Chapter 64: Controversies: Patient-Controlled Sedation—Ready for Prime Time?

Sedation is an induced altered state of consciousness following the administration of a sedative agent. According to the American Society of Anesthesiologists, depth of sedation exists as a continuum¹ ranging from minimal sedation to deep sedation, just prior to achieving general anesthesia (Table 64–1). With minimal sedation, patients are in a state of anxiolysis and may have impaired cognitive function, but retain protective airway reflexes and the ability to respond normally to verbal commands. Moderate sedation, previously referred to as conscious sedation, refers to a state of depressed consciousness with a purposeful response to verbal commands and light tactile stimulation, such as glabellar tap. In a state of deep sedation, patients are not easily arousable but are able to purposefully respond to repeated or painful stimuli. In cases where the level of sedation becomes deeper than initially intended, interventions in airway management or hemodynamic support may become necessary. Other similar measures of sedation such as the Observer Assessment of Alertness and Sedation Scale² are also commonly used (Table 64–2).

Historically, sedation has been widely administered in a clinician-controlled manner as a means of facilitating invasive interventions or making intolerable procedures appropriately acceptable. However, patients often have varying expectations and degrees of anxiety and discomfort as well as different sensitivities to sedative agents. This causes sedation requirements to vary widely, making it clinically challenging to predict and achieve the optimum level of sedation for each individual patient. Clinicians must rely on subjective determinants of adequate sedation with the constant concern for enhancing safety and preventing adverse events. The technique of patient-controlled sedation (PCS) may circumvent these challenges by offering patients the ability to control and titrate their desired levels of sedation.

Patient-controlled drug administration is a well-established concept. The more commonly encountered, patient-controlled analgesia (PCA), has been effectively and safely utilized for several decades as a means of providing pain relief especially in the acute postoperative setting. PCA consists of a delivery system with which patients are able to self-administer predetermined doses of analgesic medications as required for pain management. With advances in PCA pump technology, this technique operates safely with the ability to program parameters with respect to bolus dosages and lockout intervals. A similar technique and logical extension of the PCA concept using related technology is PCS.

Initial reports of PCS began independently with investigations by Rudkin et al³ and Park and Watkins⁴ in 1991. Rudkin et al reported a high level of patient satisfaction with PCS using self-administration of propofol during dental extraction surgery under local anesthesia. Meanwhile, Park, and Watkins studied the use of PCS using a combination of midazolam and fentanyl during surgical procedures under epidural anesthesia and compared this to anesthesiologist-administered sedation using the same drugs. The results of the study indicated that PCS is not only a safe and effective technique, but it also leads to higher levels of patient comfort and satisfaction. Subsequent investigations under various clinical conditions have led to similar results using different combinations of medications.⁵

Although seemingly identical in design, PCA and PCS have fundamental differences that limit the similarities in clinical application and associated adverse events. PCA primarily acts on postoperative pain, which tends to be uniform and predictable for each individual. PCA typically utilizes medications with slower onsets of action but with prolonged duration, such as morphine. In this way, PCA is designed to operate safely in the absence of continuous monitoring from an anesthetic-care provider. In contrast, PCS especially in the intraoperative setting requires the flexibility to respond rapidly to constantly changing levels of stimulation. PCS typically utilizes easily titratable medications that have rapid onsets of action that are conducive to the rapidly changing environment in which it is required. Although PCS has been often shown to be generally as safe as conventional anesthetist-administered sedation, experience with PCS in the absence of an anesthetic-care provider has generally not been supported due to the potential for adverse events that are uncommonly seen with PCA.⁵ For instance, adverse events such as respiratory depression and excessively deep levels of sedation have been reported to occur in association with PCS, similar to anesthetist-administered sedation.⁶ Due to inherent differences, PCA and PCS must differ in the delicate balance between efficacy and safety. Ultimately, with regard to patient safety, as the requirement for effective sedation increases, patient monitoring must also become more intense so that complications can be easily detected and managed expeditiously.

Interest in the use of PCS has generally been focused on a variety of ambulatory procedures which are performed under local or regional anesthesia. Common surgical applications include ambulatory surgery procedures of short duration, dental procedures, ophthalmic surgery, gynecologic or lower abdominal surgery, neurologic surgery, and orthopedic surgery.⁵ PCS is also beneficial for nonoperative procedures associated with discomfort such as endoscopy, colonoscopy, and lithotripsy. Furthermore, PCS may be utilized for perioperative anxiolysis in select patients.

PCS typically requires highly potent medications with rapid onsets of action in order to provide effective and reliable sedation in the rapidly changing environment associated with the operating room or procedure room. Several medications such as propofol, benzodiazepines, and opioids have been extensively studied either alone or in various combinations. Each of the agents has been found to be equally safe and effective,⁷ but present with varying advantages and disadvantages (Table 64–3).

Propofol (Diprivan)

Propofol has the ideal pharmacokinetic properties for PCS as it has rapid onset, short time to peak effect as well as a short context sensitive half-life that makes it easily titratable. However, its main disadvantage is the high incidence of pain on injection that may make intravenous injection uncomfortable.⁵ Propofol in high doses is also associated with apnea and cardiovascular depression. Propofol is often used successfully as a sole sedative agent but may be supplemented with other agents.

Benzodiazepines

Benzodiazepines, particularly midazolam, are effective sedative agents with the additional effects of amnesia and anxiolysis. However, midazolam has the disadvantage of relatively prolonged recovery.⁸ It appears to be associated with the greatest degree of memory impairment, intraoperatively and postoperatively.

Opioids

Opioids, such as fentanyl, alfentanil, and remifentanil, are also commonly used as adjunctive agents in PCS. Opioids are suggested to be useful in treating the discomfort and restlessness from prolonged immobilization⁷ during longer procedures, or generally those lasting greater than 2 to 3 hours. The main disadvantages of opioids are transient intraoperative pulse oximetric desaturations and the potential for respiratory depression, especially when given in combination with benzodiazepines. It is also associated with a high incidence of postoperative nausea and vomiting.

In PCS, patients are clearly instructed preoperatively on the proper use of the infusion device as well as the purpose of sedation. Sedation is carried out via an infusion pump with a reservoir, which is connected to a handheld button that only the patient can control. When the button is pressed, the pump delivers a bolus of a predetermined dosage of medication. A lockout period, or a time interval in which another dose cannot be administered, may or may not be programmed. When present, it appears to offer a safety mechanism by preventing excessive drug administration and subsequent oversedation and loss of consciousness.⁷ The patients are instructed to press the button until they reach the desired level of sedation to allow them to be able to tolerate the procedure. In this way, the patients themselves can control and determine the end point of sedation.

In a prospective, randomized, controlled study, Mazanikov et al compared PCS using propofol and remifentanil with anesthesiologist-controlled patient sedation using propofol for ERCP procedures.⁹ Between the 2 groups, patient and endoscopist satisfaction were comparable. However, the study found markedly less propofol consumption and faster recovery in the PCS group. Similar results were obtained in a study conducted by Girdler et al on dental patients, with the PCS group requiring a lighter level of sedation compared to a clinician-controlled group.¹⁰ This suggests that anesthesiologist-controlled sedation may result in unnecessary deep sedation while PCS is well-accepted because patients appreciate the ability to maintain control of their sedation.

Target-Controlled Sedation

Due to the short duration of action of sedative agents, particularly propofol, a potential drawback of self-administration in bolus increments is the volatility of plasma concentrations and subsequent varying levels of sedation. Target-controlled infusion (TCI) overcomes this problem of varying blood concentrations. This method of administration utilizes a computer-controlled infusion system that can calculate and maintain target blood concentrations of propofol with great accuracy. TCI uses a pharmacokinetic model to predict the initial bolus dose and infusion rates necessary to achieve and maintain a given target concentration, avoiding peaks and troughs in plasma concentration. The target concentration can then be adjusted accordingly by the patient to achieve the optimal level of sedation.

In a study by Irwin et al, the benefits of TCI were used in combination with patient-controlled feedback¹¹ in a technique referred to as patient-maintained sedation (PMS). Based on each patient’s age and weight, a TCI system calculated the dose necessary to achieve and maintain a selected target concentration of propofol. In this case, an initial target concentration of 1 mcg/mL was chosen. The patient also had control of a handset that when pressed, increased the target concentration by 0.2 mcg/mL increments with a lockout interval of 2 minutes. When no demand boluses were required for several minutes, the system gradually decreased until a baseline target concentration of 0.2 mcg/mL was reached. Although there was wide variability amongst individuals in total consumption of propofol, optimal sedation was found to be achieved at median target concentrations of 0.8 to 0.9 mcg/mL. Following cessation of the infusion at the end of the procedure, recovery was rapid and no delays were reported in meeting discharge criteria from the recovery room. Patients expressed overall satisfaction with the technique and reported interest in using the technique again in the future.

Rodrigo et al performed a randomized study comparing outcomes between PCS and PMS using a TCI of propofol.¹² The study found no significant differences in depth of sedation, operating conditions and patient satisfaction. However, a majority of patients preferred PMS likely because it produces more stable blood concentrations and possibly less oversedation. The main disadvantage of PMS is relatively slower onset in achieving adequate sedation. The time required for adequate sedation was 8.6 minutes in the PMS group, compared to 5.7 minutes in the PCS group.

When variable rate infusions of propofol target the plasma concentration, the clinical effect lags behind the plasma concentration, reflecting the fact that the site of action of propofol is the brain rather than the plasma. Because of the inability to measure the concentration of propofol in the brain, or the effect site, it is assumed that the clinical effect of propofol reaches a plateau when the plasma and brain concentrations have equilibrated. This mathematically derived term, the effect-site concentration, therefore, corresponds to the clinical effect of propofol. In an alternative PMS system, where the effect-site compartment is targeted, sedation may be achieved rapidly and safely.

To assess both the efficacy and safety of effect-site-targeted PMS, Anderson et al recruited 20 healthy volunteers and gave them the task of attempting to oversedate themselves using this system.¹³ The initial target effect-site concentration was set at 1 mcg/mL. The system was able to overshoot, or increase the target plasma concentration up to 100% over the target effect-site concentration. The predicted plasma concentration was reduced as the target effect-site was approached (Figure 64–1). When the plasma concentration decreased to within 10% of the target effect-site concentration, the patient’s demand button was activated. Pressing the button led to an increase in the target effect-site concentration by increments of 0.2 mcg/mL. Although there was no traditional lockout time, further increases in effect-site concentration could not be requested until plasma concentration fell to within 10% of the target effect-site concentration. The system was programmed with a means of machine stepdown, in which lack of a successful press of the control button after 6 minutes led to a 0.2 mcg/mL reduction in effect-site concentration. Under continuous monitoring, volunteers were instructed to try to make themselves unconscious. End-points of the study included loss of verbal contact, no response to verbal command, machine stepdown, oxygen saturation less than 90% or the requirement for airway intervention. Of the 20 subjects enrolled in the study, 15 terminated the study through machine stepdown, 4 developed oxygen saturation less than 90%, and 1 lost verbal contact. Although the system appeared to function successfully in achieving sedation, when the safety of the system was stressed in the artificial conditions of the study, a significant number reached potentially unsafe end-points. This suggested that anesthetic supervision may be required for safe administration.

Stonell et al studied the use of effect-site PMS with propofol compared to anesthetist-administered sedation with propofol boluses in patients undergoing colonoscopy.¹⁴ Patients in the effect-site PMS group underwent sedation more slowly (13 minutes vs 3 minutes) and less deeply as determined with BIS monitoring. The more rapid induction of sedation in the anesthetist-administered sedation group resulted in a higher incidence of hypotension and oversedation, but overall did not lead to negative outcomes. Between the 2 groups, patient and endoscopist satisfaction was similar. All patients also had similar recall of events. These results suggested that although effect-site-steered PMS may be comparable to anesthetist-controlled sedation in quality, it lacks the efficiency in induction time.

The most common issue encountered during PCS is respiratory depression, manifested by a decrease in arterial oxygen saturation and respiratory rate. Oxygen supplementation, routinely via nasal cannula, is the standard of care although it may not be necessary especially in young, healthy patients.

Propofol is a known cardiovascular depressant, which may precipitate hypotension especially in elderly patients who are already mildly dehydrated from NPO status.

The potential for respiratory depression and cardiovascular complications highlights the need for close monitoring during PCS. Resuscitation equipment should be made readily available in areas where PCS is practiced and practitioners should be certified in CPR and ACLS.

Although PCS has been shown to be safe and effective, most randomized controlled trials have often involved relatively young patients. PCS investigations in elderly patients, while limited, have also resulted in similar outcomes. Herrick et al found that between elderly patients with no intraoperative sedation and those receiving PCS for cataract surgery, satisfaction was higher in the PCS group, whether or not the device was actually used.¹⁵ Many of the patients felt comfortable enough not to need sedation but appreciated the availability of intraoperative sedation, should they desire it. In a prospective, randomized, controlled trial, Lee et al compared conventional clinician-controlled sedation with PCS in elderly patients undergoing outpatient colonoscopy.¹⁶ PCS appeared to be safer with comparable effectiveness and acceptance. PCS must be used cautiously in elderly people, however, as the effect of bolus doses may not be as predictable. Therefore, smaller dosages with longer lockout periods are recommended.

Another application of PCS which may warrant further investigation is the self-administration of sedative medications in critically ill, mechanically ventilated ICU patients. In an investigation by Chlan et al, dexmedetomidine was administered via a basal infusion as well as with patient-triggered boluses.¹⁷ PCS was rated favorably for its ability to safely and adequately relieve anxiety and attain a satisfactory level of comfort.

PCS has been widely investigated for several years but has yet to achieve widespread clinical application. Reasons for hesitancy in use may involve various factors.⁵ Conceptually, the technique of PCS contradicts the traditional tenet of monitored-anesthesia care where an anesthetist proactively administers sedation based on the anticipation for intraoperative events. Also, although many investigators have reported superior outcomes with PCS, others report no difference. With this lack of consistency or definitive benefit, there is a lack of incentive to change current practice and invest in new equipment. Furthermore, not all patients desire control. As patient satisfaction may be associated with degree of control, this may not provide a benefit for all patients.

PCS is a technique which allows patients to control and titrate their own level of sedation based on anxiety or perceived discomfort from noxious stimulation during a procedure. Ample evidence has suggested the safety and efficacy of PCS when compared with conventional anesthetist-administered sedation. PCS is also associated with high levels of patient satisfaction which may be related to an increased feeling of control in being able to self-administer sedation as it is required in the rapidly changing environment of the operating room or procedure room. More technologically advanced, alternative techniques of PMS, such as target-controlled sedation or effect-site-controlled sedation, have the added benefit of being able to provide a stable level of sedation uncomplicated by variability of plasma concentration. Despite these perceived advantages, however, PCS has not gained wide acceptance in clinical practice due to a lack of consistent and definitive evidence of superior outcomes compared to the currently utilized sedation techniques. It merits further interest and evaluation because it empowers patients to participate in their own care and challenges anesthetic-care providers to reevaluate sedation practices.