Targeted Sedation

All sedatives are to be administered to a specific target level identified by a RASS or SAS level appropriate to the patient’s clinical condition (Figure 10-1).² A target level is specified every day and reevaluated whenever there is a change in sedation dosage or patient condition. One likely sedation goal is that the patient is awake and calm, specified as a target sedation level of RASS = 0, or SAS = 4. This describes a patient who follows simple verbal commands without agitation and who can sustain eye contact for at least 10 seconds, as described in Table 10-1. When the intent is to provide deep sedation, the target sedation level is specified as RASS = -3 to -5 or SAS = 1 to 2.² This describes a mechanically-ventilated patient who is not responsive to voice, but who may respond to physical stimulation (see Table 10-1).

Neuromuscular Blockade

Pharmacologic neuromuscular blockade (NMB) induces a state of physical paralysis. NMB is administered to achieve ventilator synchrony and improve oxygenation when this cannot be achieved by sedation and analgesia alone. Table 21-10 in Chapter 21 lists NMB medications, dosages, and management.

Because NMB causes a pharmacologic paralysis, the patient will not be able to respond to verbal or physical stimuli and additional monitoring methods are required. NMB is never administered unless adequate analgesia and sedation are also provided. This is because NMB paralyzes skeletal muscle but does not alleviate pain or confer sedation. It is vital that measures are in place to avoid a scenario where a patient who has received NMB cannot move, yet retains mental awareness.

Benzodiazepines

Benzodiazepines have powerful amnesic properties that inhibit reception of new sensory information.1,7 Benzodiazepines do not confer analgesia. The most frequently used benzodiazepines are diazepam (Valium), midazolam (Versed), and lorazepam (Ativan). Once a mainstay of sedation, benzodiazepines are no longer recommended for sedation of the mechanically ventilated critically ill adult.² This is because benzodiazepine-based sedative regimens are associated with worse patient outcomes, including longer duration of mechanical ventilation and delirium.^8–10

Short-acting benzodiazepines (midazolam) are still helpful for the treatment of acute short-term agitation,² because the intravenous (IV) onset of action is less than 3 minutes. However, when midazolam is administered for longer than 24 hours as a continuous infusion, the sedative effect is prolonged by its active metabolites.¹ Longer acting benzodiazepines (lorazepam and diazepam) also have a role in the management of delirium tremens (described later in the chapter) and seizures,² but these are different indications from routine sedation in critical illness.

The major unwanted side effects associated with benzodiazepines are dose-related respiratory depression and hypotension. If needed, flumazenil (Romazicon) is the antidote used to reverse benzodiazepine overdose in symptomatic patients. Flumazenil should be avoided in patients with benzodiazepine dependence, because rapid withdrawal can induce seizures.¹¹

Sedative-Hypnotic Agents

Propofol is a powerful sedative and respiratory depressant used for sedation in mechanically ventilated patients in critical care. It is immediately identifiable by its white milky appearance, always in a glass container. At high doses (>100 to 200 mcg/kg/min), propofol is intended to produce a state of general anesthesia in the operating room.¹² In the critical care unit, propofol is prescribed as a continuous infusion at lower doses (5 to 50 mcg/kg/min) to induce a state of deep sedation.¹² Because propofol is lipid soluble it quickly crosses cell membranes, including the cells that comprise the blood-brain barrier. This allows rapid onset of sedation (about 30 seconds), with immediate loss of consciousness. In addition to a rapid onset of action propofol has very short half-life with initial use (2 to 4 minutes), is rapidly eliminated from the body (30 to 60 minutes), and does not have metabolites.^12,13 This makes it an ideal sedative for use when a patient needs to be quickly awakened for a spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT), or to assess neurologic status. This feature makes propofol an ideal medication to manage rapid ventilator weaning postsurgery. Propofol is both clinically effective and cost effective because it shortens time to extubation. It is important to add an opiate to ensure adequate pain control and amnesia. Propofol is not a reliable amnesic, and patients sedated with only propofol can have vivid recollections of their experiences.

Risks of unwanted complications increase when propofol is administered long term at high doses (>4.00 mg/kg/hr for longer than 48 hours). Propofol is delivered in a fat-based emulsion, and side effects may be related to disruption of fatty acid metabolism, muscle injury, and release of toxic intracellular contents. Complications have been collectively grouped under the term Propofol Related Infusion Syndrome (PRIS) including: metabolic acidosis, muscular weakness, rhabdomyolysis, myoglobinuria, acute kidney injury, and cardiovascular dysrhythmias. PRIS affects about 1% of all patients who receive propofol; almost one third of those affected will not survive.8,13,14 Other secondary side effects related to the fat-emulsion carrier include hyperlipidemia, hypertriglyceridemia, and acute pancreatitis. Nursing vigilance is required to monitor sedation levels, and to be alert for the rare but significant risk of propofol-related complications. Serum triglycerides should be measured on all patients who receive propofol for longer than 48 hours. For additional information see Table 10-2.