Although it is a perennial topic of discussion among ICU and respiratory therapy professionals, the sedation of mechanically ventilated patients has received increased attention in recent months. With the publication of new research on sedation protocols and new guidelines on managing pain in the ICU, shortages of key sedative drugs, and the expectation that Precedex (dexmedetomidine) will soon go off patent, there are perhaps more questions about sedation practices now than ever.
To help answer some of these questions, RT Magazine has assembled the following panel of experts:
- Michael J. Cawley, PharmD, RRT, CPFT, Professor of Clinical Pharmacy, Philadelphia College of Pharmacy, University of the Sciences;
- Joseph F. Dasta, MS, RPh, Professor Emeritus, The Ohio State University College of Pharmacy, Adjunct Professor, The University of Texas at Austin;
- John W. Devlin, PharmD, FCCM, FCCP, Associate Professor, Department of Pharmacy Practice, Northeastern University, Special and Scientific Staff, Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Adjunct Associate Professor, Tufts University School of Medicine, Boston; and
- Carrie Winberg, BS, RRT, Respiratory Care Manager, Intermountain-LDS Hospital/AV Hospital, Salt Lake City.
|Michael J. Cawley,
PharmD, RRT, CPFT
|Joseph F. Dasta,
|John W. Devlin,
PharmD, FCCM, FCCP
RT: In a recent JAMA article, Mehta et al concluded that for “mechanically ventilated adults managed with protocolized sedation, the addition of daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay.”1 In light of this finding, should the practice be abandoned? In general, what sedation protocol do you recommend?
John W. Devlin: Patient unarousability in the ICU due to the excessive administration of sedation is common, and a serious concern given that it will hinder liberation from mechanical ventilation, increase delirium, and raise mortality. A strategy to down-titrate sedative therapy is therefore an important part of ICU care. The barriers associated with daily sedation interruption are numerous, particularly among nurses, and often lead to a poor uptake of this strategy at many centers.
Mehta et al evaluated whether an hourly sedation protocol in patients requiring continuous benzodiazepine therapy would maintain wakefulness (an important driver to extubation) as well as the addition of daily sedative interruption to this hourly protocol. They found that the addition of daily interruption to a patient (who was already at the desired light sedative goal due to the hourly titration) did not provide added benefit.
It is interesting that nurses managing patients across this multicenter study preferred the hourly protocol alone than with the use of daily sedative interruption. This study suggests that daily sedation interruption may not be required if a tight, around-the-clock sedation protocol is adhered to in practice. However, if it is not, daily sedative interruption remains an important additional strategy to maintain wakefulness in daily practice and should not be abandoned.
Michael J. Cawley: The study by Mehta et al makes a pretty convincing case that in comparison with protocolized sedation alone, protocolized sedation plus daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay. The study was much more real-world in design than previous trials. Many physicians I have worked with were not convinced by the previous trials supporting the use of sedation interruption, due to tight controls of study criteria. I believe this study has proven to a degree that a more real-world assessment was needed. I would not want to see the practice of sedation interruption abandoned as of yet for patients on shorter-acting agents, such as propofol or dexmedetomidine. I would imagine that trials in the near future will look at this issue.
The problem I have periodically observed with daily interruption of sedation is the negative progress made on weaning a patient from mechanical ventilation. Once the sedation is interrupted, patients become acutely agitated, resulting in ventilator dysynchrony, increased work of breathing, and pulmonary decompensation. This has resulted in a vicious cycle of more aggressive use of sedatives, thus delaying successful weaning and extubation.
There is not one gold-standard sedation protocol that is more successful than another. The best protocol is one that is endorsed by all members of the critical care team, uses a measurable sedation assessment scoring system (eg, the Sedation-Agitation Scale), and includes quality-assessment metrics to measure ventilator outcomes.
RT: How are ongoing shortages of sedatives affecting the practice of sedation of ventilated patients?
Joseph F. Dasta: It often happens during shortages of sedatives and analgesics that clinicians make use of drugs they aren’t adequately familiar with. As a result, medication errors can occur. One common source of confusion, for instance, is dosing hydromorphone during a morphine shortage. It is a 1:7 ratio, not 1:1 dosing. All health care providers need to be vigilant.
Carrie Winberg: In our institution, we focus on early ambulation for all patients, including those who are receiving vasopressors or who require significant ventilatory support. For example, a patient whose blood pressure is adequate with vasopressor support is considered safe for an ambulation trial. We routinely walk patients who are receiving greater than .60 FiO2 and high PEEP or pressure support settings. Per our protocol, the respiratory therapist must be present for ambulation of patients who are intubated, who are receiving noninvasive ventilatory support, or who are using a high-flow nasal cannula. As a result of our practice of minimal sedation, the drug shortage has not created a hardship at our facility.
Devlin: When considering the IV propofol shortage, I think it is important to consider the recommendations from the 2013 Society of Critical Care Medicine pain, agitation, and delirium [PAD] guidelines2 and other recent evidence:
- Analgesic therapy should be considered first to maintain comfort in most intubated patients;
- Intermittent sedative doses often suffice for many patients, and thus a continuously infused sedative may never be needed;
- The goal for most patients is light sedation, therefore dexmedetomidine may be a better choice than propofol in these patients;
- For patients requiring deep sedation, continuous benzodiazepine therapy, with daily interruption, will deliver a sedative regimen similar to that of propofol; and
- A large before-after propofol shortage logistic regression analysis completed at one Boston academic center3 found that reduced propofol use did not result in an increased duration of mechanical ventilation.
RT: In your experience, is the higher cost of Precedex (dexmedetomidine) versus propofol and midazolam balanced by the decrease in duration of mechanical ventilation and length of ICU stay? Do you expect this calculation to change as Precedex goes off patent later this year?
Dasta: In 2010, I published a study in Critical Care Medicine4 on the cost minimization of dexmedetomidine versus midazolam from the SEDCOM trial.5 We showed that despite the $1,100 acquisition cost of dexmedetomidine versus $70 for midazolam, using dexmedetomidine resulted in a total ICU cost savings of nearly $10,000. These savings were driven by shorter time on the ventilator and reduced length of stay in the ICU. A cost analysis comparing dexmedetomidine with propofol has not been conducted.
Clearly, the acquisition cost of dexmedetomidine will fall when the drug goes off patent, perhaps not until mid-2014. All else being equal, the savings in total ICU cost using generic dexmedetomidine would be greater, depending on its price. The cost-effectiveness of sedatives is briefly discussed in the recently published PAD guidelines, as is the use of dexmedetomidine in patients predisposed to delirium in the ICU.
Cawley: Once the acquisition cost of dexmedetomidine drops after the drug goes off patent, the price gap between it and propofol and midazolam will narrow significantly. Data have demonstrated that although the cost of dexmedetomidine was significantly higher than that of midazolam, the high cost of the drug was negated by its effects on significantly lowering overall ICU expenditures.4 Unfortunately, many directors of departments work in “silos” and are mostly concerned with defending department budgets. For that reason, pharmacy directors may tend to focus only on lowering drug costs instead of considering more expensive agents that will decrease overall ICU expenditures. To make rational decisions on the use of sedatives in the ICU, these data should be discussed and evaluated not only by clinicians, but also by pharmacy directors and members of pharmacy and therapeutics committees.
RT: What are the most reliable methods for assessing a patient’s level of consciousness? How are these best used to expedite weaning?
Winberg: We routinely assess our patients using the following assessment tools: the Confusion Assessment Method for the ICU (CAM-ICU), Glasgow Coma Score (GCS), and the Richmond Agitation Sedation Score (RASS). As a result of our practice of minimal sedation, we have patients who are more alert and cooperative. This allows them to actively participate in their recovery with the ultimate goal of liberation from the ventilator.
Dasta: The PAD guidelines recommend using validated sedation scales like the Sedation-Agitation Scale (SAS) and RASS to determine the level of sedation. Talking with the patient is important as well. Using “objective” tools like the bispectral index (BIS) is also discussed in PAD. They are not recommended in the routine patient, particularly since PAD recommends titrating to a light level of sedation. However, there may be a role for BIS in more complex patients who are heavily sedated and those requiring neuromuscular blocking agents. This is a small patient population in most ICUs.
RT: What is the incidence of drug-induced delirium? Can you estimate its impact on the weaning process?
Dasta: Drugs like benzodiazepines and opioids predispose patients to develop delirium; however, the precise incidence is not known. It is well established that patients with delirium from any cause are more difficult to wean from the ventilator. This is why PAD recommends several ways to minimize exposure to deliriogenic drugs such as benzodiazepines and to use techniques like early mobilization.
Devlin: There are many factors (including medications) that are potentially associated with delirium (ie, that are present in a patient who develops delirium) in the ICU, but because there are far fewer factors (including many medications) that have been shown to be independent causes for delirium, a specific incidence is hard to provide. All of this said, the medication list of ICU patients who develop delirium should be carefully reviewed, and medications that could potentiate delirium should be discontinued whenever possible. RT
- Mehta S, Burry L, Cook D, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308:1985–1992.
- Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:278–280.
- 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;40:406–11.
- Dasta JF, Kane-Gill SL, Pencina M, et al. A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med. 2010;38:497–503.
- Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489–99.