Clinical Investigations Respiration 2006;73:791–798 DOI: 10.1159/000090777

Received: July 22, 2004 Accepted after revision: August 31, 2005 Published online: January 16, 2006

Noninvasive Ventilation in Childhood Acute Neuromuscular Respiratory Failure: A Pilot Study M. Piastra a M. Antonelli b E. Caresta a A. Chiaretti a G. Polidori a G. Conti b a

Pediatric Intensive Care Unit and b Department of Anesthesiology and Critical Care, Catholic University Medical School, Rome, Italy

Key Words Emergency presentation
Helmet
Hypoxemic respiratory failure
Intensive care
Neuromuscular disorders
Noninvasive ventilation
Pediatric intensive care unit

Abstract Background: Over a 36-month study period, 10 nonconsecutive neuromuscular pediatric patients (6 infants, mean age 10.16 months, and 4 children, mean age 9.3 years) presenting with acute respiratory failure (ARF) were treated by noninvasive positive pressure ventilation (NPPV). All patients required immediate respiratory support and fulfilled our intubation criteria. Objective: The aim of the study was to verify if early NPPV was able to avoid endotracheal intubation and to improve both oxygenation and ventilation within 24 h from admission in this clinical setting. Patients and Methods: A prospective pilot study was carried out on neuromuscular patients admitted to the pediatric intensive care unit (PICU) of the Catholic University of Rome because of ARF and managed exclusively with NPPV for at least 24 h following admission. All patients were treated using a flowtriggered mechanical ventilator through a face mask or using the new helmet interface. Results: Eight patients were successfully ventilated during the observation period and 2 early failures occurred. Among children un-

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dergoing face mask NPPV, the PaO2/FiO2 ratio increased from a median value of 75 (range 48–149) to 240 (range 133–385; p ! 0.001) and 328 (range 180–371; p ! 0.001) at selected time points (3 and 12 h after NPPV introduction, respectively); the alveolar-to-arterial oxygenation difference showed a similar trend, i.e. decreasing from a median value of 589 (range 213–659) to 128 (range 62– 527; p ! 0.01) and 69 (range 45–207; p ! 0.001), respectively. Hypercarbic ARF resolved within 6 h from admission even in the most severe cases. Conclusions: NPPV was a safe and effective first-line therapeutic approach in hypoxemic ARF children/infants with neuromuscular disease. It seems of importance to identify children with neuromuscular disorders who may be able to achieve residual ventilator-free breathing and to perform an NPPV trial avoiding tracheal intubation. Life-threatening respiratory distress and very young age should not preclude NPPV application in the PICU setting. The new helmet interface represents a promising tool for noninvasive ventilation in older children. Copyright © 2006 S. Karger AG, Basel

Introduction

Noninvasive ventilation denotes techniques improving alveolar ventilation without tracheal intubation. Pulmonary complications frequently arise in the course of

Dr. M. Piastra Terapia Intensiva Pediatrica Università Cattolica, Policlinico Gemelli Largo Gemelli, 8, IT–00168 Roma (Italy) Tel. +39 06 3015 5203, Fax +39 06 323 1741, E-Mail [email protected]

neuromuscular disorders (NMD), often precipitating acute respiratory failure (ARF). Usually, pediatric patients with NMD and respiratory failure eventually undergo tracheal intubation for ventilatory assistance and airway suctioning. Subsequently, failure to wean may lead to muscle atrophy causing early fatigue of the diaphragm. The need for tracheal intubation mostly occurs in association with respiratory infections or surgery, because of the limited clearance of tracheobronchial secretions of the neuromuscular patient. Moreover, a combination of bronchodilators, agents with a fluidifying effect and supplemental oxygen may also be provided via the endotracheal tube. However, none of these ancillary treatments (including chest physiotherapy and removal of secretions via the endotracheal tube) has been demonstrated to reduce the need for tracheostomy for the typical neuromuscular patient [1]. The potential advantages of a noninvasive approach, when applicable, are evident. Both in acute and in chronic respiratory failure patients, the presence of an artificial airway increases the risk of local airway injury, barotrauma and susceptibility to nosocomial infections [2, 3]. Negative pressure ventilators were firstly used (e.g. the iron lung, adopted during the polio epidemics). Problems occurring with negative pressure ventilation (upper airway obstruction and sleep hypoxemia) may be overcome by positive pressure, which allows also for cough augmentation and preserves protective mechanisms of the airways, speech and swallowing, thus increasing patient comfort. In adults, noninvasive positive pressure ventilation (NPPV) has been applied mostly in patients with chronic obstructive pulmonary disease and cardiogenic pulmonary edema, but its application in acute hypoxemic respiratory failure is increasing. Some of our cases presented infrequent disorders, e.g. Ullrich and nemaline myopathies. Apart from muscular weakness, a moderate-severe kyphoscoliosis represented a common landmark in our older children, eventually leading to respiratory failure and thus affecting their prognosis. NPPV has been described as beneficial in these conditions [4–6].

Patients and Methods Study Design The aim of the study was to examine the short-term efficacy and the feasibility of first-line NPPV application in 10 non-consecutive NMD pediatric patients admitted to the emergency department (ED) and pediatric intensive care unit (PICU) of the Catholic University Medical School because of ARF from January 2001 to January 2003. Data were not compared with a historical control group

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because of patient heterogeneity both regarding age at presentation and ventilatory management. All patients referred to PICU were still spontaneously breathing: patients admitted with an endotracheal tube in place were not considered eligible for this study. NPPV Administration NPPV was provided in all patients using a flow-triggered intensive care ventilator (Siemens Servo 300 ventilator; Siemens-Elema, Solna, Sweden). NPPV was performed in all patients by using pressure support and/or pressure control – compensating for leaks around the mask – to achieve the best possible synchronization with spontaneous breathing. In the presence of a significant leak, the inspiratory pressure target is never reached, resulting in a very long inflation time, as the unit delivers massive amounts of inspiratory flow in an attempt to attain the preset inspiratory pressure. Utilizing Servo 300, even the young child can trigger supplemental ventilations, both in assisted and in controlled mode: a flow-sensitive trigger permitted a better synchronization of the patient’s spontaneous breathing; moreover, the preset inspiratory time (pressure controlled) demonstrated efficacious compensation for leaks around the mask, thus limiting the need for a tight-fitting interface and/or further patient sedation. When applicable, a relatively low ventilator frequency was set (8–10 beats/min), thus allowing the patient spontaneous breathing; for safety reasons, respiratory back up ventilations were programmed. Peak inspiratory pressure was increased by the attending physician to obtain an exhaled tidal volume of 5–6 ml/kg maintaining a PaCO2 value !65 mm Hg and pH 17.25; positive end expiratory pressure (PEEP) was adjusted to maintain oxygen saturation 192% with a required fraction of inspired oxygen (FiO2) !0.6. For each patient, maximal settings of the mechanical ventilator have been listed in table 1. The helmet (CaStar, Starmed, Mirandola, Italy) is a new ventilatory device made of transparent latex-free PVC; it is secured by two armpit braces at two hooks (anterior/posterior) on the metallic ring joining the helmet with a soft collar. This collar facilitates neck adhesion thus enabling a sealed connection. During positive pressure ventilation, the soft collar seals comfortably to the neck and the shoulders, avoiding air leakage. The helmet is available in four sizes (3 adult and 1 pediatric sizes) to ensure comfort and a proper seal. The whole apparatus is connected to the ventilator using a conventional respiratory circuit. The two ports of the helmet act as inlet/outlet flow of the gas. The same inspiratory and expiratory valves of the mechanical ventilator are used, similar to conventional ventilation. Two seal connections with an adjustable diaphragm allow the passage of tubes (nasogastric or feeding-drinking tubes). The transparency of the device allows the children to see and interact with the parents, nurses and environment. The head of the bed is kept at an angle of 30–45°. After helmet positioning, pressure support can be progressively increased by 2–3 cm H2O to improve ventilatory performance, reflected by oxygen need and respiratory rate decrease, and the disappearance of accessory muscle activity. PEEP is increased from 5 to 12 cm H2O to achieve a peripheral oxygen saturation of at least 92% with the lowest FiO2 possible. In our clinical experience, involving also pediatric patients with hemato-oncological diseases, we used only flow triggers: the continuous flow was automatically adjusted by the ventilator as during conventional support. In case of air leaks, the following options were available: (a) readjustment of the helmet, using the smallest helmet type; (b) slight reduction in the pressure support and PEEP, if clinically compatible, and (c) when pressure support

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produces prolonged inflations because of air leaks, it is possible to shift to pressure-targeted time-cycled breaths. As explained above, the Siemens Servo 300 also works in the pressure-controlled mode, to obtain supplemental breaths by triggering. We always set the flow trigger in these patients, to facilitate easier patient-machine interaction. We did not use nasal masks in our critically ill PICU patients: a face mask was preferred, enabling a better ventilation control even in the acute phase. The face mask was provided with a tight-fitting securing system and an inflatable cushion for better sealing (fig. 1). In the intensive care unit, standard monitoring was applied in all the patients, consisting of an arterial catheter in the radial or femoral artery for continuous recording of arterial blood pressure and blood sampling and a catheter inserted into the right internal jugular vein for measurement of central venous pressure. Peripheral oxygen saturation was continuously monitored with a pulse oximeter, concomitant with ECG, respiratory rate and end-tidal CO2 monitoring. Transcutaneous monitoring of O2 and CO2 was also performed, particularly in younger patients. Children were given low-dose midazolam (1–2
g/kg/min), remifentanil (0.1– 0.2
g/kg/min) or sufentanil (0.25
g/kg/h) to improve compliance with the procedure. Initially, NPPV was delivered continuously

Fig. 1. Face mask with tight-fitting securing system. Note the inflatable cushion to ensure good sealing and patient comfort (Koo® Medical, Shangai, People’s Republic of China).

Table 1. Patient characteristics and maximal settings of the mechanical ventilator Patient

Age

1

6y

2

8y

3

10 y

4

12 y

5

7m

6

10 m

7

15 m

8

8m

9

18 m

10

3m

NMD

Ullrich myopathy nemaline myopathy spinal cord hamartomatosis seronegative myasthenia gravis SMA I juvenile myasthenia gravis mitochondrial myopathy SMA I

Cause of ARF

ARF presentation

Admission PaCO2 PaO2/FiO2

Early NPPV Max. MV outcome settings in PICU PIP/PEEP

NPPV application from admission

Clinical outcome at hospital discharge

airway infection

hypoxia

59

140

success

15/6

<72 h

muscle fatigue

severe hypercapnia

94

149

success

18/4

120 h

airway infection

severe hypoxia

28

48

success

20/8

<56 h

home BiPaP ventilation home BiPaP ventilation recovery, SB

myasthenic crisis

hypoxic-hypercapnic ARF

61

20

success

16/12

<72 h

recovery, SB

airway infection

respiratory arrestbradycardia hypoxic ARF

43

90

success

15/4

<84 h

49

54

success

21/6

48 h

tracheostomyHMV recovery, SB

hypoxic ARF

40

75

success

12/4

180 h

hypoxic-hypercapnic ARF severe ARF

64

48

success

23/7

<96 h

48

116

failure-ET at 4 h

20/6

<24 h

severe ARF

50

152

failure-ET at 6 h

25/6

<24 h

severe muscular failure-airway infection airway infection airway infection, muscle fatigue muscle fatigue, airway bleeding

chronic myopathycongenital nephrotic syndrome cerebellar muscle weakness, ischemia-severe hypoventilation, muscular atelectasis hypotonia

tracheostomyHMV tracheostomyHMV died 24 months, no PICU discharge died 12 months, no PICU discharge

SB = Spontaneous breathing; ET = endotracheal intubation; BiPAP = bilevel positive airway pressure; SMA = spinal muscular atrophy; HMV = home mechanical ventilation; ARF = acute respiratory failure; MV = mechanical ventilator; y = years; m = months.

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way pressure therapy were also introduced. In all cases, the clinicians tried to facilitate intermittent or nocturnal ventilatory support, aiming to achieve a combination of adequate oxygenation and partial unloading of respiratory muscles. Prevention and treatment of atelectasis were considered essential components of the treatment: frequent chest physiokinesitherapy was performed, combined with gentle aspiration of tracheal secretions.

100 2 90

80

Statistical Analysis Repeated measures ANOVA with Bonferroni’s multiple comparison test for comparisons of quantitative variables at different time points was applied in this children group (Graph Pad Software, San Diego, Calif., USA). All values are expressed as median (range) unless otherwise specified, and p values !0.05 were considered significant.

70

60

8 4 1

50

6

40

7

5

30

3

Results

20

10 PICU admission to 48 h

0

a

100

PaCO2 (mm Hg)

75

50

25 PICU admission to 48 h 0

b

Serial PaCO2 determinations

Fig. 2. Individual carbon dioxide values (a) and mean PaCO2 trend (b) in patients responding to face mask and helmet NPPV during the first 24–36 h of application.

(118–20 h or more on the 1st day) with pauses without mask of 5–10 min to perform airway aspiration. Subsequently, periods of rest/spontaneous breathing were introduced, in which supplemental oxygen was added via a nasal cannula or Venturi mask, thus the patient was able to drink, cough or expectorate. On subsequent days, ventilatory assistance was gradually reduced, depending on the clinical status; periods of mask/nasal continuous positive air-

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NPPV through a facial mask or helmet was a safe and effective mode of improving alveolar ventilation. The treatment was successful in 8 of 10 patients and failed in 2 patients. The reasons for early NPPV failure were airway obstruction in a 3-month-old baby suffering from a generalized hypotonia, and intractable airway bleeding in a 18-month-old female with metabolic muscle weakness. In successfully treated patients, blood gas monitoring via an indwelling arterial catheter demonstrated improved oxygenation within 1.5–3 h from NPPV onset. The PaO2/ FiO2 ratio increased from a median value of 75 (range 48–149) to 240 (range 133–385; p ! 0.001) and 328 (range 180–371; p ! 0.001) at selected time points (3 and 12 h after NPPV introduction, respectively). Alveolar-to-arterial oxygenation difference (A-aDO2) showed a similar trend: decreasing from a median value of 589 (range 213– 659) to 128 (range 62–527; p ! 0.01) and 69 (range 45– 207; p ! 0.001), respectively. No patient needed tracheal intubation within 24 h from NPPV introduction, and no signs of air trapping, hypercapnia or respiratory acidosis were recorded in the same interval. Patients with hypercapnic ventilatory failure normalized their PaCO2 as a result of improved ventilation within 6–8 h (fig. 2a, b). No severe complications occurred during NPPV administration, except for 1 case of nasal bridge erosion. According to the study design, NPPV was continuously delivered for a minimum period of 24 h. The clinical outcome was as follows: 2 children were eventually discharged from the PICU on intermittent NPPV, 3 infants underwent NPPV in the acute phase, but respiratory failure repeatedly occurred requiring multiple PICU admissions. Elective tracheostomy was performed following several episodes of respiratory failure to permit home

Piastra /Antonelli /Caresta /Chiaretti / Polidori /Conti

PaO2/FiO2

450

1

400

2

350

3

300

4

250

5

200 150

6 7

100 50 0

a

T0

T1

T2

T0

T1

T2

700 1 600

2 3

500

4

A-aDO2

5 400

6 7

300 200

Fig. 3. PaO2/FiO2 (a) and A-aDO2 (b) values in children successfully treated with face mask NPPV. Data have been collected at onset (time: 0) and at two selected time points (T1 and T2: 3 and 12 h after the start of NPPV, respectively).

100 0

b

care. The remaining 3 patients could be discharged home on spontaneous breathing. PaO2/FiO2 and AaDO2 trends from admission (time T0) until control time points (T1 and T2) are shown in figure 3a, b. Figure 4 shows the NPPV application and corresponding chest film at presentation in our series’ youngest patients (aged 7, 10 and 8 months, respectively).

Discussion

Intubation and mechanical ventilation are frequently necessary and unavoidable means to treat the critically ill infant or child who undergoes severe respiratory failure. Neuromuscular patients represent a distinct subgroup, characterized by a slow decrease in muscle function, often precipitated by acute events. They have been described as ideal candidates for non-invasive ventilation, mostly for intermittent support. Older NMD patients often ex-

Noninvasive Ventilation in Neuromuscular Respiratory Failure

hibit an increased compliance to medical maneuvers: nevertheless, the best way to obtain patient compliance is based upon the patient’s recognition that the device leads to symptomatic improvement. Children with chronic respiratory failure associated with NMD or severe kyphoscoliosis often receive NPPV in the domestic setting [7] or as a component of a weaning procedure from invasive ventilation [8]. Pediatric application of NPPV has been extensively reviewed by Teague [9] in 1997. More recently, Akingbola and Hopkins [10] examined all the reports on NPPV application in patients with hypoxic and hypercarbic respiratory failure. As previously stated, alveolar hypoventilation is a common and frequently terminal complication of chronic respiratory failure associated with progressive neuromuscular and obstructive lung disease (e.g. cystic fibrosis). Previously published clinical studies included few NMD patients with really hypoxemic ARF; sometimes they were presumptively excluded or not clearly ad-

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Fig. 4. NPPV application and corresponding chest film at presentation in our series’ youngest patients (aged 7, 10 and 8 months, respectively).

dressed; NMD infants treated exclusively using noninvasive ventilation are even rarer. As a consequence, NPPV in PICU and ED in children with ARF is influenced mostly by the experience of the clinician, by the diagnosis and by the availability of resources. As a general rule, infants or children admitted to a general ED for acute respiratory distress or referred from peripheral facilities are more likely to undergo conventional management. On the contrary, those with known chronic respiratory failure having previous multiple ED/ICU admissions are more frequently referred to experienced specialists or pediatric

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intensivists. Few data retrieved from individual studies are available about NPPV application in Duchenne’s muscular dystrophy [11, 12] and chronic respiratory failure (mostly cystic fibrosis) [13–15]. In 1998, Niranjan and Bach [16] described a group of 10 adolescent patients (8/10 with a diagnosis of Duchenne’s muscular dystrophy, average age 16.9 years): 4 of the 10 patients presenting with acute ventilatory failure were managed successfully without intubation; the remaining 6 patients were initially intubated, successfully extubated and switched to continuous NPPV. Fortenberry et al. [17] adopted bi-

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level positive airway pressure in 28 pediatric patients (median age 8 years, range 4–204 months) and concluded that NPPV may be safe and effective in children with mild-to-moderate hypoxemic respiratory insufficiency, and particularly useful in patients whose underlying condition warrants avoidance of intubation. Of interest, there was no neuromuscular patient in this series because they were specifically excluded from the analysis; in this group, before therapy, values of PaCO2 were 45 8 11 torr, whereas PaO2 before therapy was 71 8 13 torr. In 1994, Padman et al. [7] described a group of 15 patients (age 4–21 years, no average is indicated); 1 treatment failure is described in a 4-year-old myopathic subject due to the difficulty in managing secretions. In the last decade, several reports on the successful management of pediatric patients with NPPV have been published [10, 18–22]. They mostly refer to adolescents or older children, whereas infants and younger children (particularly those affected by uncommon NMD) pose a great challenge to the clinicians. First of all, they are frequently managed before a definitive diagnosis and related prognosis are achieved. Of importance, we probably describe the youngest NMD patients that were resuscitated from life-threatening ARF without intubation and then administered NPPV using an intensive care ventilator, in lieu of the bilevel positive airway pressure treatment using a nasal piece. In our opinion, treatment of the younger patients with noninvasive techniques is particularly challenging: a narrow airway anatomy (difficult or impossible to clear secretions in the absence of efficacious coughing) and a lack of patient/parental compliance are often insurmountable difficulties and eventually lead to conventional management. Undoubtedly, poor patient compliance and the need for increasing sedation to control agitation/anxiety remain a limiting factor in children !6 years. In our experience, a low-dose midazolam infusion was well tolerated and did not result in NPPV discontinuation; in selected cases, treatment with a short-acting opioid (as remifentanil or sufentanil) was adopted. The need for frequent tracheal secretion suctioning further limited the application of noninvasive ventilation in pediatric patients, possibly leading to a change to conventional ventilation. Negative pressure ventilation had previously been adopted (even in older children of our study); its efficacy appears consistently lower than that of NPPV. A severe kyphoscoliosis (e.g. cases 1 and 3), a problem frequently associated with NMD, poses particular problems using external ventilation devices, since it may be very difficult to adapt the device to the chest wall. Moreover, negative support can induce or aggravate upper airway obstruction

[6]. Another important limitation to the above-described studies is that they mostly refer to subacute or chronic situations; on the contrary, in adults, ventilation without prior placement of an endotracheal tube is now extensively employed [23], and it has been used both in hypercarbic and in hypoxic ARF in emergency and critical care. Of particular interest, Vianello et al. [24] recently performed a prospective trial on NPPV in adults with ARF of neuromuscular origin: the results are encouraging for the use of NPPV, though an appropriate patient selection seems to be of fundamental importance. The literature is still meager on the use of NPPV in children affected by ARF of neuromuscular origin, particularly regarding uncommon disorders. For these conditions, it is not easy to define the disease stage needing irreversible ventilatory support and/or tracheostomy. Superimposed acute events, e.g. airway infections or surgery, may eventually resolve and some degree of spontaneous breathing may be restored. Therefore, in light of the potential benefits and the apparently low risks of NPPV in an ICU setting, an individualized assessment instead of rigid guidelines may be appropriated. This strategy can lead to the identification of children who are likely to benefit from NPPV. In these patients, an early application of ventilatory support may actually affect the clinical outcome. This is particularly important when the clinical history may suggest a considerable period of ventilator-free survival. We decided to offer this modality in the ICU even to the younger age group, though different options were subsequently preferred (e.g. tracheotomy for home ventilation and airway suctioning). In fact, logistic and familyrelated issues can become predominant: for infants living in a rural area, a noninvasive program is often inapplicable or potentially harmful. In contrast to adult patients (for whom NPPV has been extensively adopted in particular conditions such as chronic obstructive pulmonary disease [25–27] and pulmonary edema [28, 29]), there are no well-defined pediatric intensive care settings in which NPPV can be considered as standard therapy [30–34]. In our opinion, it is important to identify NMD patients who will benefit from residual ventilator-free breathing and to avoid tracheal intubation as long as possible. Moreover, following the acute phase, noninvasive methods may be used as a bridge to intermittent nocturnal assisted ventilation [35]. Based on our initial experience, our uniform policy is to initially adopt a noninvasive approach or to try early weaning by switching to noninvasive support in neuromuscular pediatric patients admitted with both hypoxic or hypercarbic ARF.

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