Chapter 11. Sedation-Analgesia during Local & Regional Anesthesia

During local and regional anesthesia, it is a common practice to administer both sedative and analgesic medications to enhance patient comfort during the operation. Use of local anesthetic infiltration and peripheral nerve blocks (PNBs) techniques in combination with intravenous (IV) sedative–hypnotic and analgesic drugs is commonly referred to as monitored anesthesia care (MAC). In many centers around the world, over 50% of all ambulatory (day-surgery) procedures are performed utilizing these techniques (Table 11–1).1 When patients undergo surgical procedures under local anesthesia with IV sedation—analgesia in the operating room (OR), the old terminology used to describe the care of these patients as “conscious sedation.” As the term implies, conscious sedation was a minimally depressed level of consciousness that retained the patient's ability to maintain an airway independently and continuously and to respond appropriately to physical stimulation and verbal commands. The American Society of Anesthesiologists (ASA) avoids this term in their Practice Guidelines for Sedation and Analgesia by Non-anesthesiologists2 because it is imprecise and instead refers to this practice of anesthesia as MAC.

According to the ASA,2 MAC is the term used to describe the administration of local anesthesia alone or the use of anesthetic drugs for a patient undergoing diagnostic or therapeutic procedures with or without local anesthesia. The ASA defines MAC “as instances in which an anesthesiologist has been called upon to provide specific anesthesia services to a particular patient undergoing a planned procedure in connection with which a patient receives local anesthesia or, in some cases, no anesthesia at all. In such a case, the anesthesiologist is providing specific services to the patient, is in control of his or her vital signs, and is available to administer anesthetics or provide other medical care as appropriate.” The standard of care for patients receiving MAC should be the same as for patients undergoing general anesthesia or central neuroaxial blockade and should include a complete preoperative assessment, intraoperative monitoring, and postoperative care in the recovery room prior to discharge.

Vigilant monitoring is required because patients may rapidly progress from a “light” level of sedation to “deep” sedation and ultimately, unconsciousness (Figure 11–1).1 As a result, patients may be at risk for airway obstruction, oxygen desaturation, and even aspiration.3 Therefore, supplemental oxygen is commonly administered with end-expiratory CO2 monitoring for assessing ventilatory rate, presence of airway obstruction, and apnea.4 Although cerebral monitoring (eg, electroencephalographic [EEG] bispectral index [BIS]) has been used successfully to assess the sedative effects of both midazolam5 and propofol6 during procedures performed using local anesthesia and PNBs, the confounding effects of the surgical stimulus and patient discomfort on the cerebral index can make it difficult to interpret the findings.7 In addition, background noise in the OR can affect the cerebral index at “light” levels of sedation.8 Nevertheless, some investigators have suggested that the BIS is useful for monitoring the central nervous system during surgery under local or regional anesthesia with IV sedation.9

A wide variety of pharmacologic agents are commonly administered during administration of local anesthesia or PNBs, as well as during surgical procedures under local anesthesia (or PNBs) to produce sedation, analgesia, and anxiolysis, while optimizing the surgical conditions and ensuring cardiorespiratory stability and a rapid recovery of cognitive functioning without untoward side effects (Table 11–2).10 Systemic opioid and nonopioid analgesics are used to reduce discomfort associated with injection of local anesthetics and prolonged immobilization, as well as procedure-related pain that is not amendable to local anesthesia (eg, endoscopy).

Sedative–hypnotic drugs are also commonly used to make procedures more tolerable for patients by reducing anxiety and providing an appropriate degree of intraoperative sedation and amnesia. During longer surgical procedures, patients may become restless, bored, or uncomfortable when forced to remain immobile. Therefore, sedative–hypnotic drugs, as well as nonpharmacologic approaches (eg, music), may prove beneficial because they allow patients to rest during the operation. Patients' anxiety can be reduced by using benzodiazepines, as well as by good preoperative communication, keeping the patient warm and covered, and allowing the patient to listen to relaxing music during the procedure. This chapter will discuss the commonly used adjunctive techniques to enhance patient comfort during local and regional anesthesia.

Many different sedative–analgesic drugs have been used for premedication (including barbiturates, benzodiazepines, opioid analgesics, and α2-agonists) (Table 11–3).10 Midazolam remains the most popular premedication because of its predictable sedative, anxiolytic, and amnestic properties irrespective of the route of administration (ie, oral, topical, or parenteral).11–14 In addition, midazolam decreases the seizure threshold (as do other benzodiazepines). A wide variety of drug delivery systems such as intermittent boluses, variable-rate infusions, and target-controlled infusions, as well as patient-controlled sedation–analgesia techniques have been utilized during procedures under local and regional anesthesia.15,16

Although benzodiazepines (eg, diazepam, midazolam) were formerly the most popular sedatives for “conscious sedation,”17,18 their use has declined with the introduction of more titratable IV sedative–hypnotics (eg, methohexital, etomidate, propofol) and analgesics (eg, alfentanil, remifentanil).15,19 Methohexital, a shorter acting barbiturate than thiopental, was the IV sedative–hypnotic of choice prior to the introduction of propofol. Etomidate, a popular IV induction agent for cardiovascular surgery, can be administered by continuous infusion (5–20 mcg/kg/min) and may be particularly useful for sedation of elderly patients and those with significant underlying cardiac disease because to its minimal cardiovascular depressant properties. However, when combined with opioid analgesics, etomidate is associated with an increased risk of postoperative nausea and vomiting (PONV).

Propofol, the current IV sedative–hypnotic of choice, has been found to be equivalent to both midazolam and methohexital in providing adequate sedation and amnesia during superficial procedures under local anesthesia and PNBs.20–23 Importantly, compared with other available sedative–hypnotic drugs, use of propofol is associated with less residual postoperative sedation, amnesia, and nausea and vomiting. Propofol facilitates fast-tracking (ie, bypassing the postanesthesia care unit), which requires reduced recovery time and an earlier “home readiness” state. Use of the benzodiazepine antagonist, flumazenil, also reduces the residual sedative–amnestic effects of midazolam and allows for the early recovery profile after midazolam sedation, which compares favorably with propofol.24 However, the short duration of action of the reversal drug can lead to varying degrees of resedation in the postdischarge period.

The most popular sedative technique consists of a small dose of midazolam (1–2 mg) for premedication (or induction of sedation), and propofol (0.5–0.75 mg/kg followed by a variable-rate infusion at 25–100 mcg/kg/min).20,25 Methohexital has also been used successfully during MAC by intermittent boluses (10–20 mg) or as a variable-rate infusion (20–60 mcg/kg/min).19,26 Although residual sedation appears to be somewhat greater with methohexital than propofol, there were no differences in the recovery times to ambulating and discharge home when comparing infusions of methohexital (40 mcg/kg/min) and propofol (50 mcg/kg/min) during a MAC technique.26 In addition, there was a significantly higher incidence of pain on injection in the propofol infusion group. Therefore, methohexital remains a cost-effective alternative to propofol for sedation during MAC despite the fact that it is less convenient to use because it has to be reconstituted. Careful titration of these IV anesthetics is essential to maintaining the desired level of sedation while avoiding ventilatory depression during surgery and to ensuring a prompt recovery of cognitive functioning after surgery.

In an effort to enhance patient comfort, both opioid and nonopioid analgesics have been used to supplement the sedative–hypnotics.27–31 Although fentanyl remains the most commonly used opioid analgesic, remifentanil has become increasingly popular because its faster onset and recovery characteristics may minimize the potential for adverse drug interactions in the postoperative period. However, to avoid ventilatory depression and apnea, careful titration is necessary when remifentanil is combined with midazolam and propofol.30–35 Of interest, some investigators have suggested that remifentanil fails to improve the quality of propofol sedation36 A variety of nonsteroidal antiinflammatory drugs (NSAIDs) (eg, ibuprofen, ketorolac, piritramide, celecoxib) may also prove useful in preventing pain and discomfort that is refractory to local anesthetics.37–40 However, with effective local anesthesia, the addition of an NSAID provides only minimal intraoperative improvement in the local analgesic effect.27,38,41

Opioid analgesics are routinely administered to alleviate the discomfort associated with injection of the local anesthetic solution and to treat pain not amenable to local anesthesia.28 In addition, the concomitant use of opioid analgesics reduces the sedative–hypnotic dosage requirement and thereby minimizes residual sedation. Avramov and White29 first described the combined use of alfentanil (0.3–0.4 mcg/kg/min) and propofol (25, 50, or 75 mcg/kg/min) infusions for MAC. Compared with the opioid alone, concomitant use of propofol significantly reduced the alfentanil dosage requirement (30–50%) and the incidence of PONV. Comparing alfentanil (0.25 mcg/kg/min) and remifentanil (0.05 mcg/kg/min) infusions when administered as an adjuvant to propofol, Dilger and colleagues30 reported that the remifentanil group required fewer “rescue” doses of local anesthetic during MAC for breast surgery.

When administered in combination with small doses of midazolam an infusion of remifentanil (0.05–0.15 mcg/kg/ min) can provide adequate sedation and analgesia during minor surgical procedures performed with the patient under local anesthesia.31,32 Sá Rêgo and coworkers35 compared the use of intermittent remifentanil boluses (25 mcg) vs a continuous variable-rate infusion (0.025–0.15 mcg/kg/min) when administered to patients receiving a MAC technique involving midazolam (2 mg) and propofol (25–50 mcg/kg/min). Patient comfort was higher during the procedure when remifentanil was administered by a variable-rate infusion. However, the patients receiving the propofol–remifentanil infusion also experienced a higher incidence of desaturation (30% vs 0%) compared with those receiving small intermittent boluses of remifentanil during a propofol infusion.

In direct comparisons of remifentanil and propofol administered by continuous infusion after premedication with midazolam, there was a decreased level of intraoperative sedation and a greater degree of respiratory depression with remifentanil (vs propofol) administration.33,34 Therefore, remifentanil infusions must be carefully titrated to avoid excessive respiratory depression in the presence of midazolam or propofol (or both). Using remifentanil in combination with local anesthetics obviates the disadvantage associated with the minimal residual analgesia when remifentanil is used during painful procedures. Unfortunately, even the short-acting opioid analgesic remifentanil can increase PONV and the need for antiemetic prophylaxis.42

Given the increased risk of ventilatory depression when opioid analgesics are combined with sedative–hypnotics, a variety of nonopioid analgesics have been evaluated during MAC. Ketorolac, a potent, parenterally active NSAID, has been used as an analgesic supplement to propofol sedation during local anesthesia.27,37–39 Use of ketorolac was associated with a lower incidence of pruritus, nausea, and vomiting than fentanyl. However, when used with propofol sedation, ketorolac-treated patients required higher intraoperative doses of propofol and more supplemental opioid analgesia compared with those given fentanyl.27,37 Piritramide, 0.05 mg/kg IV, prior to PNBs can reduce pain perception and the endocrine stress response during cataract surgery.40

Low-dose ketamine (0.25–0.75 mg/kg) combined with either midazolam or propofol has also been administered before injection of local anesthetics in outpatients undergoing a variety of surgical procedures.18,43–47 Ketamine has the advantage over opioid analgesics of producing less ventilatory depression and PONV while providing better intraoperative analgesia than the NSAIDs, when it is combined with propofol as part of a MAC technique. Importantly, both midazolam and propofol are highly effectively in attenuating the dysphoric and psychomimetic side effects associated with ketamine administration.18,45,46 When used for sedation during local anesthesia, newer formulations of propofol may reduce pain on injection (eg, propofol-MCT/LCT,48 a propofol prodrug [fospropofol disodium] called Aquavan)49 and the risk of hyperlipidemia (eg, Ampofol) during prolonged sedation.50

The α2-agonists reduce central sympathetic outflow and have been shown to produce both anxiolysis and sedation.10 Kumar and colleagues51 demonstrated that oral clonidine (300 mcg) provided effective anxiolysis for elderly patients undergoing ophthalmic surgery under local anesthesia and also decreased the incidence of intraoperative hypertension and tachycardia. Dexmedetomidine, a more selective and potent α2-agonist, significantly decreased anxiety levels and reduced the requirements for supplemental opioid analgesic medications when given before IV regional anesthesia for hand surgery.52 When comparing dexmedetomidine with midazolam for sedation, Aho and coworkers53 described a faster recovery from sedation when dexmedetomidine was followed by reversal with the specific α2-antagonist atipamezole. Unfortunately, the midazolam-treated patients did not receive the reversal drug flumazenil. In the early studies, administration of dexmedetomidine during local anesthesia was associated with severe bradycardia. However, more recent studies54,55 involving lower dosages have been associated with good intraoperative hemodynamic stability and reduced patient discomfort during local anesthesia compared with midazolam and propofol.

Other nonopioid analgesics that may be useful adjuvants to local anesthesia in the future include novel compounds like gabapentin and pregabalin,56–58 as well as adenosine59 and compounds that can elevate levels of this endogenous compound. For example, pregabalin (300 mg) produced a significantly longer duration of analgesia than ibuprofen (400 mg) after oral surgery under local anesthesia.57 Although lacking any intrinsic analgesic properties, dexamethasone has been found to facilitate an earlier discharge after MAC independent of its well-known antiemetic properties.60 Perhaps one of the most intriguing new analgesic compounds in development is capsaicin (ALGRX 4975) for injection, as well as a gel formulation for intraoperative topical applications. Although capsaicin causes transient discomfort on administration, it can produce prolonged analgesia by producing localized degradation of the C-neuron endings. Topical treatment with capsaicin may offer other clinical advantages over existing analgesic drugs used to prevent postoperative pain in combination with local anesthetics (eg, by reducing tissue swelling).61

Several investigators have evaluated the use of patient-controlled sedation–analgesia.62–67 Although self-administration of midazolam and propofol can be an effective alternative to MAC in selected patients, careful monitoring is required to optimize surgical conditions and patient safety.62 Osborne and colleagues65 reported that patient-controlled sedation with propofol was preferred by the patients over a standard propofol infusion during MAC. Nevertheless, many patients prefer to have an expert in charge of sedative–analgesic drug administration during surgery.62 Interestingly, patient-controlled sedation requirements were similar for cataract surgery under topical and retrobulbar anesthesia.66 Use of intraoperative patient-controlled analgesia with potent opioids can produce significant ventilatory depression when patients are also receiving sedative–hypnotic drugs.62 However, a recent study suggested patient-controlled remifentanil administration in combination with midazolam sedation is “a safe and reliable” method in conjunction with local anesthesia for oral surgery.67

Subanesthetic concentrations of inhaled anesthetics (eg, N2O, 30–50% in oxygen or sevoflurane 0.3–0.6% inspired) can also be used to supplement local and regional anesthesia.68,69 However, this technique did not offer any significant advantages over IV midazolam70 or propofol.71 The primary concerns in using inhaled anesthetics are the ease with which the patient can drift into an unconscious state or develop upper airway obstruction, as well as the issue of OR air pollution. Therefore, volatile anesthetics are rarely used, and N2O is only used to supplement inadequate local anesthesia or PNBs not well-controlled by potent parenteral opioid analgesics.

Finally, nonpharmacologic therapies like music,72,73 electroanalgesia,74,75 and hypnosis76 may also prove useful in enhancing patient comfort and in reducing the sedative and analgesic requirements during surgical procedures under local anesthesia in the future. If effective, these nonpharmacologic approaches have the potential of reducing drug-related side effects and adverse drug interactions during the perioperative period (Table 11–4).77

Due to the presence of an anesthesia provider, the cost for MAC is obviously higher than for OR nurse-administered “conscious sedation.” Although some studies have suggested that patient outcomes are comparable for the two methods,78 these findings have been seriously questioned because of flaws in the study design.70 Although so-called “unmonitored” local anesthesia can be used as an alternative to MAC for minor surgical procedures,71 most patients (and surgeons) prefer the presence of an anesthesia provider to ensure optimal sedation and analgesia during surgery under local anesthesia.79 From a cost–benefit perspective, local anesthesia and PNBs with or without sedation offer significant advantages in addition to reduced costs compared with general and central neuroaxial anesthesia.79 One study found that when MAC was used for assisted reproductive procedures the patients' experienced improved pregnancy rates compared with the same procedures performed under general anesthesia.80

In women undergoing laparoscopic tubal sterilization with a MAC technique, the anesthetic drug costs were found to be significantly reduced relative to general anesthesia (US $21 vs $46, respectively).81 The MAC technique was also associated with less time in the OR, a higher degree of alertness on the evening of the day of surgery, as well as decreased postoperative pain (33% vs 80%) and sore throats (3% vs 70%), contributing to a significant reduction in the overall perioperative costs. Patel and coworkdes82 reported that the use of MAC sedation resulted in a 6- to 7-min decrease in OR exit time compared with general anesthesia with desflurane, contributing to enhanced turnover of cases. Similarly, comparative studies involving general endotracheal anesthesia, central neuroaxial blockade, and MAC techniques for inguinal herniorrhaphy (Table 11–5)83 and anorectal (Table 11–6)84 procedures have consistently found improved recovery profiles, decreased side effects, greater patient satisfaction, and reduced anesthetic costs with MAC.83–85 More recent studies86–88involving outpatients undergoing orthopedic procedures have also found superior recovery profiles with PNB compared with those for general anesthesia, contributing to a more favorable cost–benefit profile. The use of topical local anesthetics has also offered significant advantages for outpatients undergoing ophthalmologic (eg, cataract)66 and plastic (eg, facial laser resurfacing) surgery procedures.89 The effect of the anesthetic technique on cost and recovery time is an increasingly important consideration in today's clinical practice environment because of the heavy emphasis on “fast-tracking” recovery processes.

In summary, the use of local (infiltration) or regional anesthesia with IV sedation–analgesia is the anesthetic technique of choice for providing cost-effective anesthetic care for patients undergoing superficial (noncavitary) surgical procedures (Table 11–7).1,90 The most important factors in achieving the desired clinical outcome and highest patient satisfaction are achieving effective local analgesia and carefully titrating intravenous sedative and analgesic medications to avoid ventilatory depression and to ensure a prompt recovery of cognitive functioning following surgery. The recommended loading and maintenance doses of the most commonly used IV-selective analgesic drugs are summarized in Table 11–8.90

In conclusion, use of sedation–analgesia techniques in combination with local anesthesia and regional anesthesia achieve the best outcome for the patient at the lowest cost to the health care system. When properly applied, the use of MAC techniques can provide excellent operating conditions while optimizing patient comfort and safety during the operation, while ensuring a prompt resumption of normal activities of daily living after surgery.