Affiliations: From the Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago.

Financial/nonfinancial disclosures: The author has reported

to CHEST that no potential conflicts of interest exist with any
companies/organizations whose products or services may be discussed in this article.
Correspondence to: John P. Kress, MD, Department of Medicine,
Section of Pulmonary and Critical Care, University of Chicago,
5841 S Maryland Ave, MC 6026, Chicago, IL 60637; e-mail:
jkress@medicine.bsd.uchicago.edu
2012 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.12-1995

References
1. Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D,
Sherman G. The use of continuous IV sedation is associated
with prolongation of mechanical ventilation. Chest. 1998;
114(2):541-548.
2. Finfer SR, OConnor AM, Fisher MM. A prospective randomised
pilot study of sedation regimens in a general ICU population:
a reality-based medicine study. Crit Care. 1999;3(3):79-83.
3. Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of
intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med.
2006;34(5):1326-1332.
4. Jacobi J, Fraser GL, Coursin DB, et al; Task Force of the
American College of Critical Care Medicine (ACCM) of the
Society of Critical Care Medicine (SCCM), American Society
of Health-System Pharmacists (ASHP), American College of
Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.
Crit Care Med. 2002;30(1):119-141.
5. Mehta S, Burry L, Martinez-Motta JC, et al; 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;36(7):2092-2099.
6. Mehta SBL, Cook DJ, Steinberg M, et al. Sleep: a multicenter
randomized trial of daily awakening in critically ill patients
being managed with a sedation protocol. Am J Respir Crit Care
Med. 2012;185:A3882.
7. Kress JP, Vinayak AG, Levitt J, et al. Daily sedative interruption in mechanically ventilated patients at risk for coronary
artery disease. Crit Care Med. 2007;35(2):365-371.
8. Kress JP, Pohlman AS, OConnor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing
mechanical ventilation. N Engl J Med. 2000;342(20):1471-1477.
9. Girard TD, Kress JP, Fuchs BD, et al. 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;371(9607):126-134.
10. de Wit M, Gennings C, Jenvey WI, Epstein SK. Randomized
trial comparing daily interruption of sedation and nursingimplemented sedation algorithm in medical intensive care
unit patients. Crit Care. 2008;12(3):R70.
11. 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;32(6):1272-1276.
12. Morris PE, Goad A, Thompson C, et al. Early intensive care
unit mobility therapy in the treatment of acute respiratory
failure. Crit Care Med. 2008;36(8):2238-2243.
13. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated,
critically ill patients: a randomised controlled trial. Lancet.
2009;373(9678):1874-1882.

14. 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;168(12):1457-1461.
15. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an
independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006;104(1):21-26.
16. Coursin D. Sedation and Delirium in the ICU: What Do the
New Guidelines Say? Houston, TX: Society of Critical Care
Medicine; 2012.

Counterpoint: Should All ICU

Patients Receive Continuous
Sedation? No
drug administration is considered part of
Sedative
the standard care of critically ill patients. Nowhere

is this more evident than in the treatment of those

requiring mechanical ventilation. The overarching
concerns addressed by sedation include mitigating
patient discomfort and facilitating ventilation, along
with other parts of routine ICU care. Emphasizing
the importance of these goals, a retrospective analysis
of the 174 ICUs contributing data to Project IMPACT
(Cerner Corp) showed that the use of IV infusions of
sedative agents nearly doubled over the years 2001
to 2007, even when accounting for severity of illness.1
Oversedation has been implicated in a multitude of
morbidities, including increased complications, delirium, prolonged mechanical ventilation, and increases
in ICU and hospital length of stay. In fact, editorial
comments to contemporary investigations on sedative
practice frequently include pleas to harken back to
observations made by Dr Thomas Petty. This visionary
of current critical care practice was concerned that
what he was seeing now were sedated patients, lying
without motion, appearing dead in a state of suspended life.2
Dr Petty made this poignant statement in response
to an observational study that showed that continuous
sedative practices were associated with prolonged
mechanical ventilation.3 Subsequently, successive trials
have continued to support the notion that limiting
the sedative experience is beneficial. Brook et al4
showed that a protocolized approach to continuous
sedative practice curtailed drug totals and the duration of mechanical ventilation.
The next leap forward came from Dr Kress et al,5
who showed in a single-center experience that incorporating a daily interruption into sedation and analgesia was achievable in a majority of patients undergoing
mechanical ventilation and led to improvements in
length of ICU stay and reduced ventilator time.
This effect was seen regardless of whether the sedative agent used was propofol or the benzodiazepine,
midazolam. This practice of sedative interruption has

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been subsequently shown to produce no increase in

either myocardial ischemia6 or long-term neuropsychiatric outcomes,7 two postulated impediments that
could arise from the increased awareness and sedative curtailment.
To further support these findings, a larger study
including multiple ICUs showed that the coupling
of this sedative holiday with a planned spontaneous
breathing trial led to more days off the ventilator than
did a management protocol of sedative holiday that
left spontaneous breathing attempts to the discretion
of the care team. In fact, those that were randomized
to have both daily awakenings from sedation and routine breathing trials were more likely to be alive over
the following year than were those in the control arm.8
Growing evidence seemed to suggest that the more
aggressive the caregivers were with allowing the critically ill patient to be naive of suspension interventions, the more likely they were to recover and survive.
Several deliberate studies as well as several unintended opportunities focused on reductions in sedative
infusion use have also suggested no decline in clinical outcomes. Roberts et al9 took a before-and-after
look at the impact of the national propofol shortage
on the ventilator outcomes in their institutions surgical ICUs. The proportion of ventilator time spent
with continuous infusion of sedative decreased from
94% to 59%. More dexmedetomidine, midazolam,
and lorazepam were used, and when adjusted for
case mix, there were no differences in mechanical
ventilation outcomes. Furthermore, Salgado et al10
shared an observational, feasibility study that targeted minimal sedation goals over a 2-month period
in a medical-surgical ICU. They reported that they
were able to reduce continuous sedatives to only
20% of the patient time requiring mechanical ventilation without any significant safety concerns.
As the natural extension of this timeline, Strm et al11
performed a prospective study that randomized patients
to no sedation. The control arm received propofol
initially and underwent daily sedative interruption
to a goal of being awake and able to follow commands. After 48 h of sedative infusion, the control arm
was switched to midazolam with ongoing sedative
interruption. The no sedation group spent fewer days
requiring mechanical ventilation, the ICU, or the
hospital. Fewer than one out of five patients in the
no sedation group required a period of continuous sedation. This was mainly because management of hypoxemic respiratory failure was possible.
Strm et als11 study emphasized many nonsedative
management strategies, including the use of analgesia and haloperidol and early mobilization.
The conventional wisdom that all, or even most, critically ill patients require continuous sedation clearly
appears to be debunked. The successful management

of critically ill patients who are mechanically ventilated involves a more multifaceted approach. Beyond
attention to sedation, the following factors have clearly
been shown to influence ICU outcomes: the use of
analgesia, delirium, and increased activity.
In the no sedation study, Strm et al11 initially
treated patients in the intervention arm with analgesia in the form of opiate drug boluses. Although there
was no statistically significant difference in total morphine dosages between groups, this intervention may
have led to better acceptance of artificial ventilation.
To avoid the cumulative effect of morphine attributable to impaired renal metabolism, newer agents
such as fentanyl and remifentanil are more commonly
used currently.
Equally important to adequate analgesia is attention
to minimizing delirium, defined as an acute-in-onset
change in mental status with possible fluctuations over
time. Several tools are commonly used to measure
its frequency, including the Confusion Assessment
Method for the ICU12 and the Intensive Care Delirium
Screening Checklist.13 Confusion Assessment Method
for the ICU-positive delirium remains common and
is associated with an array of poor clinical outcomes.
Determining interventions that reduce delirium
remains a challenge. Nonpharmacologic management
includes reorientation strategies, mobilization, and
minimization of sedative totals. The choice of sedative agents also seems to influence delirium incidence, with the benzodiazepines (lorazepam and
midazolam) appearing to cause more delirium than
the opiates.14 Newer sedatives, such as propofol or
dexmedetomidine, may have lower delirium effects.15
Although much hope is placed on the role of antipsychotics in the treatment of delirium, little confirmatory evidence exists. A smaller pilot study suggests
that the combined effect of the atypical antipsychotic,
quetiapine, and the typical antipsychotic, haloperidol, may reduce delirium features and even improve
outcomes.16 Further confirmation of the benefits of
pharmacologic therapies and their characterization is
required.
One intervention shown to decrease delirium incidence is early physiotherapy. It has been postulated
that critical illness may aggravate the weakness and
neuromuscular dysfunction caused by concomitant sedative administration. A protocol of awakening patients
and having them participate in physical therapy earlier
in their ICU stay (within 72 h of undergoing mechanical ventilation) led to more ventilator-free days, less
delirium, and greater functional status.17 Early mobilization offers a sedative-limiting option leading to
reductions in ventilator requirements.
Many instances suggest that the critically ill patient
may not be harmed, and may even benefit, as a consequence of minimizing or even avoiding continuous

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CHEST / 142 / 5 / NOVEMBER 2012

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References

Figure 1. Evidence that decreasing suspended life improves outcomes in critically ill patients who are mechanically ventilated.

sedative infusions. Recent studies have confirmed

that incrementally decreasing the intensity of lifesuspending sedation and practices is also associated
with improved ICU outcomes (Fig 1). A recently
offered evidence-guided mnemonic, ABCDE, can
assist physicians in the key aspects of what has been
termed the animated intensive care unit: Awakening,
Breathing, Choice of Sedation and analgesia, Delirium
monitoring, and Early mobilization.18
Prophetically, Dr Petty had been telling us all along
that when it comes to sedative agent choice, a correct option may be little to no sedative drug at all.
This approach may apply to more patients than we
imagine. Yet, as mentioned at the outset, sedative
infusion use seems to be on the increase. Reversing
this trend may require further investigation and the
use of multidisciplinary, nursing-implemented protocols that have been effective in improving outcomes.
Future clinical trials or individual ICU benchmarking
strategies should involve national or local multidisciplinary experts, respectively, to determine which
protocolized approaches best optimize all parts of
the animated strategy. They would likely use sedation scales, delirium monitoring and therapy, and
mobilization strategies, with the ultimate goal of
more aggressively identifying those who do not require
continuous sedative drug administration.
Ajeet G. Vinayak, MD
Washington, DC
Affiliations: From Georgetown University Hospital.
Financial/nonfinancial disclosures: The author has reported
to CHEST that no potential conflicts of interest exist with any
companies/organizations whose products or services may be discussed in this article.
Correspondence to: Ajeet G. Vinayak, MD, Georgetown University Hospital, 4th Floor Main Bldg, 3800 Reservoir Rd NW,
Washington, DC 20007; e-mail: vinayak@gunet.georgetown.edu
2012 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.12-1997

1. Wunsch H, Kahn JM, Kramer AA, Rubenfeld GD. Use of

intravenous infusion sedation among mechanically ventilated
patients in the United States. Crit Care Med. 2009;37(12):
3031-3039.
2. Petty TL. Suspended life or extending death? Chest. 1998;
114(2):360-361.
3. 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;
114(2):541-548.
4. Brook AD, Ahrens TS, Schaiff R, et al. Effect of a nursingimplemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;27(12):2609-2615.
5. Kress JP, Pohlman AS, OConnor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):
1471-1477.
6. Kress JP, Vinayak AG, Levitt J, et al. Daily sedative interruption in mechanically ventilated patients at risk for coronary
artery disease. Crit Care Med. 2007;35(2):365-371.
7. 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;168(12):1457-1461.
8. Girard TD, Kress JP, Fuchs BD, et al. 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;371(9607):126-134.
9. Roberts R, Ruthazer R, Chi A, et al. Impact of a national
propofol shortage on duration of mechanical ventilation at an
academic medical center. Crit Care Med. 2012;40(2):406-411.
10. Salgado DR, Favory R, Goulart M, Brimioulle S, Vincent JL.
Toward less sedation in the intensive care unit: a prospective
observational study. J Crit Care. 2011;26(2):113-121.
11. Strm T, Martinussen T, Toft P. A protocol of no sedation for
critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-480.
12. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion
assessment method for the intensive care unit (CAM-ICU).
JAMA. 2001;286(21):2703-2710.
13. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y.
Intensive Care Delirium Screening Checklist: evaluation of a
new screening tool. Intensive Care Med. 2001;27(5):859-864.
14. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation
with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653.
15. Riker RR, Shehabi Y, Bokesch PM, et al; SEDCOM (Safety and
Efficacy of Dexmedetomidine Compared With Midazolam)
Study Group. Dexmedetomidine vs midazolam for sedation
of critically ill patients: a randomized trial. JAMA. 2009;
301(5):489-499.
16. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of
quetiapine in critically ill patients with delirium: a prospective,
multicenter, randomized, double-blind, placebo-controlled
pilot study. Crit Care Med. 2010;38(2):419-427.
17. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early
physical and occupational therapy in mechanically ventilated,
critically ill patients: a randomised controlled trial. Lancet.
2009;373(9678):1874-1882.
18. Morandi A, Brummel NE, Ely EW. Sedation, delirium and
mechanical ventilation: the ABCDE approach. Curr Opin
Crit Care. 2011;17(1):43-49.

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