Handbook of Critical Care Drug Therapy

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 9 - Neurologic and Psychiatric Therapeutics

Chapter 9

Neurologic and Psychiatric Therapeutics

P.162

TABLE 9.1. Seizures Urgent Management

Drug Dosage Comment
Thiamine 100 mg IV/IM To avoid Wernicke's encephalopathy in alcoholics after glucose administration
Dextrose 50% 25 50 ml IV For hypoglycemic seizures
Diazepam 2.5 10 mg IV, repeat after 5 10 min if needed May cause respiratory depression and hypotension

Seizures may recur because duration of efficacy is short
Phenytoin 10 20 mg/kg IV Maximum infusion rate 50 mg/min

Precipitates if injected into glucose-containing solutions

Arrhythmias develop during rapid administration; monitor ECG

Can produce hypotension
Fosphenytoin 10 20 PE/kg IV Fosphenytoin should be prescribed in PE

Fosphenytoin 75 mg = phenytoin 50 mg

Infusion rate should be 100 150 mg PE/min

Continuous monitoring of ECG, BP, and respiration is essential during IV loading

Peak phenytoin levels occur approximately 2 h after the end of the loading infusion

Fosphenytoin should not be administered IM for the treatment of status epilepticus
Phenobarbital 10 20 mg/kg IV Maximum infusion rate 50 mg/min

Respiratory depression and hypotension should be anticipated
Thiopental 25 100 mg IV Hypotension and apnea are expected

5 mg/kg induces general anesthesia, but with a variable response
Neuromuscular blocking agents See Table 2.4 Neuromuscular blocking agents possess no anticonvulsant properties

For intractable seizures or life-threatening acidosis or muscle contractions

Use of these agents can mask seizure activity; therefore, EEG monitoring is required
General anesthesia For intractable seizures or life-threatening acidosis or muscle contractions
ECG, electrocardiogram; EEG, electroencephalogram; IV, intravenous; IM, intramuscular; PE, phenytoin sodium equivalent; BP, blood pressure

P.163

P.164

TABLE 9.2. Seizures Maintenance Therapy

Drug Daily Dosage Optimal Blood Level ( g/ml) Comment
Carbamazepine 5 25 mg/kg PO divided tid-qid 4 8 Metabolized to active metabolite

Side effects: nystagmus, dysarthria, diplopia, ataxia, drowsiness, nausea, blood dyscrasias, hepatotoxicity
Fosphenytoin Maintenance dose: 4 6 mg/kg PE total daily dose

IV/IM divided doses q8h

Temporary substitution for oral Dilantin: same as daily oral Dilantin dose in mg

 10 20 (measured as phenytoin)

Free level 1 2

 Fosphenytoin 75 mg = phenytoin 50 mg

Maximum infusion rate 150 mg PE/min

IV infusion requires continuous ECG, BP, and respiratory monitoring

Administer fosphenytoin substitution doses at the same frequency as oral Dilantin

Side effects: tingling, paresthesias after IV administration; other side effects similar to phenytoin
Gabapentin 900 mg PO divided tid Side effects: fatigue, somnolence, dizziness, ataxia
Lamotrigine 25 mg PO every other day if on valproic acid + enzyme inducer; 50 mg/d if not on valproic acid, but on enzyme inducer Side effects: rash, abnormal thinking, dizziness, ataxia, nervousness, somnolence, diplopia, nausea, vomiting, weight gain
Phenobarbital 2 5 mg/kg PO/IV qd 10 40 Maximum infusion rate 50 mg/min

Side effects: drowsiness, nystagmus, ataxia, skin rash, learning difficulties
Phenytoin 4 8 mg/kg PO/IV qd Total level:10 20

Free level 1 2

 Maximum infusion rate 50 mg/min

Side effects: nystagmus, ataxia, dyskinesias, sedation, gingival hyperplasia, hirsutism, blood dyscrasias, rashes, systemic lupus erythematosus, peripheral neuropathy
Primidone 5 20 mg/kg PO divided tid Primidone: 5 15

Phenobarbital: 15 40

 Metabolized to phenobarbital, which contributes to pharmacologic activity

Side effects: sedation, nystagmus, ataxia, vertigo, nausea, skin rashes, megaloblastic anemia
Topiramate Goal of 200 mg PO bid

Starting dose 50 mg PO bid

 Adequate fluid intake should be maintained to minimize the risk of kidney stone formation

Side effects: psychomotor slowing, difficulty in concentrating, speech and language problems, somnolence and fatigue, kidney stone formation
Valproic acid 10 60 mg/kg PO divided tid 50 100 Side effects: nausea, vomiting, diarrhea, drowsiness, alopecia, weight gain, hepatotoxicity, thrombocytopenia, tremor
Valproate sodium injection 10 60 mg/kg IV divided tid-qid

IV dose equals the oral dose when used as a temporary substitute for oral therapy

 IV product is intended for temporary substitution of oral valproate in same daily dose and dosing interval

IV dose should be infused as a 60 min infusion, but not faster than 20 mg/min
BP, blood pressure; ECG, electrocardiogram; IM, intramuscular; IV, intravenous; PE, phenytoin sodium equivalent; PO, by mouth

P.165

TABLE 9.3. Increased Intracranial Pressure

Agent Dosage Comment
Adjunctive therapy Airway and hemodynamic management may be indicated

Neurosurgical consultation
Mannitol 0.25 1.0 g/kg IV, then 0.25 0.5 g/kg IV q4h As needed to maintain ICP without exceeding serum osmolality of 320 400 mOsm

Adverse effects: transient immediate hypervolemia followed by diuresis and hypovolemia; hyperosmolar state; possible rebound increase in ICP after termination, particularly if mannitol is retained by abnormal tissue; exacerbation of intracranial bleeding
Hypertonic saline 23.4% Standard dose of 30 ml (120 mEq) over 15 20 min (2ml/min)

Maximum dose 60 ml

 Must be administered through a central line

Administration without a central line is an absolute contraindication

This is for acute osmotherapy with the goal of reduced ICP

Obtain serum sodium after every dose of 30 ml of 23.4% saline
Hypertonic saline 3% Mixture 3% saline (50% as acetate 50% as chloride)

Or mixture as 3% saline (100% as chloride)

Starting dose 40 50 ml/h

Titrate to serum sodium goal (140 160 meq)

Serum sodium concentration of 160 is the maximum tolerated serum sodium concentration

Common bolus volume is 250 cc

 Must be administered through a central line

Administration without a central line is an absolute contraindication

Obtain serum sodium levels every 2 4 h while infusing and immediately after bolusing
Hypertonic saline 2% Given as an IV bolus or continuous infusion

Serum sodium should be monitored every 4 h while in the infusion

 No absolute contraindications
Furosemide 10 20 mg IV q4h Titrated

Decreases edema and CSF production

Does not produce rapid decreases in ICP
Pentobarbital 3 5 mg/kg IV bolus, over 30 min then 1 mg/kg/h

Loading dose:

   10mg/kg/h for 3 h then

   2mg/kg/h

 Monitoring: EEG burst suppression, therapeutic level of 20 50 g/ml

Burst suppression goal 1:10 to 1:30 ratio of complexes to seconds
Lidocaine 0.5 1.5 mg/kg IV or intratracheally Useful with acute airway manipulations to reduce coughing

Can precipitate seizures
Dexamethasone 4 20 mg IV q6h Decreases brain swelling with vasogenic edema

Increases mortality in head trauma
CSF, cerebral spinal fluid; EEG, electroencephalogram; ICP, intracranial pressure; IV, intravenous

P.166

TABLE 9.4. Cerebral Vasospasm

Goal Treatment Comments
If arterial pressure excessively elevated, lower toward normal range Trimethaphan or labetalol Refer to Tables 3.11 and 3.12; vasodilator agents may increase intracranial blood volume and intracranial pressure and are usually avoided in symptomatic vasospasm
Ensure adequate intravascular volume Colloid and/or crystalloid solutions as appropriate Fluids maximize cardiac performance and blunt catecholamine release and activation of renin-angiotensin system; if cerebral edema is severe, may need invasive monitoring
Avoid arterial hypotension If hypotension does not correct with fluids, use phenylephrine CPP = mean arterial pressure - intracranial pressure

Phenylephrine does not constrict cerebral vessels; alternatives are dopamine or norepinephrine, dobutamine
Ensure adequate oxygenation Supplemental oxygen as needed Maximize cerebral oxygen delivery
Decrease severity of neurologic deficits Nimodipine 60 mg PO q4h for 21 d Calcium channel blocker that affects cerebral vessels preferentially; in subarachnoid hemorrhage protects against calcium-induced ischemic cell damage through unknown mechanisms; no side effects except occasional hypotension
Reversal of neurologic deterioration caused by vasospasm Expansion of intravascular volume and elevation of systemic arterial pressure Rapid expansion of intravascular volume with colloid and crystalloid to pulmonary artery wedge pressure of 12 18 mm Hg; raise systemic arterial pressure in increments of 10 mm Hg with dopamine until deficits reverse; hazardous if initiated in the presence of an untreated or unruptured aneurysm
CPP, cerebral perfusion pressure; PO, by mouth

P.167

P.168

P.169

TABLE 9.5. Psychiatric Disorders

Disorder Treatment Dosage Comments
Anxiety and Agitation Benzodiazepines are the treatment of choice in controlling psychotic agitation and when panic and phobic anxiety account for agitated behavior
Benzodiazepines Diazepam PO: 2 10 mg bid-qid Rapid onset

Especially useful for rapid tranquilization
IV/IM: 2 10 mg q4 6h prn Available in IV and oral liquid dosage forms

Active metabolites accumulate with multiple doses

Reduced metabolism in the elderly and patients with liver disease

Potential for drug interactions

May cause excessive sedation
Lorazepam PO: 0.5 3 mg bid-tid

IV/IM: 1 2 mg q1 4h prn

 Slower onset than diazepam

Available in IV and oral liquid dosage forms

No active metabolites

May cause excessive sedation
Alprazolam PO: 0.25 1 mg bid-tid Useful in patients who have a panic or phobic component to their anxiety

Lower doses should be used in elderly patients, patients with liver disease or low albumin
Delirium Neuroleptic medications are thought to be specific for the treatment of delirium and psychosis, attendant agitation may be controlled more effectively by the use of a benzodiazepine with a neuroleptic agent
Neuroleptics Haloperidol (See Table 9.6)

Mild agitation: 0.5 2 mg IV

Moderate agitation: 2 5 mg IV

Severe agitation: 5 10 mg IV

Continuous infusion: 2 10 mg/h

Less severe symptoms: 0.5 2 mg PO/IV/IM qhs-bid

 IV medication required in acute delirium

IM administration is not recommended because of the potential for erratic absorption in hemodynamically unstable patients

Oral dose has about half of the potency of the IV dose

Torsade de pointes is a potential complication

Monitor QT interval and electrolytes when using high doses or continuous infusions, or in combination with other drugs that prolong QT interval
Benzodiazepines Lorazepam IV/IM: 1 10 mg q1 4h prn Promotes additional calming when used in combination or alternating with haloperidol

May result in decreased doses of haloperidol needed for clinical effect

Diazepam or midazolam may be used in place of lorazepam when agitation is explosive and rapid control is desired
Depression
Psychostimulants Methylphenidate PO: 2.5 20 mg bid Useful in patients who are lethargic, hard to mobilize, listless, or who show no interest in their care

Give the afternoon dose before 3:00 PM so that the ability to fall asleep is not impaired
Conventional antidepressants   Useful if the response to psychostimulants is partial or ineffective

Tricyclic antidepressants have a slow onset, have anticholinergic side effects, and can affect the cardiac conduction system

The patient's medical record should be reviewed to determine if he or she has previously been treated with antidepressants and to assess his or her response to these agents
Doxepin PO: 25 mg qhs Useful in depressed patients who have difficulty in falling asleep

Increase by 25 mg nightly until an adequate sleep dose is achieved
Nortriptyline PO: 25 mg qhs Increase 25 mg weekly up to 75 mg qhs, aiming for a serum concentration between 50 150 ng/ml
Serotonin reuptake inhibitors   Potential adverse effects of this class of antidepressants are overstimulation, agitation, and increased anxiety
Fluoxetine PO: 20 mg q AM Metabolized through the cytochrome P450 system and has the potential for drug interactions
Paroxetine PO: 20 mg q AM Metabolized through the cytochrome P450 system and is a potent inhibitor of this enzyme system; serious potential for many drug interactions
Sertraline PO: 50 mg q AM Least potential for drug interactions
Nefazodone PO: 50 mg qhs Possesses antidepressant and antianxiety properties, so it is useful in patients with an anxiety component to their depression

An alternative to doxepin
Citalopram 20 mg PO qd starting up to 60 mg PO qd maximum SSRI antidepressant and reduced anxiety
Escitalopram 10 mg PO qd starting

May increase to 20 mg after 1 wk

 SSRI antidepressant and reduced anxiety
Venlafaxine 75 mg qd total daily dose

Immediate release 25 mg PO tid or 37.5 mg bid

Sustained release 75 mg PO qd

 SSRI antidepressant and reduced anxiety
Bupropion 100 mg PO bid starting dose

Maximum 450 mg PO in bid or sustained release

 Side effects are seizures

SSRI with decreased depression and anxiety
IM, intramuscular; IV, intravenous; PO, by mouth; SSRI, selective serotonin reuptake inhibitor

P.170

TABLE 9.6. Guidelines for Intravenous Haloperidol

Severity of Agitation Haloperidol Dose
Mild 0.5 2 mg
Moderate 2 5 mg
Severe 5 10 mg
  1. Allow 10 to 15 minutes between doses.

  2. For continued agitation, double the previous dose.

  3. For continued agitation after 3 doses, give lorazepam 0.5 10 mg IV either concurrently or alternating with haloperidol every 30 minutes.

  4. Consider a haloperidol continuous infusion (2 10 mg/h) if the agitation is poorly controlled with intermittent IV doses.

  5. Once the patient is calm, determine the total dose of haloperidol administered, and give this dose over the next 24 hours. The daily requirement can be divided into 2 doses, with the largest dose administered at bedtime.

  6. Give this dose for 24 48 hours; if the patient remains calm, begin reducing the dose by 50% every day.

  7. If the patient is stable and able to take oral medications, the tapering doses may be given orally (the oral dose = 2 the IV dose).

  8. Monitor QT interval and decrease dose or discontinue if QT interval prolonged because of risk of serious arrhythmia.

P.171

TABLE 9.7. Alcohol Withdrawal Drug Therapy

Drug Typical Dosage Comment
Supportive Care
Folate

Thiamine

 1 mg PO/IV/IM qd

100 mg IM/PO qd 3 d

 Folate, thiamine, and multivitamins should be given before the administration of dextrose to avoid precipitating Wernicke's syndrome
Multivitamin

Magnesium

 1 PO qd

1 2 g IV/IM qd-tid 3 d

 Fluid and electrolytes should be administered to correct fluid and electrolyte disturbances

IV multivitamins 1 vial/day in IV fluid
Benzodiazepines Although there is no evidence that one benzodiazepine is more effective than another, benzodiazepines with long half-lives and active metabolites may be beneficial in alcohol withdrawal because they may help to smooth a tapering effect

Late-onset seizures have been reported in patients being treated with short-acting benzodiazepines
Diazepam 5 10 mg PO tid, tapering over 5 10 d Active metabolites

Long half-life
Lorazepam 1 2 mg IV q4 6h titrated to sedation, tapering over 5 10 d No active metabolites

Intermediate half-life

Preferred agent in patients with liver disease
Control of Adrenergic Symptoms
Atenolol 25 50 mg PO qd
Metoprolol 5 20 mg IV q4h
Clonidine 0.1 0.4 mg PO q8 12h Central acting sympathomimetic that may diminish the use of sedatives; weekly patch (0.1 0.3 mg) may be used but is delayed in onset
Other    
Alcohol 5% solution for IV infusion Postpones withdrawal, toxic, difficult to titrate, and generally is not recommended
Haloperidol 2.5 150 mg/day in divided doses May lower the seizure threshold; usually not indicated even when withdrawal hallucinations occur
Phenytoin 15 mg/kg load then 300 mg per day For treatment of seizures
IM, intramuscular; IV, intravenous; PO, by mouth

Note: The need for prophylaxis in patients undergoing alcohol withdrawal has been questioned recently. Therapy based on symptoms may be equally effective and diminish the need to treat large numbers of patients who may not experience withdrawal.

P.172

TABLE 9.8. Treatment of Withdrawal Reactions

Agent Therapy Comments
Alcohol See Table 9.7
Benzodiazepines
Short, intermediate-acting Lorazepam 2 mg PO qid-tid, then taper over 5 7 d
Long-acting Diazepam 5 10 mg PO qid-tid 5 d, then taper over 5 7 d Active metabolites are beneficial in tapering agent after discontinuation
Opiates
Replacement therapy Methadone 20 mg PO or 10 mg IM 1 dose

A second dose may be given if significant relief is not obtained 1 h after the 1st dose

 Dosing for withdrawal reactions requires less methadone than dosing for methadone maintenance; some patients require 20 40 mg daily to avoid psychological withdrawal
Sympatholytic therapy Clonidine 6 g/kg PO loading dose followed by 6 17 g/kg/d PO divided tid 7 d, then taper over 3 d Hypotension may be associated with higher doses

May use clonidine topical patches for tapering regimen

Dose may be decreased by changing patches every 3 d
IM, intramuscular; PO, by mouth

P.173

TABLE 9.9. Myasthenia Gravis

Problem Management Comment
Acute diagnosis Edrophonium 2 mg (0.2 ml) IV initially, if tolerated 8 mg (0.8 ml) IV after 30 s (results in improvement in muscle strength, 5 min duration)

Or

Neostigmine 1.5 mg IM (duration 2 h)

 Assessment of patient with fluctuating weakness of voluntary muscles with symptoms of diplopia, ptosis, difficulty swallowing

Atropine sulfate (0.6 mg IV/IM) should be available to reverse muscarinic effects

Monitor respiratory function, avoid aminoglycosides
Therapy Chronic therapy:

Neostigmine 7.5 30 mg PO qid or pyridostigmine 30 180 mg PO qid

Corticosteroids (prednisone 60 100 PO qd) in patients who respond poorly to anticholinergics and have undergone thymectomy. Alternatively azathioprine may be given 2 3 mg/kg/d

Plasmapheresis

 Conversion to IV dose is 1:60 conversion; with the IV dose being 1/60 of the oral dose of neostigmine and pyridostigmine

Thus 60 qid of pyridostigmine bromide equaling 1,240 mg TTL daily dose would equal 4mg/ day of IV neostigmine as an IV infusion given over 24 h
IM, intramuscular; IV, intravenous; PO, by mouth; TTL, total

P.174

TABLE 9.10. Acute Spinal Cord Injury

Problem Management Comment
Airway Skilled and experienced operator necessary to prevent secondary injury

Neutral traction during placement of airway

 Lesions above C3 C4 require intubation and mechanical ventilation because of loss of diaphragm (C3 C5)

Lesions below C5 C6 may result in reduced vital capacity and flow and require mechanical ventilation
Hypotension Fluid resuscitation often with central pressure monitoring

Vasopressors (see Table 3.8) after fluid resuscitation

 Causes other than spinal shock should be aggressively sought because of associated thoracic and abdominal trauma
Bradydysrhythmias Atropine 0.5 1 mg IV

Pacemaker

 If cardiac accelerator nerves (T1 T4) are involved, bradycardia and bradydysrhythmias may occur because of loss of sympathetic tone and unopposed vagal activity
Tachydysrhythmias -Blockers (see Table 3.6) Often accompany autonomic hyperreflexia

If hypertension present, -adrenergic blockade required with -blockers
Loss of neurologic function Stabilization of spine by traction and surgical fixation

Surgical decompression of subdural or epidural hematomas

Methylprednisolone 30 mg/kg IV, infused over 15 min; after 45 min, continuous infusion (5.4 mg/kg/h) for 23 h

 Methylprednisolone treatment should be initiated as soon as possible (i.e., within 3 h of injury)

Recent trials suggest that when therapy is initiated 3 8 h after injury, patients should be maintained on therapy for 48 h
Autonomic hyperreflexia Minimize episodes of noxious or visceral stimuli (e.g., bladder or bowel distension)

Pharmacologic therapy: trimethaphan, phentolamine (see Table 3.12)

 Usually when flaccid paralysis or spinal shock occurs, it occurs below level of injury
Abnormal response to depolarizing muscle relaxants Avoid depolarizing agents 12 h after injury (e.g., succinylcholine) and use nondepolarizing neuromuscular blockade (see Table 2.4) Massive amounts of K+ can be released from skeletal muscle to extracellular space following depolarizing muscle relaxant

Magnitude of K+ release is a function of muscle mass affected and may occur before spasticity is apparent
IV, intravenous

P.175

TABLE 9.11. Thrombolysis for Acute Ischemic Stroke

Agent Dosage Comments
Tissue plasminogen activator 0.9 mg/kg (maximum dose 90 mg) infused over 60 min, with 10% of total dose given as IV bolus over 1 min Indicated for thrombotic arterial occlusion with no evidence of intracranial hemorrhage on CT scan

Treatment should be started within 3 h after onset of symptoms

Antithrombotic and antiplatelet drugs should be withheld for 24 h

Contraindications intracranial hemorrhage, or other bleeding riska
CT, computed tomography

aSuspicion of subarachnoid hemorrhage or other bleeding, recent intracranial surgery or head trauma, recent major surgery, uncontrolled hypertension, intracranial neoplasm, aneurysm or vascular malformation, recent treatment with heparin or warfarin, or platelet count <100,000/cu mm.

P.176

TABLE 9.12. Experimental Therapies for Acute Hemorrhagic and Ischemic Stroke

Agent Dosing Comments
Acute Hemorrhagic Stroke
Recombinant activated factor VIIa (Table 8.2) 20,80 g/kg dosing in IV push over 2 min

Presently in randomized phase III trial

80 g/kg is the preferred dose for hemorrhage

Must administer within 3 h of onset of ICH

 Many adverse events including myocardial ischemia, pulmonary embolus, and ischemic stroke have been documented in this setting
Ischemic Stroke
Tenecteplase Phase 2-B study of TNK in acute ischemic stroke (TNK-S2B)

Dosing:

0.1 mg/kg TNK,

0.25 mg/kg TNK, or

0.4 mg/kg TNK

Given as an IV bolus within 3 h of onset

 This is an experimental therapy and is currently only used in the clinical research setting with informed consent and IRB approval
Desmoteplase 62.5 g/kg, 90 g/kg, 125 g/kg IV given as a single bolus 3 9 h if patient has a perfusion mismatch on MRI or CT perfusion scans This is an experimental drug and is currently only used in the clinical research setting with informed consent and IRB approval
CT, computed tomography; ICH, intracranial hemorrhage; IRB, institutional review board; MRI, magnetic resonance imaging

Related

Категории