Effect of Inspiratory Muscle Training in Children with Prolonged Invasive Mechanical Ventilation: Report of Six Cases - Juniper Publishers

 Pediatrics & Neonatology - Juniper Publishers

Abstract

Objectives: This study aims at evaluating whether muscle training using moderate loads will cause an increase in inspiratory muscle strength, which was assessed by the measurement of maximal inspiratory pressure (PIMAX) in patients dependent on mechanical ventilation.

Methods: This is a retrospective study conducted in 2 Pediatric Intensive Care Units from January 2016 to December 2017. All patients who underwent muscle training during the period of the study were included. PIMAX was measured using a manovacuometer. Three measurements were made with an occlusion time of 15 seconds and a recovery interval of 2 minutes between them. Muscle training was performed following the institutional protocol (4 sets of 6 repetitions with a load equivalent to 60% of PIMAX) 1x/day, 6 days a week, excluding the day of the measurement of PIMAX.

Results: Six patients undergoing prolonged mechanical ventilation (average time of mechanical ventilation of 9647 hours) who underwent muscle training to disconnect mechanical ventilation were included. The measurements of PIMAX pre-training were compared to weeks 1 to 4. A significant difference on PIMAX was observed after the second week of training (p <0.001). Five patients progressed to IMV disconnection.

Conclusion: Our study supports the performance of IMT using moderate loads (60%), without risk of muscle fatigue as it resulted in a significant increase in PIMAX after 2 weeks of training, with positive outcomes regarding weaning from mechanical ventilation.

Keywords: Inspiratory muscle training, pediatrics, muscle strength, maximal respiratory pressure

Introduction

For patients under invasive mechanical ventilation (IMV), about 30% of patients evolve to prolonged weaning, and 5% has been dependence on IMV. When weaning failure occurs, the assessment of causes must be guided by three pillars: inadequate respiratory drive, increased respiratory effort, and weakness of the respiratory muscles [1]. For decades, ventilator-induced diaphragmatic dysfunction has been described as one of the main complications of IMV and it involves structural myofibrillar lesions leading to atrophy and functional abnormality [2-4]. Diaphragmatic weakness has been associated with an imbalance between myofibrillar protein synthesis and muscle proteolysis [5]. Furthermore, in critically ill patients, immobility, systemic infection, and inflammation may contribute to skeletal muscle dysfunction [6,7].

Inspiratory muscle training (IMT) with a linear load device has been performed in adult patients with good outcomes. It was observed increased inspiratory muscle strength, increased inspiratory muscle resistance, dyspnea reduction, increased exercise tolerance and improved quality of life [8]. Initially, the loads used were extremely low (20-30% of PIMAX) as it was feared high loads would cause muscle fatigue. However, this training profile had no impact on PIMAX or on outcomes of disconnection from IMV [9,10]. The training of adults with moderate to high loads was described by Martin et al as having excellent results in terms of disconnection from the IMV, with no report of muscle fatigue and significant increase in PIMAX [11,12].

There is still a scarcity of literature on pediatric population, and most of it consists of descriptions of isolated case reports evaluating low-load muscle training in patients with difficult ventilator weaning [13,14].

Objectives

This study aims at assessing whether moderate-load muscular training increases the inspiratory muscle strength, which was evaluated by measurements of maximal inspiratory pressure (PIMAX) in patients dependent on mechanical ventilation.

Methods

This is a retrospective study conducted in 2 Pediatric Intensive Care Units from January 2016 to December 2017. All patients who underwent muscle training during the period of the study were included. This research involving human participants all clinical investigation were conducted according to the principles expressed in the Declaration of Helsinki (1975, revised in 2000) and that it meets the ethical guidelines, including adherence to the legal requirements of the study country. The research was submitted to the ethics committee: Ethics and research committee of the Albert Einstein Hospital number: 62561516.9.2001.0071 and Ethics and research committee of Municipal Health Secretary number: 62561516.9.0000.0086. The informed consent term was waived by the ethics and research committee. This study received no funding.

The study included patients who underwent muscle training and were admitted to the Pediatric Intensive Care Units of two hospitals – one private and the other public – in the city of São Paulo, from January 2016 to December 2017.

Measurement of maximal inspiratory pressure

For the PIMAX measurements we used a Murenas manovacuometer (Juiz de Fora, MG, Brazil) with a scale from 0 to 150 cm H₂O and variations of 5 cm H₂O. Three measurements were made, with an occlusion time of 15 seconds and a 2-minute interval between them. During the interval, the patient was reconnected to the mechanical ventilator for recovery. Ventilation was measured using the pre-established protocol by trained physiotherapists.

Muscle training

Low intensity muscle training is defined when loads below 50% are used, moderate intensity muscle training when the loads used range from 60 to 80%, and high intensity muscle training when loads are greater than 90%. The higher the load, the lower the number of repetitions must be used. The training followed an institutional protocol of 1x/day, 6 days a week, excluding the day of the measurement of PIMAX. The training consisted of 4 sets of 6 repetitions for each section with a load calculated at 60% of PIMAX. The device used for muscle training was Threshold IMT (Respironics Inc; Murrysville, PA, USA).

Statistical Analysis

Regarding quantitative variables, the sample was characterized by mean, standard deviation, minimum and maximum, median and percentages; regarding qualitative variables, the sample was characterized by relative and absolute frequencies. To assess patients’ strength gain, we used the Generalized Estimation Equation Model – GEE. The dependent variable was PIMAX, and the independent variables were time (in weeks) and age (in months). Residual analysis was performed graphically. The analyses were performed using SPSS software (IBM Corp, 2016), v23.0, and a significance level of 5% was considered.

Results

Six patients in prolonged mechanical ventilation and undergoing muscle training in to be disconnected from mechanical ventilation were included. Table 1 presents the main demographic characteristics and post-training outcomes. Table 2 shows the estimated averages in a model that considered age as a control covariate given the variability of patients age. It also includes comparisons between the different stages with Bonferroni correction of the p-value. Pre-training PIMAX was compared to the PIMAX on weeks 1 to 4; only two patients showed results at week 4. We observed a significant difference in PIMAX after the second week of training. Figure 1 shows the patients’ average PIMAX profiles over time. We can observe a significant increase in PIMAX from the second week on.

Discussion

Our study was the first to conduct moderate load (60% of PIMAX) inspiratory muscle training in pediatric population. In addition to the excellent tolerance observed in patients, a significant increase over time in the PIMAX was demonstrated. Several studies have observed that atrophy of the diaphragm and other skeletal muscles in patients dependent on mechanical ventilation is quite common and occurs fast, starting within the first 24 hours of hospital admission [3,15-18]. Glau CL et al. [16] assessed 56 IMV dependent children using ultrasound and found that the diaphragm loses 3.4% of its thickness per IMV day, and that diaphragmatic atrophy is associated with increased IMV time and increased hospital stay.16 Despite the impact of diaphragmatic atrophy on late outcomes, studies discussing the functional rehabilitation of those patients are extremely rare. The patients included in our study presented complex diagnoses with multiple organ dysfunctions, with 9,000 hours of IMV time. Several authors have identified that specific risk factors such as prolonged mechanical ventilation [19-21], use of neuromuscular blockers [16], sepsis and multiple organ dysfunction syndrome [22-24] aggravated muscle mass loss. Most of these risk factors were identified in our population.

In our study, muscle atrophy was characterized by loss of muscle strength, which was assessed through PIMAX. Measurement of PIMAX is an effective method for assessing inspiratory muscles strength [25,26]. The maximum negative pressure generated during temporary airway occlusion is commonly used to measure inspiratory muscle strength in children under mechanical ventilation as it is easy to execute and is not invasive. A normal or almost normal rate of PIMAX is useful to rule out weakness of the respiratory muscles and obviates the need for complex and/or invasive testing [26-28]. So far, few pediatric studies have evaluated the effect of inspiratory muscle training on muscle strength and on clinical outcomes, such as the duration of ventilatory assistance [12-14], limiting themselves to the description of clinical cases. When considering a protocol for inspiratory muscle training, it was unclear whether moderate load training could cause muscle fatigue since the diaphragm contracts 24 hours/day without a break.

Our protocol was designed based on the recommended load for a peripheral muscle strength training program, in which it is established by physiology that 6 maximal or submaximal contractions produce an almost optimal increase in strength and no muscle fatigue. Our study has limitations. The first is the small number of patients in the sample. However, although our sample is small, we share how challenging it is to gather this number of patients and this study is the largest so far conducted with the pediatric population. The second is that the presence of complex diagnoses caused the stabilization of patients and the indication for IMT to occur after a long period of mechanical ventilation. The third is that there was no control group to compare strength gains in patients not submitted to the training protocol. Our study presented a safe and effective protocol for gaining PIMAX that favored the weaning of patients on prolonged mechanical ventilation, however, a randomized study and the presence of a control group is necessary for the validation of these findings.

Conclusion

Our study supports performance of IMT using moderate loads (60%) without risk of muscle fatigue, as it resulted in a significant increase in PIMAX after 2 weeks of training and in positive outcomes in weaning from mechanical ventilation. Finally, we suggest increase in PIMAX measurements for all children with prolonged use of IMT due to its low cost, applicability and to help clinicians to find the right time in the difficult decision of disconnecting these patients off the ventilator.

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New-born with Cervical Ectopic Thymus: An Uncommon Developmental Disorder Which Has to be Consider in the Differential Diagnosis of Unilateral Neck Mass in Children - Juniper Publishers

Pediatrics & Neonatology - Juniper Publishers 

Case Report

The aim of this paper is to report an unusual case of ectopic cervical thymus (CET) in a one-month-old infant and to underline the importance of considering it in the differential diagnosis of neck masses in children. A one-month-old male infant was referred to our Emergency Department for evaluation of a right-sided neck swelling, which was noted by his parents about 2 days before. The mother’s pregnancy (medically assisted procreation) was full term and uncomplicated. The patient had never required admission to the hospital or surgery. Family history was negative for thyroid disease and malignancy. On physical examination, his height and weight were normal in his peers. Vital signs were normal. The cervical mass was soft, mobile, painless, and 4×3-cm rounded, in the right submandibular region without a palpable margin. No overlying skin changes, or pits were evident. No palpable cervical lymph nodes and history of difficulty in feeding, breathing, and crying were present. Past medical history was unremarkable and without a history of radiation exposure. His thyroid gland was not enlarged. 

Bio humoral work up included full blood count, electrolytes, tumour markers (aFP, bHCG, CEA, Ca 19-9), thyroid function, inflammatory parameters; we did also the immunological exams (lymphocyte and NK population, Ig G, Ig A, Ig M count, vanilmandelic acid and T cell receptor excision circles); all values resulted within range whereas ultrasonography revealed a nonhomogeneous, mainly cystic structure. On magnetic resonance imaging (MRI) examination (Figure 1), a homogenous mass was identified. The mass was 4 x 3cm in diameter, slightly hyperintense on T1-weighted images and was markedly hyperintense on T2-weighted images. The signal characteristics reflected that of the normal-appearing thymus gland in the right upper mediastinum. The lesion determined moderate compression of adjacent structures, particularly the parotid gland behind. The mass had features compatible with ectopic thymic tissue. Initially, agree with onco-haematologists and radiologists, we decided to wait and to follow up the baby clinically and with an ultrasound after two and four weeks. During the second check, we noticed that the mass slightly grew up and at the ultrasound the dimensions were increased. Therefore, after careful preparations, at the age of 3 months, the patient underwent a complete excision of the mass under general anesthesia (Figure 2). We used routine cervical approach, and found the mass was soft, yellow white (Fig. 3), with clear margins and located in the carotid triangular area, posterior to the sternocleidomastoid, deeper to it are arteria carotis communis, carotid artery bifurcation and jugular vein. The postoperative course was unremarkable, and the wound healed well. The patient was discharged on the 6th postoperative day. The final histopathological report confirmed the diagnosis of ectopic thymus.

Brief Discussion

Ectopic thymic tissue may be placed anywhere along the cervical pathway of the thymopharyngeal duct [1] from the mandible angle to the manubrium of the sternum. These migrational anomalies may represent an unusual cause of pediatric neck lump but it is rarely considered in the differential diagnosis of neck swellings. To date, the real incidence of CET is still unknown yet; to our knowledge, there are not more than 130 cases reported till now, with about 10% occurring in infants [1]; it has unusually been reported preoperatively in the literature, in fact it is generally identified incidentally at autopsy or postoperative pathologic examination. Histologically, an ectopic thymus can either be cystic or solid. Nowak et al. [2] reviewed 91 cases of CET: 65 cases were cystic forms, more common than the solid forms (26 cases). They also reported that CET usually occurs between the ages of 2 and 13 years. In a review of 46 CET cases, 39 (85%) were male, and in 22 (56%) of these, the mass was detected on the right side [3]. 

The most frequently presenting symptom is painless swelling. Other symptoms, such as stridor, dyspnea, and/or dysphagia caused by compression of the trachea and/or oesophagus, may occur in 10% of cases [4]. The thymus is a specialized organ in the immune system: its functions are the “teaching” of T-lymphocytes and the production and excretion of thymosin’s and hormones [5]. In patients with a CET, only half or less of the organ can be present in the chest, particularly on the side of the mass: presurgical recognising of existence of normal mediastinal thymus is imperative to avoid over-investigation, or biopsy/surgery with unintended total thymectomy, and subsequent immunodeficiency, specifically in infants and children. The clear preoperative diagnosis of CET is difficult and hardly made preoperatively. In almost all reviewed children, definitive diagnosis has relied on histopathologic examination after surgery [5]. CET is usually misdiagnosed as cystic hygroma, cystic teratoma, lymphoproliferative disorders, reactive adenopathy, and vascular tumours [1]. MRI can help as in the diagnosis of CET, determining if the mass’s density is similar to that of normal thymus, as to demonstrate the presence of a mediastinal thymus. Fine-needle biopsy combined with flow cytometry analysis have been used in the pediatric population [1,6]. But the sensitivity and specificity for fine-needle biopsy of thymic tissue are not known in the children.

The natural history of the CET is unknown. Nearly all cases reported in the literature have been surgically removed. Schloegel and Gottschall [7] proposed a clinical algorithm for the management of CET and suggested that “wait and watch” is the ideal choice for these patients. But due to the lack of reports demonstrating that CET would atrophy after puberty, we consider that pathological examination at the moment is still the definite method of diagnosis. In view of this, we advise that excision is a good option for CET, not only to obtain pathology specimens but also to correct facial asymmetry and avoid clinical symptoms. The best age above which safe removal of the thymus can be performed has not been determined. Accordingly, an accurate evaluation of thepresence of the normal mediastinal thymus should be undertaken prior to removal of an ectopic cervical thymus, especially in children younger than one year of age, to prevent the risk of immunocompromised [8-10]. For our patient, we chose to conduct the total excision of the lesion based on what previously declared, but also because of the growth speed of the mass, which was rather rapid. Moreover, in our department, this kind of neck tumour was usually resected, and other conservative management methods were not generally practiced. To conclude, ectopic cervical location of the thymus is a very rarely diagnosed developmental disorder in children. Our case highlights the role of histopathology to confirm the correct diagnosis, the importance of investigating the mediastinal thymus and immunology status before surgery. Although difficult to differentiate from other conditions, it is important for clinicians to be aware of its rarity and it has to be considered in the differential diagnosis of unilateral solid–cystic neck mass in pediatric age.r fine-needle biopsy of thymic tissue are not known in the children.

Learning Points

1. Ectopic cervical thymus must be considered in the differential diagnosis of unilateral neck masses in children.

2. Before surgery, it is mandatory to scan the presence of a mediastinal thymus to avoid a total thymectomy; the best radiological exam to demonstrate it is the MRI.Consider, before surgery, to make all immunology tests. 

3. Consider, before surgery, to make all immunology tests.

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