The SCCM, through the ICU Liberation Collaborative, has developed the evidence-based ABCDEF (also known as the ICU Liberation bundle or A2F bundle) care bundle as a quality improvement initiative [4]. The components of this bundle are:

Both sedative and analgesic agents are commonly administered to critically ill patients [5]. The following questions can be addressed to help optimize the management of these patients and to prevent the inappropriate use of analgesics and sedatives in critically ill patients [5]:

Patients who receive optimal analgesia and sedation have less pain and anxiety, which allows for invasive procedures, reduces stress and oxygen consumption, and improves synchrony with mechanical ventilation [2,6,7]. Providing an appropriate level of analgesia and sedation to ICU patients in particular can improve patient outcomes, including duration of ICU stay and duration of mechanical ventilation [2,6]. However, a large number of critically ill patients do not receive optimal analgesia and sedation.

Pain in adult patients in the ICU has been identified as a great source of stress [1,3]. The resultant catecholamines that are released into the circulation can negatively impact the patient's condition. Patients may experience arterial vasoconstriction, impaired perfusion to tissues, and reduced tissue-oxygen partial pressure. In addition, pain can cause catabolic hypermetabolism (e.g., hyperglycemia, lipolysis, breakdown of muscle). These effects can impair wound healing and increase the risk of wound infection. Acute pain is an important risk factor for the development of debilitating chronic pain (often neuropathic pain) [3].

All patients in the ICU setting should be evaluated for pain. Vital signs, such as heart rate and blood pressure, can suggest that a patient is in pain. However, vital signs alone should not be used for pain assessment in adult ICU patients, as these can be confounded by underlying conditions or medications (e.g., vasopressors, inotropes) [10]. Although a patient's own report of pain is the best evaluation, critically ill patients are often not able to communicate [3]. The Critical-Care Pain Observation Tool (CPOT) is one tool that is recommended for medical, postoperative, and trauma patients who are not able to self-report [3]. This tool includes four categories: facial expressions, body movements, muscle tension, and ventilator compliance or vocalizations for extubated patients [11,12]. The Behavioral Pain Scale (BPS) is another tool that is recommended for adult ICU patients who are unable to communicate verbally. This scale has three items of assessment: facial expression, upper limb movements, and compliance with mechanical ventilation [12,13]. This tool is available for both intubated and non-intubated patients [3].

The benefits of analgesic agents for pain control in critically ill patients must be balanced with the risks associated with the medications themselves (e.g., respiratory depression, hemodynamic compromise, addiction potential) [6]. In addition, too much or too little analgesia can increase risks such as nosocomial infections, delirium, prolonged duration of mechanical ventilation, and increased duration of ICU and hospital stay [2].

Patients in the ICU have less predictable pharmacokinetics and pharmacodynamics than non-critically ill patients due to hemodynamic instability, altered protein binding, drug interactions, and impaired organ function [6].

Nonpharmacologic methods, such as relaxation, massage, music therapy, lumbar support, injury stabilization, application of cold, and repositioning, can help improve patient comfort and decrease pain [2,3,6]. However, these methods are considered complementary in critically ill patients and are unlikely to completely control pain [6].

It is important to adhere to hospital protocols for ketamine use, including contraindications, as these may vary among facilities. Examples of contraindications include:

Potential adverse effects to consider when using opioids in patients in an ICU include:

Fentanyl is commonly used for continuous pain control. It has a relatively short half-life (two to four hours), which makes it easily titrated when given as a continuous infusion [6]. Fentanyl is metabolized in the liver, has no active metabolites, and may accumulate in patients with liver impairment [9]. Fentanyl is lipophilic and may accumulate in fat and muscle with prolonged infusions, increasing the half-life in patients with obesity [6]. The accumulated drug may be released after the infusion is stopped, leading to prolonged activity. However, fentanyl is often preferred because it does not undergo elimination via the kidney. Fentanyl also causes less hypotension than morphine.

All patients receiving opioids should be on an effective bowel regimen. It is important to initiate bowel regimens when the opioid is started instead of waiting for symptoms to develop. Bowel regimens typically include a scheduled osmotic (e.g., polyethylene glycol [PEG] 3350) or stimulant laxative (e.g., bisacodyl). These two can be combined if necessary. Other medications, such as magnesium citrate, glycerin suppositories, or enemas, can be added on if these are not effective. Although adding a stool softener (e.g., docusate) to a stimulant laxative is widely recommended, small studies show that this approach is not beneficial [59; 60].

The bowel regimen should be individualized based on patient characteristics and special considerations. Unique considerations include [22]:

Opioid allergy is a common patient complaint. However, less than 2% of opioid reactions are "true allergies" and may be more appropriately categorized as pseudoallergies. A pseudoallergy is a side effect of opioids that can resemble an allergy but is usually caused by histamine release from mast cells. Symptoms of a pseudoallergy often include flushing, itching, rash, or hives. Opioids most associated with pseudoallergies include codeine, morphine, and meperidine. True allergies are more likely with symptoms such as severe hypotension; breathing, speaking, or swallowing difficulties; or swelling of the face, lips, mouth, tongue, pharynx, or larynx. Patients allergic to one opioid are thought to be less likely to react to an opioid in a different structural class (Table 2). Because true allergy is rare, there is not enough information to assess the chance of cross-reactivity. In addition, several opioids' product labeling contraindicates their use in patients with true allergies to any opioid.

To reduce drug accumulation and oversedation, the following strategies may be helpful:

Potential consequences of undersedation include [7]:

Conversely, potential consequences of oversedation are [7]:

Side effects of propofol include hypotension (occurring in up to 25% of patients), bradycardia, respiratory depression, neuroexcitatory effects, pancreatitis, and hypertriglyceridemia [2,6,7]. Propofol is supplied as a lipid emulsion. Triglycerides should be monitored in patients at risk for hypertriglyceridemia and during prolonged therapy. In addition, calories from propofol should be counted toward a patient's caloric goals [2]. The 10% lipid emulsion of many propofol formulations has approximately 1.1 kcal (0.1 g of fat) per mL of propofol [32].

Historically, benzodiazepines have been the most commonly used agents for sedation in the ICU setting [2]. However, guidelines now recommend benzodiazepines as second-line therapy, with dexmedetomidine, propofol, and analgesia-based sedation regimens being preferred [3,6]. Benzodiazepines seem to be associated with poorer patient outcomes, such as development of delirium, longer duration of mechanical ventilation, and longer duration of ICU stay in medical, surgical, trauma, and burn patients [2,6,7]. Still, the use of benzodiazepines remains important in critically ill patients for treatment of seizures and alcohol withdrawal. They also have a role in deep sedation (when indicated) or to reduce doses of other sedatives [3].

With the use of a peripheral nerve stimulator and the co-administration of sedation, the ICU staff can closely monitor a patient's degree of neuromuscular blockade [72]. Patients requiring prolonged neuromuscular blockade in the ICU are best treated with intravenous infusions of intermediate-acting agents. As with all hospitalized patients, the goal is to treat the underlying disease or injury as quickly as possible, and then wean the patient from the ventilator in a quick and efficient manner. While intermittent boluses of neuromuscular blockers will prevent patient movement, they may impede the reversal and weaning process. A large loading dose of neuromuscular blocking drug, given to ensure quick onset, has the disadvantage of exceeding the therapeutic dose levels and extinguishing the train-of-four response (no twitches). Until the dose begins to degrade, there is no way to determine the extent of neuromuscular blockade. Indeed, there may be a supramaximal dose, resulting in prolonged blockade. The infusion dose, though taking a bit longer to set up, stops at the desired point. The lack of peaks and nadirs ensures the correct dose throughout the administration of the drug, easing recovery from neuromuscular blockade.

Withdrawal from analgesics and sedatives is linked to longer time on the ventilator and in the ICU. Several strategies have been identified to help prevent withdrawal when stopping high doses of ICU analgesics and sedatives, including identifying patients at risk for withdrawal, such as:

Delirium in ICU patients is associated with long-term cognitive impairment, increased mortality, increased duration of mechanical ventilation, and increased duration of ICU and hospital stay [2,3,7]. The cause of delirium is not clear, although it has been associated with the use of sedative medications, such as benzodiazepines, and patient factors, such as cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration [2,6]. Oversedation and undersedation are also risk factors for the development of delirium [45]. Strategies to reduce these factors, which may help decrease the risk of delirium, include [2]:

When present, clinicians should work to ensure that the underlying causes of delirium are addressed. This assessment is guided by the mnemonic THINK:

If use of an antipsychotic is necessary, start with a low dose and titrate to symptom control [43,50]. For example, haloperidol may be administered at a dosage of 1–5 mg IV every 12 hours, as needed, with consideration to reducing starting dose by 50% in older adult patients [51]. IV haloperidol can be given every four to eight hours if needed, but the total daily dose should not exceed 20 mg.