El taller, instrumento en la enseñanza de la arquitectura

T Sharshar, JP Lefaucheur, S Bastuji-Garin, B De Jonghe, for the Groupe de Réflexion et d’Etude des Neuromyopathies En Réanimation (GRENER)

Réanimation Médicale, Hôpital Raymond Poincaré, 104 bd Raymond Poincaré, 92380 Garches, France

Objectives: Although the incidence of electrophysiological and muscle histological abnormalities in ICU patients has been largely described, the clinical incidence of ICU acquired paraly- sis (ICUAP) remains poorly explored. The objective of this study was to assess clinical incidence, risk factors and outcome of ICUAP.

Method: All consecutive patients without pre-existent neuromus- cular disease were daily screened for awakeness in the 5 partici- pating ICUs after 7 days of mechanical ventilation (MV). The first day patient was considered awake (based on a specific awake- ness scale) was Day 1. Patients with a neuromuscular score (NMS) < 48 (on a scale ranging from 0, totally paralyzed to 60, normal muscle strength) on Day 7 were considered as having ICUAP. These patients underwent an electrophysiologic (EP) examination within the next 72 hours. Patients with persistent paralysis (NMS < 48) on Day 14 underwent a muscle biopsy. Potential risk factors (including demographic, metabolic, drug- related and organ failure-related variables) were recorded between ICU admission and Day 1. Odd ratios (OR) with 95% CI were separately computed for each potential risk factor. Then, sig- nificant factors were simultaneously included in a multivariate logistic regression model (BMDP software).

Results: Among the 95 patients who satisfactorily woke up, the incidence rate of ICUAP was 25.3% (95% CI 16.9–35.2). EP examination showed a sensory-motor axonopathy in all cases. A specific muscle involvement, not exclusively related to the nerve involvement, was observed in all the patients who underwent a muscle biopsy. The median duration of ICUAP was 21 days. ICUAP patients had a significantly longer duration of MV after Day 1 (18.2 ± 36.3 vs 7.6 ± 19.2 days, P= 0.03) and longer ICU length of stay after Day 1 (27.6 ± 31.4 vs 14.6 ± 19.6 days, P= 0.02), compared to patients without ICUAP. Two patients remained paralyzed after 6 months. In multivariate logistic regression, the number of days with organ failure ≥2 (OR 1.28 [1.11–1.49]), duration of MV (OR 1.10 [1.00–1.22]), administration of corticosteroids (OR 14.90 [3.20–69.8]) prior to day 1, and female sex (OR 4.66 [1.19–18.3]) were independent predictors of ICUAP.

Conclusion: Clinically detected ICUAP was a frequent finding among patients mechanically ventilated ≥7 days and was associ- ated with a prolonged duration of MV and ICU length of stay. Both the peripheral nerve and the muscle were involved in the paralysis. Some risk factors might be accessible to preventive measures. Supported by GlaxoWellcome.

P190 The clinical course of acute quadruplegia of the critically ill

J Manv_{ák*, M Nováková†, Z Lukᚇ, M Schreiber§, P Kunc§, H Matulová§, E Havel*, L Sobotka*, Z Zadák*}

*Department of Metabolic Care, †_{Department of Rehabilitation, and} § _{Department of Neurology, University Hospital, Charles University,}

Hradec Králové, Czech Republic; ‡_{Department of Pathology II, Childrens Hospital, Brno, Czech Republic} Aim of the study: To describe the clinical course of acute quadru-

plegia of intensive care.

Setting: Ten bed medical ICU in university hospital Hradec Králové.

Patients: Twelve consecutive patients with acute quadruplegia that occured during critical illness.

Study period: Fifteen months.

Design: Prospective observational study.

Methods: For precise diagnosis of the neuromuscular disorder, clini- cal, biochemical, electrophysiological examinations and skeletal muscle biopsies were performed. During the whole stay in the hospi- tal, skeletal muscle strength was clinically examined and quantified

S89 by a standard six grade scale (no movement: 0, palpable contraction:

1, movement with help: 2, spontaneous movement against gravity: 3, reduced muscle strength: 4, full stength: 5). Length of stay in the ICU and in the hospital, the duration of mechanical ventilation and need of tracheostomy were recorded. None of the patients recieved any neuromuscular blocking agents or corticosteroids.

Results: Out of the 12 patients, 4 had to be excluded due to con- commitant focal cerebral laesion impairing motor functions. Two patients had to be referred to another hospital and thus were lost for the study. In the remaining six patients, a combination of axonal sensory-motor polyneuropathy in electrophysiology and myopathy in histological specimen was found. The mortality in these patients was 50% (3 of 6). The complete muscle strength examination was performed in three survivors. The clinical course of these patients is summarized in the Table.

Conclusions: Neuromuscular failure during critical illness is a serious medical and economical problem. All the surviving patients with acute quadruplegia of intensive care recieved mechanical ven- tilation for more than 3 months, requiring a very long stay in the ICU and a prolonged rehabilitation. On discharge, peroneal paresis was present in all survivors. In our ICU, more than one bed is per- manently occupied by patients with severe neuromuscular failure. These neuromuscular disorders developed in patients who were

not treated with neuromuscular blocking agents or corticosteroids. Supported by grant IGA No. NB 5197-3. Table

Patient Patient Patient

No 1 No 2 No 3

Primary diagnosis Aortic valve Aortic valve Mediastinitis replacement replacement empyema

Maximum daily SOFA 18 13 18

Mechanical ventilation (days) 112 114 98

Tracheostomy (days) 126 204 120

Muscle strength 3° on day 160 56 58

First ambulation with help 174 196 136

on day

ICU stay (days) 150 236 114

Length of stay in hospital 198 254 154

(days)

On discharge, peroneal paresis was present in all the patients.

P191 Clinical assessment of level of sedation in the intensive care unit: a correlation study

JE Colomé-Ruiz, D Rubio-Payán, JC Lescas-Vásquez, L Natera-Ramírez, E Rivero-Sigarroa, M Méndez-Beltrán, JC Robledo-Pascual, J Pedroza-Granados, G Domínguez-Cherit

División de Medicina Crítica, Instituto Nacional de Ciencias Médicas y Nutrición ‘Salvador Zubirán’, México, DF Mexico

Background: Sedation and analgesia are common techniques widely used in the intensive care unit. Since complications such as prolonged sedative effects and associated long-term mechani- cal ventilation use are common, a careful assessment of level of sedation is warranted to avoid such complications. Nowadays, noninvasive devices like Bispectral Analysis (BIS) recorders are commercially available and are actually considered gold standard tests in level of sedation assessment; however, clinical scales (Ramsay’s and the Observer’s assessment of Alertness/Sedation [OAA/S] scales) are cheaper and more widely performed in criti- cally ill patients. In the present study we compared clinical assess- ment scales with BIS recordings.

Methods: Prospectively we analyzed nine mechanically ventilated patients under deep sedation. We excluded patients with muscle relaxants, metabolic encephalopathy or primary central nervous disease. All patients were simultaneously evaluated with a BIS device, and with clinical assessment scales (Ramsay and OAA/S). At least 9 periodic measurements in 24 hours were performed in each patient, recording neuronal activity level and the signal quality index (SQI) with the BIS device, excluding all measurements with a

SQI more or equal to 50%. Data comparisons among BIS record- ings and each clinical scale were analyzed with Pearson’s and Spearman’s correlation, and determination coefficients, consider- ing significant a 0.75 and a 0.11 value for each category (accord- ing to Colton), with a significance level set on 0.05.

Results: Eighty-five measurements were analyzed. Correlation and determination coefficients are shown in the following Table.

Correlation coefficients

Clinical Determination

scale Pearson’s Spearman’s coefficient P

Ramsay –0.319 –0.340 0.115 0.001

OAA/S –0.153 –0.137 0.018 0.2

Conclusions: According to our statistical results, no clinical scale is strongly correlated to Bispectral Analysis in our sedated patients. Bispectral analysis is advised over clinical assessment to evaluate level of sedation in intensive care unit patients.

P192 Bispectal Index (BIS) correlates with Ramsay and Cook Sedation Scores in intensive care unit patients A Melissaki, T Kyriakopoulou, E Kupcova, A Efthymiou, G Kribeni, M Sartzi, Ch Kardamis

ICU, Agios Savvas General Hospital, 171 Alexandras Ave, GR-11522 Athens, Greece

Introduction: It is well known that the administration of sedation and analgesia constitute an inseparable section of the therapeutic approach of patients of the ICU. The follow-up and evaluation of the level of sedation has been considered indispensable, both for obtaining the desirable clinical objectives and, also, to avoid clini-

cal complications. In an effort of creating a stable and objective system of evaluation of the level of sedation, we used various methods, the known scales and, recently the Bispectral Index (BIS) which constitutes a variable modification, a variant of the EEG. The

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aim of this study was to investigate the probable correlation between BIS and the Ramsay and Cook scales.

Material and methods: Twenty-six patients (18 males and 8 females) of a mean age of 55.46 ± 21.25, APACHE II Score 13.50 ± 5.21, who were hospitalized from August 4 to October 31, 2000 and were subjected to respiratory mechanical support were investi- gated. Patients who had damage of the neurological system or those who had received muscle relaxants were excluded from the study. All the patients, during evaluation and measurements were under stable sedation and analgesia (Fentanyl, Propofol or Myda- zolam) under continuous intravenous infusion. The evaluation of the level of sedation was carried out during the same time period by means of two different scales: The Ramsay (0–6), Cook’s (4–19) and BIS (0–100). The BIS registration lasted 60 min and the final value was calculated from the average of the total recorded 10 min values. The measurements were taken under consideration if the SQI (Signal Quality Index) was higher than 80%. The statistical analysis was carried out by the Jonckheere–Terpstra test.

Results: The results are depicted analytically in Table 1. Between BIS and the Ramsay Scale, a correlation or a degree statistically significant (P= 0.012) were observed. The Cook Scale was not statistically significant (P= 0.091).

Conclusions: BIS is satisfactory correlated with the Ramsay scale and its indications correspond to the clinical condition of the patient, where the sedation level is concerned, as opposed to the Cook scale for which no significant correlation was established. The BIS values in the ICU and the corroboration of our results require further study.

Table 1

BIS vs Ramsay P= 0.012

BIS vs Cook P= 0.091

P193 Assessment of sedation level and EEG recovery after major operation by spectral entropy H Yppärilä*, S Westeren-Punnonen*, T Musialowicz†_{, M Särkelä}‡_{, J Karhu*, J Partanen*, H Viertiö-Oja}‡

*Department of Clinical Neurophysiology, and †_{Department of Anesthesiology and Intensive Care, Kuopio University Hospital, PO Box}

1777, 70211 Kuopio, Finland; ‡_{Datex-Ohmeda Division, Instrumentarium Corp, PO Box 900, FIN-00031 Datex-Ohmeda, Finland} Entropy quantifies the amount of disorder in a system and charac-

terizes chaotic behaviour. The complexity of a signal can be char- acterized by spectral entropy, which gives the amount of disorder in frequency space [1]. If an EEG signal includes a wide spectrum of frequencies, its spectral entropy has a high value (near one), and in case of few relevant frequencies spectral entropy is low (near zero). Spectral entropy has been shown to be an effective tool in measuring depth of anaesthesia [2].

In this study, we investigated whether spectral entropy can distin- guish between the different sedation levels corresponding to the Ramsay Scores 2, 4, and 6. In order to study spectral entropy during different sedation levels, EEG was recorded from 26 patients scheduled for an elective cardiopulmonary bypass opera- tion with propofol/alfentanil/isoflurane/pancuronium anaesthesia [3]. Postoperative sedation was maintained with propofol to keep the sedation level at Ramsay Score 6 (not responding to any com- mands) until the patients were hemodynamically stable. EEG was recorded 5 times for each patient: 1 day before the operation (Ramsay Score 2), after premedication 1 hour before the operation (Ramsay Score 2 or 3), immediately after the operation (Ramsay Score 6), after the patient had opened his eyes for the first time (Ramsay Score 4), and the following morning (Ramsay Score 2 or 3). The EEG signal was recorded bipolarly between electrodes Fz–M1, Cz–M2, C3–P3 and C4–P4. It was amplified and digitized continuously at 100 Hz using the Datex-Ohmeda EEG module and stored to a PC for off-line analysis. Spectral entropy values were evaluated for 5 s epochs in two frequency bands: 0.5–32 Hz and 7–32 Hz. Epochs including artefacts were removed from the data before the calculation.

Spectral entropy for the range 0.5–32 Hz differentiated statistically significantly whether the patient was awake (Score 2) or asleep (Scores 4–6) (P< 0.05). Spectral entropy for 7–32 Hz was able

to differentiate the sedation levels 4 and 6 (P< 0.001). Sedation levels 2, 4, and 6 could thus be distinguished by using spectral entropy. For comparison, we analyzed whether spectral edge fre- quency or auditory evoked potentials can distinguish between these levels. These methods failed in separating levels 6 and 4. There was considerable variation in spectral entropy values between the patients having the same Ramsay Score. This may be due to the physiological variation of different EEG-patterns between individuals.

We divided the patients into two groups according to how the EEG, measured the following morning after the operation, was recovered compared to the EEG 1 day before the operation. In both recordings the patients were awake. The spectral entropy values 1 day after the operation were significantly lower in the group in which the EEG was not at all recovered compared to the group in which the EEG was almost recovered.

Our results indicate that spectral entropy can be a useful tool for assessment of the sedation level of a patient. The performance of spectral entropy in distinguishing Ramsay Score levels 2, 4, and 6 was superior in comparison to spectral edge frequency and audi- tory evoked potentials. However, in patients with postoperative EEG significantly slower compared to preoperative EEG, spectral entropy remained at a low level and was not able to indicate whether the patient had waken up. A relation between postopera- tive EEG slowing and mild subclinical cerebral injuries has been discussed by Vanninen et al[4]. Our results suggest that spectral entropy might provide diagnostic information of such a state. References:

1. Rezek IA et al: IEEE Trans Biomed Eng1998, 45:1186. 2. Viertiö-Oja H et al: Anesthesiology2000, 93:A1369.

3. Jakob S et al: Comp Methods Programs Biomed2000, 63:161. 4. Vanninen R et al: Arch Neurol1998, 55:618.

S91 P194 One center’s experience with the phase IIIb randomized multi center study comparing the safety and efficacy of

dexmedetomidine to propofol for ICU sedation following coronary artery bypass graft surgery SK Appavu, TR Haley, A Khorasani, SR Patel, V Bhargava

Division of Surgical Critical Care, Cook County Hospital, Chicago, IL, USA

The criteria for an ideal ICU sedative agent includes rapid onset of sedation, a short half life, easy arousability, anxiolysis, and absence of respiratory depression or hemodynamic side effects. Dexmedeto- midine, an alpha 2 adrenergic receptor agonist has been demon- strated to induce sedation with easy arousability and have no respiratory depression or hemodynamic compromise. We partici- pated in a Multi center open label study to compare the safety and efficacy of dexmedetomidine (Dex) to propofol (Prop) based stan- dard of care for ICU sedation following coronary artery bypass graft (CABG) surgery. The study was formally approved by our institu- tional review board. Adults with coronary artery disease, scheduled to undergo CABG surgery and signed the informed consent were randomized to receive either Dex or Prop. At the end of the opera- tive procedure, at the time of the last sternal suture, patients in the Dex group received a 20 min infusion of Dex at a rate of 3

µg/kg/hour. followed by a continuous infusion at 0.4 µg/kg/hour. The patients in the Prop group received a Prop infusion at 10

µg/kg/min. The patients were then transferred to the SICU, where the medication dose was titrated to maintain a Ramsay sedation score of 2–3 for 24 hours. Data collection included vital signs, level of consciousness, hemodynamic parameters, hematologic and bio- chemical surveys, Ramsay sedation score, and the nurse’s assess- ment of the following: patient’s anxiety level, quality of sedation, the

patient’s ability to tolerate the ICU environment, the ability to toler- ate weaning and extubation, ease of communication with the patient and ease of patient management.

Results: Twenty patients were enrolled. Eighteen were studied and two were excluded because their scheduled surgery was can- celled. Ten patients received Dex; eight males and 2 females. Their mean age was 55.2 years. Eight patients received Prop; seven males and one female. Their mean age was 61.25 years. No signifi- cant hematologic or biochemical abnormality was noted in any of the patients. All the Dex patients received the highest scores for ease of sedation, ability to tolerate the ICU environment, ability to tolerate ventilator weaning and extubation, ease of communication and ease of patient management. Among patients receiving propo- fol, 75% received the highest scores for quality of sedation and ability to tolerate ICU environment. Fifty percent received the highest scores for ability to tolerate ventilator weaning and extuba- tion and 62% received the highest scores for ease of communica- tion and ease of patient management.

Conclusion: Dexmedetomidine is a safe agent for ICU sedation. It is superior to propofol for sedation among patients undergoing CABG surgery.

P195 A comparison between dexmedetomidine and propofol for sedation in the intensive care unit RM Venn, RM Grounds

St George’s Hospital Intensive Care Unit, Blackshaw Road, London SW17 0QT, UK

Introduction: This study compares the highly selective alpha-2 agonist, dexmedetomidine, with propofol for the sedation of post- operative patients requiring mechanical ventilation in the ICU. Methods: Twenty adult patients expected to require at least 8 h arti- ficial ventilation following major abdominal/pelvic surgery, were ran- domised to receive sedation with either dexmedetomidine or propofol. Additional analgesia was provided by alfentanil infusions if clinically indicated. Patients received a loading dose of dexmedeto- midine 2.5µg/kg/h over 10 min followed by a maintenance infusion of 0.2–2.5µg/kg/h. Propofol and alfentanil were infused according to the manufacturers’ recommendations. Patients were maintained at a Ramsay Sedation Score > 2 by adjustments to the sedative regimen. Heart rate, arterial and central venous pressures were monitored continuously and recorded at 10 min intervals for the first 30 min and then hourly. Venous samples were taken for haemato- logical and biochemical profiles immediately on arrival in the ICU, and then at 24 h and 48 h. Extubation was performed when clini- cally indicated and time from cessation of sedation infusion to extu- bation was recorded. Patients completed a questionnaire [1], 48–72 h following discharge from the ICU.

Results: There were no differences in patient and ICU characteris- tics between the two groups.

Heart rates were significantly lower (P= 0.034) in the dexmedeto- midine group. There were no differences in arterial pressure, central venous pressure and haematological/biochemical profiles between the groups.

Conclusion: Dexmedetomidine appears to be safe and acceptable to both clinician and patient in the ICU. Depth of sedation is com- parable to propofol and extubation time equally rapid. Furthermore dexmedetomidine provides analgesia and attenuation of the cardio- vascular responses to stress, with the potential to minimise ischaemic events.

Supported by Abbott UK. Reference:

1. Hewitt PB: BMJ1970, 4:669–673.

Dexmedetomidine (n= 10) Propofol (n= 10) Pvalue

Sedation, median (IQR) Ramsay score 5 (4–6) 5 (4–5) 0.68

Bispectral Index 46 (36–58) 53 (41–64) 0.32

Analgesia (Alfentanil), median (IQR) (mg/h) 0.8 (0.7–1.2) 2.5 (2.2–2.9) 0.004

Extubation time mean (SD) (min) 27.5 (12) 25 (10) 0.63

Patient experiences Amnesia for ICU 8 3

Amnesia for IPPV 3 2

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Introduction: To date the pharmacokinetics of the sedative agent, dexmedetomidine, has only been reported in volunteers [1,2]. This study investigated the pharmacokinetic profile of dexmedetomidine infusions in human patients requiring postoperative sedation and ventilation in the ICU.

Methods: Ten adult patients who were expected to require a