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Article Reviewed:

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Muscle weakness in critically ill children.

Banwell BL, Mildner RJ, Hassall AC, Becker LE, Vajsar J, Shemie SD.

Neurology. 2003 Dec 23;61(12):1779-82. [abstract]

Reviewed by Jeffrey Alten, MD with M. Michele Mariscalco, MD, Baylor College of Medicine

Review posted August 6, 2004

I. What is being studied?:

The study objective:

To establish the incidence of ICU acquired muscle weakness in a general population of pediatric intensive care patients. The authors also described the clinical features and prognosis of children who developed clinical weakness in the PICU.

The study design:

A prospective cohort observational study.

The outcomes assessed:

Patients were screened for weakness after 24 hours in the PICU. Weakness was identified via a Medical Research Council score < 5 in any one muscle group and subsequently verified by staff neurologist examination. The Medical Research Council (MRC) score assesses 3 muscle groups from the each of the upper and lower limbs. Scores are from 0 (paralysis) to 5 (normal) for each muscle group, with a maximum score of 60 (1).

In addition, the researchers described and categorized the characteristics of the ICU acquired weakness with the use of EMG, nerve conduction studies, and muscle biopsy.

II. Are the results in the study valid?

Primary questions:

1. Was there a representative and well-defined sample of patients at a similar point in the course of the disease?

Maybe. During a one-year study period, all consecutive patients, aged 3 months to 17 years, admitted to one academic pediatric intensive care unit for greater than 24 hours were evaluated for clinical weakness two to three times a week. If a child developed weakness, they were referred to a staff neurologist for comprehensive neurological examination, and the child's family was consented for further electrodiagnostic studies and muscle biopsy. Based on the inclusion criteria (greater than 24 hour PICU admission), the patients were temporally similar, but the course of their disease would likely not be the same (e.g., comparing a patient with DKA at day 2 of their disease to a patient with multiorgan failure at day 2 of their disease would be quite different). However, the authors did follow patients throughout their ICU stay, thus they would also be following patients at similar points of their disease course, such as the point at which they are ready to transfer from the PICU.

2. Was follow-up sufficiently long and complete?

No. Of the 14 patients identified with clinical weakness, 11 survived. Nine of these 11 patients were available for follow-up. All nine were evaluated at three months and 8 still had persistent proximal weakness. Although 8 patients still had symptoms, only two patients were followed beyond three months. Adult studies and case reports suggest ICU acquired weakness may persist several months to a few years (2,3). A recent study demonstrated > 90% of adult ICU patients with acquired weakness resolved their weakness within 9 months, with a mean duration weakness about 45 days (3). Thus, it is clear from the adult experience and this small group of children that children with ICU acquired weakness will likely need to be followed longer than 3 months in future studies.

Secondary questions:

3. Were objective and unbiased outcome criteria used?

Yes. The outcome measured was development of muscle weakness in PICU patients. A patient was identified as having weakness if they met one or more of three criteria. The first, Medical Research Council (MRC) score, is a reliable and well-described assessment of clinical weakness (1). The second and third criteria, reduced or absent tendon reflexes and failure to wean from mechanical ventilation in the absence of clinical weakness have both been associated with adult ICU acquired weakness (5). The possibility of identifying false-positive cases was controlled by having a confirmatory detailed neurological examination performed by a neurologist. In this study, all 14 of the patients did indeed have significant weakness in all 4 limbs as part of their clinical findings.

The use of EMG, nerve conduction studies, and muscle biopsy to help identify and characterize ICU acquired weakness is also well described in the adult literature (6).

4. Was there adjustment for important prognostic factors?

While identifying patients with weakness, the authors excluded those patients with pre-existing neuromuscular disease, CNS disease, and peripheral neuropathy. These patients likely had baseline weakness and could falsely elevate the incidence of acquired muscle weakness identified.

In this observational study, the investigators did not perform a statistical comparison between the cohort with ICU acquired weakness and a control group. Thus, no adjustment for possible prognostic factors was performed. In their identified ICU acquired weakness cohort, the investigators did calculate the incidence of some factors felt to be associated with the development of ICU acquired weakness in adult studies such as corticosteroids, neuromuscular blockade, sepsis, multi-organ failure, mechanical ventilation, and length of ICU stay (5). In the control group, the length of ICU stay, the incidence of organ transplantation and incidence of prolonged mechanical ventilation was provided, but not statistically compared to the weakness cohort. It would have been interesting for the other potential risk factors mentioned above to be compared between groups.

III. What are the results?

1. How large is the likelihood of the outcome event(s) in a specified period of time?

The incidence of acquired weakness in this pediatric ICU population admitted greater than 24 hours was 1.7% (14 out of 830 eligible patients). The calculated 95% confidence interval was 0.9% to 2.8%.

Two other patients were identified as having acquired weakness in the screening process, but did not undergo comprehensive neurological examination because of parental refusal to participate with one patient and extreme patient irritability in the other. Interestingly, the incidence of acquired weakness varies with age in that it is 0.7% in children from 3 months to 3 years of age and is 5.1% in those older than 10 years of age. There were no patients identified in the 3 to 10 year old range.

Five of the 14 weakness cohort patients underwent EMG, with 4 demonstrating myopathy. Seven of the patients underwent nerve conduction studies with five classified as abnormal.

When comparing the weakness cohort to all PICU patients admitted greater than 24 hours, the weakness cohort had longer ICU stay, higher incidence of mechanical ventilation > 5 days, and were more likely to be a transplant patient. Using data provided in the article, I calculated the relative risk for developing muscle weakness for children in these two groups. This additional statistical analysis demonstrated that children with a diagnosis of transplantation were 12.5 times more likely to develop weakness after 24 hours in the PICU than children without this diagnosis, and children ventilated longer than 5 days were 13 times more likely to develop weakness compared to those ventilated less than 5 days.

Relative Risk for transplant patients:

	WEAKNESS	No Weakness	Total
Transplant	8	72	80
No Transplant	6	744	750
Totals	14	816	830

Control event rate: 6/750 = 0.008
Exposure Event Rate: 8/80 = 0.1

Relative Risk: 0.1/0.008 = 12.5
95% Confidence interval: 4.4-35

Relative Risk for children ventilated > 5 days:

	WEAKNESS	No Weakness	Total
Ventilator > 5 days	12	234	246
No Ventilator > 5days	2	531	533
Totals	14	765	779

Control Event Rate: 2/533 = 0.00375
Exposure Event Rate: 12/246 = 0.04878

Relative Risk: 0.004/0.049 = 13
95% Confidence interval: 2.9-57.6

2. How precise are the estimates of likelihood?

The 95% confidence intervals for the likelihood of developing weakness in patients ventilated > 5 days and children with a diagnosis of organ transplant are provided above. The confidence intervals indicate statistical significance but are very wide. The authors performed no statistical analysis in this observational study, thus we do not know any additional risks of acquiring muscle weakness outside the two calculated risk factors above.

IV. Will the results help me in caring for my patients?

1. Were the study patients and their management similar to my own?

Yes. The patients in this study were likely similar to those in any tertiary pediatric intensive care unit.

2. Will the results lead directly to selecting or avoiding therapy?

No. The study did not attempt to identify any therapy or modifiable risk factors associated with the development of ICU acquired weakness in children. Until a pediatric study is performed, we must extrapolate information from adult studies, which suggest a potential association between ICU acquired weakness and corticosteroid or neuromuscular blockade - mandating their judicious use (5).

3. Are the results useful for reassuring or counseling patients?

In discussing prognosis with parents, it is reassuring that the incidence of ICU acquired weakness in this hospital was low. But given the extreme heterogeneity of PICU patients with respect to diagnosis and severity of disease, and likely differential risk factors for developing weakness, it would be more beneficial to know the incidence of weakness in subsets of PICU patients. After calculating the relative risk for the transplant children and those with mechanical ventilation > 5 days, I would consider informing families of children in these subsets there is a high likelihood their child will develop significant muscle weakness.

This paper represents one of the first investigations into ICU acquired weakness in children. There is much to be studied about risk factors, characteristics, and prognosis of ICU acquired weakness in children before we can counsel parents in this area. For now, we can say the overall incidence is low in a general PICU population, but likely higher in a subset of "sicker" patients, such as those with organ transplantation and prolonged mechanical ventilation.

References

1. Kleyweg R, VanDerMeché F, Schmitz P. Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome. Muscle Nerve. 1991;14:1103Ð1109. [abstract]
2. Fletcher SN, Kennedy DD, Ghosh IR, et al. Persistent neuromuscular and neurophysiologic abnormalities in long-term survivors of prolonged critical illness. Critical Care Medicine 2003, 31:1012-1016. [abstract]
3. van der Schaaf M, Beelen A, de Groot IJ. Critical illness polyneuropathy: a summary of the literature on rehabilitation outcome. Disability Rehabilitation 2000, 22: 808-810. [abstract]
4. De Jonghe B, Sharshar T, Lefaucheur JP, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002, 288:2859-2867. [abstract] [PedsCCM EB Journal Club Review]
5. De Jonghe B, Sharshar T, Hopkinson N, Outin H. Paresis following mechanical ventilation. Current Opinions in Critical Care 2004, 10:47-52. [abstract]
6. De Jonghe B, Cook D, Sharshar T, Lefaucheur JP, Carlet J, Outin H. Acquired neuromuscular disorders in critically ill patients: a systematic review. Intensive Care Medicine 1998, 24:1242-1250. [abstract]

 

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