RT spoke with respiratory clinicians about proven practices for monitoring ventilated patients on sedatives.
While necessary in many cases, the use of sedatives for patients undergoing mechanical ventilation can increase mortality risk via respiratory distress and other adverse events. In addition to the right technology, RTs and clinicians who are monitoring sedated patients need to have proper practices in place to ensure patient safety. To discuss the topic, RT spoke with two respiratory clinicians:
- John Devlin, PharmD, BCCCP, FCCM, FCCP; professor, Department of Pharmacy and Health Systems Sciences, Northeastern University; Special and Scientific Staff, Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center;
- Kenneth Miller, MEd, RRT-ACCS, RRT-NPS, AE-C; clinical educator, Dept Dean of Wellness, Respiratory Care Services, Lehigh Valley Health Network.
Miller and Dr Devlin offered their insights on the topic, including suggestions for developing sedation protocols.
- DSI: Daily Sedation Interruption
- PS: Protocolized Sedation
- SAT: Spontaneous Awakening Trial
- SBT: Spontaneous Breathing Trial
- RASS: Richmond Agitation and Sedation Scale
- VAS: Visual Analogue Scale
- CPOT: Critical-
Care Pain Observation Tool
- BIS: Bispectral index monitoring
- PAD: Pain, Agitation & Delirium (PAD) Guidelines
- GCS: Glasgow Coma Scale
- RCT: Randomized controlled trial
- p-r-n: Abbreviation meaning “when necessary” (from the Latin pro re nata)
RT: In general, what are the three most important considerations for creating a sedation protocol?
John Devlin: The key considerations when creating an ICU sedation protocol include:
- A light level of sedation (ie RASS = -1) should be the primary sedation target for most patients;
- Pain should be regularly assessed (verbal patient = 10cm VAS; nonverbal patient CPOT) and treated before sedative therapy is considered;
- If a patient does in fact require a continuous IV sedative (and addressing number 1 and 2 will preclude the need for IV sedative therapy in many patients), the first choice IV sedative should be propofol or dexmedetomidine; benzodiazepines should be relegated to patients with agitation related to acute alcohol withdrawal or in the rare patient who requires deep sedation (eg concomitant paralytic use);
- A method for sedative de-escalation should is important (protocolized assessment (at least every 4 hours, SAT or both);
- A formal evaluation at least once daily by the ICU team for the continued need of continuous sedation.
Kenneth Miller: The three most important elements of a sedation protocol are the following:
- Development of an interdisciplinary team to develop clinical end-points and to achieve clinician buy in. This team should include providers, RNs, Pharmacists, and RRTs.
- Development an algorithm approach to the protocol including special sedation interruption time frames, clinical end-points, and determination of which sedative drugs or going be administrated and if administered by bolus or infusion.
- Empower the bedside RRT and RN to enact the protocol when specific criteria is met and assign specific designated pharmacist to the ICU team to act as an educational resource and medication expert.
We currently recommend using a sedation protocol that encompasses an awake and breathe sedation holiday along with a spontaneous breathing trial assessment. This type of protocol places the responsibility of ventilator liberation on the bedside RRT and RN to facilitate and achieve.
RT: In recent years, ongoing shortages of sedatives (such as propofol) commonly used for the sedation of ventilated patients have been resolved. however, how did these shortages affect patient care and what has the industry done to ensure future shortages do not occur?
Devlin: Unfortunately, given that all IV sedatives (including dexmedetomidine, propofol, lorazepam and midazolam) are all now generic, without tighter manufacturer regulation by the FDA, intermittent injectable drug shortages, like those that have occurred with propofol and many other IV medications commonly used in the ICU, will likely persist. Although propofol shortages will result in greater dexmedetomidine and benzodiazepine use, evaluations of prior propofol shortages, including one1 conducted by my colleagues and I, suggest that this shortage may not have the degree of effect on patient outcomes (eg duration of mechanical ventilation) that some might expect.
Miller: The sedative shortage caused the clinical ICU teams to examine all sedative drugs that were available for infusion or bolus. The storage has turned monolithic sedation administration to diverse drug administration. Often these additive agents work as effective as or better than historical choices. There is a greater stress placed on bolus infusion versus continuous drip infusion. I believe the shortages have minimal effect on patient care since there a similar agents that often can achieve the same clinical endpoints.
Regarding the drug shortages, the drug industry has attempted to better inventory which institutions used which sedative drugs, but shortages still continue based on drug resource lack or excessive stock piling which can lead to drug expiration. The drug storage has required providers to reassess the administration of sedative drugs in general. Often the pharmacy department has similar drug types available to be used as a replacement.
RT: A 2012 JAMA article2 concluded that the addition of daily sedation interruption to protocolized sedation did not reduce MV duration or ICU stay for adults. A related 2016 study3 of pediatric patients concluded that DSI + PS was even associated with increased mortality compared to PS only. Given this evidence and more, should clinicians do away with the practice of daily sedation interruption?
Devlin: One has to be careful not to conclude from this JAMA 2012 study2 that there is no role for DSI/SAT completion in patient’s receiving continuous IV sedation. As co-investigator in this study who enrolled more than 50 patients in it, it is important to note that sedation protocol used in the study required nurses to titrate sedative therapy hourly to maintain patients at the desired sedative goal with an emphasis of ‘titrating it off” (similar to a DSI/SAT) when the patient remained deeply sedated despite down-titration to the lowest infusion rate. This compares to other far less rigorous sedative protocols (eg Brook, et al4) where sedative therapy is titrated only every six hours and titrating it off is not emphasized.
In addition, patients in both arms of the study were maintained at far deeper levels of sedation than the light level of sedation (RASS = -1) currently advocated in the PAD 2013 guidelines. This may be due in part to the fact that all study patients were managed with a benzodiazepine (versus propofol or dexmedetomidine). In short, unless patients are managed with an aggressive nurse-driven sedation protocol when sedative discontinuation is a clear goal, SAT remains the best strategy to de-escalate, and in many cases permanently stop, continuous IV sedatives in critically ill adults.
Miller: There are a plethora of reasons on why ventilator duration may not be reduced. Drug delirium is a major contributor to critical illness that results from an ICU admission. Daily sedation interruption does not only provide assessment of ventilator liberation but allows clinicians to evaluate the patient neurological status. No we should not stop daily sedation trials. I think it would be an unsafe practice to stop daily sedation and the result would to lead to more ICU complications and a longer duration.
RT: In your experience, what are the pros and cons of dexmedetomidine (Precedex) versus propofol versus midazolam? Seeing as all three drugs are approved for sedation of ventilated patients, what factors should departments consider when choosing one over the other?
Devlin: Compared to continuously administered benzodiazepines, dexmedetomidine is associated with faster extubation, a shorter time in the ICU and less delirium. One large European study found that time to extubation and duration of ICU was similar between dexmedetomidine and propofol-treated patients; delirium was not evaluated in this study. A large multicenter US dexmedetomidine versus propofol randomized controlled trial (RCT) in critically ill adults with sepsis is nearing completion. Therefore, the PAD 2013 guidelines recommend use of either dexmedetomine or propofol versus a benzodiazepine but do not provide guidance on whether dexmedetomidine or propofol is the better non-benzodiazepine sedative choice.
In the absence of RCT comparative evidence, when choosing between propofol and dexmedetomidine, clinicians should consider the depth of ICU sedation required (propofol will result in deeper sedation than dexmedetomidine), the presence of delirium (dexmedetomidine may be preferred in this population, particularly when delirium-related agitation is precluding extubation) and the current acquisition cost for each agent at their institution.
Miller: Midazolam is commonly used for sedation in critically ill patients but concerns persist as to whether it induces delirium, and also prolongs mechanical ventilation and ICU stay, due to its accumulation in lipid stores with prolonged administration.
Precedex provides sedation with minimal respiratory depression. It also works well with patients that have combativeness and has less hemodynamically side-effects than the other sedative drugs. However, it is more expensive (30 times greater than Midazolam) and can cause increase restlessness in head-injured patients.
In a JAMA study5 that compared Precedex with other sedatives, among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients’ ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine.
RT: What are the most reliable methods for assessing a patient’s level of consciousness? How are these best used to expedite weaning?
Devlin: The regular use of sedative screening tool (eg RASS) by a trained evaluator remains the best way to assess level of sedation in most critically ill adults. While objective assessment methods (eg BIS monitoring) may have a role to monitor sedation in patients requiring deep sedation (particularly those on paralytics), it offers no advantages to RASS assessment in patients managed to lighter sedative goals. Aggressive sedative deescalation/discontinuation is required to optimize SBT screening efforts and conduct successful weaning trials. Patients who become agitated during an SBT trial may benefit from intermittent doses of IV opioids (if pain is detected) or antipsychotics like haloperidol (if delirium is present). Dexmedetomidine, given its lack of effect on respiratory drive, should be considered if delirium associated agitation is present.
Miller: All patients are give a daily sedation holiday and then we:
- Assess the patient’s Glasgow score (>8) and verbal responsive the patient-prior to extubating.
- Assess the patient’s ability to protect their airway, obtain a vital capacity, and negative inspiratory force measurement.
- If the above are within extubation criteria the patient is placed on a spontaneous breathing trial for liberation assessment.
RT: What is the incidence of drug-induced delirium? Can you estimate its impact on the weaning process?
Devlin: When a benzodiazepine is initiated in a critically ill adult, the risk that the patient will transition to delirium the next day is markedly increased. For example, in one study I collaborated on with a group of Dutch researchers (Zaal, et al6), for every 5mg of midazolam administered the risk for the patient developing delirium the next day was 4%. For a patient who is started on a continuous infusion of midazolam at 3mg/hr, the likelihood of this patient developing delirium the next day would be 58% (24 x 3mg = 72mg would be 72/5 = 14.4 x 4 = 58%).
Given that delirium will hinder weaning efforts and benzodiazepine use often leads to deep sedation (that may preclude SBT success), the current PAD guidelines do not advocate routine benzodiazepine use. The risk for delirium with other ICU medications (eg, opioids, steroids and anticholinergics) are not nearly as well established, and thus concerns about delirium (and potentially weaning) generally do not outweigh the clinical benefit these agents will provide.
Miller: Delirium increases ICU and ventilator duration by not allowing the patient to fully participate in their own care. It results in confusion, agitation, aggressive behaviors which often prevents early mobility such as walking with ventilator and can prevent the patient from protecting the airway. It also often require higher administration of sedative drugs which result in adverse neurological, GI, and hemodynamic effects. Delirium does not only increase ICU duration but its effects continue into the post ICU rehabilitation care. Often delirium prevents rehabilitation goals to be achieve and can lead to psychosomatic long-term problems.
RT: A 2015 study7 in BMC Pulmonary Medicine supported the use of sedation during noninvasive ventilation to potentially avoid NIV failure in agitated patients. Does your facility currently employ the use of sedation for NIV patients and, if so, do your safety protocols differ for NIV versus MV? If your facility does not use sedation for NIV patients, what are your thoughts on the practice?
Devlin: This retrospective BMC cohort study mirrors the findings of a randomized, double-bind, placebo-controlled dexmedetomidine NIV efficacy and safety trial8 that my colleagues and I recently published. In this study we found that the early initiation of very low-dose dexmedetomidine in patients with acute respiratory failure managed with NIV allowed patients (particularly those patients with poorer NIV tolerance) to tolerate NIV longer and avoid intubation more frequently.
Miller: We routinely provide anxiety control for NIV patients but administer a prn or bolus drug regime vs an infusion drip. We do not follow a specific sedation protocol for NIV patients but more of an individual approach.
In my opinion a sedation protocol for NIV patients would be difficult to adhere to since there are so many different ways to apply NIV and often the level of consciousness is a clinical end-point to determine failure or success. Often mental alertness is the assessment of carbon dioxide level and used to determine intubation versus NIV success.
In all forms of ventilation there needs to be a balance between sedation and wakefulness; if the balance is tipped too heavy to either side, clinical endpoints will be difficult to achieve. RT
For more information, contact [email protected].
- Roberts R et al. Crit Care Med. 2012;40:406-11.
- 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.
- Vet NJ, et al. A randomized controlled trial of daily sedation interruption in critically ill children. Intensive Care Med. 2016;42(2):233-44.
- Brook AD, et al. Crit Care Med. 1991; 27:2609-15.
- Jakob S, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: Two randomized controlled trials. JAMA, March 21, 2012—Vol 307, No. 11.
- Zaal I, et al. Intensive Care Med. 2015;41; 2130-7.
- Takeshi M, et al. Role of sedation for agitated patients undergoing noninvasive ventilation: clinical practice in a tertiary referral hospital. BMC Pulmonary Medicine. 201515:71.
- Devlin JW, et al. Chest. 2014;145:1204.