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.
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
aaRefers to specific intubating stylettes and not to those routinely used to stiffen ETT during routine intubation.
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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.
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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.
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.
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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.
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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
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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.
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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.
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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
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).
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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
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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
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
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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).