Daily sedative interruption versus intermittent sedation in mechanically ventilated critically ill patients: a randomized trial

Antonio Paulo Nassar Junior, Marcelo Park, Antonio Paulo Nassar Junior, Marcelo Park

Abstract

Background: Daily sedative interruption and intermittent sedation are effective in abbreviating the time on mechanical ventilation. Whether one is superior to the other has not yet been determined. Our aim was to compare daily interruption and intermittent sedation during the mechanical ventilation period in a low nurse staffing ICU.

Methods: Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge.

Results: A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160). There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165), hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus 40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not different between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P < 0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P < 0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay.

Conclusions: There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses.

Trial registration: ClinicalTrials.gov Identifier: NCT00824239.

Keywords: Conscious sedation; Critical care and outcome assessment; Mechanical ventilation; Sedation.

Figures

Figure 1
Figure 1
Assessment and randomization.
Figure 2
Figure 2
Kaplan-Meier plot of length of mechanical ventilation.
Figure 3
Figure 3
Drug dosages of both groups up to the fifth day after mechanical ventilation initiation. Panel (A) shows the median dosage of fentanyl of all 60 patients (P < 0.001 for time interaction and P = 0.015 for group interaction); panel (B) shows the median dosage of midazolam of all 60 patients (P = 0.025 for time interaction and P = 0.002 for group interaction); panel (C) shows the median dosage of propofol of all 60 patients (P = 0.124 for time interaction and P = 0.549 for group interaction); panel (D) shows the median dosage of fentanyl of patients who used fentanyl in at least one day during the first five days after ICU admission (P = 0.729 for time interaction and P = 0.021 for group interaction); panel (E) shows the median dosage of midazolam of patients who used midazolam in at least one day during the first five days after ICU admission (P = 0.299 for time interaction and P = 0.169 for group interaction); and panel (F) shows the median dosage of propofol of patients who used propofol in at least one day during the first five days after ICU admission (P = 0.907 for time interaction and P = 0.641 for group interaction).
Figure 4
Figure 4
Physiologic variables of both groups up to the fifth day after mechanical ventilation initiation. Panels (A) (mixed model fixed effects P = 0.412 for time interaction and P = 0.202 for group interaction) and (D) (mixed model fixed effects P = 0.047 for time interaction and P = 0.608 for group interaction) show the maximal and minimal heart rate; panels (B) (mixed model fixed effects P < 0.001 for time interaction and P = 0.566 for group interaction) and (E) (mixed model fixed effects P < 0.001 for time interaction and P = 0.524 for group interaction) show the mean arterial blood pressure; and panels (C) (mixed model fixed effects P = 0.462 for time interaction and P = 0.801 for group interaction) and (F) (mixed model fixed effects P = 0.991 for time interaction and P = 0.259 for group interaction) show the respiratory rate.
Figure 5
Figure 5
Respiratory variables of both groups up to the fifth day after mechanical ventilation initiation. Panel (A) shows the peak pressure of all patients (P = 0.002 for time interaction and P = 0.549 for group interaction); panel (B) shows the driving pressure of all patients (P = 0.456 for time interaction and P = 0.549 for group interaction); panel (C) shows the median dosage of propofol of all patients (P = 0.001 for time interaction and P = 0.929 for group interaction); panel (D) shows the driving pressure of all patients (P = 0.549 for time interaction and P = 0.001 for group interaction); panel (E) shows the PaO2/FiO2 (P/F) ratio of the patients (P = 0.002 for time interaction and P = 0.793 for group interaction); and panel (F) shows the PaCO2 of all patients (P = 0.151 for time interaction and P = 0.334 for group interaction). *P < 0.05 versus intermittent sedation group, Mann-Whitney post hoc test. #P < 0.05 versus first day of the same group, Mann-Whitney post hoc test.

References

    1. Salluh JI, Dal-Pizzol F, Mello PV, Friedman G, Silva E, Teles JM, Lobo SM, Bozza FA, Soares M. Delirium recognition and sedation practices in critically ill patients: a survey on the attitudes of 1015 Brazilian critical care physicians. J Crit Care. 2009;4:556–562. doi: 10.1016/j.jcrc.2009.04.004.
    1. Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998;4:541–548. doi: 10.1378/chest.114.2.541.
    1. Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L. Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;4:724–731. doi: 10.1164/rccm.201203-0522OC.
    1. Ouimet S, Riker R, Bergeron N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med. 2007;4:1007–1013. doi: 10.1007/s00134-007-0618-y.
    1. Kress JP, Gehlbach B, Lacy M, Pliskin N, Pohlman AS, Hall JB. The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med. 2003;4:1457–1461. doi: 10.1164/rccm.200303-455OC.
    1. Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;4:1471–1477. doi: 10.1056/NEJM200005183422002.
    1. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;4:126–134. doi: 10.1016/S0140-6736(08)60105-1.
    1. Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;4:2609–2615. doi: 10.1097/00003246-199912000-00001.
    1. Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;4:475–480. doi: 10.1016/S0140-6736(09)62072-9.
    1. Rothen HU, Stricker K, Einfalt J, Bauer P, Metnitz PG, Moreno RP, Takala J. Variability in outcome and resource use in intensive care units. Intensive Care Med. 2007;4:1329–1336. doi: 10.1007/s00134-007-0690-3.
    1. McGahan M, Kucharski G, Coyer F. Nurse staffing levels and the incidence of mortality and morbidity in the adult intensive care unit: a literature review. Aust Crit Care. 2012;4:64–77. doi: 10.1016/j.aucc.2012.03.003.
    1. Nassar Junior AP, Pires Neto RC, de Figueiredo WB, Park M. Validity, reliability and applicability of Portuguese versions of sedation-agitation scales among critically ill patients. Sao Paulo Med J. 2008;4:215–219. doi: 10.1590/S1516-31802008000400003.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;4:818–829. doi: 10.1097/00003246-198510000-00009.
    1. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU) JAMA. 2001;4:2703–2710. doi: 10.1001/jama.286.21.2703.
    1. Queijo AF, Padilha KG. Nursing Activities Score (NAS): adaptação transcultural e validação para a língua portuguesa. Rev Esc Enferm USP. 2009;4:1018–1025. doi: 10.1590/S0080-62342009000500004.
    1. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. 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. 1996;4:707–710. doi: 10.1007/BF01709751.
    1. Horowitz M, Wilner N, Alvarez W. Impact of event scale: a measure of subjective stress. Psychosom Med. 1979;4:209–218. doi: 10.1097/00006842-197905000-00004.
    1. Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, Heidegger CP, Weiss NS. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009;4:2527–2534. doi: 10.1097/CCM.0b013e3181a5689f.
    1. Bucknall TK, Manias E, Presneill JJ. A randomized trial of protocol-directed sedation management for mechanical ventilation in an Australian intensive care unit. Crit Care Med. 2008;4:1444–1450. doi: 10.1097/CCM.0b013e318168f82d.
    1. Schweickert WD, Gehlbach BK, Pohlman AS, Hall JB, Kress JP. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med. 2004;4:1272–1276. doi: 10.1097/01.CCM.0000127263.54807.79.
    1. Jackson JC, Girard TD, Gordon SM, Thompson JL, Shintani AK, Thomason JW, Pun BT, Canonico AE, Dunn JG, Bernard GR, Dittus RS, Ely EW. Long-term cognitive and psychological outcomes in the awakening and breathing controlled trial. Am J Respir Crit Care Med. 2010;4:183–191. doi: 10.1164/rccm.200903-0442OC.
    1. Jackson DL, Proudfoot CW, Cann KF, Walsh T. A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety. Crit Care. 2010;4:R59. doi: 10.1186/cc8956.
    1. de Wit M, Gennings C, Jenvey WI, Epstein SK. Randomized trial comparing daily interruption of sedation and nursing-implemented sedation algorithm in medical intensive care unit patients. Crit Care. 2008;4:R70. doi: 10.1186/cc6908.
    1. Mehta S, Burry L, Martinez-Motta JC, Stewart TE, Hallett D, McDonald E, Clarke F, Macdonald R, Granton J, Matte A, Wong C, Suri A, Cook DJ. Canadian Critical Care Trials Group. A randomized trial of daily awakening in critically ill patients managed with a sedation protocol: a pilot trial. Crit Care Med. 2008;4:2092–2099. doi: 10.1097/CCM.0b013e31817bff85.
    1. Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, Herridge M, Ferguson N, Devlin J, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Skrobik Y, Hébert P, Sabri E, Meade M. SLEAP Investigators; Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;4:1985–1992. doi: 10.1001/jama.2012.13872.
    1. Anifantaki S, Prinianakis G, Vitsaksaki E, Katsouli V, Mari S, Symianakis A, Tassouli G, Tsaka E, Georgopoulos D. Daily interruption of sedative infusions in an adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs. 2009;4:1054–1060. doi: 10.1111/j.1365-2648.2009.04967.x.
    1. Shehabi Y, Chan L, Kadiman S, Alias A, Ismail WN, Tan MA, Khoo TM, Ali SB, Saman MA, Shaltut A, Tan CC, Yong CY, Bailey M, Bailey M. Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med. 2013;4:910–918. doi: 10.1007/s00134-013-2830-2.
    1. Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;4:1151–1160. doi: 10.1001/jama.2012.304.
    1. Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Murray L, Seppelt IM, Webb S, Weisbrodt L. Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study*. Crit Care Med. 2013;4:1983–1991. doi: 10.1097/CCM.0b013e31828a437d.
    1. Kress JP, Vinayak AG, Levitt J, Schweickert WD, Gehlbach BK, Zimmerman F, Pohlman AS, Hall JB. Daily sedative interruption in mechanically ventilated patients at risk for coronary artery disease. Crit Care Med. 2007;4:365–371. doi: 10.1097/01.CCM.0000254334.46406.B3.
    1. Marini JJ. Spontaneously regulated vs. controlled ventilation of acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care. 2011;4:24–29. doi: 10.1097/MCC.0b013e328342726e.
    1. Stroem T, Stylsvig M, Toft P. Long term psychological effects of a no sedation protocol in critically ill patients. Crit Care. 2011;4:R293. doi: 10.1186/cc10586.
    1. Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R. American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;4:278–280. doi: 10.1097/CCM.0b013e3182783b72.
    1. Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;4:489–499. doi: 10.1001/jama.2009.56.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe