Case reports

 Beatrice Vasile, Corinna Boniotti, Patrizia Bardini, Cristina Agapiti, Fabrizio Bordiga, Daniela Strabla, Carmen Santagata, Silvana Molinaro e Adriana Baraldi

 Pediatric Anesthesia and Resuscitation Unit, Civil Hospital of Brescia

INTRODUCTION

We present the case of a 5-year old boy, weighing 17 kg, who was admitted to the Pediatric Resuscitation Unit for severe respiratory insufficiency and pneumomediastinum provoked by a flare-up of bronchial asthma and right bronchopneumonia, and subjected to High Frequency Oscillatory Ventilation (HFOV) and treatment with Curosurf.

MEDICAL HISTORY NOTES

Child born at normal term after pregnancy with normal foetal development and natural birth (weight at birth 3150); perinatal period and psychosomatic development in the norm. Whooping cough, scarlet fever and an episode of asthmatic bronchitis reported approx. one year earlier.
A fortnight before the child’s admission to the Pediatric Resuscitation Unit, he had presented with a dry, irritable cough (treated with aerosol therapy), which then worsened, with onset of dyspnea and high temperature. He was therefore admitted to the Pediatrics Department, where asthmatic bronchitis and right bronchopneumonia was diagnosed. The child was then urgently transferred to the Pediatric Resuscitation Unit due to the onset of serious bilateral laterocervical emphysema with dyspnea, jugular recesses and chest/abdominal asynchronism.

CLINICAL PICTURE

On arrival in the Pediatric Resuscitation Unit, the patient was intubated and placed under volume Controlled Mechanical Ventilation (CMV). Invasive monitoring of the arterial pressure was initiated and a Central Venous Catheter (CVC) was positioned in the right femoral vein. The patient was duly sedated and curarized and infusional treatment with bronchodilators, antibiotics and cortisones was initiated. The Controlled Mechanical Ventilation (CMV) initially restored acceptable gas exchange (paO₂ /FiO₂ ratio >150) with fractions of inspiratory O₂ (FiO₂) progressively dropping from 100% to 55%, permissive hypercapnia paCO₂ <70 mmHg and peak pressures (Ppeak) inferior to 30 cm H₂O.
However, 24 hours after the patient’s admission to the Pediatric Resuscitation Unit, the gas exchange situation began to progressively worsen, following the onset of a series of complications. The appearance of a right parapneumonic pleural effusion required the fitting of a chest drainage system; subsequently, a homolateral pneumothorax (PNX) occurred as a result of the underlying parenchymal atelectasis.
After the fitting of the chest drainage system and notwithstanding the increased expansion obtained on the right, the gas exchange situation became increasingly more serious (hypercapnia CO₂ >70, hypoxemia with pa₂ /FiO2 ratio<100, Ppeak>40, Pmean>20 and the need for PEEP>10), due to the onset of pericardial thickening on the left and left basal PNX flap.
Conventional ventilation was therefore changed, on the 4th day, to High Frequency Oscillatory Ventilation (HFOV), associated with Curosurf therapy (broncholavage and “therapeutic” administration of the drug).
During the 24 hours that followed, despite the further worsening of the radiological picture (chest drainage system required also on the left where the PNX had become hypertensive), a marked improvement was observed as regards gas exchange situation (ph from 7.19 to 7.51, paCO₂ from 107 to 43.3, paO 2 from 73 to 93.5, paO₂ /FiO₂ ratio from 73 to 110, FiO₂ from 100 to 85%) (Figure 1).
Already as of the next day, given the stability of the ventilatory parameters and as the improvement of the radiological situation progressed, we were able, gradually and steadily, to reduce the FiO₂ from 85 to 55%, with acceptable gas exchange (pH 7.51+0.01 (mean+SD), paO₂ 76+3.3, paCO₂ 41.3+2.4, paO₂ /FiO₂ ratio 172+1.5) (Figure 1).
Seventy-two hours after the start of HFOV and the lavages with diluted Curosurf, the marked improvement of the gas exchange and radiological picture enabled us to change to conventional mechanical ventilation.

On the 9 th day, the Curosurf was administered by bronchoscopy selectively to the right and left hemisystems, in doses of 50 mg/kg, after which the patient was extubated.
The favourable evolution of the clinical picture enabled the removal of the chest drainage system on the 12 th day and the child was discharged from the Pediatric Resuscitation Unit on the 17 th day (the delay being due to complications not connected with respiratory problems).

TREATMENT

In the clinical case presented, the Curosurf administration pattern provided for: the performing of at least 6 daily lavages with two 5-ml doses of the drug diluted in physiological solution, reaching a final concentration equivalent to 5 mg/ml for 5 consecutive days and a final administration of "therapeutic" Curosurf equivalent to 50 mg/kg, divided into equal parts for each of the hemisystems. During the lavages, the patient was further sedated and/or curarized in order to safeguard against coughing, causing the premature elimination of the drug from the bronchi. The procedure was performed in sterile conditions with the aid of a syringe connected to an endotracheal catheter inserted in the tracheal tube until it wedges into place, momentarily disconnecting the patient from the ventilator. If necessary, for the 5 minutes leading up to the procedure and the 5 minutes following it, the patient was ventilated with O₂ at 100%. Approx.1 minute after the instillation of the drug, during which the patient was ventilated manually, we proceeded with bronchoaspiration, ensuring that at least 50% of the volume inspired was effectively recovered (4-5 aspirations).
Ventilatory parameters were adjusted on the basis of the new pulmonary compliance and on the basis of the respiratory exchanges subsequent to each lavage. Leading up to extubation on the 9 th day a bronchoscopy was performed in order to determine the conditions of the airways and remove any plugs or secretions that might be present. The instrument was then inserted in the main right and left bronchus for the purpose of administering undiluted Curosurf (80mg/ml) at a dose of 425 mg for each hemisystem. To safeguard against the drug being eliminated, bronchoaspiration was not performed on the patient in the hour following the treatment.

DISCUSSION

The case presented posed difficult problems regarding the handling of respiratory insufficiency, secondary to the presence of a series of pathological conditions: hyperreactivity and plugging of the airways, parenchymal thickening typical of pneumonia/atelectasis, bilateral pneumothorax and pleural effusion.
The ventilatory strategy adopted initially involved conventional ventilation, in volume controlled mode with the use of low TVs (8-6 ml/kg, in order to avoid volutrauma) and suitable PEEP levels (10- 12 cm H₂0,in order to avoid atelectrauma), enabling permissive hypercapnia. The unfavourable evolution towards a state of ever decreasing pulmonary compliance (due to the overlapping of pleuric effusion, parapneumonic atelectasia) showed, nonetheless, how, over the course of time, it became necessary to increase the PEEP (>15) in order to maintain sufficient lung volume at the end of expiration; in concomitance with the sudden increase in Ppeak (>40), a PNX occurred generating considerable hypoxia (PaO 2 /FiO 2 ratio=70), significant hypercapnia (paCO₂ =121) and it became impossible to ventilate the patient.
In such dramatic circumstances, preserving oxygenation and ventilation while maintaining maximum recruitment was no longer possible using conventional ventilation. The most appropriate solution was to start HFOV in association with Curosurf therapy. When HFOV is performed using TVs similar to the volume of the dead space at frequencies of 3 -15 Hertz (180 at 900cycles/min), it has been demonstrated, in numerous clinical trials, to have the capacity to ventilate successfully without risking the hyperinflation (volutrauma) and the collapse/re-opening of the alveoli (atelectrauma) that occur during conventional ventilation respiratory cycles [1].
Having better control of the mean pressure levels of the airways and of alveolar inflation levels, HFOV is able to improve oxygenation [1].
By controlling the amplitude of the TV oscillations during each cycle, HFOV can also control the efficacy of the ventilation (CO₂ removal) to a greater degree.
Given these characteristics, it appeared to be the best ventilation strategy for our case, where the worsening of pulmonary compliance had led to severe conditions of hypoxia and hypercapnia.
As far as surfactant therapy is concerned, definitive clinical data have already demonstrated its efficacy in the treatment of RDS in premature infants, in improving oxygenation (increase in functional residual capacity and recruitment of atelectatic areas) and in reducing the incidence of PNX [2]. Its use in the treatment of pneumonia, sepsis, asthma, ARDS (conditions characterized by a deficit of endogenous surfactant as a result of damage to the alveolocapillary barrier and/or direct lesions of type II pneumocytes) is currently being assessed.
Recent data have revealed, moreover, that certain surfactant components possess antibacterial properties [1], which deserve further investigation with a view to the future use of surfactant in infectious and inflammatory diseases of the lung [7]. Broncholavages with diluted surfactant, although still an empirical form of therapy, have proved nonetheless to be more efficacious than conventional broncholavages with saline solution in preserving the endogenous surfactant [4]. The presence of dense bronchial secretions, associated with pneumonia and atelectatic thickening as per our case, prompted us to administer broncholavages associated with a final dose of therapeutic Curosurf. The concomitant use of HFOV and surfactant is borne out in medical/scientific literature by two experimental works which demonstrate how surfactant has the capacity to considerably reduce ventilation pressure levels during HFOV compared to conventional ventilation techniques [5-6].
The rescue therapy adopted in our case (HFOV associated with Curosurf therapy), which derived from the scientific bases described earlier, proved itself, in a matter of hours, to be clearly beneficial. The improvement in respiratory gas exchange that took place in the first 24 hours (15% reduction in FiO₂, 13% increase in PaO₂/FiO₂ ratio), while, at the same time, a marked deterioration was observed in the radiological picture (PNX-induced atelectasia and new thickening phenomena), can only be partially attributed to the use of HFOV.
After 48 hours had elapsed , given the minimal variations in ventilatory parameters (the adjustments required in consideration of the better compliance) and the concomitant improvement in the radiological picture, we gradually and steadily reduced the FiO₂ from 85 to 55%, achieving normocapnia, a paO2/FiO₂ ratio >150 and a reduction of 45% in the OI. After only 72 hours, the marked improvement in respiratory gas exchange (normocapnia, paO₂/FiO₂ ratio >250, 75 % reduction in OI) and in the radiological picture enabled us to change over to conventional mechanical ventilation. After 9 days in the Intensive Care Unit, the patient was extubated.
Our case demonstrated how the association of non conventional ventilation and pharmacological techniques such as HFOV and Curosurf therapy combined to improve a situation of inhomogeneous low pulmonary compliance, secondary to the presence of various concomitant pleuroparenchymal diseases. Of course, the efficacy and safety of these two techniques can only be demonstrated by conducting randomized clinical trials on sufficiently numerous study populations.

REFERENCES

1. Rodriguez RJ. Management of respiratory distress syndrome: an update. Respir Care. 2003 Mar;48(3):279-86
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3. Wu H, Kuzmenko A, Wan S et al. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest. 2003 May;111(10):1589-602.
4. Wiswell TE, Smith RM, Katz LB et al. Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999 Oct;160(4):1188-95.
5. van Kaam AH, Haitsma JJ, Lachmann B et al. Response to exogenous surfactant is different during open lung and conventional ventilation. Crit Care Med. 2004 Mar;32(3):774-80.
6. Kerr CL, McCaig LA, Veldhuizen RA, Lewis JF. High-frequency oscillation and exogenous surfactant administration in lung-injured adult sheep. Crit Care Med. 2003 Oct;31(10):2520-6.
7. Luchetti M, Ferrero F, Gallini C, Natale A, Pigna A, Tortorolo L, Marraro G. Multicenter, randomized, controlled study of porcine surfactant in severe respiratory syncytial virus-induced respiratory failure. Pediatr Crit Care Med. 2002 Jul;3(3):261-268.
8. Il Surfattante nella Patologia Respiratoria Acuta" Editor Nicola Dirozzi, Daniela Perrotta. Edizione fuori commercio Riservata ai Sigg.Medici SEEd srl in collaborazione con Chiesi Farmaceutici.

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