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ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 3  |  Page : 748-754

Critical illness myopathy and polyneuropathy in children admitted to the ICU


Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission28-Jun-2016
Date of Acceptance02-Jan-2017
Date of Web Publication15-Nov-2017

Correspondence Address:
Nahla M Said
Banha City, El-Qaluobeia Governorate, 13511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_320_16

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  Abstract 

Objective
The aim of the present study was to detect critical illness polyneuropathy and myopathy in children admitted to the ICU in relation to clinical findings and therapeutic regimen.
Background
Critical illness polyneuropathy and myopathy is a frequent complication of critical illness, acutely and primarily affecting the motor and sensory axons. This disorder can cause severe limb weakness and prolonged weaning.
Patients and methods
This study included 75 patients with different diseases admitted to the pediatric ICU at Menoufia University and was conducted for the period of 2 years. The patients were divided into five groups. All patients underwent nerve conduction, and electromyography was carried out on the seventh day of admission to ICU.
Results
The mean age of the patients was 4.5 ± 2.3 years. Twenty-four (24%) patients developed critical illness neuropathy and myopathy, among whom 21 (28%) patients developed axonal polyneuropathy, one (1.3%) had demyelinating polyneuropathy, and two (2.7%) cases were myopathic. In children with sepsis the prevalence of axonal polyneuropathy was five (33.3%) cases, one case had axonal polyneuropathy and one had myopathy. Among children with chest diseases, four cases of the ventilated ones had axonal polyneuropathy, six (40%) cases of the sepsis ventilated children developed axonal polyneuropathy, and one was myopathic. One child of the ventilated children due to chest disease had demyelinating polyneuropathy, whereas the other five cases had axonal polyneuropathy. Overall, 66.7% of the deaths were of those who developed axonal polyneuropathy, and 85.7, 47.6, and 90.5% of the deaths were of those who were hyperglycemic, ventilated, and acidotic, respectively.
Conclusion
The incidence of critical illness axonal polyneuropathy was 28%, 1.3% for demyelinating polyneuropathy, and 2.7% for critical illness myopathy.

Keywords: critical illness polyneuropathy and myopathy, ICU, nerve conduction, and electromyography


How to cite this article:
Mahmoud AT, Tawfik MA, Abd El-Naby Abdella SA, Said NM. Critical illness myopathy and polyneuropathy in children admitted to the ICU. Menoufia Med J 2017;30:748-54

How to cite this URL:
Mahmoud AT, Tawfik MA, Abd El-Naby Abdella SA, Said NM. Critical illness myopathy and polyneuropathy in children admitted to the ICU. Menoufia Med J [serial online] 2017 [cited 2019 Dec 10];30:748-54. Available from: http://www.mmj.eg.net/text.asp?2017/30/3/748/218260


  Introduction Top


Critical illness polyneuropathy and myopathy (CIP/CIM) is a frequent complication of critical illness, and can cause severe limb weakness and prolonged weaning [1].

As regards the incidence rates reported in ICU in sepsis or systemic inflammatory response syndrome patients, 70% develop critical illness polyneuropathy (CIP). The incidence increases to up to 100% in multiple-organ failure [2]. Similarly, about 60% of patients with acute respiratory distress syndrome suffer from this disease [3]. In unselected patients receiving mechanical ventilation for at least 4–7 days, the occurrence of CIP/CIM was reported to be 25–33% on clinical evaluation and up to 58% on electrophysiological evaluation. Of patients in the ICU for at least 7 days, 49–77% will acquire CIP/CIM. A neuromuscular disorder with a predominant muscle component [critical illness myopathy (CIM)] develops in at least one-third of ICU patients treated for status asthmatics [4].

A large number of risk factors for CIP/CIM have been identified, such as hypoxia, hypotension, hyperpyrexia age, aminoglycosides use, female sex, severity of illness the duration of organ dysfunction, renal failure and renal replacement therapy, hyperosmolality, and parenteral nutrition [5]. Low serum albumin, duration of ICU stay, vasopressor and catecholamine support and central neurologic failure, and hyperglycemia also have been identified as risk factors [6]. Sepsis remains one of the leading causes of mortality in critically ill patients. Sepsis is currently estimated to be the cause of 1.5% of deaths each year [7] [Figure 1].
Figure 1: Risk factors involved in muscle wasting and ICUAW. ICUAW, ICU-acquired weakness; IFN, interferon; IL, interleukin; TGF, transforming growth factor; TNF, tumor necrosis factor.

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The pathophysiology of CIP and CIM is complex and still unclear. Bolton hypothesized that sepsis-related disturbance of the microcirculation in peripheral nerves and muscles are a crucial event in the pathogenesis. In CIP this may be mediated by the enhanced expression of E-selectin in the vascular endothelium of the peripheral nerves. Hyperglycemia also may impair the microcirculation to the peripheral nerve. Moreover, cytokines secreted in sepsis have histamine-like properties that may increase microvascular permeability [8].

The pathophysiology of CIM is also complex, involving metabolic, inflammatory, and bioenergetics alterations. Protein catabolism and muscle wasting are observed in CIM. In addition, proteolytic pathways involving calpain have also been reported [9]. Glutamine is known to stimulate protein synthesis and inhibit protein breakdown. There appears to be a relative deficiency of glutamine due to increased demands in critical illness [10].

Decreased levels of anabolic hormones and increased levels of catabolic hormones may contribute to myofilament loss and apoptosis in CIM [11]. Channelopathy is another mechanism that has been suggested in the pathophysiology [Figure 1].

This study aimed to detect CIP/CIM in children admitted to the ICU in relation to clinical findings and outcome.


  Patients and Methods Top


This study was carried out in the pediatric intensive care unit (PICU), Pediatric Department, Menoufia University Hospital, from 2014 to 2016 on 75 patients, 39 boys and 36 girls, aged from 2 months to 15 years, who presented with different diseases during the study period.

The study protocol was approved by the local ethics committee of Menoufia University, and a written consent was obtained from the parents of the children.

Patients' criteria

Patients were enrolled in the study according to each individual disease [Table 1].
Table 1: Demographic data of the all studied patients

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  • Patients admitted with sepsis: 15 patients (eight boys and seven girls). Patients were diagnosed according to the criteria of diagnosis
  • Patients admitted with respiratory problems: 15 patients (eight boys and seven girls). Seven patients had pneumonia, two were asthmatic, and six patients were diagnosed with bronchiolitis
  • Patients admitted because of different causes who needed mechanical ventilation for more than 1 weak: 15 patients (seven boys and eight girls). Five patients had hemolytic uremic syndrome, four had heart failure, two had cardiomyopathy, and four suffered from trauma and intracerebral hemorrhage
  • Patients admitted to the PICU with sepsis needing mechanical ventilation: 15 patients (eight boys and seven girls)
  • Patients admitted to the PICU with respiratory problems needing mechanical ventilations: 15 patients (seven boys and eight girls). In total, 12 patients were diagnosed with pneumonia and three with asthma.


Control group

Fifteen apparently healthy children (seven boys and eight girls) matched with the patients as regards age, sex, and socioeconomic status, and aged from 1.5 to 11 years were enrolled as the control group.

All patients and controls were subjected to the following:

  • Detailed history taking, physical examination, and vital signs
  • Neurological examination, including general observation, head examination, cranial nerves examination, and motor and sensory examination.


All participants underwent the following investigations.

  • Complete blood count, alanine transaminase (ALT), and aspartate transaminase (AST)
  • Blood urea nitrogen and creatinine, random blood glucose, and prothrombin time
  • Computed tomography brain and chest radiography.


As regards neurophysiologic tests, nerve conduction study (NCS) and electromyography (EMG) on the seventh day of admission to the ICU were carried out on both tibial and peroneal nerves and their muscles.

Exclusion criteria

Peripheral nervous system disease and previous myopathy and polyneuropathy due to any other disease (e.g., diabetes mellitus, thyroid dysfunction).

Statistical analysis

The data collected were tabulated and analyzed by using the statistical package for the social science software, version 17 (SPSS Inc., Chicago, Illinois, USA) [12].

The results were expressed as range and mean ± SD. The c2-test, Mann–Whitney test, t-test, and Kruskal–Wallis test were used for different statistical analyses. P values less than 0.05 were considered statistically significant.

Pearson's correlation coefficient was used for normally distributed quantitative variables, whereas Spearman's correlation was used for quantitative variables that were not normally distributed or when one of the variables was qualitative.


  Results Top


Our study included 75 patients with different diseases admitted to the PICU at Menoufia University. They were divided into five groups. All patients underwent nerve conduction and EMG on the seventh day of admission to the ICU. The mean age was 4.5 ± 2.3 years. Twenty-four (24%) patients developed critical illness neuropathy, among whom 21 (28%) patients developed axonal polyneuropathy, one (1.3%) had demyelinating polyneuropathy, and two (2.7%) cases were myopathic. Among children with sepsis, there were five (33.3%) cases of axonal polyneuropathy, one case of axonal polyneuropathy, and one case was myopathic. Among children with chest disease, four cases among the ventilated ones had axonal polyneuropathy, six (40%) cases of sepsis ventilated children developed axonal polyneuropathy, and one was myopathic. One of the ventilated children due to chest disease had demyelinating polyneuropathy, whereas the other five cases had axonal polyneuropathy. Overall, 66.7% of the deaths were because of axonal polyneuropathy, and 85.7, 47.6, and 90.5% of the deaths were of those who were hyperglycemic, ventilated, acidotic, respectively.


  Discussion Top


CIP/CIM are complications of critical illness that present with muscle weakness and failure to wean from the ventilator [13].

This study was conducted in Menoufia University Hospital on patients attending the PICU. The study included 75 patients admitted to PICU suffering from different diseases, and 15 controls.

The mean age of the patients was 4.5 ± 2.3 years – 52% boys and 48% girls. Twelve patients belonged to the age group older than 2 years or more, 38 patients to the age group 2–5 years, and 25 patients to 5–11 years [Table 2].
Table 2: Demographic data of the two studied groups (patient, control)

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The mean age of the controls was 3.9 ± 2.4 years – 46.7% boys and 53.3% girls. Three patients belonged to the age group less than 2 years, nine patients to 2–5 years, and three patients to 5–11 years.

After carrying out neurological examinations, we documented that 32 (42.7%) patients had clinically detected hypotonia and decreased power, 17 (22.7%) had hyporeflexia, whereas cranial nerves and sensations were intact in all cases. Only 24 cases had electrophysiological abnormalities.

ICU acquired weakness (ICUAW) is characterized by symmetrical and flaccid weakness of the limbs, which is more pronounced in the proximal muscles than in the distal muscles. Facial and ocular muscles are often spared, and tendon reflexes are generally reduced, although these can be normal. In the case of coexistent CIP, sensory symptoms may be present, including reduced or absent sensitivity to pain, temperature, and vibration [14].

Routine investigations were carried out and the diagnostic criteria were fulfilled. High white blood cells in patients who were ventilated with sepsis or chest problems × 103 (20 ± 4.4, 17.4 ± 3). Platelet counts were significantly low in patients with sepsis (136.3 ± 76.6) and the ventilated ones (121 ± 23). The prevalence of thrombocytopenia at admission to ICU has been reported to be around 20–30% [15].

In addition, in our study we reported elevated liver enzymes, as ALT was 188 ± 138.9 U/l and AST was 181 ± 120.7 U/l in sepsis patients with ventilator, and, also, all patients' prothrombin times were affected, and more decrease was noted in sepsis patients (0.62 ± 0.1).

Septic shock with hypoxic hepatitis (HH) represents up to 32% of all HH cases in ICU patients. Endotoxins and proinflammatory mediators could have an important role in potentiating HH development. The enzymatic pattern of HH starts with sharp but unsustain increases in AST, ALT, and lactate dehydrogenase levels 24 h after the initiation of shock early and dramatic drop in prothrombin levels [16].

As regards arterial blood gases (ABGs), acidosis was detected in all patients but more in sepsis ventilated patients: pH (7.25 ± 0.1), HCO3(19.9 ± 2.3), and PCO2(31.5 ± 5.6); followed by sepsis only patients: pH (7.28 ± 0.1), HCO3(20 ± 4.4), and PCO2(38 ± 9.7).

Acidosis is a common problem in patients with sepsis and other critical illness; it alters the release of nitric oxide and other inflammatory mediators. A decreased pH affects synthesis and release of tumor necrosis factors and interleukin-6 [17].

High random blood sugar was found in all patients, with higher values in sepsis and ventilated ones (211.7 ± 35).

Van den Berghe et al. [18] reported a 34% relative risk reduction of in-hospital mortality when blood glucose was maintained at between 80 and 110 mg/day.

In our study, five (33.3%) patients from a total of 15 sepsis patients developed axonal polyneuropathy on the seventh day of ICU admission detected in NCS as the amplitude of both left and right tibial and peroneal nerves was low, with normal conduction velocity and latency. One of the asthmatic patients developed axonal polyneuropathy (6.7%).

Four cases of critically ventilated children due to causes other than sepsis or respiratory diseases developed axonal polyneuropathy, representing 26.7% of the total cases of this group. The number of affected children increased with those had sepsis ventilated children to six (40%) cases developed axonal polyneuropathy, last group those with chest disease who need mechanical ventilation four cases of pneumonia developed axonal polyneuropathy, one status asthmatics child who was ventilated had demyelinating polyneuropathy represented as low amplitude, prolonged latency pattern of both tibial, peroneal nerves and reduced conduction velocity. with decrease interference pattern only with no signs of denervation of tibialis anterior muscle, gastrocnemius medial head and gluteus maximus in EMG.

The risk for the development of axonal polyneuropathy increased in our patients with sepsis and ventilated children (40%), followed by sepsis only as a risk factor (33.3%), which equally occurred in ventilated children with chest problems. Latronico et al. [11] stated that in CIP, the pathological finding is axonal degeneration. The pathogenesis of such axonal degeneration remains incompletely understood, and in part can be explained by the invasiveness of nerve biopsies. Factors that play a role are microvascular changes in the endoneurium evoked by sepsis, which promotes vascular permeability and allows penetration of toxic factors into the nerve ends [19] reported that neuromuscular weakness is a common occurrence in patients who are critically ill, developing in 25% or more of patients who are in the ICU and ventilated for at least 7 days.

In the this study, 33.3% sepsis patients developed axonal polyneuropathy on the seventh day of ICU admission, and the number of affected children increased with those had sepsis ventilated children to six (40%) cases developed axonal polyneuropathy. Whereas Wang et al. [20] noted that, CIP and/or CIM developed in 70% of the patients with sepsis or systemic inflammatory response syndrome and up to 100% of the patients with multiple-organ failure.

On the other hand, Latronico and Bolton [13] did not find an association between CIP and systemic inflammatory response syndrome, sepsis, drugs, or nutrition.

As regards critical illness, myopathy was detected only in two (13.4%) cases. One of the asthmatic children and one of the sepsis ventilated children had myopathic changes in the form of small polyphasic motor units and early recruitment of gluteus maximus only, whereas the tibialis anterior muscle and gastrocnemius medial head had normal motor unit and normal interference pattern, with no signs of denervation [Table 3].
Table 3: Comparison between the patient and the control groups regarding the electrophysiological study

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According to Chawla and Gruener [21], critical illness neuropathy and CIM are now the most commonly acquired neuromuscular conditions in the ICU setting with a risk for development, which may reach 50% in patients with sepsis.

In their study, Charles and colleagues concluded that neuromuscular blocking agents, such as pancuronium bromide or the shorter acting vecuronium, and steroids, singly or in combination, induced either a pure axonal motor neuropathy or a primary myopathy. These agents will generally have been used for longer than 24 h [8].

The positive cases represented 24 (32%) of total 75 cases A total of 21 (28%) cases had axonal polyneuropathy, one (1.3%) was demyelinating, and two (2.7%) cases were myopathic [Table 4] and [Table 5].
Table 4: Descriptive for the positive cases

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Table 5: Descriptive for positive cases in each group

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The outcomes of our cases, 21 (28%) of 75 studied cases died; this result was significantly related to the duration of the hospital stay as the mean time in the ICU was 21.4 ± 6.5 and 15.9 ± 3.5 for the dead and the survived ones, respectively, and this was in agreement with Campellone and colleagues [22],[23] who found that the mean time in the ICU for those with CIM was 49 ± 36 days but only 14 ± 14 days for those without CIM. Whereas Hermans et al. reported that 11% of the patients treated in the ICU for at least 24 h developed ICUAW, and when the ICU stay increased to 7–10 days, ICUAW at awakening was present in 24–55% [24].

Axonal polyneuropathy was predominant in 66.7% of the dead cases, but only one (4.8%) case was myopathic compared with 28.6% of the dead patients had normal electrophysiological studies. Nguyen and Nguyen Huu stated that, the distribution of polyneuropathy and myopathy in critically ill patients treated more than 10 days in the ICU was 48 and 22%, respectively. Compared with patients without CIP/CIM, patients with CIP/CIM experienced a mortality rate of 49 versus 30% [23].

Hyperglycemia was major risk factor as the mortality was 85.7% of hyperglycemic children who had CIP/CIM. The incidence of CIP/CIM and duration of PICU stay and mechanical ventilation were significantly reduced in the hyperglycemic patients treated with insulin compared with the controls [24]. Furthermore, van den Berghe and colleagues reported a 34% relative risk reduction of in-hospital mortality when blood glucose was maintained at between 80 and 110 mg/day.

Overall, 90.5% of the patients who died had acidosis. Gunnerson et al. [25] stated that 64% of his studied critically ill patients had a metabolic acidosis and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (P < 0.001). Whereas 47.6% of the dead ones were ventilated. As recorded by Khalil et al. [26], 33% of the patients with peripheral neuropathy failed weaning trials and finally died [Table 6] and [Table 7].
Table 6: The fate of the cases

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Table 7: The relations between the outcome of the cases and the risk factors

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  Conclusion Top


Many risk factors are involved in the development of CIP/CIM, such as sepsis, mechanical ventilation, immobilization, hyperglycemia, and acidosis. Higher mortality rates are associated with those patients who develop CIP/CIM, and this was associated longer hospital stay. NCS and EMG must be carried out in every patient with prolonged stay in the ICU for early detection of CIP/CIM. Early management of severe sepsis and septic shock are also necessary. Early mobilization of ventilated patients has been being beneficial to minimize the duration of ventilator dependence. In addition, in the ICU blood glucose needs to be strictly controlled and hyperglycemia avoided.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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