6.4.9Malignant Hyperthermia Susceptibility

Patients with susceptibility to malignant hyperthermia (MH) can be successfully managed on an outpatient basis if they are closely monitored postoperatively for at least 4 h [108]. Triggering agents include volatile inhalation agents such as halothane, enflurane, desflurane, isoflurane, and sevoflurane. Even trace amounts of these agents lingering in an anesthesia machine or breathing circuit may precipitate a MH crisis. Succinylcholine and chlopromazine are other commonly used medications, which are known triggers of MH. However, many nontriggering medications may be safely used for local anesthesia, sedation-analgesia, postoperative pain control, and even, general anesthesia [109]. Nevertheless, anesthesia for patients suspected to have MH susceptibility should not be performed at an office-based setting. Standardized protocol to manage MH (available from the Malignant Hyperthermia Association of the United States, MHAUS) and supplies of dantrolene and cold intravenous fluids should be available for all patients.

Preferably, patients with MH susceptibility should be referred to an anesthesiologist for prior consultation. Intravenous dantrolene [110] and iced intravenous fluids are still the preferred treatment. MHAUS may be contacted at 800-98MHAUS and the MH hotline is 800-MH-HYPER.

6.5 Selections and Delivery of Anesthesia

Anesthesia may be divided into four broad categories, local anesthesia, and local anesthesia combined with sedation, regional anesthesia, and general anesthesia.

The ultimate decision to select the type of anesthesia depends on the type and extent of the surgery planned, the patient’s underlying health condition, and the psychological disposition of the patient. For example, a limited procedure in a calm, healthy patient could certainly be performed using strictly local anesthesia without sedation. As the scope of the surgery broadens, or the patient’s anxiety level increases, the local anesthesia may be supplemented with oral or parenteral analgesic or anxiolytic medication. As the complexity of the surgery increases, general anesthesia may be the most appropriate choice.

6.5.1 Local Anesthesia

A variety of local anesthetics are available for infiltrative anesthesia. The selection of the local anesthetic depends on the duration of anesthesia required and the volume of anesthetic needed. The traditionally accepted, pharmacological profiles of common anesthetics used for infiltrative anesthesia for adults are summarized in Table 6.5 [111].

The maximum doses may vary widely depending on the type of tissue injected [112], the rate of administration [113], the age, underlying health, and body habitus of the patient [114], the degree of competitive protein binding [115], and possible cytochrome inhibition of concomitantly administered medications [116]. The maximum tolerable limits of local anesthetics have been redefined with the development of the tumescent anesthetic technique [117]. Lidocaine doses up to 35 mg/kg were found to be safe, if administered in conjunction with dilute epinephrine during liposuction [118]. With the tumescent technique, peak plasma

levels occur 6–24 h after administration [118, 119]. More recently, doses up to 55 mg/kg have been found to be within the therapeutic safety margin [120]. However, recent guidelines by the American Academy of Cosmetic Surgery recommend a maximum dose of 45–50 mg/kg [14].

Certainly, significant toxicity has been associated with high doses of lidocaine as a result of tumescent anesthesia during liposuction [121]. The systemic toxicity of local anesthetic has been directly related to the serum concentration by many authors [113, 118–122]. Early signs of toxicity, usually occurring at serum levels of about 3–4 Pg/ml for lidocaine, include circumoral numbness and lightheadedness, and tinnitus. As the serum concentration increases toward 8 Pg/ml, tachycardia, tachypnea, confusion, disorientation, visual disturbance, muscular twitching, and cardiac depression may occur. At still higher serum levels above 8 Pg/ml, unconsciousness and seizures may ensue. Complete cardiorespiratory arrest may occur between 10 and 20 Pg/ml [113, 122]. However, the toxicity of lidocaine may not always correlate exactly with the plasma level of lidocaine presumably because of the variable extent of protein binding in each patient and the presence of active metabolites [113] and other factors already discussed including the age, ethnicity, health, and body habitus of the patient, and additional medications.

Ropivacaine, a long lasting local anesthetic has less cardiovascular toxicity than bupivacaine and may be a safer alternative to bupivacaine if a local anesthetic of longer duration is required [122, 123]. The cardiovascular toxicity of bupivacaine and etidocaine is much greater than lidocaine [122–124]. While bupivacaine toxicity has been associated with sustained ventricular tachycardia and sudden profound cardiovascular collapse [125, 126], the incidence of ventricular dysarrhythmias has not been as widely acknowledged with lidocaine or mepivacaine toxicity. In fact, ventricular tachycardia of fibrillation was not observed despite the use of supraconvulsant doses of intravenous doses of lidocaine, etidocaine, or mepivacaine in the animal model [123].

Indeed, during administration of infiltrative lidocaine anesthesia, rapid anesthetic injection into a highly vascular area or accidental intravascular injection leading to a sudden toxic level of anesthetic resulting in sudden onset of seizures or even cardiac arrest or cardiovascular collapse has been documented [127, 128]. One particularly disconcerting case

presented by Christie [129] confirms the fatal consequence of a lidocaine injection of 200 mg in a healthy patient. Seizure and death occurred following a relatively low dose of lidocaine and a serum level of only 0.4 mg/100 ml or 4 Pg/ml. A second patient suffered cardiac arrest with a blood level of 0.58 mg/100 ml or 5.8 Pg/ml [129]. Although continued postmortem metabolism may artificially reduce serum lidocaine levels, the reported serum levels associated with mortality in these patients were well below the 8–20 Pg/ ml considered necessary to cause seizures, myocardial depression, and cardiorespiratory arrest. The 4 Pg/ml level reported by Christie is uncomfortably close to the maximum serum levels reported by Ostad et al. [120] of 3.4 and 3.6 Pg/ml following tumescent lidocaine doses of 51.3 and 76.7 mg/kg, respectively. Similar near toxic levels were reported in individual patients receiving about 35 mg/kg of lidocaine by Samdal et al. [130]. Pitman [131] reported that toxic manifestations occurred 8 h postoperatively after a total dose of 48.8 mg/kg which resulted from a 12-h plasma lidocaine level of 3.7 Pg/kg. Ostad et al. [120] conclude that because of the poor correlation of lidocaine doses with the plasma lidocaine levels, an extrapolation of the maximum safe dose of lidocaine for liposuction cannot be determined. Given the devastating consequences of toxicity due to local anesthetics, physicians must exercise extreme caution when administering these medications.

Patients who report previous allergies to anesthetics may present a challenge to surgeons performing liposuction. Although local anesthetics of the aminoester class such as procaine are associated with allergic reactions, true allergic phenomena to local anesthetics of the aminoamide class, such as lidocaine, are extremely rare [132, 133]. Allergic reactions may occur to the preservative in the multidose vials. Tachycardia and generalized flushing may occur with rapid absorption of the epinephrine contained in some standard local anesthetic preparations. The development of vasovagal reactions after injections of any kind may cause hypotension, bradycardia, diaphoresis, pallor, nausea, and loss of consciousness. These adverse reactions may be misinterpreted by the patient and even the physician as allergic reactions [132]. A careful history from the patient describing the apparent reaction usually clarifies the cause. If there is still concern about the possibility of true allergy to local anesthetic, then the patient should be referred to an allergist for skin testing [133].

In the event of a seizure following a toxic dose of local anesthetic, proper airway management and maintaining oxygenation is critical. Seizure activity may be aborted with intravenous diazepam (10–20 mg), midazolam (5–10 mg), or thiopental (100–200 mg). Although the ventricular arrhythmias associated with bupivacaine toxicity are notoriously intractable [125, 126], treatment is still possible using large doses of atropine, epinephrine, and bretylium [134, 135]. Some studies indicate that lidocaine should not be used during the resuscitation of a patient from bupivacaine toxicity [136]. Pain associated with local anesthetic administration is due to pH of the solution and the may be reduced by the addition of 1 meq of sodium bicarbonate to 10 ml of anesthetic [137].

Topical anesthetics in a phospholipid base have become more popular as a technique for administering local anesthetics. Application of these topical agents may provide limited anesthesia over specific areas such as the face for minor procedures including limited laser resurfacing. EMLA (eutectic mixture of local anesthetics), a combination of lidocaine and prilocaine, was the first commercially available preparation. The topical anesthetic preparation must be applied under an occlusive dressing at least 60 min prior to the procedure to develop adequate local anesthesia [138]. Even after 60 min the anesthesia may not be complete and the patient may still experience significant discomfort. Many physicians prefer to use their own customized formula, which they obtain from a compounding pharmacy. However, these compounded formulas are not monitored by the FDA and compounding pharmacies may vary in the quality control standards. Some of the formulas may contain up to 40% local anesthetics in various combinations. This type of preparation could deliver up to 400 mg/g of ointment to the patient. The application of 30 g of a compounded formula containing a total of 20% local anesthetic over a wide area with subsequent occlusive dressing could expose the patient to 6,000 mg of local anesthetic. Studies have demonstrated that systemic absorption of local anesthetic after application of topical local anesthetic is limited to less than 5% [139, 140]. Even with limited systemic absorption, the development of toxic blood levels of local anesthetic, with the ensuing catastrophic results, would not be hard to envision if a large quantity of a concentrated compounded anesthetic ointment were applied under an occlusive dressing. There has been at least one case report of death after application

of a compounded local anesthetic ointment while preparing for cosmetic surgery [141]. Physicians who prescribe compounded topical local anesthetics to patients prior to surgery should reevaluate the concentration of these medications as well as the total dose of medication that may be delivered to the patient. Frequently, the patient is given the topical anesthetic to be applied at home prior to arrival to the office or surgical center.

6.5.2Sedative-Analgesic Medication (SAM)

Most minimally invasive procedures may be performed with a combination of local anesthesia and supplemental sedative-analgesic medication (SAM) administered orally (p.o.), intramuscularly (i.m.), or intravenously (i.v.). The goals of administering supplemental medications are to reduce anxiety (anxiolytics), the level of consciousness (sedation), unanticipated pain (analgesia), and, in some cases, to eliminate recall of the surgery (amnesia).

Sedation may be defined as the reduction of the level of consciousness usually resulting from pharmacological interventions. The level of sedation may be further divided into four broad categories, minimal sedation, moderate sedation, deep sedation (also referred to as conscious sedation), and general anesthesia. During minimal sedation patients may respond normally to verbal commands but have impaired cognitive function and coordination. Life-preserving protective reflexes (LPPRs), ventilatory, and cardiovascular functions are generally maintained during minimal sedation. During moderate sedation, while the level consciousness is depressed, the patient should respond in a purposeful manner to soft verbal commands. LPPRs, ventilation, and cardiovascular function are generally maintained in most patients. During deep sedation, the patient becomes difficult to arouse and may respond purposely only with loud verbal or painful tactile stimulation. During deep sedation the patient has a probability of loss of LPPRs and a depression of ventilatory function. Cardiovascular function is usually maintained. Finally, during general anesthesia, there is complete loss of consciousness and the patient is not arousable by any means. There is a high likelihood of loss of LPPRs and suppression of ventilatory and cardiac function under general anesthesia [142].

Life-preserving protective reflexes (LPPRs) may be defined as the involuntary physical and physiological responses that maintain the patient’s life which, if interrupted, result in inevitable and catastrophic physiological consequences. The most obvious examples of LPPRs are the ability to maintain an open airway, swallowing, coughing, gagging, and spontaneous breathing. Some involuntary physical movements such as head turning or attempts to assume an erect posture may be considered LPPRs if these reflex actions occur in an attempt to improve airway patency such as expelling oropharyngeal contents. The myriad of homeostatic mechanisms to maintain blood pressure, heart function, and body temperature may even be considered LPPRs. When patient enters deep sedation, and the level of consciousness is depressed to the point that the patient is not able to respond purposefully to verbal commands or physical stimulation, there is a significant probability of loss of LPPRs. Ultimately, as total loss of consciousness occurs under general anesthesia and the patient no longer responds to verbal command or painful stimuli, the patient most likely looses the LPPRs [142].

In actual practice, the delineation between the levels of sedation becomes challenging at best. The loss of consciousness occurs as a continuum. With each incremental change in the level of consciousness, the likelihood of loss of LPPRs increases. The level of consciousness may vary from moment to moment, depending on the level of surgical stimulation. Since the definition of conscious sedation is vague, current ASA guidelines consider the term sedation-analgesia a more relevant term than conscious sedation [15]. The term sedative-analgesic medication (SAM) has been adopted by some facilities. Monitored anesthesia care (MAC) has been generally defined as the medical management of patients receiving local anesthesia during surgery with or without the use of supplemental medications. MAC usually refers to services provided by the anesthesiologist or the CRNA. The term “local standby” is no longer used because it mischaracterizes the purpose and activity of the anesthesiologist or CRNA.

Surgical procedures performed using a combination of local anesthetic and SAM usually have a shorter recovery time than similar procedures performed under regional or general anesthesia [143]. Using local anesthesia alone, without the benefit of supplemental medication is associated with a greater risk of cardiovascular

and hemodynamic perturbations such as tachycardia, arrhythmias, and hypertension particularly in patients with preexisting cardiac disease or hypertension [144]. Patients usually prefer sedation while undergoing surgery with local anesthetics [145]. While the addition of sedatives and analgesics during surgery using local anesthesia seems to have some advantages, use of SAM during local anesthesia is certainly not free of risk. A study by the Federated Ambulatory Surgical Association concluded that local anesthesia, with supplemental medications, was associated with more than twice the number of complications than with local anesthesia alone. Furthermore, local anesthesia with SAM was associated with greater risks than general anesthesia [146]. Significant respiratory depression as determined by the development of hypoxemia, hypercarbia, and respiratory acidosis has been documented in patients after receiving even minimal doses of medications. This respiratory depression persists even in the recovery period [147, 148].

One explanation for the frequency of complications in patients receiving SAM is the wide variability of patients’ responses to these medications. Up to 20-fold differences in the dose requirements for some medications such as diazepam, and up to fivefold variation for some narcotics such as fentanyl have been documented in some patients [149, 150]. Even small doses of fentanyl as low as 2 Pg/kg, considered by many physicians as subclinical, produce respiratory depression for more than 1 h in some patients [151]. Combinations of even small doses of sedatives, such as midazolam, and narcotics, such as fentanyl, may act synergistically (effects greater than an additive effect) in producing adverse side effects such as respiratory depression and hemodynamic instability [152]. The clearance of many medications may vary depending on the amount and duration of administration, a phenomenon known as context-sensitive half-life. The net result is increased sensitivity and duration of action to medication for longer surgical cases [153]. Because of these variations and interactions, predicting any given patient’s dose-response is a daunting task. Patients appearing awake and responsive may, in an instant, slip into unintended levels of deep sedation with greater potential of loss of LPPRs. Careful titration of these medications to the desired effect combined with vigilant monitoring are the critical elements in avoiding complications associated with the use of SAM. Klein acknowledges that most of the complications attributed to midazolam

and narcotic combinations occurred as a result of inadequate monitoring [154]. Supplemental medication may be administered via multiple routes including oral, nasal, transmucosal, transcutaneous, intravenous, intramuscular, and rectal. While intermittent bolus has been the traditional method to administer medication, continuous infusion and patient controlled delivery result in comparable safety and patient satisfaction [155, 156].

Benzodiazepines such as diazepam, midazolam, and lorezepam remain popular for sedation and anxiolytics. Patients and physicians especially appreciate the potent amnestic effects of this class of medications, especially midazolam (using midazolam “means never having to say you’re sorry”) The disadvantages of diazepam include the higher incidence of pain on intravenous administration, the possibility of phlebitis [157], and the prolonged half-life of up to 20–50 h. Moreover, diazepam has active metabolites, which may prolong the effects of the medication even into the postoperative recovery time [158]. Midazolam, however, is more rapidly metabolized, allowing for a quicker and more complete recovery for outpatient surgery [158]. Because the sedative, anxiolytic and amnestic effects of midazolam are more profound than other benzodiazepines and the recovery is more rapid, patient acceptance is usually higher [159]. Since lorezepam is less affected by medications altering cytochrome P459 metabolisim [160], it has been recommended as the sedative of choice of liposuctions, which require a large dose of lidocaine tumescent anesthesia [121]. The disadvantage of lorezepam is the slower onset of action and the 11–22 h elimination half-life making titration cumbersome and postoperative recovery prolonged [158].

Generally, physicians who use SAM titrate a combination of medications from different classes to tailor the medications to the desired level of sedation and analgesia for each patient. Use of prepackaged or premixed combinations of medications defeats the purpose of the selective control of each medication. Typically, sedatives such as the benzodiazepines are combined with narcotic analgesics such as fentanyl, meperidine, or morphine during local anesthesia to decrease pain associated with local anesthetic injection or unanticipated breakthrough pain. Fentanyl has the advantage of rapid onset and duration of action of less than 60 min. However, because of synergistic action with sedative agents, even doses of 25–50 Pg can result in respiratory depression [161]. Other

medications with sedative and hypnotic effects such as a barbiturate, ketamine, or propofol are often added. Adjunctive analgesics such as ketorolac may be administered for additional analgesic activity. As long as the patient is carefully monitored, several medications may be titrated together to achieve the effects required for the patient characteristics and the complexity of the surgery. Fixed combinations of medications are not advised [15].

More potent narcotic analgesics with rapid onset of action and even shorter duration of action than fentanyl, including sufentanil, alfentanil, and remifentanil, may be administered using intermittent boluses or continuous infusion in combination with other sedative or hypnotic agents. However, extreme caution and scrupulous monitoring is required when these potent narcotics are used because of the risk of respiratory arrest [162, 163]. Use of these medications should be restricted to the anesthesiologist or the CRNA. A major disadvantage of narcotic medication is the perioperative nausea and vomiting [164].

Many surgeons feel comfortable administering SAM to patients. Others prefer to use the services of an anesthesiologist or CNRA. Prudence dictates that for prolonged or complicated surgeries or for patients with significant risk factors, the participation of the anesthesiologist or CRNA during MAC anesthesia is preferable. Regardless of who administers the anesthetic medications, the monitoring must have the same level of vigilance.

Propofol, a member of the alkylphenol family, has demonstrated its versatility as a supplemental sedativehypnotic agent for local anesthesia and of regional anesthesia. Propofol may be used alone or in combination with a variety of other medications. Rapid metabolism and clearance result in faster and more complete recovery with less postoperative hangover than other sedative-hypnotic medications such as midazolam and methohexital [143, 165]. The documented antiemetic properties of propofol yield added benefits of this medication [166]. The disadvantages of propofol include pain on intravenous injection and the lack of amnestic effect [167]. However, the addition of 3 ml of 2% lidocaine to 20 ml of propofol virtually eliminates the pain on injection with no added risk. If an amnestic response is desired, a small dose of a benzodiazepine, such as midazolam (5 mg i.v.), given in combination with propofol, provides the adequate amnesia. Rapid administration of propofol may be associated with