2 - Anesthesia - Analgesia, Sedation, and Neuromuscular Blockade

Editors: Susla, Gregory M.; Suffredini, Anthony F.; McAreavey, Dorothea; Solomon, Michael A.; Hoffman, William D.; Nyquist, Paul; Ognibene, Frederick P.; Shelhamer, James H.; Masur, Henry

Title: Handbook of Critical Care Drug Therapy, 3rd Edition

Copyright 2006 Lippincott Williams & Wilkins

> Table of Contents > Chapter 2 - Anesthesia: Analgesia, Sedation, and Neuromuscular Blockade

Chapter 2

Anesthesia: Analgesia, Sedation, and Neuromuscular Blockade

TABLE 2.1. Commonly Used Agents for Intravenous Sedation/Anesthesia

Drug	Initial IV Dosagea	Maintenance Infusiona	Comments
Barbiturates
Pentobarbital	5 20 mg/kg Onset: <1 min Duration: 15 min	1 4 mg/kg/h	Infuse loading dose over 2 h Rapid administration produces hypotension and hemodynamic instability
Thiopental	3 4 mg/kg Onset: 10 20 s Duration: 5 15 min	Not applicable	Alkaline solution; decreases cardiac index
Benzodiazepines
Diazepam	0.1 0.2 mg/kg Onset: 1 3 min Duration: 1 2 h	Not applicable	Active metabolite with long half-life (desmethyldiazepam) contributes to activity
Lorazepam	0.04 mg/kg Onset: 5 15 min Duration: 1 6 h	0.02 0.1 mg/kg/h	No active metabolites Approximately 5 times more potent than diazepam
Midazolam	0.025 0.035 mg/kg Onset: 1 3 min Duration: 30 min 3 h	0.05 5 g/kg/min	Elderly patients may develop apnea when midazolam is administered with narcotics Approximately 3 4 times more potent than diazepam Active metabolites accumulate in renal failure Unpredictable elimination in critically ill patients (e.g., shock, liver failure) Initial dose: 0.5 1 mg and titrate to effect in 0.5 2 mg increments
Other
Propofol	1 2 mg/kg Onset: <1 min Duration: 5 10 min	5 75 g/kg/min	Generally a rapid recovery Pain on injection is common with peripheral administration Hypotension may occur especially with rapid bolus in hypovolemic or elderly patients Propofol may increase serum triglyceride levels when used at high infusion rates; take caution when using in patients with pancreatitis Doses of propofol of 5 mg/kg/h have been associated with cardiac failure and death Safety of propofol has not been established for ICU sedation of children Propofol contains 1.4 mmol of PO4=/100 ml
Dexmedeto- midine	1 g/kg IV over 10 min	0.2 0.7 g/kg/h for up to 24 h	Alpha-2 adrenergic agonist with analgesic and sedative properties Numerous cardiovascular effects including brady- and tachyarrhythmias, hyper- and hypotension, and atrioventricular block Does not produce respiratory depression
Ketamine	1 2 mg/kg (or 5 10 mg/kg IM) Onset: <1 min Duration: 5 10 min	9 45 g/kg/min	Usually preserves airway reflexes Central sympathetic stimulation; hypertension; tachycardia; advantageous in hypovolemic patients Tachyphylaxis is rare
Etomidate	0.3 0.4 mg/kg Onset: <1 min Duration: 3 5 min	Not recommended Produces adrenal suppression in continuous infusion	Minimal cardiovascular effects Myoclonic muscle movements Pain on IV injection
Remifentanil	0.05 g/kg Onset: <1 min Duration: <4 min	0.05 0.2 g/kg/min	Ultrashort acting narcotic analgesic; used primarily as an intraoperative analgesic; elimination not dependent on liver or kidney function
CNS, central nervous system; ICU, intensive care unit; IM, intramuscular; IV, intravenous aBolus doses and rates of infusion should be individualized to provide the desired level of sedation with consideration of potential hemodynamic compromise. Doses should generally be reduced for elderly and hypovolemic patients. It may be beneficial to wake patients daily and assess their CNS function during maintenance infusions to determine the minimal dose required for sedation.

P.20

P.21

P.22

TABLE 2.2. Tracheal Intubation Techniques

Technique	Clinical Setting	Procedural Features	Cautions
All listed below	Indications: Upper airway obstruction Airway protection Tracheal toilet	Minimum required monitoring ECG, BP, pulse oximetry Prepare patient for 100% O2 Establish IV access for rapid administration of resuscitative drugs and fluids if necessary Equipment and drugs: Oxygen bag-mask ventilation equipment, monitors, suction laryngoscopes, ETT, stylettes, cuff, syringes, Code Blue cart Anesthetics: Neuromuscular blocking agents, Sedative/hypnotic agents	Aspiration Loss of airway Dental damage Trauma to airway Hemodynamic compromise
Awake	Anticipated difficult laryngoscopy Full stomach Minimize risk of airway loss as a result of sedation or neuromuscular blockade Assessment and protection of neurologic function in cervical spine instability Can be performed without depression of airway reflexes Requires patient cooperation	Patient maintains airway and ventilation	Vomiting from pharyngeal stimulation Hypertension and tachycardic response to intubation is undesirable in certain clinical settings (e.g., myocardial ischemia, cerebral or aortic aneurysm) Topical anesthesia of larynx or nerve blocks of larynx obtunds protective airway reflexes
Conscious: Oral	Allows largest diameter ETT	Topical anesthesia of pharynx or pharyngeal nerve blocks Intubation with direct vision
Conscious: Blind nasal		Apply vasoconstrictor and topical anesthetic to nasal mucosa Gently dilate nasal passage with soft nasal airways Gently advance ETT from nose to trachea during inhalation	Nasal bleeding, avoid in coagulopathic patients Sinusitis Avoid in craniofacial trauma
Fiberoptic (oral or nasal)		Consider administering an antisialagogue (glycopyrrolate 0.2 mg IV) Topical anesthetic and vasoconstrictor (for nasal) Insert bronchoscope through ETT and directly into trachea Advance ETT over bronchoscope and remove bronchoscope
Not Awake	Uncooperative patients Preexisting loss of consciousness (e.g., cardiac arrest, heavy sedation) Blunts tachycardic and hypertensive response Minimizes unpleasantness of procedure		Risk of apnea, aspiration, airway loss
Unsedated unconscious	Cardiac arrest	Bag-mask ventilation until intubation equipment available Immediate oral laryngoscopy and intubation
Rapid-sequence: oral (see Table 2.3)	Full stomach or risk of aspiration in a patient without an anatomically difficult airway for laryngoscopy	Administration of sedative and neuromuscular blocking agents Cricoid pressure Rapid intubation after onset of neuromuscular blockade Check ETT placement Remove cricoid pressure	Risk of airway loss Hemodynamic compromise may result from sedation or positive pressure ventilation
Reintubation	Nonfunctioning ETT (e.g., cuff leak) Placement of an ETT with different features (e.g., larger diameter)	Sedate and administer neuromuscular blockade	Chronically intubated patients may have swelling or traumatic changes of larynx making reintubation difficult Patients who are dependent on high oxygen concentrations or PEEP may become hypoxemic
Direct vision extubation and reintubation	Laryngoscopy possible	Perform laryngoscopy with existing ETT in place If glottis is visualized, remove existing ETT and replace with new one	Loss of airway
Styletted reintubationa	Difficult laryngoscopy anticipated	Insert stylette into existing ETT Remove ETT without removing stylette Insert new ETT over stylette
BP, blood pressure; ETT, endotracheal tube; ECG, electrocardiogram; IV, intravenous; PEEP, positive end-expiratory pressure aaRefers to specific intubating stylettes and not to those routinely used to stiffen ETT during routine intubation.

P.23

TABLE 2.3. Suggested Drugs for Rapid Sequence Intubation

Drug	Dosage	Comment
Sedatives/Anesthetics
Thiopental	3 4 mg/kg IV	Reduce dose in elderly and hemodynamically unstable patients (0.25 1 mg/kg) May produce hypotension and hemodynamic instability Blunts intracranial hypertensive response to intubation and is useful in hemodynamically stable patients with elevated ICP
Ketamine	1 2 mg/kg IV 4 10 mg/kg IM	Useful in hypovolemic patients as this drug tends to support the circulation; may rarely produce myocardial depression Produces hypertension, tachycardia, and elevates ICP; therefore, avoid in patients with myocardial ischemia, severe hypertension, or intracranial mass lesions
Etomidate	0.3 0.4 mg/kg IV	Hemodynamic stability Patients often have benign nonpurposeful muscle movements during induction which may be blunted by low doses of fentanyl (50 100 g)
Propofol	1 2.5 mg/kg IV	Reduce dose in elderly and hemodynamically unstable patients (0.25 0.5 mg/kg) May produce hypotension and hemodynamic instability
Muscle Relaxantsa
Cisatracurium	0.15 0.2 mg/kg IV	Slower in onset than succinylcholine Less histamine release than atracurium Hemodynamic stability Duration of action is dose-dependent (30 min 1 h)
Rocuronium	0.6 1.2 mg/kg IV	Reported as most rapid onset of nondepolarizing neuromuscular blocking drugs (60 90 s) Not recommended in Caesarean section patients Hemodynamic stability Duration of action is dose dependent (30 min 1 h)
Succinylcholine	1 mg/kg IV	Depolarizing agent Because of rapidity of onset, drug of choice unless specifically contraindicated (see Table 2.4) Duration of action [congruent]10 min for patients with normal pseudocholinesterase activity
Vecuronium	0.1 0.28 mg/kg	Slower onset than succinylcholine Hemodynamic stability Duration of action is dose dependent (30 min 1 h)
ICP, intracranial pressure; IM, intramuscular; IV, intravenous aFor most clinical situations, cost may be the overriding consideration when choosing among the available nondepolarizing muscle relaxants.

P.24

P.25

TABLE 2.4. Neuromuscular Blockade Bolus Dosing

Agent	Dosage	Onset/Duration	Comments
Depolarizing Relaxant
Succinylcholinea	Bolus: 1 2 mg/kg	Onset: 1 min Duration: 10 min	Prolonged effect in pseudocholinesterase deficiencies Contraindications: family history of malignant hyperthermia, neuromuscular disease, hyperkalemia, open eye injury, major tissue injury (burns, trauma, crush); increased intracranial pressure; not indicated for routine use in children or adolescents Side effects: bradycardia (especially in children), tachycardia, increased serum potassium
Nondepolarizing Relaxants
Atracurium	Bolus: 0.5 mg/kg	Onset: 2 min Duration: 30 40 min	Rapid injection of atracurium bolus doses >0.6 mg/kg releases histamine and may precipitate asthma or hypotension Metabolized in the plasma by Hofmann elimination and ester hydrolysis Duration not prolonged by renal or liver failure; otherwise, see comments with vecuronium
Cisatracurium	Bolus: 0.15 mg/kg	Onset: 2 min Duration: 30 40 min	Less histamine release than racemic atracurium (see above) Metabolism and duration of action similar to atracurium
Mivacurium	Bolus: 0.15 mg/kg followed in 30 s by 0.10 mg/kg	Onset: 1.5 min Duration: 25 min	Inject over 30 s May cause histamine release Metabolized by pseudocholinesterase
Rocuronium	Bolus: 0.6 mg/kg	Onset: 1 min Duration: 30 40 min	Metabolized by liver, prolonged duration in hepatic failure Duration not prolonged by renal failure Used when succinylcholine is contraindicated or not preferred
Vecuronium	Bolus: 0.1 mg/kg	Onset: 2 min Duration: >30 40 min	Metabolized by liver; duration not significantly prolonged by renal failure
	Bolus: 0.28 mg/kg	Onset: 60 s Duration: 100 min	Used when succinylcholine is contraindicated or not preferred No cardiovascular effects
aThe pharmaceutical companies that manufacture succinylcholine have changed the package insert to indicate that the drug should not be used routinely in children, except for airway emergencies, risk of aspiration, and special situations. This practice is a response to reported complications including malignant hyperthermia, masseter muscle rigidity, rhabdomyolysis, and sudden cardiac arrest in children with undiagnosed myopathies.

P.26

TABLE 2.5. Neuromuscular Blockade Maintenance Dosing

Agent	Maintenance Dosage	Duration	Comments
Short Acting
Mivacurium	0.01 0.1 mg/kg Infusion: 9 10 g/kg/min	15 min	Metabolized by pseudocholinesterase
Intermediate Acting
Atracuriuma	0.08 0.10 mg/kg Infusion: 5 9 g/kg/min	15 25 min	Elimination independent of renal or hepatic function
Cisatracuriuma	0.01 0.02 mg/kg Infusion: 1 2 g/kg/min	15 25 min	Elimination independent of renal or hepatic function
Rocuroniuma	0.1 0.2 mg/kg Infusion: 10 12 g/kg/min	10 25 min	Metabolized primarily by the liver Active metabolite significantly less potent than parent compound
Vecuroniuma	0.01 0.15 mg/kg Infusion: 1 g/kg/min	15 25 min	Bile is main route of elimination Minimal dependence on renal function, although active metabolite accumulates in renal failure
Long Acting
Doxacuriuma	0.005 0.01 mg/kg Infusion: 0.25 g/kg/min (not generally recommended)	35 45 min	Cardiovascular stability Predominantly renal elimination significant accumulation in renal failure
Pancuroniuma	0.01 0.015 mg/kg Infusion: 1 g/kg/min (not generally recommended)	25 60 min	Tachycardia (vagolytic effect) Active metabolite accumulates in renal failure
aProlonged infusions of neuromuscular blocking drugs have been associated with undesirable prolongation of neuromuscular blockade and myopathy. When indicated, general guidelines for use of infusions include: (a) periodic monitoring of neuromuscular function (train-of-four stimulation) during administration of infusions, and (b) infusions should be stopped every 24 28 hours to allow recovery of function. Concurrent steroid administration may increase likelihood of this complication.

P.27

TABLE 2.6. Reversal of Nondepolarizing Neuromuscular Blocking Drugs

Drug	Dosage	Onset/Duration	Comments
Neostigmine-Glycopyrrolate	25 75 g/kg 5 15 g/kg	Onset: 3 8 min Duration: 40 60 min
Pyridostigmine-Glycopyrrolate	100 300 g/kg 5 15 g/kg	Onset: 2 5 min Duration: 90 min	Must be used to reverse long-acting neuromuscular blocking agents (i.e., doxacurium, pancuronium)
Edrophonium-Atropine	500 1000 g/kg 10 g/kg	Onset: 30 60 s Duration: 10 min	Rapid onset; not useful for deep blockade
Use lower doses to reverse minimal blockade, maximum doses for deep blockade. The anticholinergic agent must be given to block undesired muscarinic effects of anticholinesterase drug; this applies even when the patient has a baseline tachycardia. Reversal of neuromuscular blockade is associated with a high incidence of transient arrhythmias.

P.28

TABLE 2.7. Topical Anesthetics

Agent	Concentration	Use	Comments
Cocaine	4%	Topical to nares and nasopharynx prior to nasal intubation	Vasoconstriction Controlled substance
Lidocaine	1 4%	Solution: oropharynx, tracheobronchial tree Viscous: nasal and oral pharynx	Vasodilating, therefore must be used in conjunction with a vasoconstrictor during nasal intubation Dilute solutions (1 2%) may be nebulized and inhaled to provide anesthesia for bronchoscopy Total dose should be less than 400 mg Large doses have been associated with methemoglobinemia
Eutectic Mixture Lidocaine and Prilocaine (EMLA)		Apply to skin for 1 h prior to procedures involving skin puncture	Application to inflamed skin may increase absorption Ineffective when rubbed into skin

P.29

TABLE 2.8. Local Anesthetics for Infiltration and Nerve Blocks

Drug	Concentration (Maximum Dose)	Use	Features
Lidocaine	0.5% (400 mg without epinephrine; 500 mg with epinephrine)	Local infiltration	Relatively short duration Epinephrine prolongs block and decreases peak levels
Lidocaine	1 2% (400 mg without epinephrine; 500 mg with epinephrine)	Nerve blocks	Short duration Epinephrine prolongs block and decreases peak levels
Bupivicaine	0.25 0.75%	Nerve blocks Epidural	Long duration, slow onset Addition of epinephrine may not prolong block but may decrease systemic absorption
Avoid epinephrine-containing solutions in areas supplied by end-arteries (e.g., fingers, toes, penis). Nerve blocks should be performed by personnel trained in the procedures and in treatment of local anesthetic toxicity.

P.30

TABLE 2.9. Comparison of Narcotic Analgesics

Drug	Route/Equivalencea	Onset of Action (min)	Peak Analgesic Effect (min)	Duration of Action (h)
Alfentanil	IM: 1 mg	IV: 1 2	IV: 1 2	IV: 0.25
Codeine	PO: 200 mg	PO: 30 45	PO: 60 120	PO: 4 6
	IM: 120 mg	IM: 10 30	IM: 30 60	IM: 4
Fentanyl	IM: 0.1 mg	IV: <1	IV: 1 2	IV: 0.5 1
		IM: 7 5	IM: N/A	IM: 1 2
Hydromor-phone	PO: 7.5 mg	PO: 30	PO: 90 120	PO: 4
	IM: 1.5 mg	IM: 30 60	IM: 4 5
		IV: 10 15	IV: <20	IV: 2 3
Levorphanol	PO: 4 mg	PO: 10 60	PO: 90 120	PO: 4 5
	IM: 2 mg	IM: N/A	IM: 30 60	IM: 4 5
			IV: <20	IV: 4 5
Meperidine	PO: 300 mg	PO: 15	PO: 60 90	PO: 2 4
	IM: 75 mg	IM: 10 15	IM: 60 120	IM: 2 4
		IV: 1	IV: 15 30	IV: 2 4
Methadone	PO: 20 mg	PO: 30 60	PO: 90 120	PO: 4 6b
	IM: 10 mg	IM: 10 20	IM: 60 120	IM: 4 5b
		IV: N/A	IV: 15 30	IV: 3 4b
Morphine	PO: 60 mg	PO: 15 60	PO: 60 120	PO: 4 5
	IM: 10 mg	IM: 10 30	IM: 30 60	IM: 4 5
		IV: <1	IV: 20	IV: 4 5
Oxycodone	PO: 30 mg	PO: 15 30	PO: 60	PO: 4 6
Propoxyphene	Toxicc	PO: 15 60	PO: 120	PO: 4 6
Remifentanild	IV: 0.05 0.15 g/kg	IV: <1	IV: <1	IV: 3 4 min
Sufentanil	IM: 0.01 0.02 mg	IV: <1	IV: 1 2	IV: 0.25 1
IM, intramuscular; IV, intravenous; PO, by mouth aDose in mg therapeutically equivalent to morphine 10 mg IM. IM doses are used to specify equivalent doses but are not recommended when IV access is available. bIncreases with repetitive dosing due to accumulation of drug and/or metabolites. cDose equivalent to 10 mg of morphine would be too toxic to administer. dRemifentanil is suitable for IV infusion only.

P.31

TABLE 2.10. Parenteral Analgesic Agents

Drug	Bolus Dosage	Continuous Infusion	Comments
Alfentanil	10 25 g/kg	0.5 3 g/kg/min	Safe to use in renal failure because lack of active metabolites
Codeine	15 60 mg	N/A	Usually effective for mild to moderate pain Recommended in renal failure
Fentanyl	25 50 g	50 100 g/h	Slows heart rate Chest wall rigidity can occur Increased half-life with continuous infusions
Hydromor- phone	1 4 mg	N/A	Reserved for patients who are tolerant to and are receiving high doses of opiates Recommended in renal failure
Ketorolac	15 60 mg IV followed by 15 30 mg IV q6h		Parenteral NSAID; lower doses in elderly patients; especially useful for orthopedic pain; reversible platelet dysfunction; associated with acute renal failure when given for more than 5 d Advantage over opioids: no hemodynamic effects, respiratory depression, or ileus Combined IV/IM/PO therapy limited to 5 d
Levorphanol	2 mg	N/A	Optimal IV dose has not been established Avoid in patients with increased intracranial pressure, asthma, acute alcoholism
Meperidine	25 100 mg	5 35 mg/h	Highly lipid soluble Accumulation of neurotoxic (convulsant) normeperidine metabolite in renal failure and in patients receiving large cumulative doses Avoid in patients receiving MAOI
Methadone	2.5 10 mg	N/A	Duration of action and half-life increases with repetitive dosing With repetitive doses, the dose should be lowered or the interval lengthened to avoid excessive narcosis
Morphine	2 10 mg	2 5 mg/h	Less lipid soluble versus fentanyl Histamine release with bolus doses may cause hypotension or, rarely, bronchospasm Active metabolite morphine-6-glucuronide accumulates in renal failure, producing enhanced narcosis
Remifentanil	0.05 g/kg	0.0125 0.025 g/kg/min	Ultrashort action may limit its use for pain Bolus doses are not recommended to treat postoperative pain IV tubing must be cleared after administration to avoid inadvertent bolus dose
Sufentanil	0.2 0.6 g/kg	0.01 0.05 g/kg/min	May allow for volume reduction in patients receiving large doses of continuous infusion narcotics
IV, intravenous; MAOI, monoamine oxidase inhibitor; NSAID, nonsteroidal anti-inflammatory drug

P.32

TABLE 2.11. Patient-Controlled Analgesia (PCA) Guidelines

	Morphine	Fentanyl	Hydromorphone
Standard dilution	2 mg/mL	20 g/mL	0.5 mg/mL
Demand dose	1 mg	20 g	0.2 mg
Initial lockout	6 min	6 min	6 min
Initial basal rate	0	0	0
Considerations	Generally, opioid of choice unless patient has renal insufficiency or is intolerant to morphine: nausea, vomiting, pruritus	Less accumulation may result in less confusion in elderly patients; preferred over morphine in patients with renal insufficiency to avoid accumulation of morphine metabolites
For patients who report pain on PCA, first assess the frequency of self-dosing. If the patient is not self-dosing at least 3 times per hour, encourage him or her to dose more often. Failing that, give the patient a bolus dose (2 5 mg of morphine or equivalent) and increase the demand dose to 1.5 or 2 mg of morphine or equivalent. Finally, consider an adjuvant drug (ketorolac) or a low basal rate (0.5 mg/h of morphine or equivalent).

P.33

TABLE 2.12. Oral Analgesic Agents

Agent	Onset/Duration	Dosage	Comments
Narcotic
Codeine	Onset: 15 30 min Duration: 4 6 h	30 60 mg q4h
Codeine with acetaminophen 300 mg	Onset: 15 30 min Duration: 4 6 h	1 2 tablets q4h	Available with codeine 7.5 mg, 15 mg, 30 mg, or 60 mg
Oxycodone 5 mg	Onset: 15 30 min Duration: 4 6 h	5 10 mg q4h	Sustained release preparation, Oxycontin, has been associated with illegal abuse and diversion; deaths have resulted when the pills have been crushed and the powder inhaled
Oxycodone 5 mg with acetamino- phen 325 mg	Onset: 15 30 min Duration: 4 6 h	1 2 tablets q4h
Oxycodone HCl 4.5 mg plus oxycodone terephthalate 0.38 mg with aspirin 325 mg	Onset: 15 30 min Duration: 4 6 h	1 2 tablets q4h
Propoxyphene napsylate 50 or 100 mg with acetaminophen 325 mg	Onset: 15 60 min Duration: 4 6 h	1 2 tablets q4h
Propoxyphene 32 or 65 mg	Onset: 15 60 min Duration: 4 6 h	32 65 mg q4h
Non-narcotic
Acetaminophen	Onset: 0.5 1 h Duration: 3 6 h	325 650 mg q4h
Aspirin	Onset: 0.5 h Duration: 3 6 h	325 650 mg q4h
Choline magnesium salicylate	Onset: 30 60 min Duration: N/A	1000 2000 mg bid	500 mg = ASA 650 mg May monitor with salicylate levels Does not affect platelet aggregation Available as a liquid 500 mg/5 ml
Ibuprofen	Onset: 0.5 h Duration: 3 6 h	400 800 mg tid-qid	Reversible effect on platelet aggregation Available as a liquid 100 mg/5 ml
Ketorolac	Onset: 30 60 min Duration: 4 6 h	10 mg q4 6h	Reversible platelet effect Reduce dose in elderly patients Maximum oral dose 40 mg/day Indicated only as continuation therapy to parenteral ketorolac up to a maximum duration of 5 d of combined IV/IM/PO administration
Tramadol	Onset: 1 h Duration: 3 6 h	50 100 mg q4 6h	Reduce dose in patients with renal or liver failure
IV, intravenous; IM, intramuscular, PO, by mouth

P.34

P.35

TABLE 2.13. Oral Sedative-Hypnotic Agents

Agent	Onset	Usual Dosage	Half-Life	Comments
Benzodiazepines
Alprazolam	Intermediate	Sedative: 0.25 0.5 mg PO tid	12 15 h	No active metabolites
Diazepam	Fast	Sedative: 2 10 mg PO bid-qid Pre-op medication: 5 10 mg PO 1 h before procedure	20 200 h	Active metabolites accumulate with chronic dosing and contribute to pharmacologic effect Available in a liquid dosage form (1 mg/ml and 5 mg/ml)
Lorazepam	Intermediate	Sedative: 0.5 3 mg PO bid-tid	10 20 h	No active metabolites Safe to use in liver disease
		Hypnotic: 0.5 4 mg PO qhs		Available in a liquid dosage form (2 mg/ml)
		Pre-op medication: 1 4 mg PO 1 2 h before procedure		Amnesia may be produced for as long as 4 6 h without excessive sedation when lorazepam is used as a pre-op medication
Midazolam	Fast	Pre-op medication: 0.5 0.75 mg/kg PO 1 2 h before procedure	3 6 h	Use high potency 5 mg/ml injectable form and dilute in 3 5 ml of fruit juice
Oxazepam	Slow	Sedative: 10 30 mg PO tid-qid Hypnotic: 10 30 mg PO qhs	5 20 h	No active metabolites
Temazepam	Intermediate	Sedative: N/A Hypnotic: 7.5 30 mg PO qhs	10 17 h	No active metabolites
Barbiturates
Pentobar- bital	Fast	Sedative: N/A Hypnotic: 100 mg PO qhs Pre-op medication: 100 mg PO 1 2 h before procedure	22 h	Geriatric or debilitated patients may react to usual doses with excitement, confusion, or mental depression; lower doses may be required in these patients
Secobarbital	Fast	Sedative: N/A Hypnotic: 100 mg PO qhs Pre-op medication: 200 300 mg PO 1 2 h before procedure	28 h	Geriatric or debilitated patients may react to usual doses with excitement, confusion, or mental depression; lower doses may be required in these patients
Other agents
Chloralhy-drate	Intermediate	Sedative: 250 mg PO tid after meals Hypnotic:500 1000 mg PO qhs Pre-op medication: 25 75 mg/kg up to 2 g PO 1 h before procedure	8 h TCE	Active metabolite TCE Available in liquid (10 mg/ml) and suppository (500 mg) dosage forms
Diphenhydramine	Slow	Hypnotic: 25 50 mg PO qhs	1 4 h	Available in a liquid dosage form (12.5 mg/5 ml) Half-life is prolonged in patients with liver disease
Eszopic-lone	Fast	Sedative: N/A Hypnotic: 1 3 mg PO qhs		Reduce to 1 mg in elderly patients, patients receiving CYP3A4 inhibitors and patients with severe hepatic disease
Zaleplon	Fast	Sedative: N/A Hypnotic: 5 10 mg PO qhs	1 h	The initial dose should be reduced to 5 mg in elderly and in patients with liver disease
Zolpidem	Fast	Sedative: N/A Hypnotic: 5 10 mg PO qhs	2.5 h	No active metabolites An initial dose of 5 mg should be used in patients with liver disease
Amitripty-line	Slow	25 100 mg qhs		Sedating tricyclic antidepressant Contraindicated in acute recovery phase of myocardial infarction
Quetiapine	Intermediate	25 100 mg qhs		Sedating dibenzothiazepine antiphychotic May result in orthostatic hypotension or tachyarrhythmias Anticholinergic effects (dry mouth, constipation)
PO, by mouth; TCE, trichloroethanol

P.36

TABLE 2.14. Malignant Hyperthermia Therapy

Typical Presentation
Setting: Intraoperative or early postoperative.
Clinical: Tachycardia, tachypnea, ventricular arrhythmias, muscle rigidity, fever
Laboratory: Combined respiratory and metabolic acidosis, hyperkalemia, hypercalcemia, myoglobinuria, elevation in creatine phosphokinase.
Protocol for treatment
Discontinue triggering drug (succinylcholine, inhalational anesthetic).
Hyperventilate with 100% oxygen.
Dantrolene 2.5 mg/kg IV repeated every 5 10 min as dictated by the clinical situation. Although 10 mg/kg is often reported as a maximum total dose, more dantrolene may be needed.
Follow usual guidelines for treatment of metabolic acidosis, hyperkalemia (calcium has not been investigated in this setting), hyperthermia (external ice, gastric lavage), disseminated intravascular coagulation, prevention and treatment of myoglobinuric renal failure.
Procainamide as needed for arrhythmias refractory to general measures. Avoid calcium channel blockers in conjunction with dantrolene.
For health care providers having questions on patient management, the Malignant Hyperthermia Association of the United States operates a hot line: 1-800-644-9737.

IV, intravenous

P.37

P.38

TABLE 2.15. Neuroleptic Malignant Syndrome

Typical Presentation
Setting: Most cases within 30 days of antipsychotic (neuroleptic) drug administration (incidence ~0.07 0.4%) or withdrawal of dopamine agonist (e.g., levodopa, amantadine).
Viewed as extreme extrapyramidal adverse effect versus idiosyncratic drug reaction related to antidopaminergic effects in central nervous system. Increased risk in highly agitated restrained patient.
Clinical Presentation: Hyperthermia caused by muscle rigidity, vasoconstriction, and possibly central nervous system effect. Dehydration, mental status changes (obtundation), autonomic instability (tachycardia, oscillations in blood pressure).
Laboratory: Elevated serum creatine phosphokinase, leukocytosis, metabolic acidosis.
Protocol for treatment
Discontinue antipsychotics if muscle rigidity impairs breathing or swallowing.
Control temperature (cooling blankets, ice baths, antipyretics; avoid NSAID because of renal effects), correct fluid and electrolyte disturbances.
Anticholinergics (if temperature <38.9 C): benztropine (up to 8 mg/d, PO, IM, IV), may worsen hyperthermia.
Dopamine agonists (if temperature >38.9 C): amantadine 200 300 mg/d PO, bromocriptine 7.5 75 mg/day PO, carbidopa/levodopa 300 800 mg/d PO.
Dantrolene 4 8 mg/kg/d PO/IV.

IV, intravenous; IM, intramuscular, PO, by mouth