Midazolam anesthesia

Midazolam (Versed), a short-acting benzodiazepine CNS depressant, is used as a preanesthetic drug to relieve anxiety for induction of anesthesia for conscious sedation before minor procedures, such as endoscopic procedures and to supplement nitrous oxide and oxygen for short surgical procedures. When the drug is used for induction anesthesia, the patient gradually loses consciousness during a period of 1 to 2 minutes. 

The answer is a. (Hardman, p 373. Katzung, pp 430-431.) Midazolam is useful for sedation because it produces a higher incidence of amnesia and has a more rapid onset of action and a shorter half-life than other benzodiazepines used in anesthesia... 

Midazolam is a rapidly metabolized benzodiazepine (p. 228) that is used for induction of anesthesia. The longer-acting lorazepam is preferred as adjunct anesthetic in prolonged cardiac surgery with cardiopulmonary bypass its am-nesiogenic effect is pronounced. 

The synthesis of these compounds will be described in Section 3.1, Opioid analgesics. Besides opioids, benzodiazepines (diazepam, lorazepam, and midazolam), which have anxiolytic, sedative, and anticonvulsant effects, that cause amnesia and muscle relaxation, are frequently used to relieve patients anxiety during anesthesia. 

General anesthesia - Remifentanil is not recommended as the sole agent in general anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. Remifentanil is synergistic with other anesthetics and doses of thiopental, propofol, isoflurane, and midazolam have been... 

Midazolam (Versed), diazepam (Valium), and lo-razepam (Ativan) are benzodiazepine derivatives that are useful in anesthesia. Midazolam is the most popular of these agents for the induction of anesthesia. Its popularity is related to its aqueous solubility and to its short duration of action, which permits a prompt return of psychomotor competence. Unlike midazolam, lor-azepam and diazepam are not water soluble and must be formulated in propylene glycol the latter is irritating to the vasculature on parenteral administration. 

Benzodiazepines have the capacity to produce a calming effect and to cause anterograde amnesia, in which the patient cannot recall events that took place for some time after the drug was administered. Benzodiazepine-induced sedation and amnesia are deemed useful in the preparation of patients for anesthesia, surgery, and other frightening or unpleasant medical and dental procedures and diagnostic tests. Midazolam is a frequently used anesthetic benzodiazepine (see Chapter 25). 

Most BZs are completely absorbed from the gastrointestinal (GI) tract. The one exception is clorazepate, a pro-drug that undergoes acid hydrolysis in the stomach and is decarboxylated to form N-desmethyl-diazepam, which is then completely absorbed into the bloodstream (Bellantuono et ak, 1980 Hobbs et ak, 1996 Chouinard et ak, 1999). In contrast, most BZs, with the exception of lorazepam and midazolam, are not consistently absorbed from intramuscular injection (Chouinard et ak, 1999). Lorazepam is available as a sublingual form that reaches clinical effect at the same rate as an oral dose. In general, intravenous administration is used only for anesthesia or for the acute management of seizures. When BZs are given via this route, the onset of action is almost immediate (Chouinard et ak, 1999). 

Benzodiazepines—including diazepam, lorazepam, and midazolam—are used intravenously in anesthesia (see Chapter 25), often in combination with other agents. Not surprisingly, benzodiazepines given in large doses as adjuncts to general anesthetics may contribute to a persistent postanesthetic respiratory depression. This is probably related to their relatively long half-lives and the formation of active metabolites. However, such depressant actions of the benzodiazepines are usually reversible with flumazenil. 

Midazolam Slow onset and recovery flumazenil reversal available Used in balanced anesthesia and conscious sedation provides cardiovascular stability and marked amnesia... 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

Diazepam, lorazepam, and midazolam are used for preanesthetic medication and as adjuvants during surgical procedures performed under local anesthesia. As a result of their sedative, anxiolytic, and amnestic properties, and their ability to control acute agitation, these compounds are considered to be the drugs of choice for premedication. (The basic pharmacology of benzodiazepines is discussed in Chapter 22.) Diazepam and lorazepam are not water-soluble, and their intravenous use necessitates nonaqueous vehicles, which cause pain and local irritation. Midazolam is water-soluble and is the benzodiazepine of choice for parenteral administration. It is important that the drug becomes lipid-soluble at physiologic pH and can readily cross the blood-brain barrier to produce its central effects. 

The technique typically involves the use of intravenous midazolam for premedication (to provide anxiolysis, amnesia, and mild sedation) followed by a titrated, variable-rate propofol infusion (to provide moderate to deep levels of sedation), and a potent opioid analgesic or ketamine (to minimize the discomfort associated with the injection of local anesthesia and the surgical manipulations). 

Deep sedation is similar to a light state of general (intravenous) anesthesia involving decreased consciousness from which the patient is not easily aroused. Because deep sedation is often accompanied by a loss of protective reflexes, an inability to maintain a patent airway, and lack of verbal responsiveness to surgical stimuli, this state may be indistinguishable from intravenous anesthesia. Intravenous agents used in deep sedation protocols include the sedative-hypnotics thiopental, methohexital, midazolam, or propofol, the potent opioid analgesics, and ketamine. 

Induce and maintain anesthesia using a mixture of fentanyl/ fluanisone with midazolam (Hypnorm/Hypnovel see Note 4). The dosage for these agents is 0.25 mL of each active ingredient plus 0.5 mL of water given IP at a rate of 0.1 mL per mouse. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Adjunctive use of potent opioids (eg, fentanyl and related compounds) contributes cardiovascular stability, enhanced sedation, and profound analgesia. Other intravenous agents such as the benzodiazepines (eg, midazolam, diazepam) have slower onset and recovery features and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines can be used to provide a basal level of sedation and amnesia when used in conjunction with other anesthetic agents. 

Many diagnostic, therapeutic, and minor surgical procedures require neither general anesthesia nor the availability of specialized equipment and facilities necessary for inhaled anesthesia. In this setting, regional or local anesthesia supplemented with midazolam or propofol and opioid analgesics may be a more appropriate and safer approach than general anesthesia. 

During all valvuloplasty interventions antibiotics (e.g., cefuroxime, I, 5 g, i.v.) are administered. Patients allergic to penicillin should receive vancomycin I g intravenously. Most physicians perform transcatheter valvuloplasty in the fasting state under mild sedation, Substances that are frequently used are meperidine, promethazine, and chlorpromazine, given intramuscularly or intermittent doses of midazolam (0.05 to 0.1 mg/kg, i.v.) and/or fentanyl (0.5 to 1.0 Lig/kg, i.v.). Some operators also apply ketamine or general anesthesia for all interventional cases. 

General anesthetics are rarely given alone. In addition to the analgesic agents just mentioned, benzodiazepines (midazolam, Versed diazepam, Valium ) are commonly used as adjuncts for the relief of anxiety, amnesia, and sedation prior to induction of anesthesia. Neuromuscular blockers (e.g., succinylcholine or pancuronium) can also be administered during the induction of anesthesia to relax skeletal muscles. 

The rats are fasted for about 4 h and are anesthetized with 80 mg/kg bw Ketamin plus 5 mg/kg Midazolam administered intravenously into the tail vein via an indwelling venous catheter. The amount corresponds to a volume of about 0.3 mL. Anesthesia is monitored by checking the reflexes and is maintained by repeat dosing of ketamine/midazolam. 

Droperidol 5-7.5 mg given during induction of anesthesia was associated with impaired well-being scores 6 hours postoperatively in a randomized double-blind comparison of similar doses of droperidol (n = 78) and midazolam (n = 72) for preventing postoperative nausea and vomiting (2). 

In 113 patients undergoing general anesthesia, intravenous midazolam 15 mg slowed recovery of the twitch height after vecuronium and atracurium compared with diazepam. The recovery index was not altered (162). However, in another study in 20 patients, midazolam 0.3 mg/kg did not affect the duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation produced by suxamethonium 1 mg/kg, nor the duration of blockade and adequacy of relaxation for tracheal intubation produced by pancuronium 0.025 mg/kg in incremental doses until 99% depression of muscle-twitch tension was obtained (161). Furthermore, in 60 patients undergoing maintenance anesthesia randomly assigned to one of six regimens (etomidate, fentanyl, midazolam, propofol, thiopental plus nitrous oxide, or isoflurane plus nitrous oxide), midazolam did not alter rocuronium dosage requirements (165). 

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