most patients to improve with conventional approaches. Early recognition of response failures can lead to pre-emptive changes in strategy. Those patients that do not respond need to be re-assessed. In these patients, strong consideration should be given to alternative modes of support and adjuvant therapies. Reference List (1) Lands LC. Applying physiology to conventional mechanical ventilation. Paediatr Respir Rev 2006;7(Supplement 1):S33-S36. (2) Greenough A, Donn SM. Matching Ventilatory Support Strategies to Respiratory Pathophysiology. Clinics in Perinatology 2007 Mar;34(1): (3) Turner. Insights in pediatric ventilation: timing of intubation, ventilatory strategies, and weaning. Current opinion in critical care 2007;13(1): (4) Courtney SE, Barrington KJ. Continuous Positive Airway Pressure and Noninvasive Ventilation. Clinics in Perinatology 2007 Mar;34(1): (5) Aghai. Synchronized nasal intermittent positive pressure ventilation (SNIPPV) decreases work of breathing (WOB) in premature infants with respiratory distress syndrome (RDS) compared to nasal continuous positive airway pressure (NCPAP). Pediatr Pulmonol 2006;41(9): (6) Santin. A prospective observational pilot study of synchronized nasal intermittent positive pressure ventilation (SNIPPV) as a primary mode of ventilation in infants > or = 28 weeks with respiratory distress syndrome (RDS). Journal of perinatology 2004;24(8): (7) Akingbola. Noninvasive positive-pressure ventilation in pediatric status asthmaticus. Pediatric critical care medicine 2002;3(2): (8) Beers SL, Abramo TJ, Bracken A, Wiebe RA. Bilevel positive airway pressure in the treatment of status asthmaticus in pediatrics. The American Journal of Emergency Medicine 2007 Jan;25(1):6-9. (9) Chan KPW, Stewart TE, Mehta S. High-Frequency Oscillatory Ventilation for Adult Patients With ARDS. Chest 2007 Jun 1;131(6): (10) Lampland AL, Mammel MC. The Role of High-Frequency Ventilation in Neonates: Evidence-Based Recommendations. Clinics in Perinatology 2007 Mar;34(1):

7 (11) Bollen C, Uiterwaal C, van Vught A. Meta-regression analysis of high-frequency ventilation vs conventional ventilation in infant respiratory distress syndrome. Intensive Care Med 2007 Apr 7;33(4): (12) Kinsella. Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn. The Journal of Pediatrics 1997;131(1 Pt 1): (13) Dani. Effects of pressure support ventilation plus volume guarantee vs. highfrequency oscillatory ventilation on lung inflammation in preterm infants. Pediatr Pulmonol 2006;41(3): (14) Krishnan. Airway pressure release ventilation: a pediatric case series. Pediatr Pulmonol 2007;42(1):83-8. (15) Wiswell TE, Tin W, Ohler K. Evidence-Based Use of Adjunctive Therapies to Ventilation. Clinics in Perinatology 2007 Mar;34(1): (16) Curley MAQ, Hibberd PL, Fineman LD, Wypij D, Shih MC, Thompson JE, et al. Effect of Prone Positioning on Clinical Outcomes in Children With Acute Lung Injury: A Randomized Controlled Trial. JAMA: The Journal of the American Medical Association 2005 Jul 13;294(2): (17) Stevens TP, Sinkin RA. Surfactant Replacement Therapy. Chest 2007 May 1;131(5): (18) Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, et al. Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury: A Randomized Controlled Trial. JAMA: The Journal of the American Medical Association 2005 Jan 26;293(4): (19) Sinha. Surfactant for respiratory distress syndrome: are there important clinical differences among preparations? Curr Opin Pediatr 2007;19(2): (20) Mazela. Aerosolized surfactants. Curr Opin Pediatr 2007;19(2): (21) Soll. Surfactant for meconium aspiration syndrome in full term infants. The Cochrane database of systematic reviews 2000;(2). (22) Finer N, Barrington K. Nitric oxide for respiratory failure in infants born at or near term. The Cochrane database of systematic reviews 2006;(4). (23) Barrington K, Finer N. Nitric oxide for respiratory failure in preterm infants. The Cochrane database of systematic reviews 2007;(3). (24) Kinsella JP, Abman SH. Inhaled Nitric Oxide in the Premature Newborn. The Journal of Pediatrics 2007 Jul;151(1):10-5.

8 (25) Guthrie. Initial dosing of inhaled nitric oxide in infants with hypoxic respiratory failure. Journal of perinatology 2004;24(5): (26) Ballard. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 2006;355(4): (27) Kinsella. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med 2006;355(4): (28) Strube. Ketamine by continuous infusion in status asthmaticus. Anaesthesia 1986;41(10): (29) Shankar V, Churchwell K, Deshpande J. Isoflurane therapy for severe refractory status asthmaticus in children. Intensive Care Med 2006 Jun 20;32(6): (30) Beasley. Magnesium in the treatment of asthma. Curr Opin Allergy Clin Immunol 2007;7(1):