Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Article Reviewed:

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Paresis acquired in the intensive care unit: a prospective multicenter study.

De Jonghe B, Sharshar T, Lefaucheur JP, et al.

JAMA. 2002;288(22):2859-67. [abstract]

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

Review posted October 6, 2003

I. What is being studied?:

The study objective:

To determine the clinical incidence, risk factors, and outcomes of ICU acquired paresis in long term mechanically ventilated patients recovering from critical illness in medical and surgical ICUs. A secondary objective was to gain insight into the electrophysiologic and histologic changes in those patients with ICU acquired paresis.

The study design:

This was a prospective cohort study.

The patients included:

Patients from 3 medical and 2 surgical ICUs were eligible if 1) they required mechanical ventilation for at least 7 days and 2) had achieved "awakeness" (based on passing 3 out of 5 screening questions to determine alertness and comprehension).

The patients excluded:

Those patients with disease of the peripheral nervous system, bihemispheric or brainstem lesions, fewer than 2 limbs in which muscle strength could be tested, a language barrier, or if they were referred from another ICU were excluded from the study.

332 patients out of 1246 screened (1/4) had > 7days mechanical ventilation. Of those 332 patients only 95 were eligible because 126 met exclusion criteria, and 109 did not "awaken".

The outcomes assessed:

The primary outcome measured was incidence of ICU acquired paresis. Association of ICU acquired paresis with the 39 potential independent risk factor variables and medications listed in tables 1 and 2 was also analyzed. In addition, duration of ICU acquired paresis and a comparison of the duration of mechanical ventilation between paresis and control groups were assessed.

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?

Yes. Seven days after meeting entry criteria, these 95 patients underwent muscle strength evaluation using the Medical Research Council (MRC) score that assessed 3 muscle groups from the each of the upper and lower limbs. Scores were 0 (paralysis) to 5 (normal) for each muscle group, with a maximum score of 60. Those patients with MRC scores less than 48 were deemed to have ICU acquired paresis, and those with scores of 48 or higher were controls. This cutoff point was determined a priori. Data collection was prospective and included 39 different demographic, preexisting disease state, metabolic, and organ dysfunction related variables that might be associated with the onset of paresis. This data was collected from ICU admission to the first day of awakening. In addition, 5 groups of medications suspected of being associated with paresis were identified (see tables 1 and 2 in the article). Patients that received at least one dose prior to awakening, total days of treatment, and total cumulative doses were recorded. Duration of mechanical ventilation and duration of paresis were recorded after awakening

All patients with MRC < 48 underwent electrophysiologic evaluation within 72 hours of identification. Patients with persistent paresis at day 14 underwent muscle biopsy.

All patients were in the recovery phase of their critical illness, having achieved satisfactory awakening after being mechanically ventilated for at least 7 days. The patients were from both medical and surgical ICUs from 3 university and 1 university based hospitals. This represented a diverse general adult ICU population.

2. Was follow-up sufficiently long and complete?

Yes. The researchers did a fairly good job of follow-up. Follow-up was continued for nine months on those patients that developed paresis (24 total). 7 patients died, and only one patient was lost to follow-up. It would have been beneficial to add some follow-up on the control patients including a comparison with the paresis group for either death after ICU or home status.

Secondary questions:

3. Were objective and unbiased outcome criteria used?

The investigators satisfied this question by utilizing an objective clinical assessment of clinical weakness (MRC score, as described above). Clinically significant weakness (ICU acquired paresis) was a priori determined to be a score less than 48 on this scale. They attempted to eliminate bias by having the same qualified neurologist train all the examiners to score the patients and assess for weakness in the same manner. Despite this, there still remains the possibility of inter-examiner variability assigning each patient a strength score. It doesn't seem from the text that more than one person performed the test on each patient. Therefore, the accuracy of the MRC score is clearly in question A few points difference between examiners could have one examiner determine the patient to have weakness based on the MRC scale, and another examiner to not. Analyzing for the bias of MRC scoring among examiners would have been useful.

In addition, the majority of the ICUAP patients were still on the ventilator at day 7 when the testing was first done (average length of mechanical vent was 18 days after day one) whereas at least half of the control group was off the vent at day 7 (average length of mechanical ventilation was 7 days in control group). The influence of sedatives and cooperativeness of an intubated patient is potentially a significant factor here.

4. Was there adjustment for important prognostic factors?

Yes, there was a comprehensive univariate and multivariate analysis of potential prognostic factors. See results below.

III. What are the results?

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

Incidence of ICU acquired paresis in the 95 patients ventilated for at least seven days who achieved satisfactory awakening was 25.3% (24 patients). As for the secondary objective to identify risk factors associated with ICU acquired paresis, after multivariate regression analysis, only female sex (OR 4.66; 95% CI 1.19 - 18.30), number of days with dysfunction in > 2 organ (1.28; 1.11 - 1.49), duration of mechanical ventilation (1.10; 1.00 - 1.22, referring to increased odds per day of additional mechanical ventilation), and corticosteroid administration (14.9; 3.2 - 69.8) remained significantly associated with the development of ICU acquired paresis. Please see table 3 in the article.

Mean duration of mechanical ventilation after day 1 of awakening was longer in paresis patients, 18.2 days, as opposed to controls, 7.6 days.

2. How precise are the estimates of likelihood?

Fairly precise, based on the 95% confidence interval provided for the incidence of ICU paresis (16.9% to 35.2%). Of the secondary objectives female sex and corticosteroid administration had large 95% confidence intervals. The goodness of fit for the regression analysis model of the paresis associated variables was 0.92.

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

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

Maybe. Despite being adult as opposed to pediatric patients, many of the diagnoses in this general adult ICU population (sepsis, pneumonia, etc.) are similar to the pediatric disease processes that lead to prolonged intubation and the associated ICU acquired paresis. However, one could argue that children may be more resilient in their resistance and/or recovery from paresis than the older patient population in this study (mean age 62), i.e., less static with still developing/growing neuromuscular system. A similar analysis of pediatric ICU patients would be very valuable. Only scattered case reports are reported in children (1).

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

No. The 4 independent risk factors statistically associated with ICU acquired paresis after multivariate analysis in this study were female sex, number of days with dysfunction of 2 or more organs, duration of mechanical ventilation, and corticosteroid use. None of the other medications or metabolic risk factors mentioned above in section I, proved to be significantly associated with paresis (Thus, nothing to avoid or select). Despite the fact that corticosteroid use had a very high OR of 14.9 (95% CI 3.2 - 69.8) for association with ICU acquired paresis, this would not prevent me from using corticosteroids in clinically indicated and potentially life saving situations, but as the authors point out, it would make me evaluate more closely my definition of "clinically indicated."

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

The results may allow me to counsel the patients and families of those ventilated for at least seven days that have a high likelihood (25% in this study) of developing clinically significant weakness, but the majority of these patients, if they survive their primary illness, will improve to near normal within 9 months. (In this study, 15 out of 16 resolved their paresis in 9 months, with a mean duration of paresis about 45 days). As above though, children may have a smaller incidence of paresis, if indeed older age leads to increased incidence of paresis when compared to children.

References

1. Petersen B, Schneider C, Strassburg HM, Schrod L. Critical illness neuropathy in pediatric intensive care patients. Pediatr Neurol. 1999 Oct;21(4):749-53. [abstract]

 

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