Sedative-hypnotic drugs as well as narcotics are commonly used perioperatively to make regional anesthesia more tolerable for patients by reducing anxiety and providing an appropriate degree of sedation, amnesia, and analgesia.

        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.

Figure 11-1. The dose-dependent spectrum of central nervous system depression produced by sedative-hypnotic drugs. MAC = monitored anesthesia care; LOC = loss of consciousness; LPR = loss of protective reflexes.

        USE OF ADJUNCTIVE SEDATIVE-HYPNOTIC DRUGS

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).

Clinical Pearls

        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.

Clinical Pearls

    Routes of administration: PO = oral, IM = intramuscular, IV = intravenous, SQ = subcutaneous/tissue, TENS = transcutaneous electrical nerve stimulation, and PR = per rectum.

    Reprinted, with permission, from White PF: Perioperative Drug Manual, Elsevier/Saunders Publishers, 2005.

        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 costeffective 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

        ROLE OF OPIOID & NONOPIOID ANALGESICS

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.

    Reprinted, with permission, from White PF: Perioperative Drug Manual, Elsevier/Saunders Publishers, 2005.

Clinical Pearls

        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 meg) 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 meg) 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 ocα₂-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 studies^54,55 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

        MISCELLANEOUS TECHNIQUES USED TO SUPPLEMENT LOCAL ANESTHESIA

Several investigators have evaluated the use of patientcontrolled 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 patientcontrolled 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, N₂0, 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.

Related posts:

Regional Anesthesia in the Patient with Preexisting Neurologic Disease. Preemptive Analgesia, Regional Anesthesia, & the Prevention of Chronic Postoperative Pain. Newer Amide Anesthetics & Sustained-Release Local Anesthetics1. Diagnosis & Management of Intraspinal, Epidural, & Peripheral Nerve Hematoma. Histology of Peripheral Nerves. Supraclavicular Brachial Plexus Block.