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Published in: Intensive Care Medicine 3/2013

01-03-2013 | Original

Automated sedation outperforms manual administration of propofol and remifentanil in critically ill patients with deep sedation: a randomized phase II trial

Authors: Morgan Le Guen, Ngai Liu, Eric Bourgeois, Thierry Chazot, Daniel I. Sessler, Jean-Jacques Rouby, Marc Fischler

Published in: Intensive Care Medicine | Issue 3/2013

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Abstract

Purpose

To compare automated administration of propofol and remifentanil guided by the Bispectral index (BIS) versus manual administration of short-acting drugs in critical care patients requiring deep sedation. The primary outcome was the percentage of BIS values between 40 and 60 (BIS40–60).

Methods

This randomized controlled phase II trial in the intensive care unit (ICU) was conducted in adults with multiorgan failure. Thirty-one patients were assigned to receive sedation with propofol or remifentanil either by an automated or a manual system, both targeting BIS40–60. Performance and feasibility of an automated administration were assessed.

Results

The study groups were well balanced in terms of demographic characteristics. Study duration averaged 18 [8–24] h in the automated group and 14 [9–21] h in the manual group (p = 0.81). Adequate sedation (BIS40–60) was significantly more frequent in the automated group 77 [59–82] % than in the manual group 36 [22–56] %, with p = 0.001. Propofol consumption was reduced by a factor of 2 in the automated group with a median change of infusion rates of 39 ± 9 times per hour. In contrast, there were only 2 ± 1 propofol and 1 ± 1 remifentanil dose changes per hour in the manual group compared to 40 ± 9 for remifentanil in the automated group (p < 0.001). Vasopressors were more often discontinued or reduced in the automated group than in the manual control group (36 [6–40] vs. 12 [4–20] modifications, p = 0.03).

Conclusions

Continuous titration of propofol and remifentanil sedation with an automatic controller maintains deep sedation better than manual control in severely ill patients. It is associated with reduced sedative and vasopressor use.
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Literature
1.
go back to reference Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 30:119–141PubMedCrossRef Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 30:119–141PubMedCrossRef
2.
go back to reference Soliman HM, Melot C, Vincent JL (2001) Sedative and analgesic practice in the intensive care unit: the results of a European survey. Br J Anaesth 87:186–192PubMedCrossRef Soliman HM, Melot C, Vincent JL (2001) Sedative and analgesic practice in the intensive care unit: the results of a European survey. Br J Anaesth 87:186–192PubMedCrossRef
3.
go back to reference Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G (1998) The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest 114:541–548PubMedCrossRef Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G (1998) The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest 114:541–548PubMedCrossRef
4.
go back to reference Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL (2007) Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology 106:687–695 (quiz 891–682)PubMedCrossRef Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL (2007) Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology 106:687–695 (quiz 891–682)PubMedCrossRef
5.
go back to reference Society of Critical Care Medicine and American Society of Health-System Pharmacists (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Am J Health Syst Pharm 59:150–178 Society of Critical Care Medicine and American Society of Health-System Pharmacists (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Am J Health Syst Pharm 59:150–178
6.
go back to reference Kress JP, Pohlman AS, O’Connor MF, Hall JB (2000) Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 342:1471–1477PubMedCrossRef Kress JP, Pohlman AS, O’Connor MF, Hall JB (2000) Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 342:1471–1477PubMedCrossRef
7.
go back to reference Strom T, Martinussen T, Toft P (2010) A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 375:475–480PubMedCrossRef Strom T, Martinussen T, Toft P (2010) A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 375:475–480PubMedCrossRef
8.
go back to reference Rinehart J, Liu N, Alexander B, Cannesson M (2012) Review article: closed-loop systems in anesthesia: is there a potential for closed-loop fluid management and hemodynamic optimization? Anesth Analg 114:130–143PubMedCrossRef Rinehart J, Liu N, Alexander B, Cannesson M (2012) Review article: closed-loop systems in anesthesia: is there a potential for closed-loop fluid management and hemodynamic optimization? Anesth Analg 114:130–143PubMedCrossRef
9.
go back to reference Agarwal J, Puri GD, Mathew PJ (2009) Comparison of closed loop vs. manual administration of propofol using the Bispectral index in cardiac surgery. Acta Anaesthesiol Scand 53:390–397PubMedCrossRef Agarwal J, Puri GD, Mathew PJ (2009) Comparison of closed loop vs. manual administration of propofol using the Bispectral index in cardiac surgery. Acta Anaesthesiol Scand 53:390–397PubMedCrossRef
10.
go back to reference Liu N, Chazot T, Trillat B, Michel-Cherqui M, Marandon JY, Law-Koune JD, Rives B, Fischler M (2008) Closed-loop control of consciousness during lung transplantation: an observational study. J Cardiothorac Vasc Anesth 22:611–615PubMedCrossRef Liu N, Chazot T, Trillat B, Michel-Cherqui M, Marandon JY, Law-Koune JD, Rives B, Fischler M (2008) Closed-loop control of consciousness during lung transplantation: an observational study. J Cardiothorac Vasc Anesth 22:611–615PubMedCrossRef
11.
go back to reference Liu N, Chazot T, Hamada S, Landais A, Boichut N, Dussaussoy C, Trillat B, Beydon L, Samain E, Sessler DI, Fischler M (2011) Closed-loop coadministration of propofol and remifentanil guided by bispectral index: a randomized multicenter study. Anesth Analg 112:546–557PubMedCrossRef Liu N, Chazot T, Hamada S, Landais A, Boichut N, Dussaussoy C, Trillat B, Beydon L, Samain E, Sessler DI, Fischler M (2011) Closed-loop coadministration of propofol and remifentanil guided by bispectral index: a randomized multicenter study. Anesth Analg 112:546–557PubMedCrossRef
13.
go back to reference Cantraine FR, Coussaert EJ (2000) The first object oriented monitor for intravenous anesthesia. J Clin Monit Comput 16:3–10PubMedCrossRef Cantraine FR, Coussaert EJ (2000) The first object oriented monitor for intravenous anesthesia. J Clin Monit Comput 16:3–10PubMedCrossRef
14.
go back to reference Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, Youngs EJ (1998) The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology 88:1170–1182PubMedCrossRef Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, Youngs EJ (1998) The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology 88:1170–1182PubMedCrossRef
15.
go back to reference Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL (1997) Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 86:10–23PubMedCrossRef Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL (1997) Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 86:10–23PubMedCrossRef
16.
go back to reference Payen JF, Bru O, Bosson JL, Lagrasta A, Novel E, Deschaux I, Lavagne P, Jacquot C (2001) Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 29:2258–2263PubMedCrossRef Payen JF, Bru O, Bosson JL, Lagrasta A, Novel E, Deschaux I, Lavagne P, Jacquot C (2001) Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 29:2258–2263PubMedCrossRef
17.
go back to reference Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRef Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRef
18.
go back to reference Le Gall JR, Neumann A, Hemery F, Bleriot JP, Fulgencio JP, Garrigues B, Gouzes C, Lepage E, Moine P, Villers D (2005) Mortality prediction using SAPS II: an update for French intensive care units. Crit Care 9:R645–R652PubMedCrossRef Le Gall JR, Neumann A, Hemery F, Bleriot JP, Fulgencio JP, Garrigues B, Gouzes C, Lepage E, Moine P, Villers D (2005) Mortality prediction using SAPS II: an update for French intensive care units. Crit Care 9:R645–R652PubMedCrossRef
19.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710PubMedCrossRef Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710PubMedCrossRef
20.
21.
go back to reference Besch G, Liu N, Samain E, Pericard C, Boichut N, Mercier M, Chazot T, Pili-Floury S (2011) Occurrence of and risk factors for electroencephalogram burst suppression during propofol-remifentanil anaesthesia. Br J Anaesth 107:749–756PubMedCrossRef Besch G, Liu N, Samain E, Pericard C, Boichut N, Mercier M, Chazot T, Pili-Floury S (2011) Occurrence of and risk factors for electroencephalogram burst suppression during propofol-remifentanil anaesthesia. Br J Anaesth 107:749–756PubMedCrossRef
22.
go back to reference Liu N, Chazot T, Trillat B, Pirracchio R, Law-Koune JD, Barvais L, Fischler M (2006) Feasibility of closed-loop titration of propofol guided by the Bispectral Index for general anaesthesia induction: a prospective randomized study. Eur J Anaesthesiol 23:465–469PubMedCrossRef Liu N, Chazot T, Trillat B, Pirracchio R, Law-Koune JD, Barvais L, Fischler M (2006) Feasibility of closed-loop titration of propofol guided by the Bispectral Index for general anaesthesia induction: a prospective randomized study. Eur J Anaesthesiol 23:465–469PubMedCrossRef
23.
go back to reference Ramsay MA, Savege TM, Simpson BR, Goodwin R (1974) Controlled sedation with alphaxalone-alphadolone. Br Med J 2:656–659PubMedCrossRef Ramsay MA, Savege TM, Simpson BR, Goodwin R (1974) Controlled sedation with alphaxalone-alphadolone. Br Med J 2:656–659PubMedCrossRef
24.
25.
go back to reference Johansen JW (2006) Update on bispectral index monitoring. Best Pract Res Clin Anaesthesiol 20:81–99PubMedCrossRef Johansen JW (2006) Update on bispectral index monitoring. Best Pract Res Clin Anaesthesiol 20:81–99PubMedCrossRef
26.
go back to reference Karamchandani K, Rewari V, Trikha A, Batra RK (2010) Bispectral index correlates well with Richmond agitation sedation scale in mechanically ventilated critically ill patients. J Anesth 24:394–398PubMedCrossRef Karamchandani K, Rewari V, Trikha A, Batra RK (2010) Bispectral index correlates well with Richmond agitation sedation scale in mechanically ventilated critically ill patients. J Anesth 24:394–398PubMedCrossRef
27.
go back to reference Trouiller P, Fangio P, Paugam-Burtz C, Appere-de-Vecchi C, Merckx P, Louvet N, Pease S, Outin H, Mantz J, De Jonghe B (2009) Frequency and clinical impact of preserved bispectral index activity during deep sedation in mechanically ventilated ICU patients. Intensive Care Med 35:2096–2104PubMedCrossRef Trouiller P, Fangio P, Paugam-Burtz C, Appere-de-Vecchi C, Merckx P, Louvet N, Pease S, Outin H, Mantz J, De Jonghe B (2009) Frequency and clinical impact of preserved bispectral index activity during deep sedation in mechanically ventilated ICU patients. Intensive Care Med 35:2096–2104PubMedCrossRef
28.
go back to reference Olson DM, Thoyre SM, Peterson ED, Graffagnino C (2009) A randomized evaluation of bispectral index-augmented sedation assessment in neurological patients. Neurocrit Care 11:20–27PubMedCrossRef Olson DM, Thoyre SM, Peterson ED, Graffagnino C (2009) A randomized evaluation of bispectral index-augmented sedation assessment in neurological patients. Neurocrit Care 11:20–27PubMedCrossRef
29.
go back to reference Frenzel D, Greim CA, Sommer C, Bauerle K, Roewer N (2002) Is the bispectral index appropriate for monitoring the sedation level of mechanically ventilated surgical ICU patients? Intensive Care Med 28:178–183PubMedCrossRef Frenzel D, Greim CA, Sommer C, Bauerle K, Roewer N (2002) Is the bispectral index appropriate for monitoring the sedation level of mechanically ventilated surgical ICU patients? Intensive Care Med 28:178–183PubMedCrossRef
30.
go back to reference Tonner PH, Weiler N, Paris A, Scholz J (2003) Sedation and analgesia in the intensive care unit. Curr Opin Anaesthesiol 16:113–121PubMedCrossRef Tonner PH, Weiler N, Paris A, Scholz J (2003) Sedation and analgesia in the intensive care unit. Curr Opin Anaesthesiol 16:113–121PubMedCrossRef
31.
go back to reference Consales G, Chelazzi C, Rinaldi S, De Gaudio AR (2006) Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units. Minerva Anestesiol 72:329–336PubMed Consales G, Chelazzi C, Rinaldi S, De Gaudio AR (2006) Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units. Minerva Anestesiol 72:329–336PubMed
32.
go back to reference Guignard B, Menigaux C, Dupont X, Fletcher D, Chauvin M (2000) The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation. Anesth Analg 90:161–167PubMedCrossRef Guignard B, Menigaux C, Dupont X, Fletcher D, Chauvin M (2000) The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation. Anesth Analg 90:161–167PubMedCrossRef
33.
go back to reference Liu N, Chazot T, Huybrechts I, Law-Koune JD, Barvais L, Fischler M (2005) The influence of a muscle relaxant bolus on bispectral and datex-ohmeda entropy values during propofol-remifentanil induced loss of consciousness. Anesth Analg 101:1713–1718PubMedCrossRef Liu N, Chazot T, Huybrechts I, Law-Koune JD, Barvais L, Fischler M (2005) The influence of a muscle relaxant bolus on bispectral and datex-ohmeda entropy values during propofol-remifentanil induced loss of consciousness. Anesth Analg 101:1713–1718PubMedCrossRef
34.
go back to reference Sackey PV (2008) Frontal EEG for intensive care unit sedation: treating numbers or patients? Crit Care 12:186PubMedCrossRef Sackey PV (2008) Frontal EEG for intensive care unit sedation: treating numbers or patients? Crit Care 12:186PubMedCrossRef
35.
go back to reference Nasraway SS Jr, Wu EC, Kelleher RM, Yasuda CM, Donnelly AM (2002) How reliable is the Bispectral Index in critically ill patients? A prospective, comparative, single-blinded observer study. Crit Care Med 30:1483–1487CrossRef Nasraway SS Jr, Wu EC, Kelleher RM, Yasuda CM, Donnelly AM (2002) How reliable is the Bispectral Index in critically ill patients? A prospective, comparative, single-blinded observer study. Crit Care Med 30:1483–1487CrossRef
36.
go back to reference Solanki A, Puri GD, Mathew PJ (2010) Bispectral index-controlled postoperative sedation in cardiac surgery patients: a comparative trial between closed loop and manual administration of propofol. Eur J Anaesthesiol 27:708–713PubMed Solanki A, Puri GD, Mathew PJ (2010) Bispectral index-controlled postoperative sedation in cardiac surgery patients: a comparative trial between closed loop and manual administration of propofol. Eur J Anaesthesiol 27:708–713PubMed
37.
go back to reference Strom T, Toft P (2011) Time to wake up the patients in the ICU: a crazy idea or common sense? Minerva Anestesiol 77:59–63PubMed Strom T, Toft P (2011) Time to wake up the patients in the ICU: a crazy idea or common sense? Minerva Anestesiol 77:59–63PubMed
38.
go back to reference Vasile B, Rasulo F, Candiani A, Latronico N (2003) The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med 29:1417–1425PubMedCrossRef Vasile B, Rasulo F, Candiani A, Latronico N (2003) The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med 29:1417–1425PubMedCrossRef
39.
go back to reference Seder DB, Fraser GL, Robbins T, Libby L, Riker RR (2010) The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 36:281–288PubMedCrossRef Seder DB, Fraser GL, Robbins T, Libby L, Riker RR (2010) The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 36:281–288PubMedCrossRef
40.
go back to reference Menache CC, Bourgeois BF, Volpe JJ (2002) Prognostic value of neonatal discontinuous EEG. Pediatr Neurol 27:93–101PubMedCrossRef Menache CC, Bourgeois BF, Volpe JJ (2002) Prognostic value of neonatal discontinuous EEG. Pediatr Neurol 27:93–101PubMedCrossRef
41.
go back to reference Watson PL, Shintani AK, Tyson R, Pandharipande PP, Pun BT, Ely EW (2008) Presence of electroencephalogram burst suppression in sedated, critically ill patients is associated with increased mortality. Crit Care Med 36:3171–3177PubMedCrossRef Watson PL, Shintani AK, Tyson R, Pandharipande PP, Pun BT, Ely EW (2008) Presence of electroencephalogram burst suppression in sedated, critically ill patients is associated with increased mortality. Crit Care Med 36:3171–3177PubMedCrossRef
42.
go back to reference Monk TG, Weldon BC (2010) Anesthetic depth is a predictor of mortality: it’s time to take the next step. Anesthesiology 112:1070–1072PubMedCrossRef Monk TG, Weldon BC (2010) Anesthetic depth is a predictor of mortality: it’s time to take the next step. Anesthesiology 112:1070–1072PubMedCrossRef
Metadata
Title
Automated sedation outperforms manual administration of propofol and remifentanil in critically ill patients with deep sedation: a randomized phase II trial
Authors
Morgan Le Guen
Ngai Liu
Eric Bourgeois
Thierry Chazot
Daniel I. Sessler
Jean-Jacques Rouby
Marc Fischler
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 3/2013
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-012-2762-2

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