Improving nutritional therapy of persistent critically ill patients by organisational measures: A before and after study.

BACKGROUND & AIMS: Critically ill patients requiring prolonged intensive care (ICU) treatment are at high risk of malnutrition, which latter contributes to worsening outcome. Having observed that despite the presence of a nutrition protocol and dieticians, the patients with persistent critical illness (PCI) had been underfed during their ICU stay and particularly during the first 10 days, the aim was to analyse the impact of the organisational changes that were proposed to prevent the observed malnutrition. METHODS: Before (Period A) and after (Period B) study enrolling critically ill patients consecutively admitted, requiring >10 days of ICU treatment. The intervention consisted in increasing the early morning interactions between dieticians, nurses, and physicians, while modifying the computer visualisation of the dietician proposals. The primary endpoint was a reduction in the cumulative energy balance in period B. The ICU stay was divided in early ICU stay (first 10 days) and late ICU stay (day 11 to day 30). Other variables: protein, glucose, and prealbumin. RESULTS: Altogether, 205 patients (150 and 55 in period A and B respectively) were enrolled in the PCI program. Patient characteristics were similar over both periods except for lower SAPSII score in period B. There was no difference in nutritional pattern in the first 10 days between periods. The cumulate energy balance was less negative from day 11-30 in period B than in A (-884 vs -1566 kcal; p = 0.033). There was a one-day reduction in the median duration of fasting in period B (p < 0.0001). Overall compliance with nutrition protocol improved in period B with an earlier first indirect calorimetry (p = 0.003) and prealbumin measurement (p < 0.001), the latter increasing significantly more during ICU stay. CONCLUSION: Organizational changes that allowed an early identification of patients at nutritional risk, an increased targeted dieticians intervention and a better inter-disciplinary work was associated with a reduction in undue fasting, and significantly improved energy balances.

Muscle LIM protein is upregulated in fast skeletal muscle during transition toward slower phenotypes.

Muscle LIM protein (MLP) is constitutively expressed in slow, but undetectable in fast, muscles of the rat. Here we show that MLP was upregulated at both the mRNA and protein levels under experimental conditions leading to transitions from fast to slower phenotypes. Chronic low-frequency stimulation and mechanical overloading by synergist removal both induced fast-to-slow shifts in myosin heavy chain (MHC) isoforms and expression of MLP in fast muscles. High amounts of MLP mRNA and protein were also present in fast muscles of the myotonic, hyperactive ADR mouse. Hypothyroidism evoked shifts in myosin composition toward slower isoforms and increased the MLP protein content of soleus (SOL) muscle but failed to induce MLP in fast muscles. Unweighting by hindlimb suspension elicited slow-to-fast transitions in MHC expression without altering MLP levels in SOL muscle. Hyperthyroidism shifted the MHC pattern toward faster isoforms but did not affect MLP content in SOL muscle. We conclude that alterations in MLP expression are associated with transitions from fast to slower phenotypes but not with slow-to-fast muscle fiber transitions.

Muscle LIM protein: expressed in slow muscle and induced in fast muscle by enhanced contractile activity.

To identify early changes in gene expression during the fast-to-slow transition induced by chronic low-frequency stimulation, total RNA was extracted from 12-h-stimulated tibialis anterior (TA) muscles of rats and amplified by differential display RT-PCR. Among the signals of differentially expressed mRNAs, a cDNA approximately 300 bp in length, which was almost undetectable in control TA muscles but prominent in stimulated TA and normal soleus muscles, was identified. This cDNA was cloned and identified as corresponding to the mRNA of the muscle LIM protein (MLP). Its differential expression in control, stimulated TA, and soleus muscles was verified by Northern blotting. Antibodies against MLP were used to identify by immunoblot analysis a protein of 22 kDa, the predicted molecular mass of MLP. Immunohistochemistry revealed strong reactivity for MLP in all fibers of normal soleus muscle and faint staining of some type IIA and type I fibers in control TA muscle. These fibers increased in number and staining intensity in 4-day-stimulated TA muscle. MLP thus seems to play an essential role during the rearrangement of cytoskeletal and/or myofibrillar structures in transforming adult muscle fibers.

Parathyroid hormone-related protein is rapidly up-regulated in blood vessels of rat skeletal muscle by low-frequency stimulation.

To identify early changes in gene expression of fast-twitch rat muscle exposed to chronic low-frequency stimulation, differential display was applied comparing mRNA patterns between control and 12-h stimulated tibialis anterior (TA) muscles. Among the signals of differentially expressed mRNAs, a cDNA of approximately 300 bp was identified as specific to the parathyroid-hormone-related protein (PTHrP). As verified by semi-quantitative reverse transcriptase polymerase chain reaction, this mRNA was present at low levels in normal slow-twitch soleus and fast-twitch TA muscles, but was approximately 80-fold elevated in TA muscles after 12 h of low-frequency stimulation. With ongoing stimulation for 2 or 4 days PTHrP mRNA returned to basal levels. PTHrP was located exclusively in blood vessels of both control and stimulated muscles. PTHrP immunohistochemistry revealed enhanced capillarization in 8-day stimulated muscles. In view of its vasodilative effect the up-regulation of PTHrP could be an important initial step related to enhanced capillarization in response to increased contractile activity.