Optimizing Sustained Use of Sedation in Mechanically Ventilated Patients: Focus on Safety

Abstract

Optimizing sustained use of ICU sedation in mechanically ventilated patients requires careful consideration of drug-specific characteristics (E.G. pharmacokinetics), consideration of potential adverse effects in susceptible patients, and utilization of sedation-minimizing strategies. In the era of anxiolytic dosing protocols adjusted to specific patient behaviors as defined by sedation scales in conjunction with daily interruption, midazolam is a reasonable option for long-term sedation. Propofol is an appealing agent for ICU sedation due to it's pharmacokinetic profile and a reduced propensity to result in prolonged sedation. However, care should be taken to monitor for potential devastating adverse effects including hypertriglyceridemia and propofol-related infusion syndrome (PRIS). Dexmedetomidine unreliably provides adequate sedation at doses currently approved by the FDA, though upward titration of dexmedetomidine coupled with rescue benzodiazepines and/or fentanyl appears to be safe and comparable to benzodiazepines in the achievement of light to moderate Richmond Agitation Sedation Scale (RASS) goals. Clinicians should closely monitor patients receiving dexmedetomidine for hemodynamic-altering bradycardia. Strategies that promote frequent patient assessment with corresponding sedative dose minimization have demonstrated the benefits of limiting oversedation. Implementation of a sedation protocol requires careful consideration of ICU resources and staffing such that efforts made are sustainable and will be safe and effective for the patient population affected.

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

“…The development of valid and reliable bedside assessment tools to measure pain, sedation, agitation, and delirium in ICU patients has allowed clinicians to manage patients better and to evaluate outcomes associated with both nonpharmacologic and pharmacologic interventions (2,3). Our expanded knowledge of the clinical pharmacology of medications commonly administered to treat pain, agitation, and delirium (PAD) in ICU patients has increased our appreciation for both the short-and long-term consequences of prolonged exposure to these agents (4)(5)(6). We have learned that the methods of administering and titrating these medications can affect patient outcomes as much as drug choice (7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Effect of Sedation on Pain Perception

“…5,6 In the intensive care unit sedation is used extensively for intubated patients. 7,8 Other examples include various non-surgical diagnostic procedures that require sedation, such as gastrointestinal endoscopy and bronchoscopy. 9 Despite the ubiquitous use of sedative anesthetic drugs, the neurophysiologic mechanism of their action is poorly understood and sedation and anesthetic depth can only be determined by relatively unreliable physiological data.…”

Arousal from sedation in wake-up tests requires careful risk stratification*

“…Analgesia as well as sedation can be achieved by continuous or discontinuous administration of different opioids and sedatives, respectively (7)(8)(9). Sedation and analgesia are integral parts of contemporary intensive care treatment of patients suffering from encephalopathy, including brain injury, caused by e.g., trauma, stroke, and infections.…”