Insulin reduces Neuromuscular Complications and Prolonged Mechanical Ventilation in a Medical ICU. Online data supplement

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Tobias Rodgers
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1 Insulin reduces Neuromuscular Complications and Prolonged Mechanical Ventilation in a Medical ICU Greet Hermans 1, Alexander Wilmer 1, Wouter Meersseman 1, Ilse Milants 2, Pieter J. Wouters 2, Herman Bobbaers 1, Frans Bruyninckx 3, Greet Van den Berghe 2 Online data supplement 71

2 Patients and methods Glucose measurements Whole-blood glucose levels were measured during the entire ICU stay at one-to-fourhour intervals in arterial blood or, when an arterial catheter was not available, in capillary blood. A point-of-care glucometer was used (HemoCue B-glucoseanalyser, Hemocue). Glucose levels as wel as insulin dose were documented by the nurse on the patient file. Diagnosis of CIP/CIM To date, 2 diagnostic approaches exist for CIP/CIM; the clinical one and the electrophysiological one. Both have strong points and weaknesses. Some authors have used the MRC sum score to grade weakness. This clinical examination is quickly performed and allows some quantification of weakness. However, this score was developed for and validated in patients with Guillain-Barré, not for ICU patients. As a voluntary test, a significant subset of patients will not be evaluable due to reduced consciousness or inadequate mental status. Also there is a risk to underestimate power [1]. Finally, the MRC sum score lacks information concerning the ethiology of the weakness. ENMG on the other had, is much more difficult to perform in the ICU and to our knowledge, no reproducibility studies have been performed. However, it does not require patients cooperation and therefore can be performed in more patients in ICU and also earlier in the disease. ENMG also allows excluding patients with other causes of neuromuscular dysfunction. Moreover, it was shown that electrophysiological testing provided a reliable tool to predict paresis in critically ill patients [2]. Therefore, we chose in this study to use electroneuromyography to diagnose CIP/CIM. Electroneuromyography 72

3 All patients who were still in ICU on day 7 after admission (N=443) were screened for CIP/CIM by electroneuromyography (ENMG) of all limbs. ENMG was repeated weekly for the duration of ICU stay. Patients with pre-existing neuromuscular disorders were excluded. ENMGs were evaluated by an independent investigator, unaware of treatment allocation. The diagnosis of CIP/CIM was exclusively based on the presence of abundant spontaneous activity in the form of positive sharp waves and fibrillation potentials in multiple distal and proximal muscles in all extremities. The differentiation between abundant and nonabundant was made as follows: if spontaneous electrical activity was limited to increased insertional activity, then it was considered as non-abundant. If spontaneous electrical activity was sustained with fibrillation potentials and/or positive sharp waves, then it was considered as abundant. The EMG abnormalities had to be present in at least 3 muscle groups in at least 3 different limbs. We analysed M Extensor digitorum communis, M biceps, M quadriceps and M gastrocnemius. When findings were equivocal, more muscles were evaluated. Muscles innervated by nerves susceptible to pressure palsies were avoided. These were mainly those innervated by n peroneus and n ulnaris. Myopathy could not be excluded electromyographically as patients were often uncooperative or unconscious. Muscle biopsies were not systematically performed. Time of diagnosis for patients with CIP/CIM was defined as the time point of the first positive ENMG. For patients without CIP/CIM, time of diagnosis was defined as the time point of the last negative ENMG. Feeding protocol As soon as patients were hemodynamically stable, enteral feeding was started. In accordance with routine guidelines, we aimed at a total of 22 to 30 kcal per kilogram of body 73

4 weight per 24 hours with balanced composition (0.08 to 0.25g of nitrogen per kilogram of bodyweight per 24 hours and 20-40% of nonprotein kilocalories as lipids) [3] When enteral feeding was started, the aim was to reach the target amount of kilocalories within 72h, depending on procedures and tolerance as reflected by the gastric residual, vomiting, diarrhoea, aspiration and abdominal distension. Ventilation and weaning strategies Patients were daily evaluated for the need for sedatives and analgesics and the lowest dose possible to keep the patient comfortable was used. For this purpose we used the sedation agitation score (SAS score) [4,5] aiming at a level of four. As soon as recovery started, short acting drugs (propofol and/or remifentanyl) were used. For each type of pathology we used written guidelines how to ventilate these patients. All patients were weaned conform the guidelines of the consensus conference on weaning [6]. This means that patients were daily evaluated for readiness for weaning based on improvement of the reason for mechanical ventilation, cardiovascular status, gas exchange parameters, ventilatory settings and neurological status. If these criteria were fulfilled a weaning-trial was performed using spontaneous breathing trials of at least 30 and up to 120 minutes. If the spontaneous breathing trial was successful, based on subjective tolerance, respiratory and hemodynamic parameters, patients were extubated. ICU discharge To reduce the risk of bias and also avoid potential problems of outflow to the regular ward, we defined criteria for patients to be ready for discharge. These consisted of absence of vital organ support, receiving at least two thirds of the caloric intake by the normal enteral route or being effectively sent to a ward. 74

5 Definition of risk factors for CIP/CIM The baseline risk factors that were entered into the models were those that determine severity of illness. These were TISS-28 scores, APACHE-II, age, BMI, upon admission organ function, ALT and glycemia, history of malignancy, upon admission hyperinflammation (CRP>150 mg/dl), diabetes and diagnostic category. Known risk factors occurring during ICU stay were calculated for each patient from admission up to diagnosis of the presence or absence of CIP/CIM. This time frame was also entered into the analysis. Known risk factors examined were: prolonged treatment (continuous infusion) with neuromuscular blocking agents, treatment with aminoglycoside antibiotics, glucocorticoids, norepinephrine, hemofiltration or hemodialysis, maximal SOFA score, mean daily caloric intake, parenteral nutrition and bacteremia. 75

6 Reference List (E1) Pandit L, Agrawal A. Neuromuscular disorders in critical illness. Clin Neurol Neurosurg 2006; 108(7): (E2) Bercker S, Weber-Carstens S, Deja M, Grimm C, Wolf S, Behse F, Busch T, Falke KJ, Kaisers U. Critical illness polyneuropathy and myopathy in patients with acute respiratory distress syndrome. Crit Care Med 2005; 33(4): (E3) Souba WW. Nutritional support. N Engl J Med 1997; 336(1): (E4) Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994; 22(3): (E5) Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27(7): (E6) MacIntyre NR, Cook DJ, Ely EW, Jr., Epstein SK, Fink JB, Heffner JE, Hess D, Hubmayer RD, Scheinhorn DJ. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest 2001; 120(6 Suppl):375S-395S. 76

Spontaneous Breathing Trial and Mechanical Ventilation Weaning Process

Spontaneous Breathing Trial and Mechanical Ventilation Weaning Process Page 1 of 5 ASSESSMENT INTERVENTION Patient receiving mechanical ventilation Baseline ventilatory mode/ settings RT and RN to assess criteria 1 for SBT Does patient meet criteria? RT to initiate SBT Does