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 http://med.oxfordradcliffe.net/guidelines/

 

http://www.cdc.gov/ncidod/hip/SSI/SSI.pdf

 

GUIDELINES FOR SURGICAL TREATMENT OF

GASTROESOPHAGEAL REFLUX DISEASE (GERD)

 

Pre-operative Fasting Guidelines

J. Roger Maltby, MB, BChir, FRCA, FRCPC,

 

Guidelines & Recommendations Prevention of Healthcare-Associated Infections

Blood/marrow transplants

Infection Control in Healthcare settings, Immunizations

Occupational Health Guidelines for Healthcare Settings

 

Myocardial infarction.

from http://www.guidelines.gov/summary/summary.aspx?view_id=1&doc_id=5668

 

MAJOR RECOMMENDATIONSThe levels of evidence [A-D] supporting the recommendations are defined at the end of the "Major Recommendations" field.

Aims

  • If a person at risk of a myocardial infarction (MI) has an acute coronary syndrome lasting over 20 minutes, an imminent MI must be suspected. Instead of chest pain, acute dyspnoea may be the primary symptom.
  • An acute coronary syndrome without myocardial damage is often unstable angina, which calls for active treatment.
  • The diagnosis should be made without delay since early therapy improves the prognosis decisively.
  • Thrombolytic therapy is given as early as possible in all cases with a clinical picture of imminent MI and corresponding electrocardiogram (ECG) changes. See the Finnish Medical Society Duodecim guideline "Thrombolytic Therapy in Acute Myocardial Infarction."
  • Acute angioplasty (percutaneous transluminal coronary angioplasty [PTCA], percutaneous coronary intervention [PCI]) is an alternative or a complementary procedure to thrombolytic therapy ("Primary angioplasty versus intravenous, thrombolysis" 2002; Sim, et al., 1995; DARE-953385, 1999; Grines, et al., 1999) [A]. Angioplasty is probably preferred, at least in ST elevation MI (Keeley, Boura, & Grines, 2003).
  • If there are no contraindications, aspirin and a beta-blocker should be started for all patients and, for most patients, also an angiotensin-converting enzyme (ACE) inhibitor and a statin on the first days of treatment.
  • Health care system should include a planned care pathway for coronary patients.

Diagnosis

ECG Diagnosis

  • Points for taking an ECG: acute care, emergency room, 12 hours later, on day 2, upon discharge from hospital, and thereafter as deemed necessary.
  • ECG is the most important diagnostic procedure. To start with, the positions of the chest leads must be marked on the skin to allow detection of meaningful changes on the ECG. By monitoring the ECG, the efficacy of the treatment can be assessed. However, in the early stages there may be no changes in ECG, and the changes may be first evident after hours or even days. An ECG diagnosis is made more difficult by an old infarction, left bundle branch block, or posterior infarction.
  • In posterior wall infarction, a reciprocal ST segment depression in V1–V4 simulates ischaemia. A posterior infarction is, however, often inferoposterior and, in addition to ST segment depression, ST segment elevations are found in leads III and aVF.
  • ST depression is suggestive of ischaemia and/or unstable angina pectoris. Extensive ST depressions in connection with a clinical picture of MI can indicate subendocardial damage.

Tests Following the ECG

  • Troponin is the most important new marker and is replacing creatine kinase (CK).
  • CK and CK-MB or CK-MB mass (CK-MBm).
  • A negative troponin T, troponin I, or CK-MBm result 9 to 12 hours after the onset of symptoms practically rules out MI.
  • Troponin T test is also valuable, if the time lapse since the beginning of the symptoms is more than 24 hours (the concentration remains elevated longer than that of CK). An elevated troponin T or troponin I concentration predicts adverse events irrespective of ECG findings (Olatidoye, et al., 1998; DARE-981100, 2000) [A].
  • The tests should be performed 3 times in case of suspected infarction: on arrival of the patient and 12 and 24 hours after arrival.
  • Blood haemoglobin, leukocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)
  • Serum sodium and potassium, and chest radiograph if needed

Troponin-T or Troponin-I

  • Principal indicators of myocardial damage, which can also be determined by means of rapid testing methods suited for primary health care. A reading device facilitates the interpretation.
  • Troponin is more myocardium-specific than CK-MB and is also very sensitive.
  • The concentration increases rapidly (in 4 to 6 hours) after myocardial damage, and the elevated levels persist for at least one week.
  • Indications:
    • To verify or exclude MI (or myocarditis) when at least 6 hours have elapsed from the onset of pain. Unstable angina pectoris may give positive results, indicating slight myocardial damage, which means that the prognosis is serious regardless of the ECG findings and active treatment is necessary. The normal reference concentration is zero, or the method-dependent threshold is often given as <0.5 micrograms/L.
    • A negative result within 12 hours after the onset of pain excludes infarction.
    • Also used for the diagnosis of infarction when the patient's arrival for treatment is delayed, and CK and aspartate aminotransferase (AST) have returned to normal.
    • Troponin verifies MI in cases where high CK concentration from skeletal muscle increases the CK-MB concentration over normal limits.
  • Mild elevations in the concentration that exceed the threshold are often seen in cardiac surgery. The threshold level that would verify the diagnosis of MI has not been defined for the situations. Mild elevations may also occur in connection when prolonged tachycardia causes a strain on the sick heart.

Serum CK-MB Mass

  • More specific and sensitive than CK-MB
  • Abnormal within 6 to 8 hours from the beginning of the pain, and remains abnormal for 1 to 2 days.
  • Slightly positive values may indicate mild myocardial damage that requires active treatment. Unlike with troponin, the normal concentration of CK-MB is not zero. There is an uncertain borderline area of 5 to 10 micrograms/L between the positive and negative result.

Myoglobin

  • Reacts most rapidly to myocardial damage and is positive from the first hours onward
  • Not a specific indicator of myocardial damage. Negative myoglobin is valuable in exclusion diagnosis.
  • Lack of reference values limits use.

Differential Diagnosis

  • The most important differential diagnoses include
    • myopericarditis
    • aortic dissection
    • pulmonary embolism
    • unstable angina pectoris
    • oesophageal pain
  • See the NGC summary of the Finnish Medical Society Duodecim guideline Differential Diagnosis of Chest Pain.

Treatment

  • Oxygen, if there are problems in oxygenation (pulmonary oedema)
  • For treating pain
    • Glyceryl nitrate: mouth spray or sublingual tablet
    • Morphine 4 to 6 mg intravenously (i.v.), additionally 4 mg 1 to 3 times at 5-minute intervals, if necessary. Oxycodone 3 to 5 mg i.v. is an alternative.
    • A beta-blocker (metoprolol, atenolol, practolol) 2 to 5 mg i.v. may sometimes ease the pain.
  • Aspirin 250 mg, chewable tablet or dissolved in water, unless there are contraindications (active ulcer, hypersensitivity to aspirin, anticoagulation) ("Collaborative overview of randomised trials of antiplatelet therapy" 1994; DARE-948032, 1999) [A].
  • A beta-blocker (Danchin, DeBenedetti, & Urban, 2002) [A] is always instituted, unless there are contraindications (asthma, hypotension, heart insufficiency, conduction disturbance, bradycardia). The first dose can be given intravenously if the patient is in pain, or orally if the patient is pain-free and time has passed since the infarction. Beta-blockers are useful especially in patients who are tachycardic and hypertensive but do not have heart failure.
    • i.v. dose: metoprolol or atenolol 5 mg
    • Orally: metoprolol or atenolol 25 to 50 mg x 2
  • Thrombolytic therapy, unless there are contraindications ("Indications for fibrinolytic therapy," 1994; DARE-948029, 1999) [A].
  • Immediate percutaneous transluminal angioplasty (PTCA) ("Primary angioplasty versus intravenous thrombolysis," 2002; Sim, et al., 1995; DARE-953385, 1999; Grines, et al., 1999) [A] if available. May be performed when thrombolytic therapy is contraindicated. The effect is better than that of thrombolysis in the acute phase (Vaitkus, 1995; DARE-988078, 1999; "Primary angioplasty versus intravenous thrombolysis," 2002; Weaver, et al., 1997; DARE-988115, 1999) [B] and also in long-term follow-up. Stenting probably improves the outcome (Meads, et al, 2000; DARE-20018012, 2002; Grines, et al., 1999) [A]. Further treatment with clopidogrel for 3 months.
  • An ACE inhibitor to all patients with signs or symptoms of heart failure or ejection fraction (EF) <40, anterior wall infarction, or reinfarction (Domanski et al., 1999; DARE-990660, 2000; Danchin, De Benedetti, & Urban, 2002) [A]. Therapy is not usually started on the first day.
    • For example: captopril. Start with 6.25 mg and increase the dose rapidly.
  • Continuous nitrate therapy (Mehta & Yusuf, 2000) [A]
    • Administered as an infusion, if the patient has ischaemic pain and pain medication has no effect. Nitrate infusion.
    • Orally (e.g., isosorbide dinitrate 10 to 20 mg x 2 to 3)
  • Heparinization is often indicated, if the patient
    • Needs prolonged bed rest and is clearly obese (thrombosis prophylaxis)
    • Has atrial fibrillation (also permanent warfarin therapy)
    • Has ventricular aneurysm (also permanent warfarin therapy)
    • Has unstable angina pectoris
    • Has embolic complications
  • Anticoagulation with warfarin is often started in massive anterior infarction and when transient ischemic attack (TIA) or stroke (mural thrombosis) occurs with MI.

Arrhythmias in Myocardial Infarction

Objectives

  • To prevent sudden death and treat severe arrhythmias immediately
  • To prevent arrhythmias by treating the underlying conditions

Causes of Arrhythmias

  • Myocardial damage, ischaemia, and sympathetic stimulation are associated with ventricular arrhythmias.
  • Ejection failure causes supraventricular tachyarrhythmias and atrial fibrillation.
  • Vagal stimulation causes bradyarrhythmias and atrioventricular (AV) conduction disturbances, especially in cases of inferior-posterior wall infarction.
  • Reperfusion often causes benign ventricular rhythm; however, it also causes severe ventricular arrhythmias.

Ventricular Fibrillation

  • Often occurs within 2 to 4 hours of infarction. After 12 hours, a primary ventricular fibrillation is rare.
  • An early ectopic beat may initiate ventricular fibrillation in an ischaemic myocardium. Ectopic beats are not treated if cardiac monitoring is effective.
  • Treatment
    • Acute ventricular fibrillation is treated by immediate defibrillation starting with 200 joules. Prolonged ventricular fibrillation frequently calls for cardiopulmonary resuscitation (CPR).
    • To prevent recurrence of fibrillation, lidocaine is given: initially as bolus of 100 mg, which can be repeated if necessary. Thereafter, a continuous infusion of 3 to 4 mg/min is given. Amiodarone is a modern and more effective alternative to lidocaine: infuse a 150 to 300 mg bolus in 20 minutes. Thereafter infusion at 800 to 1200 mg/24 hours.
    • A beta-blocker is usually added to the therapy.

Ventricular Tachycardia

  • More than three ectopic beats and a heart rate over 120 bpm.
  • Brief, spontaneously ending bursts are seen in over 50% of patients with infarction during the first two days. They occur mainly 8 to 14 hours after, not immediately after the infarction, as ventricular fibrillation does.
  • Ventricular tachycardia leads to haemodynamic collapse or ventricular fibrillation. The severity depends on the duration, variability, frequency, and timing of tachycardia.
  • Ventricular tachycardia may be monomorphic or polymorphic
  • Treatment
    • Beta-blocker
    • Lidocaine boluses and infusion as in ventricular fibrillation, if haemodynamics is compromised. Amiodarone may be a better alternative.
    • If necessary, synchronized cardioversion shock with 50 joules is performed.
    • Late in infarction, ventricular tachycardia is, like ventricular fibrillation, a serious problem that requires further examination.

Ventricular Ectopic Beats

  • Occur in nearly all patients with painful MI
  • May cause complications if they are frequent (more than 5/min), are variable, or occur concomitantly with an early T wave
  • Treatment is usually not necessary if cardiac monitoring is effective. A beta-blocker may be indicated. Potassium level should be kept above 4.0.

Idioventricular Rhythm

Idioventricular rhythm is an arrhythmia often associated with MI. In the reperfusion phase, it may even indicate that thrombolysis has been successful. The frequency is often 70 to 80 bpm and drug therapy is not necessary.

Supraventricular Tachyarrhythmias

  • Atrial fibrillation in a patient with infarction is often associated with cardiac insufficiency and worsens the prognosis. Atrial fibrillation increases the risk of stroke, which is why low molecular weight (LMW) heparin and warfarin therapy are indicated.
  • Atrial fibrillation is often associated with the thrombosis of the right coronary artery or the circumflex branch: reperfusion also often corrects atrial fibrillation.
  • Atrial function is important in MI. In cardiac insufficiency, rapid atrial fibrillation requires active direct current (DC) cardioversion. Often, the achieved sinus rhythm does not last. In such a case, haemodynamics must be stabilised (oxygenation, treatment of pulmonary oedema, controlling of ventricular response with a beta-blocker and digitalis) after which spontaneous reversal of the rhythm is waited for. The effect of the beta-blocker is seen rapidly but that of digitalis not before several hours. Rapid ventricular response may be controlled even if cardiac insufficiency is present: the benefit often outweighs the disadvantage.
  • Selective beta-blockers are best suited for maintaining the achieved sinus rhythm.
  • Intravenous amiodarone will not reduce the contraction of the myocardium. It is effective in prophylaxis of atrial fibrillation (together with a beta-blocker) and it may be used in cardioversion of atrial fibrillation and/or slowing down the ventricular response.
  • Ibutilide is a new class III drug with a single indication: treatment of atrial fibrillation and flutter. There are limited data on its use in patients with infarction.
  • Note: A broad QRS complex tachycardia in a patient with infarction must always be treated as a ventricular tachycardia.

Bradyarrhythmias

  • A strong vagal reaction in the early stages of infarction may lead to a circulatory collapse.
  • Posteroinferior wall infarction is often associated with a functional atrioventricular block. The QRS complex is narrow and the heart rhythm is 50 to 60 even in cases of a total block. A pacemaker is rarely needed.
  • In anterior wall infarction, the proximal conduction system may be blocked: the QRS complex is wide, the substituting rhythm is slow (30-40), the patient is in a poor condition, and pacing is necessary. Prognosis is poor even with pacing.
  • Drug treatment
    • Atropine 0.5 mg i.v., repeated as necessary, for treatment of functional bradycardia.

Pacemaker

  • In anterior wall infarction, pacing is indicated if there is a 2nd or 3rd degree block. Pacing should be anticipated in case of a trifascicular block, alternating right and left bundle branch block, or if an extensive infarction is associated with left anterior hemi-block (LAFB) or left posterior hemi-block (LPFB).
  • Posteroinferior wall infarction associated with a 3rd degree atrioventricular block requires pacing if bradycardia is detrimental to haemodynamics and not responsive to treatment with atropine.
  • Sinus bradycardia may be temporarily controlled with i.v. atropine.

Table 1. Circulatory Conditions and Their Treatment after Myocardial Infarction

Condition and Treatment Symptoms and Signs
Normal circulation
  • Monitoring
  • i.v. line (saline drop)
  • Heart rate and blood pressure normal
  • No arrhythmias
  • No heart insufficiency
Hyperdynamic state
  • Beta-blocker (metoprolol, atenolol, practolol 2 to 5 mg i.v.)
  • Increased heart rate, high blood pressure
Neurovascular reflex (bradycardia-hypotension)
  • Atropine 0.5 mg i.v., repeated ad 2 mg
  • Dopamine infusion, if necessary
  • Usually in connection with posteroinferior infarction
  • Bradycardia, hypotension
Hypovolemia
  • 0.9% saline 200 mL in 5 to 10 minutes according to the response
  • Low blood pressure, low central venous pressure (CVP), tachycardia
  • Cold extremities
  • Decreased venous distension (also jugular veins)
Severe heart failure
  • Nitrate infusion
  • Dopamine infusion
  • Continuous positive airway pressure (CPAP)
  • Treatment of pulmonary oedema
  • Low blood pressure
  • Cold extremities
  • Engorged neck veins
  • Chest crackles
  • Chest radiograph

Treatment in Hospital

Follow-up and Treatment

  • Pain: morphine, nitro, beta-blocker
  • Blood pressure
  • Skin, peripheral circulation
  • Increased respiratory rate suggests cardiac insufficiency.
  • Monitoring of arrhythmias
  • ST segment changes
  • Oxygen saturation; oxygen or continuous positive airway pressure
  • A comfortable posture
  • Informing and reassuring the patient
  • Nicotine replacement therapy is started already in the hospital. Nicotine addiction may be evaluated by using the Fagerstrom test, and the planning of further treatment may be based on it.
  • In an uncomplicated infarction, patients are allowed to sit as soon as they want, they can eat unassisted, and they can be helped to a portable toilet at the bedside. Intensive monitoring is usually needed for 1 to 2 days.
  • The infarction is complicated and treatment lasts longer if the patient has had
    • Shock
    • Hypotension
    • Obvious cardiac insufficiency (usually requires thrombosis prophylaxis or anticoagulation, especially if in connection with atrial fibrillation)
    • Prolonged chest pain
    • Serious ventricular arrhythmias
    • Thromboembolic complications
    • Anatomical complications (papillary muscle dysfunction or rupture)
    • Pericarditis on days 2 to 4
  • Treatment of the patient in primary health care (in a primary health care hospital) is justifiable if the patient's prognosis is otherwise poor: those who are permanent inpatients or otherwise severely disabled and for whom invasive treatment has not been planned.

Assessment of Risk Factors in a Patient with Myocardial Infarction

  • The most important causes of mortality are
    • Reinfarction
    • Cardiac insufficiency
    • Arrhythmias
  • During hospitalization, a poor prognosis is indicated by
    • Cardiac insufficiency and extensive infarction (ejection fraction [EF] <25%)
    • Chest pain and ischaemic ST changes (send to angiography)
    • In connection with non-Q-wave infarction, risk factors for coronary heart disease (CHD) and especially diabetes mellitus
  • Evaluation of ischaemia and need for active treatment
    • Risk is highest during the first few weeks and months after infarction. Therefore, at the end of the hospital treatment, an early symptom-limited exercise test is performed on many patients to estimate the need for angioplasty and coronary surgery in particular. Refer to Table 2 in the original guideline document for more information on the assessment of risk of reinfarction and patient’s prognosis.
  • For indications of coronary angiography, see the NGC summary of the Finnish Medical Society Duodecim guideline Coronary Angiography and Indications for CABG or Angioplasty.

Care after Myocardial Infarction

Drug Treatment

  • Aspirin, beta-blocker (Freemantle, et al., 1999; DARE-999336, 2001; Sudlow et al., 2002) [A], ACE inhibitors, and statins have been shown to improve the prognosis. Glycaemic control is also important.
  • Unnecessary drugs instituted during the initial phase should be discontinued already towards the end of hospital treatment or when the patient comes to the first check-up, not on the last day in hospital.
  • Only those with cardiac insufficiency or poorly controlled blood pressure need a diuretic.
  • Aspirin 50 to 100 (-250) mg is given unless there are contraindications ("Collaborative overview of randomised trials of antiplatelet therapy," 1994; DARE-948032, 1999) [A].
  • Patients with hypertension, angina pectoris, ventricular arrhythmias, ischaemia during an exercise test, previous infarction, an enlarged heart, low ejection fraction, or a cardiac insufficiency need a beta-blocker. In practice, these drugs are given to all patients who have no contraindications. Adequate beta-blockade is achieved when the heart rate at rest is about 60 bpm.
  • Nitrate plus a beta-blocker are given to all patients with angina pectoris or ischaemia during an exercise test. Nitrate is a drug used for symptom relief that can often be discontinued.
  • An ACE inhibitor is given to all patients with clear systolic dysfunction (ejection fraction <40%) (Sudlow et al., 2002) [A]. A milder systolic dysfunction is treated with an ACE inhibitor if the patient has cardiac insufficiency (symptomatic or asymptomatic), valvular regurgitation, hypertension, or diabetic nephropathy. The indications of ACE inhibitors have been constantly extended, and they are now given to almost every patient who has had an infarction. So-called "asymptomatic cardiac insufficiency" and even secondary prevention (according to the Heart Outcomes Prevention Evaluation [HOPE] study) in high-risk patients have become indications (Yusuf et al., 2000). ACE inhibitor therapy may be more difficult if the patient has a valvular obstruction, hypotension, or uraemia. Patients on diuretics have a risk of hypotension, especially when treatment with an ACE inhibitor is started. The ACE inhibitor dose should not remain at the level of the initial dose unless hypotension and creatinine elevation prevent the titration.
  • A lipid-lowering drug (a statin) is given to all patients with serum low-density lipoprotein (LDL) cholesterol >3.0 mmol in spite of the diet (Rembold, 1996; DARE-961089, 1999) [A]. For calculation of the level, see the LDL cholesterol calculator program available on the EBM CD-ROM and the EBM Web site.
  • An anticoagulant is given if the patient has atrial fibrillation, an embolic complication, or ventricular aneurysm verified by echocardiography, often also short-term in the treatment of an extensive anterior wall infarction.
  • Elevated serum homocysteine concentration is associated with cardiovascular diseases, but it does not appear to predict arterial disease in healthy persons (Knekt et al., 2001; Institute for Clinical Systems Improvement (ICSI), 2003; HTA-20030537, 2004) [C]. See also the NGC summary of the Finnish Medical Society Duodecim guideline Coronary Heart Disease (CHD): Symptoms, Diagnosis, and Treatment.
  • A quiet moment should be reserved for discussing life after MI and living with coronary artery disease (CAD) while the patient is still in the hospital.
    • Such a discussion helps to reduce psychological problems and disability.
    • Give instructions for dealing with possible exacerbation of the disease.
    • The motivation to quit smoking is highest after an infarction:
      • nicotine replacement therapy according to individual evaluation (Fagerstrom test)
    • A cholesterol and saturated fatty acid-restriction diet and/or drug treatment
    • Exercise counseling according to individual evaluation: the patient must be able to talk while exercising.
    • Rehabilitation course
    • Secondary prevention

Sick Leave

  • Duration 2 to 3 months
  • Reexamination after about one month, usually within specialist health care.
    • History of symptoms: if the patient has had angina pectoris symptoms, consider testing exercise capacity, if the test has not been performed yet.
    • Remind the patient of the principles of healthy life style.
    • Serum lipids should be measured if they were high on an earlier measurement.
    • Control the adequacy of beta-blockade: target heart rate 50 to 60 bpm.
    • Possible depression should be diagnosed.
  • The ability to work is evaluated before the end of the sick leave. If necessary, an exercise test is carried out to assess working ability.

Related Evidence

  • Glucose-insulin-potassium probably reduces mortality in acute MI. However, its role in combination with thrombolysis or acute revascularization should be determined by larger randomized trials (Fath-Ordoubadi & Beatt, 1997; DARE-971070, 1999) [B].
  • There is little evidence from randomized trials of any significant further net clinical benefit from adding either subcutaneous or intravenous unfractionated heparin to the treatment of patients who are given aspirin (Collins et al., 1996; DARE-978036, 1999) [B].
  • Low-dose amiodarone may have a beneficial effect on total mortality after MI, but the drug has many adverse effects (Zarembski et al., 1993; DARE-940032 1999) [C].
  • Class I antiarrhythmic agents increase the risk of death after MI (Sudlow et al., 2002) [A].
  • Sotalol increases mortality in patients with MI who have left ventricle failure (Sudlow et al., 2002) [B].
  • The evidence does not support the hypothesis that verapamil use is associated with harm in patients with MI (Pepine, Faich, & Makuch, 1998; DARE-981601, 2000) [B].
  • Exertion-related MIs occur in habitually inactive people with multiple cardiac risk factors (Giri et al., 1999) [B].
  • C-reactive protein may have independent value as a predictor of cardiovascular disease risk, but conclusive evidence on its role in risk assessment is lacking (Institute for Clinical Systems Improvement (ICSI), 2003; Health Technology Assessment Database: HTA-20030537, 2004; Blue Cross Blue Shield Association (BCBS), 2003; HTA-20030742, 2004;Health Technology Advisory Committee (HTAC), 2002; HTA-20030446, 2004) [C].

Definitions:

Levels of Evidence

  1. Strong research-based evidence. Multiple relevant, high-quality scientific studies with homogeneous results.
  2. Moderate research-based evidence. At least one relevant, high-quality study or multiple adequate studies.
  3. Limited research-based evidence. At least one adequate scientific study.
  4. No research-based evidence. Expert panel evaluation of other information.

 

 

Upper Limits for Glycemic Targets in Pregnancy

 

Prelabor   

  

Preprandial  

1-hour postprandial   

 Labor and delivery

100 mg/dL (5.6 mmol/L)

120 mg/dL (6.7 mmol/L)   

 100 mg/dL (5.6 mmol/L)

  

 

Preoperative Testing

Test

Routine Use Indicated?

Indications

Coagulation studies

No

Stigmata liver disease, hx coagulopathy, (PT/INR, PTT). possible DIC, anticoagulation, alcohol abuse

Bleeding Time

No

Unreliable test. Very subjective.

CBC

No

Possible hematologic or infectious process, significant blood loss predicted

Electrolytes

No

Diuretic use, hx or renal or cardiac disease, possible dehydration by history or physical

Glucose

No

Diabetics, obese patients, undergoing vascular procedures, other reason for increased glucose (e.g., steroids)

BUN/Creatinine

No

Over 60, history renal, cardiac or vascular disease

Urinalysis

No

Symptomatic patients, diabetics, pregnancy

Pregnancy

No

If indicated by history

Liver Enzymes

No

Historical or physical evidence of liver disease

ECG and CXR

No

As indicated by history and physical

 

Classification of Operative Wounds and Risk of Infection
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Classification
Criteria
Risk (%)
Clean Elective, not emergency, nontraumatic, primarily closed; no acute inflammation; no break in technique; respiratory, gastrointestinal, biliary and genitourinary tracts not entered < 2
Clean-contaminated Urgent or emergency case that is otherwise clean; elective opening of respiratory, gastrointestinal, biliary or genitourinary tract with minimal spillage (e.g., appendectomy) not encountering infected urine or bile; minor technique break < 10
Contaminated Nonpurulent inflammation; gross spillage from gastrointestinal tract; entry into biliary or genitourinary tract in the presence of infected bile or urine; major break in technique; penetrating trauma < 4 hours old; chronic open wounds to be grafted or covered ~ 20
Dirty Purulent inflammation (e.g., abscess); preoperative perforation of respiratory, gastrointestinal, biliary or genitourinary tract; penetrating trauma > 4 hours old ~ 40
Information from Cruse PJ, Foord R. The epidemiology of wound infection. A 10-year prospective study of 62,939 wounds. Surg Clin North Am 1980;60:27-40.
Factors Associated with Increased Risk of Infection
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Systemic factors
Diabetes
Corticosteroid use
Obesity
Extremes of age
Malnutrition
Recent surgery
Massive transfusion
Multiple (3 or more) preoperative comorbid medical diagnoses
ASA class 3, 4 or 5

Local factors
Foreign body
Electrocautery
Injection with epinephrine
Wound drains
Hair removal with razor
Previous irradiation of site
ASA=American Society of Anesthesiologists
Half-Lives of Selected Antibiotics Commonly Used for Prophylaxis
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Antibiotic
Half-life (hours)
Cefazolin (Ancef, Kefzol)
Vancomycin (Vancocin)
Cefoxitin (Mefoxin)
Cefotetan (Cefotan)
Aminoglycosides
Metronidazole (Flagyl)
Clindamycin (Cleocin)
Ciprofloxacin (Cipro)		 1.8
3 to 9
0.6 to 1
3 to 4.6
2
8
2.4 to 3
3 to 5
Procedure-Specific Recommendations for Prophylaxis
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Procedure
Likely organisms
Recommended antibiotic*
Adult dose†
Cutaneous Staphylococcus aureus,
Staphylococcus epidermidis‡		 No uniform recommendation§
Head and neck S. aureus, streptococci Cefazolin (Ancef, Kefzol) 1 to 2 g intravenously
Neurosurgery S. aureus, S. epidermidis Cefazolin 1 to 2 g intravenously
Thoracic S. aureus, S. epidermidis Cefazolin 1 to 2 g intravenously
Cardiac S. aureus, S. epidermidis Cefazolin|| 1 to 2 g intravenously
Abdominal
Gastroduodenal
Gram-positive cocci, enteric
gram-negative bacilli 		High risk: cefazolin 1 to 2 g intravenously
Colorectal¶
Enteric gram-negative bacilli,
anaerobes 		Oral: neomycin (Neosporin)
and erythromycin base 		1 g orally (3 doses)#
Parenteral: cefotetan (Cefotan)
or cefoxitin (Mefoxin) 		1 to 2 g intravenously
Appendectomy
Enteric gram-negative bacilli,
anaerobes 		Cefotetan or cefoxitin 1 to 2 g intravenously
Biliary
Enteric gram-negative bacilli High risk: cefazolin 1 to 2 g intravenously
Gynecologic and
obstetric		 Enteric gram-negative bacilli,
group B streptococcus,
anaerobes 		Cefazolin** 1 to 2 g intravenously
Urologic S. aureus, enteric
gram-negative bacilli 		Cefazolin†† 1 to 2 g intravenously
Orthopedic S. aureus, S. epidermidis Cefazolin 1 to 2 g intravenously
Noncardiac vascular S. aureus, S. epidermidis,
enteric gram-negative bacilli		 Cefazolin 1 to 2 g intravenously
Breast and hernia S. aureus, S. epidermidis High risk: cefazolin‡‡ 1 to 2 g intravenously

*-- For patients allergic to penicillins or cephalosporins, vancomycin (Vancocin), 1 g intravenously, may be used instead to provide activity against gram-positive cocci. If enteric gram-negative bacilli are among the likely organisms, aztreonam (Azactam), 1 to 2 g, or an aminoglycoside, 3 mg per kg, must be given in addition to vancomycin. If anaerobic flora are expected, aztreonam and clindamycin (Cleocin), 900 mg, are the recommended combination in patients who are allergic to penicillin or cephalosporins.

†--Antibiotic should be given approximately 30 minutes before skin incision and repeated at 1 to 2 half-lives (e.g., for cefazolin, every 3 to 4 hours). Common pediatric doses--cefazolin: 30 mg per kg; cefoxitin: 25 mg per kg; cefotetan: pediatric doses have not been established by the manufacturer; vancomycin: 15 mg per kg.

‡--The specific nature of the wound, the type of contamination and the degree of contamination also influence the microbiology of the wound.

§--Appropriate local wound care is indicated (see text). Cefazolin may be used.

||--Standard regimens employ mechanical cleansing of the bowel (see text).

¶--One g of each agent is administered at 19, 18 and nine hours before surgery.

#--Despite the presence of gram-negative bacilli and anaerobes among the likely organisms, no data demonstrate superiority of an agent or agents alternative to cefazolin.

**--Indications are variable and not firmly established (see text).

††--Prophylaxis is considered acceptable but not strongly indicated in low-risk patients.

‡‡--Vancomycin can be used if a high level of methicillin (Staphcillin) resistance has been noted in the hospital.

 

Epidural Anaesthesia
Dr Leon Visser,

Epidural anaesthesia can be used as sole anaesthetic for procedures involving the lower limbs, pelvis, perineum and lower abdomen. It is possible to perform upper abdominal and thoracic procedures under epidural anaesthesia alone, but the height of block required, with its attendant side effects, make it difficult to avoid significant patient discomfort and risk. The advantage of epidural over spinal anaesthesia is the ability to maintain continuous anaesthesia after placement of an epidural catheter, thus making it suitable for procedures of long duration. This feature also enables the use of this technique into the postoperative period for analgesia, using lower concentrations of local anaesthetic drugs or in combination with different agents.

Specific uses

  • Hip and knee surgery. Internal fixation of a fractured hip is associated with less blood loss when central neuraxial block is used. The rate of deep venous thrombosis is reduced in patients undergoing total hip and knee replacement, when epidural anaesthesia is used.
  • Vascular reconstruction of the lower limbs. Epidural anaesthesia improves distal blood flow in patients undergoing arterial reconstruction surgery.
  • Amputation. Patients given epidural anaesthesia 48-72 hours prior to lower limb amputation may have a lower incidence of phantom limb pain following surgery, although this has not been substantiated.
  • Obstetrics. Epidural analgesia is indicated in obstetric patients in difficult or high-risk labour, e.g. breech, twin pregnancy, pre-eclampsia and prolonged labour. Furthermore, Caesarean section performed under central neuraxial block is associated with a lower maternal mortality owing to anaesthetic factors than under general anaesthetic.
  • Low concentration local anaesthetics, opioids, or combinations of both are effective in the control of postoperative pain in patients undergoing abdominal and thoracic procedures. Epidural analgesia has been shown to minimise the effects of surgery on cardiopulmonary reserve, i.e. diaphragmatic splinting and the inability to cough adequately, in patients with compromised respiratory function, such as those with chronic obstructive airway disease, morbid obesity and in the elderly. Epidural analgesia allows earlier mobilization, reduces the risk of deep venous thrombosis, and allows better cooperation with chest physiotherapy, preventing chest infections.
  • Thoracic trauma with rib or sternum fractures. Adequate analgesia in patients with thoracic trauma improves respiratory function by allowing the patient to breathe adequately, cough and cooperate with chest physiotherapy

Contraindications

Absolute

  • Patient refusal
  • Coagulopathy. Insertion of an epidural needle or catheter into the epidural space may cause traumatic bleeding into the epidural space. Clotting abnormalities may lead to the development of a large haematoma leading to spinal cord compression.
  • Therapeutic anticoagulation. As above
  • Skin infection at injection site. Insertion of the epidural needle through an area of skin infection may introduce pathogenic bacteria into the epidural space, leading to serious complications such as meningitis or epidural abscess.
  • Raised intracranial pressure. Accidental dural puncture in a patient with raised ICP may lead to brainstem herniation (coning).
  • Hypovolaemia. The sympathetic blockade produced by epidurals, in combination with uncorrected hypovolaemia, may cause profound circulatory collapse.

Relative

  • Uncooperative patients may be impossible to position correctly, and be unable to remain still enough to safely insert an epidural.
  • Pre-existing neurological disorders, such as multiple sclerosis, may be a contraindication, because any new neurological symptoms may be ascribed to the epidural.
  • Fixed cardiac output states. Probably relative rather than absolute. This includes aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), mitral stenosis and complete heart block. Patients with these cardiovascular abnormalities are unable to increase their cardiac output in response to the peripheral vasodilatation caused by epidural blockade, and may develop profound circulatory collapse which is very difficult to treat.
  • Anatomical abnormalities of vertebral column may make the placement of an epidural technically impossible.
  • Prophylactic low dose heparin (see discussion below)

 

Epidurals and anticoagulants

    • Full oral anticoagulation with warfarin or standard heparin (SH) are absolute contraindications to epidural blockade.
    • Partial anticoagulation with low molecular weight heparin (LMWH) or low dose warfarin (INR <1.5) are relative contraindications.
    • Minihep (low dose standard heparin (SH), 5,000units bd s/c is not associated with an increased risk of epidural haematoma. Wait for 4 hours after a dose before performing epidural. Minihep/SH should not be given until 1 hour following epidural injection. These guidelines also apply for removal of epidural catheters.
    • LMWH (<40mg enoxaparin and dalteparin): allow 12hr interval between LMWH administration and epidural; this also applies to removal of epidural catheters.
    • NSAID's (including aspirin) do not increase the risk of epidural haematoma.
    • Intraoperative anticoagulation using 5000units i/v heparin following epidural/spinal injection appears safe, but careful postoperative observations are recommended. Bloody tap or blood in epidural catheter is controversial. Some teams delay surgery for 12hr, others (if pre-op coagulation normal) delay i/v bolus of heparin for 1hour.
    • Fibrinolytic and thrombolytic drugs: avoid epidural block for 24 hrs, check clotting prior to insertion.
    • Thrombocytopaenia: epidurals are relatively contraindicated below platelet count of 100,000/mm3.
    • An epidural haematoma should be suspected in patients who complain of severe back pain a few hours/days following any central neuraxial block or with any prolonged or abnormal neurological deficit (including. sensory loss, paraesthesiae, muscle weakness and disturbance of bladder control and anal sphincter tone). A high index of suspicion is required, with early orthopaedic or neurosurgical referral for decompression of the haematoma. Even with early recognition, the morbidity of this condition is still very high.

Suggested Recommendations and Guidelines for Surgical Prophylaxis

Introduction

Postoperative wound infections are the major source of infectious morbidity in the surgical patient. The use of perioperative antibiotics has become an essential component of the standard of care in virtually all surgical procedures and has resulted in a reduced risk of postoperative infection when sound and appropriate principles of prophylaxis are applied.

  1. There is probable risk of infection in the absence of a prophylactic agent.

  2. There is a knowledge of the probable contaminating flora associated with the operative wound or organ site.

  3. The activity of the chosen prophylactic agent should encompass the majority of pathogens likely to contaminate the wound or operative site.

  4. When more than one choice is given as a prophylactic agent, the agents or agents selected should be based on the most likely contaminating organisms.

  5. The prophylactic agent must be administered in a dose which provides an effective tissue concentration prior to intraoperative bacterial contamination. Administration must occur 30-45 minutes prior to incision (usually with the induction of anesthesia).

  6. The effective dose should be governed by the patient's weight. For cephalosporins, patients weighing >70 kg, dosage should be doubled (i.e., 70 kg: cefazolin 1 g IV, >70 kg: cefazolin 2 g IV).

  7. In procedures lasting 3 hour or less, a single prophylactic dose is usually sufficient. Procedures lasting greater than three hours require an additional effective dose. Procedures in which there is rapid blood loss and/or fluid administration will dictate more frequent prophylactic dosing. Under no circumstance should any prophylactic agent be given on-call because it often results in less than effective tissue levels at the time of incision. Postoperative prophylaxis is strongly discouraged except in the scenario of a bioprosthetic insertion in which case 2 or 3 additional prophylactic doses may be deemed sufficient (Warning: there are no standard rules on prophylaxis following prosthetic insertion and clinical experience strongly dictates practice).

  8. Vancomycin may be used for patients with severe penicillin/cephalosporin allergy.

  9. An effective and thoughtful prophylactic regimen is no substitute for exquisite surgical technique and competent postsurgical management.

MCW & FMLH
Antibiotic Guide

I. General Surgery

a. Clean Procedures

Under most circumstances antimicrobial prophylaxis is not required when performing a clean surgical procedure. However, prophylaxis should be employed under those conditions where there is a potential intrinsic risk of infections such as in:

  1. Insertion of a synthetic biomaterial device or prosthesis

  2. Clean operations performed in a patients with impaired host defenses

Agents: Cefazolin or cefuroxime.

Route/Dosage/Timing: 1 gram cefazolin IV or 750 mg cefuroxime IV 30-45 minutes before skin incision; second dose if procedure >3 hours.

Rationale: Likely infecting organism are gram-positive cocci (S. aureus or S. epidermidis) and aerobic coliforms (E. coli).


b. Upper GI & Elective Small Bowel (Stomach, Small Bowel, Pancreas, Hepatobiliary)

Agents: Ciprofloxacin
               Ceftizoxime OR ceftizoxime + metronidazole if anarobes suspected.

Route/Dosage/Timing: 400mg IV ciprofloxacin OR 1 gram ceftizoxime (500 mg metronidazole) IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Common infecting organisms: Coliforms > Enterococcus > streptococci > anaerobic clostridia, peptostreptococci, Bacteroides, Prevotella or Porphyromonous (formerly oral Bacteroides).


c. Large Bowel Resections

Agents: Oral mechanical prep (Neomycin/Erythromycin) and parenteral cephalosporin (ceftizoxime or cefotetan).

    Two Days Before Surgery

  • Bisacodyl (Dulcolax) 2 tabs

    Preoperative Day

  • Clear liquid diet only.
  • GoLYTELY prep 1 gallon bottle; begin at 9 AM.
    • Metoclopramide (Reglan) 1 tab before each of the first two glasses of GoLYTELY.
    • One large glass of GoLYTELY po every 10-20 minutes. Finish entire gallon in 1-2 hours.
  • Administer neomycin plus erythromycin base po at 1 PM, 2 PM and 10 PM; keep NPO after midnight (first dose given 20 hours before surgery).

    Operative Day

  • Completely evacuate the bowel prior to operation.

  • Parenteral drug administration 30-45 minutes prior to incision.

Route/Dosage/Timing: 1 gram ceftizoxime or cefotetan IV 30-45 minutes prior to incision; second dose if procedure lasts > 3 hours. No additional doses required.

Rationale: Likely flora includes coliforms, Enterococcus, Bacteroides, peptostreptococci and clostridia.


d. Acute Appendectomy (Non-perforated)

Agents: Single agent: Ceftizoxime or cefotetan.
Combination therapy: Ceftizoxime plus metronidazole.

Route/Dosage/Timing: Single agent: 1 gram ceftizoxime or cefotetan IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.
Combination therapy: 1 gram ceftizoxime IV plus 500 mg metronidazole IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Coliforms and anaerobic bacteria likely infecting organisms.

    Note: In perforated or gangrenous cases, clinical situation becomes therapeutic and Rx is continued as clinically indicated


II. Trauma Surgery

a. Penetrating Abdominal Trauma

Agents: Single agent: Ampicillin/sulbactam.
Combination therapy: Ceftizoxime plus metronidazole.

Route/Dosage/Timing: 3 grams ampicillin/sulbactam IV or 2 grams ceftizoxime plus 500 mg metronidazole IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Coliform and anaerobic bacteria (gram-positive & gram-negative) present in peritoneal cavity follow bowel injury.


III. Obstetrics and Gynecology

a. Vaginal or Abdominal Hysterectomy (Including Radical)

Agents: Ceftizoxime or cefotetan.

Route/Dosage/Timing: 1 gram ceftizoxime, or cefotetan IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Coliforms, Enterococcus, Streptococcus, Clostridia and Bacteroides are potential infecting organisms.


b. Cesarean Section/Hysterectomy

Agents: Cefazolin or ceftizoxime.

Route/Dosage/Timing: 1 gram cefazolin or ceftizoxime IV 30-45 minutes before skin incision; in high risk patients, may use 2 grams cefazolin or ceftizoxime IV after clamping and cutting of umbilical cord.

Rationale: Coliforms, Enterococcus, Streptococcus, Clostridia and Bacteroides potential contaminants.


IV. Urology

a. Prostatectomy

Agents: Cefazolin or ciprofloxacin.

Route/Dosage/Timing: 1 gram cefazolin IV OR 400 mg ciprofloxacin IV 30-45 minutes before skin incision; second dose of either cefazolin or ciprofloxacin after procedure.

Rationale: Coliforms and staphylococci (community strains) are major infecting organism, pseudomonads occasional pathogen.


V. Transplant Surgery

a. Kidney Transplantation

Agents: Cefazolin

Route/Dosage/Timing: 1 gram cefazolin IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Staphylococci are the predominant contaminants, gram-negative enterococci are occasionally encountered.


b. Liver Transplantation

Agents: Ampicillin/sulbactam.

Route/Dosage/Timing: 3 grams ampicillin/sulbactam IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Coliforms, enterococci and staphylococci are potential contaminating organisms.


c. Pancreas or Kidney/Pancreas

Agents: Vancomycin, imipenem/cilastatin, and fluconazole.

Route/Dosage/Timing: 1 gram vancomycin IV, 500 mg  imipenem/cilastatin IV, and 400 mg fluconazole IV 30-45 minutes before skin incision.

Rationale: Donor duodenum is often colonized with gram positive organisms such as Staphylococcus epidermis, Enterococcus, and yeast.


VI. Head and Neck Surgery

a. Clean Procedures (skin excision, neck dissections)

Agents: Cefazolin or penicillin G.

Route/Dosage/Timing: 1 gram cefazolin IV or 2-4 MU penicillin G IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Coverage against staphylococcal flora.


b. Laryngectomy & Other Head and Neck Cancer Operations

Agents: Cefazolin or ceftizoxime plus metronidazole.

Route/Dosage/Timing: 1 gram cefazolin or ceftizoxime IV and 500 mg metronidazole IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.
or 400 mg ciprofloxacin IV plus 500 mg metronidazole IV 30-45 minutes before skin incision.

Rationale: Coverage against skin staphylococci plus oral anaerobic bacteria.


c. Mandibular Fractures

Agents: Penicillin.

Route/Dosage/Timing: 2 MU penicillin (>60 kg use 4 MU) IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Coverage for oral flora.


VII. Orthopaedic Surgery

a. Total Joint Replacement

Agents: Cefazolin or cefuroxime.

Route/Dosage/Timing: 1 gram cefazolin or 750 mg cefuroxime IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Staphylococci are major infecting organism in joint replacement surgery.


b. Traumatic Open Fractures

Agents: Cefazolin (grade I & II fractures); ceftizoxime (grade III fractures).

Route/Dosage/Timing: 2 gram cefazolin or ceftizoxime IV 30-45 minutes before incision; second dose if procedure > 3 hours.

Rationale: Staphylococcal skin flora common contaminant in grade I and II fractures, coliforms often infect the serious grade III fractures.


VIII. Vascular Surgery

a. Peripheral Vascular Procedures

Agents: Cefazolin or
              Ciprofloxacin plus metronidazole.

Route/Dosage/Timing: 1 gram cefazolin IV 30-45 minutes before skin incision; second dose if procedure > 3 hours or 400 mg ciprofloxacin IV plus 500 mg metronidazole IV 30-45 minutes before skin incision.

Rationale: Staphylococci major contaminants associated with vascular graft infection; mixed microbial flora (anaerobes and aerobes) associated with abdominal aorta and diabetic foot patients.


IX. Cardiothoracic Surgery, Coronary Bypass Surgery, and Pulmonary Resection

Agents: Cefazolin or cefuroxime.

Route/Dosage/Timing: 1 gram cefazolin or 750 mg cefuroxime IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Staphylococci most common infecting organism.


X. Neurosurgery

Agents: Cefazolin.

Route/Dosage/Timing: 1 gram cefazolin IV 30-45 minutes before skin incision; second dose if procedure > 3 hours.

Rationale: Staphylococci are the predominant isolates from neurosurgical wound infections.


 Sinoe Medical Association

 
  • When Alzheimer's disease has been diagnosed, a comprehensive management plan should be developed. As the disease progresses, this plan will have to be modified to address new issues, exacerbations of other health conditions, and end-of-life decisions
  • AMERICAN FAMILY PHYSICIANS JOURNAL , June 15, 2002

 

  • Donepezil, rivastigmine, and galantamine are cholinesterase inhibitors that have been labeled for the treatment of Alzheimer's disease. Tacrine is no longer considered first-line treatment for this condition

 

  • Nonpharmacologic interventions for behavior problems associated with Alzheimer's disease may enable a reduction in the dosage, duration, or complexity of required pharmacotherapy

Cholinesterase Inhibitors for the Treatment of Cognitive Deficits in Patients with Mild to Moderate Alzheimer's Disease

Drug

Suggested dosage

Side effects

Specific cautions

Donepezil (Aricept)

Initial dosage is 5 mg once daily; if necessary, dosage can be increased to 10 mg once daily after 4 to 6 weeks.

Mild side effects, including nausea,vomiting, and diarrhea; these effects can be reduced by taking donepezil with food.
Initial increase of agitation in some patients; agitation typically subsides after a few weeks.

Conflicting evidence about possible interactions with cimetidine (Tagamet), theophylline, warfarin (Coumadin), and digoxin(Lanoxin)

Rivastigmine (Exelon)

Initial dosage of 1.5 mg twice daily (3 mg per day) is generally well tolerated; dosage can be increased as tolerated but no more quickly than by 1.5 mg twice daily (3 mg per day) every 4 weeks to maximum of 6 mg twice daily (12 mg per day). Twice-daily dosing is as efficacious as thrice-daily dosing and has comparable tolerability.

Nausea, vomiting, diarrhea, headaches, dizziness, abdominal pain, fatigue, malaise, anxiety, and agitation; these effects can be reduced by taking rivastigmine with food.

Weight loss
Interacting drugs include aminoglycosides and procainamide (Procanbid).

Galantamine (Reminyl)

Initial dosage is 4 mg twice daily (8 mg per day) taken with the morning and eveningmeals for 4 weeks; dosage is then increased to 8 mg twice daily (16 mg per day) for atleast 4 weeks. An increase to 12 mg twice daily (24 mg per day) should be considered on an individual basis, depending on clinical benefit and tolerability.

Mild side effects, including nausea, vomiting, and diarrhea; these effects can be reduced by taking galantamine with food.
No apparent association with sleep disturbances (which can occur with other cholinergic treatments)

Contraindicated for use in patients with hepatic or renal impairment

Tacrine (Cognex)

Initial dosage is 10 mg four times daily (40 mg per day) for 4 weeks; dosage is increased to 20 mg four times daily (80 mg per day) for 4 weeks, then to 30 mg four times daily (120 mg per day) for 4 weeks, etc., untilmaximum tolerated dosage is achieved. Maximum dosage is 40 mg four times daily (160 mg per day).

High incidence of side effects, including gastrointestinal problems; these effects can be reduced by taking tacrine with food.

Interacting drugs include theophylline and procainamide.
Hepatotoxicity is a problem; hence, liver tests should be performed every other week for 16 weeks and every 3 months thereafter.

Information from package inserts provided by the manufacturers of the drugs.

Nonpharmacologic Interventions for Reducing Behavioral Disturbances in Alzheimer's Disease

  • Provide the patient with a predictable routine (i.e., exercise, meals, and bedtime should be routine and punctual).
  • Allow the patient to dress in his or her own clothing and keep possessions.
  • Before performing all procedures and activities, explain them to the patient in simple language.
  • Simplify all tasks; break complex tasks into steps and provide instructions for each step.
  • Use distraction and redirection of activities to divert the patient from problematic situations.
  • Ensure that comorbid conditions are optimally treated.
  • Provide a safe environment (i.e., no sharp-edged furniture, no slippery floors or throw rugs, no obtrusive electric cords).
  • Equip doors and gates with safety locks.
  • Install grab bars by the toilet and in the shower.
  • Use calendars, clocks, labels, and newspapers for orientation
    to time.
  • Use color-coded or graphic labels (i.e., on closets, table service, drawers) as cues for orientation in the home environment.
  • Use lighting to reduce confusion and restlessness at night.
  • Avoid glare from windows and mirrors, noise from a television, and household clutter.
  • Reduce excess stimulation and outings to crowded places
    (overexposure to environmental stimuli can lead to agitation and disorientation).
  • Consider using a day care program for patients with
    Alzheimer's disease.
  • Register the patient in the Alzheimer's Association Safe Return Program

Treatment of Behavior and Mood Disorders
Antipsychotic drugs
Atypical antipsychotic agents
  Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness
  General cautions: diminished risk of developing extrapyramidal symptoms and tardive dyskinesia compared with typical antipsychotic agents
  Risperidone (Risperdal) Initial dosage: 0.25 mg per day at bedtime;maximum: 2 to 3 mg per day, usually twice daily in divided doses Comments: current research supports use of low dosages; extrapyramidal symptoms may occur at 2 mg per day.
  Olanzapine (Zyprexa) Initial dosage: 2.5 mg per day at bedtime; maximum: 10 mg per day, usually twice dailyin divided doses Comments: generally well tolerated
  Quetiapine (Seroquel) Initial dosage: 12.5 mg twice daily; maximum: 200 mg twice daily Comments: more sedating; beware of transient orthostasis.
Typical antipsychotic agents
  Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness; second-line therapy in patients who cannot tolerate or do not respond to atypical antipsychotic agents
  General cautions: current research suggests that these drugs should be avoided if possible, because they are associated with significant, often severe side effects involving the cholinergic, cardiovascular, and extrapyramidal systems; there is also an inherent risk of irreversible tardive dyskinesia, which can develop in 50% of elderly patients after continuous use of typical antipsychotic agents for 2 years.
  Haloperidol (Haldol), fluphenazine (Prolixin), thiothixene (Navane) Dosage: varies by agent Comments: anticipated extrapyramidal symptoms; if these symptoms occur, decrease dosage or switch to another agent; avoid use of benztropine (Cogentin) or trihexyphenidyl (Artane).
  Trifluoperazine (Stelazine), molindone (Moban), perphenazine (Trilafon), loxapine (Loxitane) Dosage: varies by agent Comments: agents with "in-between" side effect profile
Mood-stabilizing (antiagitation) drugs
  Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness; useful alternatives to antipsychotic agents for control of severe agitated, repetitive, and combative behaviors
  General cautions: see comments about specific agents.
  Trazodone (Desyrel) Initial dosage: 25 mg per day; maximum: 200 to 400 mg per day in divided doses Comments: use with caution in patients with premature ventricular contractions.
  Carbamazepine (Tegretol) Initial dosage: 100 mg twice daily; titrate totherapeutic blood level (4 to 8 mcg per mL) Comments: monitor complete blood cell count and liver enzyme levels regularly; carbamazepine has problematicside effects.
  Divalproex sodium (Depakote) Initial dosage: 125 mg twice daily; titrate to therapeutic blood level (40 to 90 mcg per mL) Comments: generally better tolerated than other mood stabilizers; monitor liver enzyme levels; monitor platelets, prothrombin time, and partial thromboplastin time as indicated.
Anxiolytic drugs
Benzodiazepines
  Recommended uses: management of insomnia, anxiety, and agitation
  General cautions: regular use can lead to tolerance, addiction, depression, and cognitive impairment; paradoxic agitation occurs in about 10% of patients treated with benzodiazepines; infrequent, low doses of agents with a short half-life are least problematic.
  Lorazepam (Ativan), oxazepam (Serax), temazepam (Restoril), zolpidem (Ambien), triazolam (Halcion) Dosage: varies by agent See general cautions.
Nonbenzodiazepines
  Buspirone (BuSpar) Initial dosage: 5 mg twice daily; maximum: 20 mg three times daily Comments: useful only in patients with mild to moderate agitation; may take 2 to 4 weeks to become effective
Antidepressant drugs
  Recommended uses: see comments on specific agents.
  General cautions: selection of an antidepressant is usually based on previous treatment response, tolerance, and the advantage of potential side effects (e.g., sedation versus activation); a full therapeutic trial requires at least 4 to 8 weeks; as a rule, dosage is increased using increments of initial dose every 5 to 7 days until therapeutic benefits or significant side effects become apparent; after 9 months, dosage reduction is used to reassess the need to medicate; discontinuing an antidepressant over 10 to 14 days limits withdrawal symptoms.
NOTE: Patients with depression and psychosis require concomitant antipsychotic medication.
Tricyclic antidepressant agents
  Desipramine (Norpramin) Initial dosage: 10 to 25 mg in the morning; maximum: 150 mg in the morning Comments: tends to be activating (i.e., reduces apathy); lower risk for cardiotoxic, hypotensive, and anticholinergiceffects; may cause tachycardia; blood levels may be helpful.
  Nortriptyline (Pamelor) Initial dosage: 10 mg at bedtime; anticipated dosage range: 10 to 40 mg per day (given twice daily) Comments: tolerance profile is similar to that for desipramine, but nortriptyline tends to be more sedating; may be useful in patients with agitated depression and insomnia; therapeutic blood level "window" of 50 to 150 ng per mL (190 to 570 nmol per L)
Heterocyclic and noncyclic antidepressant agents
  Nefazodone (Serzone) Initial dosage: 50 mg twice daily; maximum: 150 to 300 mg twice daily Comments: effective, especially in patients with associatedanxiety; reduce dose of coadministered alprazolam (Xanax) or triazolam by 50%; monitor for hepatotoxicity.
  Bupropion (Wellbutrin) Initial dosage: 37.5 mg every morning, then increase by 37.5 every 3 days; maximum: 150 mg twice daily Comments: activating; possible rapid improvement of energylevel; should not be used in agitated patients and those with seizure disorders; to minimize risk of insomnia, give second dose before 3 p.m.
  Mirtazapine (Remeron) Initial dosage: 7.5 mg at bedtime; maximum: 30 mg at bedtime Comments: potent and well tolerated; promotes sleep, appetite, and weight gain
SSRIs
  Recommended uses: may prolong half-life of other drugs by inhibiting various cytochrome P450 isoenzymes
  General cautions: typical side effects can include sweating, tremors, nervousness, insomnia or somnolence, dizziness, and various gastrointestinal and sexual disturbances.
  Fluoxetine (Prozac) Initial dosage: 10 mg every other morning; maximum: 20 mg every morning Comments: activating, very long half-life; side effects may not manifest for a few weeks.
  Paroxetine (Paxil) Initial dosage: 10 mg per day; maximum: 40 mg per day (morning or evening) Comments: less activating but more anticholinergic than other SSRIs
  Sertraline (Zoloft) Initial dosage: 25 to 50 mg per day; maximum:200 mg per day (morning or evening) Comments: well tolerated; compared with other SSRIs, sertraline has less effect on metabolism of other medications.
  Citalopram (Celexa) Initial dosage: 10 mg per day; maximum: 40 mg per day Comments: well tolerated; some patients experience nausea and sleep disturbances.
  Fluvoxamine (Luvox) Initial dosage: 50 mg twice daily; maximum: 150 mg twice daily Comments: exercise caution when using fluvoxamine with alprazolam or triazolam.
Phenethylamine
  Venlafaxine (Effexor) Initial dosage: 37.5 mg twice daily; maximum: 225 mg per day in divided doses Comments: highly potent; also inhibits norepinephrine reuptake
Lithium
  Recommended uses: for anticycling; can also be used to augment antidepressant drugs
  General cautions: at higher lithium dosages, elderly patients are prone to develop neurotoxicity.
  Lithium Initial dosage: 150 mg per day Comments: blood levels of 0.2 to 0.6 mEq per L (0.2 to
0.6 mmol per L) are generally adequate and are usually
achieved with dosage of 150 to 300 mg per day.
Electroconvulsive therapy
  Recommended uses: may be required in patients who are at risk of injuring or starving themselves, patients who are severely psychotic, and patients who cannot tolerate or do not respond to antidepressants

SSRIs = selective serotonin reuptake inhibitors.

Information from Roland Jacobs, M.D. Dr. Jacobs is a member of the California Workgroup on Guidelines for Alzheimer's Disease Management.
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Management of Agitation in Dementia*

Preferred Medications for Subtypes of Agitation*

Subtype Treatment
Delirium (other than medication toxicity) Treat underlying medical condition.
If medication is needed, consider typical
antipsychotic.
Depression Without psychosis: antidepressant
With psychosis: antidepressant plus
antipsychotic, or electroconvulsive
therapy
Psychosis Acute: atypical antipsychotic
Long-term: atypical antipsychotic
Anxiety Acute: benzodiazepine such as lorazepam
(Ativan) or oxazepam (Serax)
Long-term: buspirone (BuSpar)
Insomnia Acute: trazodone (Desyrel); consider
benzodiazepine such as temazepam
(Restoril) or zolpidem (Ambien).
Long-term: trazodone
"Sundowning" Acute: trazodone
Long-term: trazodone; consider typical
or atypical antipsychotic.
Aggression or anger Severe
 Acute: typical or atypical antipsychotic
 Long-term: divalproex sodium
(Depakote) or atypical antipsychotic
Mild
 Acute: trazodone
 Long-term: divalproex sodium, SSRI,
trazodone, or buspirone
Osteoarthritic pain Long-term: tricyclic antidepressant, SSRI,
or trazodone

SSRI = selective serotonin reuptake inhibitor.

*--The first step is the implementation of environmental interventions; then drug therapy should be considered.
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Resources for Information on Alzheimer's Disease and Support for Patients and Caregivers

Administration on Aging
Telephone: 202-619-7501; 800-677-1116 (Eldercare Locator)
Web site: www.aoa.dhhs.gov

Alzheimer's Association
Telephone: 800-272-3900
Web site: www.alz.org

Alzheimer's Disease Education and Referral (ADEAR) Center
Telephone: 800-438-4380
Web site: www.alzheimers.org/adear

Family Caregiver Alliance Resource Center
Telephone: 415-434-3388
Web site: www.caregiver.org

National Association of Area Agencies on Aging*
Telephone: 202-296-8130
Web site: www.n4a.org

*--In addition, check local telephone directory for listing of referral agencies.
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© DANIL HAMMOUDI.MD 2004