Sedation Algorithm in Critically Ill Patients without Acute Brain Injury Critical Care Medicine 2005; 33 (1): 120-127.

1. Sedation Algorithm in Critically Ill Patients without Acute Brain InjuryCritical Care Medicine 2005; 33 (1): 120-127. Bernard De Jonghe, MD; Sylvie Bastuji-Garin, MD, PhD; Pascal Fangio, MD; Jean-Claude Lacherade, MD; Julien Jabot, MD; Corinne Appere-De-Vecchi, MD; Nathalie Rocha, RN; Herve Outin, MD. Medical Intensive Care Unit, Poissy Hospital, Poisse France (BDJ, PF, JCL, JJ, CADV, NR, HO) and the Public Health Department, University of Paris XII, Henri Mondor Hospital (AP-HP), Creteil, France (SBG)

2. Purpose of the Study 1. Assess the impact of a sedation algorithm, designed to promote high level consciousness, on the duration of mechanical ventilation. 2. Examine the relationship between the time to arousal after initiation of mechanical ventilation and the duration of mechanical ventilation.

3. Methods Study Population Inclusion Criteria Patients  16 years. Requiring mechanical ventilation for  24 hours. Exclusion criteria Acute brain injury (acute stroke, head trauma, acute encephalitis, cardiac arrest). Transfer from another ICU. Chronic mechanical ventilation. Tracheostomy. Peripheral nervous system. Moribund State.

4. Time of arousal after initiation of mechanical ventilation measure by eye opening, monitored every morning. First day patients were able to open eyes either spontaneously or on verbal request for at least 2 consecutive days. Care givers blinded to result. Mechanical ventilator weaning criteria: no longer had high grade fever, did not require catecholamines (except low dose dopamine or dobutamine), FIO2<50%, PEEP  5 cm H2O, and consciousness not severely altered.

5. Methods Control Group Sedatives and analgesics were adjusted according to the decision of experiences MD or RN. Algorithm Group Sedatives and analgesics were adjusted by MD or RN according to an algorithm designed to achieve tolerance to the ICU environment and maintain high level of consciousness. Medication Midazolam and Fentanyl

6. Adaptation To Intensive Care Environment (ATICE)-based Sedation and Analgesia Algorithm. ATICE is measured every 3 hrs, except at night in patients with satisfactory consciousness at the end of the day. ATICE is measured more frequently in patients with worsening tolerance. The algorithm is not applied while patients are receiving neuromuscular blockers, in the prone positioning, or after an end-of-life decision has been made. IV, intravenous; VAS, visual analog scale; , increase drug dosage; , decrease drug dosage, *stricter objectives of tolerance (calmness=3, ventilator synchrony=4) may be transiently used in patients with severe acute respiratory of circulatory failure; †, during the initial 48-hr postoperative period, do not decrease fentanyl dose under 50-100 g/hr.

7. Methods Data Collection Age, Gender, SAPS II score w/in 24 hours of admission. Day and time of start and end of mechanical ventilation. Acute diagnosis, presence of LV failure, sepsis, acute renal failure, COPD. Total daily dose fentanyl and midazolam and use of other opioids or sedation medications. Tracheostomy, self-extubation, pressure sores, surgery, VAP.

8. Methods Statistical analysis Primary endpoint: Duration of mechanical ventilation. Secondary endpoints: Time to arousal after initiation of mechanical ventilation, ICU LOS, total medication doses, occurrence of side effects associated with over/under sedation.

9. Methods Statistical analysis Kaplan-Meier for duration of mechanical ventilation, time to arousal, ICU LOS. Log-rank test to compare algorithm and control patients and to analyze the influence of a priori selected co-variates on mechanical ventilation duration and time to arousal. If p<0.2, multivariate Cox proportional-hazards model to in influencing independent variable. Chi-square and Fisher’s Exact Test for categorical variables. Mann-Whitney test for quantitative variables.

10. Results Baseline characteristics 102 patients enrolled in the study 54 control group 48 algorithm group No differences in baseline characteristics: Patient demographics Admission diagnosis Survival Conditions for extubation, except: Highest FIO2in last 24 hours was higher in control group (38 ± 6%) vs., algorithm group (36 ± 7%) p=0.05.

11. Results Figure 2. Kaplan-Meier representation of duration of mechanical ventilation in algorithm and control patients. Mechanical ventilation was significantly shorter in the algorithm group (4.4 days [2.1-9.8]) than in the control group (10.3 days [3.5-17.2], p=0.014).

12. Results In multivariate analysis, independent predictors of duration of mechanical ventilation included: 1. Use of the algorithm 2. Presence of underlying COPD 3. Sepsis 4. Renal failure

13. Results 0.48 (0.29-0.78) lower relative risk of remaining of mechanical ventilation Algorithm Control ICU LOS (d) 8.0 (4.0-18.1) vs. 15.0 (6.4-24.0) p=0.043 Median time to arousal(d) 2 (2-5) vs. 4 (2-9) p=0.006 Pressure sores 9 (18.6%) vs. 20 (37.0%) p=0.04 VAP 4 (8.3%) vs. 11 (20.4%) p=0.10

14. Figure 3. Duration of mechanical ventilation (median, 25th and 75th percentiles) according to time to arousal after initiation of mechanical ventilation. Time to arousal was significantly associated with duration of mechanical ventilation (p<0.001).

15. Results Control Algorithm p Value Daily dosage of M (mg) per day of MV, mean ± SD 79.1±52.7 55.7±45.7 0.007 Cumulative dosage of M (mg), mean ± SD 627±808 295±507 0.015 Duration in days of M administration, median (IQR) 4 (2-9) 3 (2-6) 0.12 Daily dosage of F (g) per day MV, mean ± SD 2189 ± 1744 2233 ± 1201 0.29 Cumulative dosage of F (g), mean ± SD 19834 ± 31315 13135 ± 21429 0.57 Duration in days of F administration, median (IQR) 4 (1-10) 3 (1-7) 0.18 MV, mechanical ventilation; IQR, interquartile range; M, midazolam; F, fentanyl.

16. Conclusion • “The use of a sedation algorithm designed to promote preserved consciousness led to a marked decrease in the duration of mechanical ventilation in patients without brain injury.”