ARTERIAL GAS EMBOLISM - Jacqueline J. Wu, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
• Arterial gas embolisms are caused by the entry of gas into the pulmonary veins or directly into the arteries of the systemic circulation.
- Gas may enter arteries as a result of overexpansion of lungs by decompression barotraumas.
- May result from paradoxical embolus
• Emboli can travel to any artery, but the most serious consequences occur when they affect the cerebral or coronary circulation.
• Synonym(s): Gas embolism; Air embolism
ALERT
Any diver who has an onset of new symptom(s) or sign(s) after recently completing a Self-Contained Underwater Breathing Apparatus. SCUBA dive of any type, to any depth, for any period of time: Serious consideration must be given that such a patient sustained a dive-related injury.
GENERAL PREVENTION
• Strict adherence to diver safety protocols, especially including the buddy system
• No diving after any dive injury or with any medical condition until evaluated and approved by a physician knowledgeable about diving medicine
EPIDEMIOLOGY
• Predominant age: Young adult
• Predominant sex: Male > Female
Prevalence
Estimated (based on injury/mortality reports collected by Divers Alert Network) to occur in approximately 4 per 100,000 sport divers per year
RISK FACTORS
• Surgery: Recent craniotomy with patient in upright position, cardiothoracic (with cardiopulmonary bypass), hip replacement, Caesarian section
• SCUBA: Arterial gas embolism is the most serious and rapidly fatal of all SCUBA diving injuries and is second only to drowning as the leading cause of death associated with sport diving. Arterial gas embolism occurs on ascent; from alveolar rupture; time to the manifestation of symptoms is nearly always 10 minutes.
• History of patent foramen ovale has been associated with a >4-fold increase in decompression illness events and 2-fold more ischemic brain lesions than in divers without this condition.
ETIOLOGY
• Cerebral air embolism
- Air bubbles occlude the brain vasculature
- ICP increases
- Unequal distribution of blood in the brain causes hyperemia and ischemia.
- Small bubbles irritate vascular wall causing breakdown of blood-brain barrier; small size allows rapid absorption and may cause only brief interruption of cerebral blood flow.
- Larger air bubbles take longer to absorb (up to several hours) and can cause primary ischemic injury with diffuse brain edema and increased ICP.
• Coronary air embolism: Caused by obstruction of coronary arteries by an air bubble
- Temporary ischemia of myocardium
- Labile BP
- Dysrhythmias
- Cardiac failure and/or arrest
• Obstruction is possible in any artery.
- Small emboli in the vessels of skeletal muscles and viscera are well-tolerated.
- Arterial gas embolisms to coronary and cerebral arteries are especially serious or fatal because of the vulnerability of heart and brain to short periods of ischemia.
ASSOCIATED CONDITIONS
• Pulmonary barotrauma leading to arterial gas embolism can also cause pneumomediastinum, subcutaneous emphysema, pneumopericardium, pneumothorax, and pneumoperitoneum.
• Always consider the possibility of decompression sickness in addition to arterial gas embolism in any SCUBA diver who has recently completed a dive.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Cerebral air embolism
- Dizziness
- Chest pain
- Cardiac arrythmia
- Paresthesias
- Minor motor weakness
- Convulsions
- Paralysis
- Nausea
- Visual disturbances
- Gas bubbles in vessels of retina
- Headache
- Asymmetric pupils
- Hemianopia
- Bradypnea
- Cheyne-Stokes breathing
- Aphasia
- Mental status changes ranging from subtle to total lack of consciousness
• Coronary arterial embolism
- Cardiac arrythmias
- Cardiac arrest
ALERT
Anesthesia and/or analgesics alter the symptomatology and may complicate evaluation of the patient's clinical status. Delayed recovery from general anesthesia may be a clue to cerebral arterial embolism.
TESTS
Lab
• Hematocrit: Increased, indicating volume depletion and extravascular shift of fluid into injured tissues
• Serum creatine kinase: Correlation between creatine kinase activity and outcome suggests that elevated serum level of this enzyme may be a marker for size and severity of arterial gas embolism.
• Urinalysis: Increased specific gravity indicates volume depletion.
Imaging
• Chest radiograph to rule out pneumothorax
• ECG
• CT scan: Changes often very subtle
• MRI: Can sometimes show increased volume of water in injured tissue (not very reliable)
DIFFERENTIAL DIAGNOSIS
Decompression sickness
TREATMENT
PRE-HOSPITAL
• General
- Life-saving measures (e.g., CPR) must take precedence to sustain life.
- Endotracheal intubation for somnolent or comatose patient
- Highest possible concentration of oxygen: Eliminates gas in the bubbles by establishing diffusion gradient that favors egress of gas from bubbles
- Place patient in flat, supine position (head down position may aggravate cerebral edema that develops).
• Hyperbaric oxygen
- 1st-line treatment of choice for arterial gas embolism: Immediate transport to a suitable hyperbaric chamber for recompression as soon as possible; do not delay because of nonessential procedures
- 100% oxygen at pressure above that of the atmosphere at sea level
- Decreases bubble size
- Prevents cerebral edema
- For assistance and advice in locating the nearest treatment chamber in your area (worldwide), call Divers Alert Network (DAN) at any hour (919) 684-4326.
• IV fluids
- To counteract hemoconcentration seen in gas embolism
- Colloids preferred over crystalloid (latter may promote cerebral edema)
- Goal is normovolemia
STABILIZATION
• See"Treatment" and "General Measures."
• Hospital-based hyperbaric chamber capable of performing a U.S. Navy Table 6A recompression (165 feet of seawater)
GENERAL MEASURES
• CPR
• Keep patient recumbent while maintaining patent airway.
• Maintain hydration with IV fluids.
• Frequent neurologic checks in the acute pretreatment and treatment phases
Diet
Nothing to be consumed until after treatment
Activity
None until after treatment
SPECIAL THERAPY
IV Fluids
• Colloids preferred over crystalloid
• Achieve normovolemia
MEDICATION (DRUGS)
First Line
Oxygen
• As high a concentration as possible
• Transfer to facility with hyperbaric chamber as soon as possible
Second Line
• Heparin
- Prevents platelet clumping
- Studies of its use are inconsistent.
• Barbituates (if indicated)
- For suppression of seizures
- Reduce ICP
- Decrease cerebral oxygen consumption
• Lidocaine
- Decreases ICP
- Improves recovery of somatosensory evoked potential following cerebral air embolism
- Preserves cerebral blood flow
FOLLOW-UP
PROGNOSIS
Complete to partial resolution with adequate treatment
COMPLICATIONS
• Long-term serious neurologic impairments
• Death
PATIENT MONITORING
Complete neurologic assessment at 1, 3, 6, and 12 months
REFERENCES
1. Muth CM, Shank ES. Gas embolism. N Engl J Med. 2000; 342:476-482.
2. Vann RD, Dovenbarger JA. Reports on decompression illness. Diving fatalities and project dive exploration, the Divers Alert Network Annual Review of Recreational Scuba Driving Injuries and Fatalities. 2002 Data Durham: Divers Alert Network. 2004:1-152.
3. Van Hulst RA, Klein J, Lachmann B. Gas embolism: Pathophysiology and treatment. Clin Physiol Funct Imaging. 2003;23:237-246.
4. Davis J. Medical Examination of Sport Scuba Divers, 2nd ed. San Antonio, TX: Medical Seminars; 1986.
Monday, January 5, 2009
ARTERIAL GAS EMBOLISM
ARTERIAL EMBOLUS AND THROMBOSIS
ARTERIAL EMBOLUS AND THROMBOSIS - Jeremy Golding, MD
BASICS
DESCRIPTION
• Acute loss of perfusion distal to occlusion of major artery owing to
- Embolus that migrates to point of occlusion or
- Clot intrinsic to point of occlusion (thrombosis)
• Both are true emergencies.
• Following obstruction of artery, soft coagulum forms both proximally and distally in areas of stagnant flow.
• As clot extends, collateral pathways become involved, and process becomes self-propagating.
• Ultimately, venous circulation can become involved.
• Extent of vascular compromise is critical and determines "golden" period of 4-6 hours. After this time, the profound ischemia leads to irreversible cellular death.
• Distribution of emboli
- Femoral artery: 30%
- Iliac artery: 15%
- Aortic bifurcation: 10%
- Popliteal artery: 10%
- Brachial: 10%
- Mesenteric arteries: 5%
- Renal: 5%
- Cerebral (estimated): 15-20%
• System(s) Affected: Cardiovascular; Hematologic/lymphatic/immunologic
GENERAL PREVENTION
• Anticoagulation in atrial arrhythmia
• Reduction of atherosclerosis risk factors
EPIDEMIOLOGY
• 50-100/100,000 hospital admissions
• A leading cause of limb loss in elderly
• Predominant age: Elderly
• Predominant sex: Male > Female
• Rare in children and during pregnancy
RISK FACTORS
Drug abuse
Genetics
Can be associated with inheritable hypercoagulable and premature atherosclerotic syndromes
ETIOLOGY
• Emboli
• Cardiac
- Atrial flutter/fibrillation
- Valve disease
- Myocardial infarction
- Cardiomyopathy
- Cardiac tumors
- Endocarditis
• Aneurysms: Cardiac, aortic, peripheral
• Thrombosis
- Atherosclerotic occlusive disease
- Aortic and peripheral aneurysms, especially popliteal
- Hypercoagulable states
- Venous gangrene
- Drug abuse
- Heparin allergy (heparin-induced thrombocytopenia)
- Vascular bypass
• Trauma
- Blunt
- Penetrating
- Vascular and cardiac interventional procedures
• Venous thrombosis with patent foramen ovale (paradoxical embolus)
ASSOCIATED CONDITIONS
• Acute mesenteric ischemia
• Renal infarction
• Carotid/cerebrovascular accident
• Multiple emboli
• Digital microembolization
DIAGNOSIS
SIGNS AND SYMPTOMS
• To estimate occlusion location
- Symptoms typically start 1 joint below occlusion.
- Palpable pulses absent below occlusion and accentuated above.
• The 5 Ps: If any one is present, frequent re-evaluations indicated. Proximal occlusions lead to more rapid progression of findings. Occlusion at aortic bifurcation can produce bilateral findings.
- Pain: Diffuse in distal area. If persists, crescendo in nature. Predominates as 1st symptom in embolism. Not alleviated by change of position.
- Pulselessness: Mandatory for diagnosis of embolism or thrombosis. Pedal pulses subject to observer error. Always compare to opposite limb.
- Pallor: Skin color pale early, cyanotic later. Check extremity temperature left to right and top to bottom. Look for signs of chronic ischemia: skin atrophy, loss of hair, thick nails.
- Paresthesia: Numbness early with thrombosis. Light touch 1st to be lost. Not reliable in diabetics. Loss of pain and pressure indicate advanced ischemia.
- Paralysis: Motor defect occurs after sensory and indicates profound ischemia.
TESTS
• EKG
• Special tests
• Noninvasive/indirect
- Doppler: Presence or absence of flow
- Ankle/arm index (AAI; aka ankle/brachial index [ABI]) = dorsal pedal/posterior tibial pressure divided by brachial pressure;
- AAI >0.30 favorable (normal >1)
Lab
For preoperative evaluation, elucidation of cause, or documentation of ischemia severity
• Myocardial/muscle isoenzymes
• Coagulation parameters
• Blood pH/bicarbonate
• Urine myoglobin
• Electrolytes
Imaging
Noninvasive/direct: Duplex imaging if time permits
Diagnostic Procedures/Surgery
Arteriography
• Rarely indicated preoperatively in threatened limb
• May help differentiate thrombosis from embolus in nonthreatened limb
• Useful with occluded grafts
DIFFERENTIAL DIAGNOSIS
• Emboli vs. thrombosis
• Emboli
- Myocardial diseases: Myocardial infarction, arrhythmias (e.g., atrial fibrillation), aneurysms
- Pain as 1st symptom
• Thrombosis
- Absence of heart disease: Infarction, arrhythmias
- Chronic vascular history
- Bilateral changes of chronic ischemia
- Numbness rather than pain as 1st symptom
- Vascular procedures: Bypass/interventional
• Other conditions
- Acute aortic dissection (chest or back pain)
- Acute deep vein thrombosis (massive swelling and warm skin)
- Low flow states
TREATMENT
GENERAL MEASURES
• Time is of the essence.
- Unless contraindicated, systemic heparinization to decrease clot propagation and prophylaxis against further emboli
- Resuscitation and stabilization of patient to extent permitted by time
- Triage, based on detailed exam, history, and Doppler examination, determines appropriate therapy.
• Early subcritical stenosis criteria
- Mild ischemic pain
- Normal neurologic exam
- Capillary refill present
- Arterial signals present by Doppler in distal extremity
- Ankle/arm index >0.30
- Treatment
Heparin (see "Medications")
Arteriography
- Embolism
Surgical removal if acceptable operative risk, for example, balloon embolectomy
Anticoagulation versus intra-arterial thrombolytics if prohibitive risk
- Thrombosis
Trial of thrombolytics and correction of arterial defect if good risk
Anticoagulation if poor risk or thrombolytics contraindicated
• Critical stenosis criteria
- Ischemic pain
- Mild neurologic deficit
- Weakness of dorsiflexion
- Minimal sensory loss: Light touch and/or vibratory
- No pulsatile flow by Doppler
- Venous flow present
- Treatment
Time to intervention is critical
Heparin (see "Medications")
Arteriography
Individualize thrombolysis and/or operative procedure (depending on extent of thrombosis and amenability for surgical removal)
Thrombolysis to optimize alternatives
Adjunctive operative therapy
Intraoperative lytic therapy: Bypass, patch angioplasty
• Late (nonsalvageable) criteria
- Profound sensory loss
- Muscle paralysis
- Absent capillary refill
- Skin marbling
- Muscle rigor
- No arterial or venous signals by Doppler
- Treatment
Arteriography usually not warranted
Attempts at reperfusion contraindicated
Anticoagulation
Definitive amputation, if possible
MEDICATION (DRUGS)
First Line
• Heparin
- 80-100 U/kg IV loading dose (~5,000-10,000 U)
- Continuous infusion sufficient to double PTT, generally 18 U/kg/h
• Contraindications
- Heparin:
Allergy
Bleeding diathesis
Trauma (e.g., head injury)
Hematuria/hemoptysis
Acute aortic dissection
- tPA/Urokinase
Nonsalvageable ischemia
Recent MI
Aneurysm
Aortic dissection
Trauma
Uncontrolled hypertension
Recent operative procedure
Second Line
Multiple thrombolytics in development
SURGERY
Angioplasty, Thromboembolectomy
FOLLOW-UP
PROGNOSIS
• 90% good outcome with prompt treatment
• Delayed/untreated associated with high mortality and limb loss
• 20-30% hospital mortality associated with causative factors
COMPLICATIONS
• Acidosis
• Myoglobinuria and acute renal failure
• Hyperkalemia
• Recurrent occlusion
• Failure to remove clot/obstruction
• Compartment syndromes/reperfusion syndrome, delayed or acute: Predisposing factors include
- Combined arterial injury
- Profound and prolonged ischemia
- Hypotension
• Clinical findings of compartment syndrome
- Severe pain
- Pain with passive muscle movement
- Hypesthesias of nerves in compartment
- Paralysis of nerves, especially peroneal foot drop
- Tender, tense edema
- Compartment pressure >30-45 mm Hg
• Consequences of unrecognized compartment syndrome
- Acute
Amputation
Sepsis
Myoglobin renal failure
Shock
Multiple organ failure
- Delayed
Ischemic contracture
Infection
Causalgia
Gangrene
• Treatment of compartment syndrome is fasciotomy.
PATIENT MONITORING
Postoperative monitoring
• Anticoagulation
• Establish brisk diuresis.
• Continued resuscitation and diagnosis, including echocardiography and other studies (see "Causes" and "Risk Factors")
• Monitor perfusion stability.
• Treat/eliminate causative factors.
REFERENCES
1. Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest.2004 Sep;126(3 Suppl):609S-26S. Available at www.ngc.gov.
2. Townsend. Sabiston Textbook of Surgery, 17th ed. Boston: Saunders, 2004.
3. Brewster DC, Chin AK, Fogarty TJ. Arterial thrombosis. In: Rutherford RB, ed. Vascular Surgery, 3rd ed. Philadelphia: WB Saunders; 1989.
4. Miller DC, Roon AJ, eds. Diagnosis and Management of Peripheral Vascular Diseases. Menlo Park, CA: Addison-Wesley; 1982.
5. Rutherford RB, Flannigan DP, Gupta SK, et al. Suggested standards of reports dealing with lower extremity ischemia. J Vasc Surg. 1986;64:80-94.
APPENDICITIS, ACUTE
APPENDICITIS, ACUTE - Andrew H.Fenton, MD
BASICS
DESCRIPTION
Acute inflammation of the vermiform appendix
• 1st described by Fitz in 1886
• McBurney described point of maximal tenderness
EPIDEMIOLOGY
• Predominant age
- Ages 10-30: Male > Female (3:2)
- Over age 30: Male = Female
- Rare in infancy
• Predominant sex: Slight male predominance
Incidence
Lifetime incidence 1 in every 15 persons (7%)
Prevalence
• 10/100,000
• Most common acute surgical condition of abdomen
ALERT
Pregnancy Considerations
• Most common extrauterine surgical emergency
• 1 in 2,000 pregnancies
• Difficult diagnosis
• Appendix displaced superolaterally by gravid uterus
• Fetal mortality rate: 2-8.5%
RISK FACTORS
• Adolescent males
• Familial tendency
• Intra-abdominal tumors
Genetics
Unknown
PATHOPHYSIOLOGY
Obstruction of appendiceal lumen
• Fecaliths (most common)
• Lymphoid tissue hypertrophy
• Inspissated barium
• Vegetable, fruit seeds and other foreign bodies
• Intestinal worms (ascarids)
• Strictures
DIAGNOSIS
SIGNS AND SYMPTOMS
• Abdominal pain (100%): Periumbilical, then right lower quadrant; lessened with flexion of thigh
• Muscle guarding
• Anorexia (almost 100%)
• Nausea (90%)
• Vomiting (75%); mild
• Obstipation
• Diarrhea; mild
• Sequence of symptom appearance (95%): Anorexia, then abdominal pain, then vomiting
• Slight temperature elevation (1C)
• Slight tachycardia
• Patient frequently lies motionless with right thigh drawn up
• Maximal tenderness at McBurney point
• Direct and referred right-lower-quadrant tenderness
• Voluntary and involuntary guarding
• Cutaneous hyperesthesia at T10-12
• Rovsing sign: Right-lower-quadrant pain with palpatory pressure in left lower quadrant
• Psoas sign: Pain with right thigh extension
• Obturator sign: Pain with internal rotation of flexed right thigh
• Retrocecal appendix: Flank tenderness in right lower quadrant
• Pelvic appendix: Local and suprapubic pain on rectal exam
ALERT
Pediatric Considerations
• Decreased diagnostic accuracy
• Higher fever, more vomiting
Geriatric Considerations
Decreased diagnostic accuracy
History
Cornerstone of diagnosis, with clinical findings
Physical Exam
• Diagnostic laparoscopy: Consider in young adult females
• Rectal and pelvic examinations
• May need intensive in-hospital observation to allow serial examination
TESTS
Lab
• Moderate leukocytosis: 10,000-18,000/mm3 in 75%
• Moderate polymorphonuclear predominance
• hCG to rule out ectopic pregnancy
• Urinalysis
- Elevated specific gravity
- Hematuria (sometimes)
- Pyuria (sometimes)
- Albuminuria (sometimes)
• Drugs that may alter lab results
- Antibiotics
- Steroids
Imaging
• Used in differential diagnosis and to detect complications
• CT scan: Diagnostic test of choice; also for abscess (1)[B]
Diagnostic Procedures/Surgery
Diagnostic laparoscopy, especially in fertile women (1)[A]
Pathological Findings
• Acute appendix inflammation
• Local vascular congestion
• Obstruction
• Gangrene
• Perforation with abscess (15-30%)
DIFFERENTIAL DIAGNOSIS
• Any cause of acute abdomen
• 75% of erroneous diagnoses accounted for by
- Acute mesenteric lymphadenitis
- No organic pathologic condition
- Acute pelvic inflammatory disease
- Ovarian cyst torsion
- Ruptured graafian follicle
- Acute gastroenteritis
• Also consider
- Urologic causes
- Testicular torsion
- Inflammatory bowel disease
- Colonic disorders
- Other gynecologic diseases
TREATMENT
GENERAL MEASURES
• For nonsurgical patients, antibiotic coverage (e.g., quinolone and metronidazole)
• Recurrence rate too high in other patients to recommend antibiotics as a primary therapy
Diet
NPO
Nursing
Pre-op preparation
SPECIAL THERAPY
IV Fluids
• Fluid resuscitation with LR
• Correct fluid and electrolyte deficits.
MEDICATION (DRUGS)
First Line
• Uncomplicated acute appendicitis: 1 preoperative dose of broad-spectrum antibiotic (2)[A]
- Cefoxitin (Mefoxin)
- Cefotetan (Cefotan)
• Gangrenous or perforating appendicitis
- Broadened antibiotic coverage for aerobic and anaerobic enteric pathogens
- Adjust dosage and choice of antibiotic based on intraoperative cultures.
- Continue antibiotics for 7 days postoperatively or until patient becomes afebrile with normal white count.
- Pathogens usually sensitive to ampicillin, gentamicin, and clindamycin
• Contraindications: Documented allergy to specific antibiotic
• Precautions: Adjust antibiotic dosages for elderly and patients with renal failure.
• Significant possible interactions: Refer to manufacturer's literature for each drug.
Second Line
• Metronidazole (Flagyl): Anaerobic coverage only
• Ampicillin-sulbactam (Unasyn)
• Ticarcillin-clavulanate (Timentin)
• Piperacillin-tazobactam (Zosyn)
SURGERY
Inpatient surgery is appropriate measure
• Immediate appendectomy; laparoscopic favored unless perforation (3)[A]
• Drainage of abscess, if present
FOLLOW-UP
DISPOSITION
Admission Criteria
Complicated appendicitis
Discharge Criteria
Tolerating PO; return of bowel function; afebrile; normal WBC
Issues for Referral
Follow-up with surgeon 1-2 weeks
PROGNOSIS
• Generally uncomplicated course in young adults with nonruptured appendicitis
• Factors increasing morbidity and mortality
- Extremes of age
- Appendiceal rupture
• Morbidity rates
- Nonperforated appendicitis: 3%
- Perforated appendicitis: 47%
• Mortality rates
- Unruptured appendicitis: 0.1%
- Ruptured appendicitis: 3%
- Patients >60 years of age: 50% of deaths from appendicitis
- Elderly patient with ruptured appendix: 15%
ALERT
Pediatric Considerations
• Rupture earlier
• Rupture rate: 15-50%
Geriatric Considerations
Rupture rate: 67-90%
COMPLICATIONS
• Wound infection
• Intra-abdominal abscess; lower rate with antibiotic prohylaxis [2A]
• Fecal fistula
• Intestinal obstruction
• Incisional hernia
• Liver abscess (rare)
• Paralytic ileus
PATIENT MONITORING
Routine visits at 2 and 6 weeks after surgery
REFERENCES
1. Mun S, Ernst RD, Chen K, et al. Rapid CT diagnosis of acute appendicitis with IV contrast material. Emerg Radiol. 2005;17:1-4 [e-pub ahead of print]
2. Andersen BR, Kallehaue FL, Andersen HK. Antibiotics versus placebo for prevention of postoperative infection after appendectomy. The Cochrane Database of Systematic Reviews 2006 issue 1. John Wiley Sons, Ltd.
3. Sauerland S, Lefering R, Neugebauer EAM. Laparoscopic versus open surgery for suspected appendicitis. The Cochrane Database of Systematic Reviews 2006 issue 1. John Wiley Sons, Ltd
AORTIC VALVULAR STENOSIS
AORTIC VALVULAR STENOSIS - Suzanne Klainer, MD
BASICS
DESCRIPTION
Acquired or congenital obstruction to left-ventricular outflow across aortic valve caused by decreased valve area. Is classified as mild, moderate, or severe based on measured area.
GENERAL PREVENTION
Prevention of Rheumatic Heart Disease for acquired postinflammatory aortic stenosis.
EPIDEMIOLOGY
• Predominant age (1)
- 30 years: Congenital
- 30-70 years: Congenital or rheumatic
- >70 years: Degenerative calcification of aortic valve
• Predominant sex: Male > Female, 2:1
Prevalence (2)
• 1.3% of 65-74 years
• 2.4% of 75-84 years
• 4% of >84 years
• Bicuspid aortic valve: 0.8% of population (3)
ALERT
Geriatric Considerations
Increased incidence of degenerative calcific aortic stenosis
RISK FACTORS
• Unicommissural valve
• Bicuspid valve
• Prior rheumatic fever
• Advanced age
• Hypercholesterolemia
• Metabolic disease (SLE, Fabry)
PATHOPHYSIOLOGY
Resistance to outflow at the aortic orifice causes increased afterload. The left ventricle responds to this pressure overload with thickening of myocardial wall, resulting in left ventricular (LV) dysfunction and CHF as well as increased myocardial oxygen demand.
ETIOLOGY
• Congenital
- Unicuspid valve
- Bicuspid valve: Not inherently stenotic, but becomes so as a result of wear-and-tear thickening and calcification; calcified bicuspid valve is most common cause of isolated aortic stenosis in adults.
- Tricuspid valve with fusion of commissures
- Hypoplastic annulus
• Acquired
- Rheumatic fever (or, rarely, other inflammatory disease)
- Degenerative calcific aortic stenosis in elderly
ASSOCIATED CONDITIONS
• Coronary artery disease (present in 50% of patients)
• Aortic regurgitation (particularly in calcified bicuspid valves and rheumatic disease)
• Mitral valve disease (primarily in rheumatic heart disease)
• LV dysfunction and CHF
• A-fibrillation associated with CHF
DIAGNOSIS
SIGNS AND SYMPTOMS
• Angina pectoris: Most frequent symptom
• Near syncope
• Syncope: Often exertional
• Exertional dyspnea
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Palpitations
• Fatigue
• Neurologic events (transient ischemic attack or cerebrovascular accident) owing to embolization
• Systolic crescendo-decrescendo murmur: Usually best heard at 2nd right sternal border (may have associated thrill); may radiate into carotid arteries
• Ejection (early systolic) click
• Prolonged ejection time
• Delayed, small carotid upstroke
• Delayed/decreased intensity of A2
• Paradoxical splitting of S2
• LV heave
• High-pitched diastolic blow: May be present at left sternal border (associated aortic regurgitation)
History
Above symptoms in elderly patient or one with history congenital heart defect or rheumatic fever
Physical Exam
• Cardiac
- Systolic crescendo-decrescendo murmur RSB, radiating to carotids
- Delayed carotid upstroke
- Left ventricular heave
- Increased intensity of A2
TESTS
ECG
• Conduction defects
• Left-atrial enlargement
• Ventricular arrhythmias
• LV hypertrophy
• ST segment depression
Lab
Elevated BNP
Imaging
• Chest radiograph
- May be normal in compensated, isolated valvular aortic stenosis
- Cardiac hypertrophy early, later cardiomegaly
- Poststenotic dilatation of ascending aorta
- Calcification of aortic valve cusps (may require fluoroscopy to visualize)
• Echocardiography
- Aortic valve morphology, thickening, calcifications
- Decreased aortic valve excursion
- Planimetry of aortic valve area
- LV hypertrophy
- LV ejection fraction
- Chamber dimensions
- Presence or absence of wall-motion abnormalities suggesting coronary artery disease
• Doppler echocardiography
- Transvalvular gradient
- Valve area
- Diastolic function
- Associated aortic regurgitation
Diagnostic Procedures/Surgery
Cardiac catheterization: Recommended for patients undergoing AV replacement at risk for CAD and for assessment of severity when AVR is planned or noninvasive studies are inconclusive (A)
• Identifies transvalvular gradient, valve area, LV ejection fraction, concomitant CAD
Pathological Findings
• LV hypertrophy
• Myocardial interstitial fibrosis
• Aortic valvular calcification in older patients
• 50% incidence of concomitant CAD
DIFFERENTIAL DIAGNOSIS
• Mitral regurgitation
- Either primary or secondary to underlying coronary artery disease or dilated cardiomyopathy
- Usually an apical, high-frequency, pansystolic murmur, often radiating to axilla
• Hypertrophic obstructive cardiomyopathy
- Also systolic crescendo-decrescendo murmur, but best heard at left sternal border and may radiate into axilla
- However, characteristically intensified by changing from squatting to standing and/or by Valsalva maneuver, lessened by changing from standing to squatting
• Aortic supravalvular stenosis
• Discrete subaortic stenosis
TREATMENT
STABILIZATION
Outpatient care except for surgical intervention or comorbid condition requiring hospital care
GENERAL MEASURES
• Asymptomatic patient with noncritical aortic stenosis: Because aortic stenosis is progressive, follow closely with appropriate evaluation.
• All patients should receive endocarditis prophylaxis prior to dental work or invasive procedures regardless of age, cause, or severity of stenosis. (4)[C]
• Patients with stenosis of rheumatic cause should receive (in addition to endocarditis prophylaxis prior to dental work or invasive procedures) rheumatic fever prophylaxis, especially if 35 years or in close contact with young children.
• Screen for and treat comorbid diseases.
- Commonly HTN, CAD, CHF, and A-fib.
ALERT
Pregnancy Considerations
• Severe critical aortic stenosis responds poorly to hemodynamic changes in pregnancy, labor, and delivery.
• Pregnancy should be avoided with critical aortic stenosis; may need Cesarean section for delivery of baby.
Diet
Only restriction is low-sodium diet in presence of CHF
Activity
In known or suspected severe aortic stenosis, vigorous physical activity contraindicated
MEDICATION (DRUGS)
• ACE I is beneficial for treatment of LV dysfunction and associated heart failure, but can cause hypotension in patients with baseline low blood pressure (5) [B].
• Statins: Anecdotal evidence suggest that statins slow progression of AS, however, recent RCT failed to support this claim (6).
• Prophylactic antibiotics for
- Bacterial endocarditis
- Rheumatic fever, where indicated
- See "General Measures"
ALERT
Use antihypertensives cautiously, because they potentially can cause hypotension in AS.
SURGERY
• Aortic valve replacement indicated in
- Patients with symptomatic severe AS, patients with severe AS undergoing CABG, or patients with severe AS undergoing aortic or other valve surgery (4)[A].
- Moderate AS undergoing cardiac surgery (4)[B]
- Asymptomatic patients with critical AS (aortic valve area 0.6.0 cm2), LV dysfunction, abnormal response to exercise, ventricular tachycardia, or increasing cardiomegaly (15 mm) (4)[C]
• Surgical valve replacement consists of removal of stenotic, native valve and placement of prosthetic mechanical or tissue valve.
• Balloon angioplasty of stenotic aortic valves
- May benefit pediatric patient with congenital disease (4)[A]
- In elderly as a bridge to AV replacement, for palliation in patients with serious comorbid conditions, and in patients who require urgent noncardiac surgery (4)[B]
FOLLOW-UP
DISPOSITION
Admission Criteria
See criteria for comorbid conditions.
Discharge Criteria
See criteria for comorbid diseases.
PROGNOSIS
• Mortality following onset of symptoms (7)
- 26% at 1 year
- 57% at 3 years
• Risk of sudden death is 0.4% per year (4)
COMPLICATIONS
• Progressive stenosis
• Sudden death
• Congestive heart failure
• Angina
• Syncope
• Hemolytic anemia
• Bleeding disorder (acquired vWF d/o) (8)
• Infective endocarditis
PATIENT MONITORING
• Symptomatic patients should be examined frequently.
• ECG every 2-5 years to assess progression in the asymptomatic patient with mild/moderate disease, respectively (4)[C]
• Advise patient to immediately report any symptoms referable to AS.
REFERENCES
1. Subramanian E. Surgical pathology of pure aortic stenosis. A study 374 cases. Mayo Clin Proc. 1984;59:683.
2. Stewart et al. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol. 1997;29:630.
3. Otto CM, Burwash, Legget, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic and exercise predictors of outcome. Circulation. 1997;95:2262.
4. Bono et al. ACC/AHA task force report. J Am Coll Cardiol 1998;32:1486.
5. Chockalingam et al. SCOPE-AS. Am Heart J. 2004;147(4):E19.
6. Crowell et al. SALTIRE. N Engl J Med. 2005;352:2389-2397.
7. Chizner et al. The natural history of aortic stenosis in adults. Am Heart J 1980;99(4):419-424.
8. Vincentelli, et al. Acquired von Willebrand in aortic stenosis. N Engl J Med. 2003;349:343.
9. Nistri, et al. Frequency of bicuspid aortic valves in young male conscripts by echocardiogram. Am J Cardiol. 2005;96:718.
MISCELLANEOUS
LV is relatively noncompliant in aortic stenosis, thus
• Atrial contraction is important component of diastolic filling.
• Loss of atrial contraction with onset of atrial fibrillation can cause acute clinical and hemodynamic deterioration.
Sunday, January 4, 2009
AORTIC DISSECTION
AORTIC DISSECTION - Jeremy Golding, MD
BASICS
DESCRIPTION
• Intimal tear in aorta resulting in hematoma formation. Accumulating blood in false lumen of arterial wall leads to propagation of this dissection.
• DeBakey classification: Based on origin site
- Type I: Originates in ascending aorta, propagates at least as far as aortic arch
- Type II: Involves only ascending aorta
- Type III: Originates in descending aorta, may propagates proximately or distally
• Stanford classification: More widely used
- Type A: Involves ascending aorta and aortic arch regardless of site of intimal tear
- Type B: Involves descending aorta
• New classification, subdivisions of DeBakey or Stanford
- 1. Classic
- 2. Medial disruption with hematoma formation
- 3. Discrete without hematoma
- 4. Plaque rupture, ulceration
- 5. Iatrogenic
• Synonym(s): Dissecting aneurysm
GENERAL PREVENTION
• Long-term control of hypertension
• Surveillance of aortic root and replacement when appropriate in patients with collagen disorders (e.g., Marfan, Ehlers-Danlos)
EPIDEMIOLOGY
• Predominant age: Depends on cause; commonly present in patients with Marfan syndrome in 3rd and 4th decades; otherwise most common between 6th and 8th decades
• Predominant sex: Male > Female (3:1)
• Mean age: Men 60 years, women 67 years
Incidence
2000 new cases diagnosed annually
Prevalence
US
• Diagnosed in 1 in 10,000 patients admitted to hospital
• Found in 1 in 350 patients at autopsy
RISK FACTORS
• Hypertension in 70% of patients
• Cystic medial necrosis
• Collagen abnormalities
- Marfan syndrome
- Ehlers-Danlos syndrome
• Inflammatory aortitis
• Takayasu arteritis
• Giant cell arteritis
• Congenital abnormalities
- Bicuspid aortic valve
- coarctation
• Pregnancy
• Chest trauma
• Cocaine use
• Cardiovascular surgery
• Elderly
• MDMA (ecstasy) use
• 1-Antitrypsin deficiency
• Smoking
Genetics
Increased incidence among family members
ETIOLOGY
• Cystic medial necrosis
• Iatrogenic during arterial catheterization
ASSOCIATED CONDITIONS
• Ehlers-Danlos syndrome
• Marfan syndrome
• Aortic stenosis
• Coarctation of aorta
• Bicuspid valve
• Turner syndrome
• Osteogenesis imperfecta
• Syphilis
• Relapsing polychondritis
• During pregnancy: Possibly cystic medionecrosis of pregnancy; unclear whether pregnancy is originating factor or contributes to worsening of a pre-existing condition
DIAGNOSIS
SIGNS AND SYMPTOMS
• Abrupt onset of sharp or tearing pain
• Shearing anterior chest pain radiating to interscapular region
• Back pain
• Syncope
• Symptoms of CHF
• Stroke
• Limb ischemia
• Abdominal pain
• Acute myocardial infarction/angina
• Spinal cord syndromes/deficits
• Hypotension or hypertension
• Wide pulse pressure
• Murmur of aortic insufficiency
• Features of tamponade
• Dullness in left lung base (effusion)
• Pulse deficits or asymmetry
• Fever
• 96% of acute aortic dissections can be identified by abrupt onset of sharp thoracic or abdominal pain in the presence of mediastinal widening on chest radiograph and asymmetry of pulses
History
Typical patient is a hypertensive man in his 60s with abrupt onset of severe chest pain.
TESTS
• Electrocardiogram
- Left ventricular hypertrophy
- Nonspecific ST-T changes
- Electrical alternans (in cardiac tamponade)
• Echocardiogram
- Dilated aortic root
- Increased aortic posterior or anterior wall thickness
- Pericardial effusion
- Oscillating intimal flap
Imaging
Chest radiograph, in stable patients
• Widening of superior mediastinum
• Left pleural effusion
• Haziness or enlargement of aortic knob
• Double density of descending aorta
• Irregular aortic contour: >5 mm separation of intimal calcification from outer aortic contour
• Rightward displacement of trachea
• Cardiomegaly
Diagnostic Procedures/Surgery
• (Sensitivity/specificity is indicated for each.)
• Chest CT (88/100%)
- Demonstration of 2 lumens with hematoma formation
- Detection of intimal flap
- Differential flow between 2 lumens
- Compression of true lumen by false lumen
• Spiral CT aortography; more sensitive and specific (99/99%)
• Aortogram (88/94%)
- Demonstration of 2 lumens
- Detection of intimal flap
- Compression of true lumen
- Ulcer-like projections of contrast
- Altered flow patterns
• Transesophageal echocardiography (99/98%): Test of choice for unstable patients
• MRI: If available and patient hemodynamically stable, test of choice for delineation of vascular anatomy (>99/99%)
• Intravascular ultrasonography: May detect with negative transesophageal echocardiography
Pathological Findings
• ~60% of intimal tears occur in proximal ascending aorta. Remainder are between origin of left subclavian artery and ligamentum arteriosum, descending aorta (20%), aortic arch (10%), and abdominal aorta.
• Although medionecrosis is found in normal aging aortas, it is more extensive in patients who develop aortic dissection.
• Cystic medial necrosis is seen in patients with defects in elastin and connective tissue organization (e.g., Marfan, Ehlers-Danlos).
• Death usually is due to rupture and tamponade.
DIFFERENTIAL DIAGNOSIS
• Myocardial infarction
• Pulmonary embolism
• Pneumonia
• Pleurisy
• Pericarditis
• Pneumothorax
• Angina
• Acute pancreatitis
• Penetrating duodenal ulcer
TREATMENT
GENERAL MEASURES
• Admit to ICU for assessment of hemodynamic stability, pain control, BP control
• Intubate; hemodynamically unstable patients
• Medical therapy
- Treatment of choice for descending dissections without complications (Type III)
- Based on decreasing BP and shearing forces of myocardial contractility (dp/dt) to decrease intimal tear and hematoma propagation
- Survival is 60-80% at 4-5 years
• Arterial BP monitoring is critical.
• Careful observation for changes in mentation, neurologic signs, or evidence of organ dysfunction
• Foley catheter to follow urine output
• Swan-Ganz catheterization may be helpful in monitoring cardiac performance and filling pressures during use of vasoactive and cardiodepressive drugs.
• Pain control difficult despite use of narcotics.
Diet
NPO until surgical evaluation is complete and patient classified as medical therapy only
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Propranolol plus nitroprusside; dosing
- Propranolol: 0.5-1 mg IV q5min until heart rate 60-70 bpm and
- Nitroprusside: Titrated to reduce systolic BP to 100-110 mm Hg (13.3-14.6 kPa)
• Contraindications
- Propranolol
Bronchial asthma
Diabetes mellitus
Raynaud disease
Sinus bradycardia
A-V heart block >1st degree
In presence of MAOIs
Cardiogenic shock
Acute CHF
Right ventricular failure from pulmonary hypertension
- Nitroprusside
In treatment of compensatory hypertension, that is, arteriovenous shunt
In patients with inadequate cerebral circulation
For use during emergency surgery in moribund patients
• Precautions
- Propranolol
Use cautiously in patients with angina pectoris, cardiac failure, impaired renal or hepatic function, thyrotoxicosis, pre-excitation syndromes, diabetes, or nonallergic bronchospasm.
Propranolol may produce bradycardia, heart block, or hypotension. Patients should not be suddenly withdrawn from -blockers.
- Nitroprusside
May not lower BP adequately; another agent may be required.
In patients with renal or hepatic insufficiency, may cause cyanide toxicity through excessive production of serum thiocyanate. Confusion and hyper-reflexia are early signs of thiocyanate toxicity. Thiocyanate inhibits uptake and binding of iodine; caution with hypothyroidism. Check thiocyanate levels after 48 hours.
Administration via infusion pump.
Methemoglobinemia may be seen rarely.
• Significant possible interactions
- Propranolol: Adenosine, albuterol, alfentanil, amiodarone, barbiturates, bromazepam, chlorothiazide, chlorpromazine, chlorpropamide, chlorprothixene, cimetidine, clonidine, dextroamphetamine, diazoxide, dihydroergotamine, diltiazem, disopyramide, tricyclic antidepressants, encainide, epinephrine, flecainide, fluvoxamine, furosemide, glipizide, halofenate, haloperidol, heparin, ibuprofen, indomethacin, insulin, isoniazid, isoproterenol, lidocaine, lidoflazine, methacholine, methyldopa, metoclopramide, naproxen, nifedipine, phenylpropanolamine, procainamide, quinidine, reserpine, rifampin, ritodrine, sulfonylureas, theophylline, thioridazine, tocainide, tubocurarine, verapamil, and warfarin
- Nitroprusside: Clonidine and other antihypertensives may have hypotensive effects.
Second Line
• Labetalol: 10-20 mg IV bolus to a maximum of 300 mg total, then titrated to response with infusion
• Trimethaphan: Infusion rate 1-2 mg/min
• Reserpine: 0.5-2 mg IM q4-8h; onset of action 1-3 hours
• Methyldopa: 250-500 mg q6h; onset of action of 4-6 hours; duration 1-12 hours
SURGERY
• Treatment of choice for all ascending aortic dissections
• Surgical indications for Type III
- Increasing size of hematoma
- Impending rupture
- Inability to control pain
- Bleeding into pleural space
• Endovascular stents, fenestration, and stent grafting
FOLLOW-UP
PROGNOSIS
• Mortality, untreated
- 24 hours: 33%
- 2 weeks: 60%
- 3 months: 90%
• Hospital survival estimate, treated medically and surgically: 70%
• Mortality, ascending dissection treated early surgically: 29-38%
• 10-year survival, treated surgically (all): 40%
• Redissection risk
- 5 years: 13%
- 10 years: 23%
COMPLICATIONS
• Redissection
• Localized saccular aneurysm
• Cardiac tamponade
• Aortic valvular insufficiency
• Progressive aortic enlargement
PATIENT MONITORING
• Maintain systolic BP at 120 mm Hg (16 kPa) or below, as tolerated.
• Routine chest films and/or chest CT may be helpful for patient treated medically long term.
• Follow-up visit at 1 month, then at 3-month intervals. During follow-up, pay careful attention to signs and symptoms of aortic insufficiency, chest or back pain, and development of saccular aneurysms as displayed on chest films.
REFERENCES
1. Beckman JA, O'Gara PT. Diseases of the aorta. Adv Intern Med. 1999;44:267-291.
2. Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22:1642.
3. Hartnell GG. Imaging of aortic aneurysms and dissection: CT and MRI. J Thorac Imaging. 2001;16:35-46.
4. Lindsay JJ. Diagnosis and treatment of diseases of the aorta. Curr Probl Cardiol. 1997;22:485-542.
5. Manninen HI, Rasanen H. Intravascular ultrasound in interventional radiology. Eur Radiol. 2000;10:1754-1762.
6. Penco M, Paparoni S, Dagianti A, et al. Usefulness of transesophageal echocardiography in the assessment of aortic dissection. Am J Cardiol. 2000;86(4A):53G-56G.
7. Pretre R, von Segesser LK. Aortic dissection. Lancet. 1997;349:1461-1464.
8. Rogers FB, Osler TM, Shackford SR. Aortic dissection after trauma: Case report and review of literature. J Trauma. 1996;41:906-908.
9. Sommer T, Fehske W, Holzknecht N, et al. Aortic dissection: A comparative study of diagnosis with spiral CT, multiplanar transesophageal echocardiography, and MR imaging. Radiology. 1996;199:347-352.
10. Umana JP, Mitchell RS. Endovascular treatment of aortic dissections and thoracic aortic aneurysms. Semin Vasc Surg. 2000;13:290-298.
11. Vonkodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med. 2000;160:2977.
Saturday, January 3, 2009
ANXIETY
ANXIETY - Mitzi Wasik, PharmD, BCPS
BASICS
DESCRIPTION (1)
A common acute or chronic, fearful emotion with associated physical symptoms. DSM-IV-R recognizes the following subtypes
• Acute situational anxiety: Response to recent stressful event, usually transient symptoms
• Generalized anxiety disorder (GAD): Persistent underlying anxiety or adjustment disorder with anxious mood and significant symptoms of motor tension, autonomic hyperactivity, and hypervigilance, lasting >6 months
• Panic disorder (PD): Recurrent unexpected attacks with at least one attack (or more) associated with persistent concern about additional attacks, worries about implications of the attack (losing control, having a heart attack), or a significant change in behavior related to the attack; often leads to agoraphobia
• Social phobia (Social Anxiety Disorder): Marked and persistent fear and avoidance of performance or social situations in which the person is exposed to unfamiliar people or scrutiny
• System(s) Affected: Nervous
GENERAL PREVENTION (2)
• Cognitive behavior therapy
• Management of stress, to extent possible
• Relaxation techniques
• Meditation
EPIDEMIOLOGY (3)
Predominant sex: Female > Male (2:1)
Incidence
• 15.7 million Americans suffer from anxiety disorders every year, 30 million will suffer at some point in their lives
• 30% of patients suffering from anxiety seek treatment.
Prevalence
• 12-month prevalence rate
- Panic disorder:1.3-1.7%
- Generalized anxiety disorder
All ages12.1-12.7%
- Social phobia: 1.7-3.7%
• Onset can occur anytime in life, from adolescent to adulthood
- Women >age 45 are most frequently affected
RISK FACTORS
Social and financial problems, medical illness, family history, lack of social support
Genetics
Panic disorder: Increased concordance in monozygotic versus dizygotic twins
ETIOLOGY
• Panic disorder, social phobia, and obsessive compulsive disorder are associated with genetic factors.
• Mediated by abnormalities of neurotransmitter systems (serotonin, norepinephrine, and gamma-aminobutyric acid [GABA])
ASSOCIATED CONDITIONS
• Depression (commonly)
• Agoraphobia
• Alcohol or substance abuse
• Somatoform disorders
DIAGNOSIS
(1,4)
SIGNS AND SYMPTOMS
History
Symptoms must occur for more days than not for 6 months
Physical Exam
• 3 (or more) criteria are required for diagnosis of GAD. Only one required in children
- Restlessness or feeling keyed up or on edge
- Easily fatigued
- Difficulty concentrating or mind going blank
- Irritability
- Muscle tension
- Sleep disturbances (difficulty falling or staying asleep)
- Difficulty controlling worry
• Persistent worry must cause significant distress, impairment in social, occupational, or other areas of functioning
• Nonspecific signs and symptoms that may be present with different subtypesunrealistic or excessive anxiety or worry, sense of impending doom, nervousness, instability, tachycardia, palpitations, systolic click murmur, hyperventilation, choking sensation, sighing respiration, nausea or abdominal distress, paresthesias, diaphoresis, dizziness or syncope, flushing, muscle tension, tremulousness, restlessness, headache, backaches, and muscle spasm
TESTS
EEG, ECG, etc.
Lab
Laboratory tests are often normal. See Differential Diagnosis for conditions to rule out.
Imaging
Usually none
Diagnostic Procedures/Surgery
Psychologic testing
• Anxiety Disorders Interview Schedule (ADIS), Hamilton's Anxiety Scale (HAM-A), Clinical Global Impression Scale (CGI), DSM-IV-R criteria
DIFFERENTIAL DIAGNOSIS
• Cardiovascular
- Ischemic heart disease, valvular heart disease, cardiomyopathies, myocarditis, arrhythmias, mitral valve prolapse (most symptomatic cases are associated with panic disorder), congestive heart failure, or myocardial infarction
• Respiratory
- Asthma, chronic obstructive pulmonary disease, pulmonary embolism, or pneumonia
• CNS
- Stroke, seizures, dementia, migraine, Parkinson disease, neoplasms
• Metabolic and hormonal
- Hyperthyroidism, pheochromocytoma, adrenal insufficiency, Cushing syndrome, hypokalemia, hypoglycemia, hyperparathyroidism
• Nutritional
- Thiamine, pyridoxine, or folate deficiency, iron deficiency anemia
• Drug-induced anxiety
- Alcohol, sympathomimetics (cocaine, amphetamines, caffeine)
• Withdrawal
- Alcohol, sedative-hypnotics
• Other
- Other psychiatric comorbidities
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient
• Based on careful workup and identification of etiology and subtype of anxiety disorders
• Identify coexistent substance abuse.
• Counseling or psychotherapy along with medications, biofeedback in selected cases
• Serial office visits
Diet
• Limit caffeine intake.
• Avoid alcohol (drug interactions).
Activity
Physical exercise
SPECIAL THERAPY
Complementary and Alternative Medicine
Kava was previously used but is no longer in favor due to liver toxicities.
MEDICATION (DRUGS) (3,5,6,7,8)
First Line
• Conditions
- Acute situational anxiety: Short-term (up to 1 month) treatment with benzodiazepines (2)[B]
- Generalized anxiety disorder
- Escitalopram (Lexapro) 10 mg/day titrated by 10 mg every week to a max of 20 mg/day (10 mg/day max) (1)[A]
- Paroxetine (Paxil) 10 mg daily titrated by 10 mg a week to a max 50 mg/day (20 mg/day most effective dose); (10 mg/day) (1)[A]
- Venlafaxine (Effexor XR) 37.5-75 mg titrated to a max of 225 mg/day (1)[A]
- Imipramine (Tofranil) 50 mg/day (max 200 mg/day, 100 mg in elderly) (1)[A]
- Fluoxetine (Prozac) 10 mg daily up to max of 20-40 mg/day (2)[C]
- Sertraline (Zoloft) 25 mg daily up to max of 200 mg/day (2)[B]
- Buspirone (Buspar) 20-30 mg/day divided b.i.d. to t.i.d. (max 60 mg/day) (1)[A]
• Panic disorder and social phobia: SSRIs, TCAs (e.g., imipramine), buproprion, trazodone, and beta-blockers (2)[B]
Second Line
• Generalized anxiety disorder
- Hydroxyzine 50-100 mg q6h (max 400 mg/day) (1) [A]
• BZDs (short-term use) (1)[A]
- Alprazolam (Xanax) 0.25 mg b.i.d. to t.i.d. increase by 0.25 mg, if needed
- Clonazepam (Klonopin) 0.5 mg t.i.d. to maximum of 1.5-4.5 mg per day
- Diazepam (Valium) 2-5 mg b.i.d. increase by 2 mg if needed
- Lorazepam (Ativan) 0.5 mg b.i.d. to t.i.d. increase by 0.5 mg if needed (response, if any, is slow, often 4-6 weeks)
• Panic disorder
- BZDs may be used short term until TCA or SSRI takes effect (2-3 weeks)
- BZDs may be helpful for initial control of symptoms until the SSRIs or TCAs are effective.
ALERT
Pediatric Considerations
• Reduced dosage of medications in adolescent
• Anxiety often comorbidly exists with ADHD
Geriatric Considerations
• Reduced dosage of medications
• Avoid TCAs and long-acting benzodiazepines.
Pregnancy Considerations
• BZDs: Contraindicated in 1st trimester of pregnancy, and with caution later in pregnancy and during lactation. May cause lethargy and weight loss in nursing infants; avoid breast-feeding if the mother is taking benzodiazepines chronically or in high doses.
• SSRIs: Taper and discontinue, if possible, in 1st trimester; may be used later in pregnancy (except paroxetine Class D).
• Precautions:
- BZDs: Advanced age, renal insufficiency, suicidal tendency, open-angle glaucoma. Sudden discontinuation increases the risk of seizures, especially with alprazolam.
- BZDs with short half-lives (e.g., alprazolam) increase the potential for dependency and protracted withdrawal symptoms; use with caution when patients with severe panic disorder are taking other CNS sedatives or with patients who have a history of substance abuse/dependence.
- Buspirone: Hepatic and/or renal dysfunction
- TCAs: Advanced age, glaucoma, benign prostate hypertrophy, hyperthyroidism, cardiovascular disease, liver disease, urinary retention, MAO inhibitor treatment
• Significant possible interactions
- BZDs (CYP inhibitors/inducers): Cimetidine, ethanol, oral contraceptives, disulfiram, levodopa, rifampin
- Buspirone: MAO inhibitors
- TCAs: Amphetamines, barbiturates, guanethidine, clonidine, epinephrine, ethanol, norepinephrine, MAO inhibitors, propoxyphene, allow 14-day washout period before starting MAOIs after TCA d/c
- SSRIs: MAO inhibitors (may cause fatal serotonin syndrome), may raise serum levels of other medications
FOLLOW-UP
PROGNOSIS
With active treatment, excellent results can often be obtained.
COMPLICATIONS
• Impaired social/occupational functioning
• Drug dependence (benzodiazepines)
• Alcohol dependence
PATIENT MONITORING
• Watch for and treat associated psychiatric disorders.
• Monitor mental status on benzodiazepines and avoid drug dependence.
• Monitor blood pressure, heart rate, and anticholinergic side effects on TCAs.
• Monitor for suicidality with SSRIs, venlafaxine, and imipramine.
REFERENCES
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000:429-484.
2. Rickels K, Moira R. Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry. 2002;63(suppl 14):9-16.
3. Lepine J. The epidemiology of anxiety disorders: Prevalence and societal costs. J Clin Psychiatry. 2002;63(suppl 14):4-8.
4. Kirkwood C, Melton S, Pharmacotherapy: A pathophysiologic approach. In: Anxiety Disorders I: Generalized Anxiety, Panic, and Social Anxiety Disorders. 6th ed. New York, NY; McGraw Hill: 2005.
5. Rickels K, Rynn M, Iyengar M, et al. Remission of generalized anxiety disorder: A review of the paroxetine clinical trials database. J Clin Psychiatry. 2006;67(1):41-47.
6. Goodman WK, Bose A, Wang Q. Treatment of generalized anxiety disorder with escitalopram: Pooled results from double-blind, placebo-controlled trials. J Affect Disord. 2005;87(2-3):161-167.
7. Mitte K, Noack P, Steil R, Hautzinger M. A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol. 2005;25(2):141-150.
8. Briggs G. Drugs In Pregnancy And Lactation: A Reference Guide to Fetal and Neonatal Risk. 7th ed. Philadelphia, PA: Lippincott Williams Wilkins; 2005.
ADDITIONAL READING
• Medline Plus, www.medlineplus.gov
• Mayo Clinic, www.mayoclinic.com
MISCELLANEOUS
Abbreviations: DSM-IV-R, Diagnostic and Statistical Manual of Mental Disorders, 4th edition Text Revision; TCA, tricyclic antidepressant; SSRI, selective serotonin reuptake inhibitor; CYP, cytochrome P450 enzymes; BZD, benzodiazepine
ANTITHROMBIN DEFICIENCY
ANTITHROMBIN DEFICIENCY - Marc JeffreyKahn, MD
BASICS
DESCRIPTION
Antithrombin is a protease that inhibits thrombin by forming an irreversible complex. Antithrombin can also inhibit factors Xa, IXa, and XIa. This process is catalyzed by the presence of heparin. Patients deficient in antithrombin have an increased incidence of venous thrombosis including venous thrombosis. Arterial thrombosis is much less common in patients deficient in antithrombin.
• System(s) Affected: Cardiovascular; Nervous; Pulmonary; Reproductive; Hemic/Lymphatic/ Immunologic
• Synonym(s): Antithrombin III deficiency
GENERAL PREVENTION
Patients with antithrombin deficiency without thrombosis do not require prophylactic treatment.
EPIDEMIOLOGY
• Predominant age: Mean age of 1st thrombosis is in the 2nd decade
• Predominant sex: Male = Female
Incidence
4% of patients with thrombophilia
Prevalence
0.16% of normal individuals
RISK FACTORS
• Oral contraceptives, pregnancy, and the use of hormone replacement therapy (HRT) increase the risk of venous thrombosis in patients with antithrombin deficiency.
• Patients with antithrombin deficiency and another prothrombotic state such as factor V Leiden or the prothrombin 20210 mutation have increased rates of thrombosis.
ALERT
Pregnancy Considerations
Increases thrombotic risk in patients with antithrombin deficiency
Genetics
• Autosomal dominant.
• Heterozygotes have an odds ratio of venous thrombosis of 10-20.
ETIOLOGY
Many mutations in the antithrombin gene have been identified.
• Type I deficiency is characterized by low levels of antigen. Type II deficiency is found when the antithrombin molecule is dysfunctional.
• Type II deficiencies are due to mutations in either the active center of antithrombin that binds the target enzyme or the heparin binding site.
• No patients homozygous for defects in the active center have been described, suggesting that this is a lethal condition. Patients heterozygous for mutations in the heparin binding site rarely have thrombotic episodes.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Deep or superficial venous thrombosis
• Recurrence rate of thrombosis is 12-17% per year.
TESTS
Lab
• Antithrombin levels in the presence of heparin
• Anti-thrombin-heparin cofactor assay
• Drugs that may alter lab results: Heparin and asparaginase can lower antithrombin levels.
• Disorders that may alter lab results
- Liver disease, DIC, nephritic syndrome, and preeclampsia reduce antithrombin levels.
- Acute thrombosis can lower antithrombin levels.
DIFFERENTIAL DIAGNOSIS
• Factor V Leiden
• Protein C deficiency
• Protein S deficiency
• Dysfibrinogenemia
• Dysplasminogenemia
• Homocysteinemia
• Prothrombin 20210 mutation
• Elevated factor VIII levels
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Routine anticoagulation for asymptomatic patients with antithrombin deficiency is not recommended. (1)[A]
• Patients with antithrombin deficiency and a 1st thrombosis should be anticoagulated initially with unfractionated heparin followed by oral anticoagulation with warfarin. (1)[A]
• The role of family screening for antithrombin deficiency is unclear, because most patients with this mutation do not have thrombosis. Screening may be considered for women considering using oral contraceptives or for pregnant women with a family history of factor protein S deficiency. (1)[C]
Diet
No restrictions
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Heparin initial bolus of 80 U/kg followed by infusion of 18 U/kg/h. Frequent monitoring of the PTT is important as nearly 1/2 of patients deficient in antithrombin require more than 40,000 U of heparin daily to adequately prolong the PTT. (1)[C] After the INR is 2-3, heparin can be stopped after 5 total days of therapy. (1)[A]
• Oral anticoagulant following the initial administration of heparin. Warfarin (Coumadin) 5 mg PO per day and adjusted to INR of 2-3. Patients should be maintained on warfarin for at least 6 months. (1)[A]
• Recurrent thrombosis requires indefinite anticoagulation. (1)[A]
• Contraindications
- Active bleeding precludes anticoagulation; risk of bleeding is a relative contraindication to long-term anticoagulation.
• Precautions
- Observe patient for signs of embolization, further thrombosis, or bleeding.
- Avoid IM injections.
- Periodically check stool and urine for occult blood and monitor CBCs including platelets.
- Heparin-thrombocytopenia and/or paradoxical thrombosis with thrombocytopenia
• Significant possible interactions
- Agents that intensify the response to oral anticoagulants: Alcohol, allopurinol, amiodarone, anabolic steroids, androgens, many antimicrobials, cimetidine, chloral hydrate, disulfiram, all NSAIDs, sulfinpyrazone, tamoxifen, thyroid hormone, vitamin E, ranitidine, salicylates, acetaminophen
- Agents that diminish the response to oral anticoagulants: Aminoglutethimide, antacids, barbiturates, carbamazepine, cholestyramine, diuretics, griseofulvin, rifampin, and oral contraceptives
Second Line
• Argatroban 0.4-0.5 mcg/kg/min. Case reports describing the use of the direct thrombin inhibitor in patients with antithrombin deficiency have been published. (2)[C]
• Antithrombin III (ATnativ, Thrombate III) 50-100 IU/min IV titrated to antithrombin level desired. Precise role in therapy remains unclear. (1)[C]
• LMWH is difficult to manage in this population. (1)[C]
FOLLOW-UP
PROGNOSIS
The odds ratio of thrombosis in a patient with antithrombin deficiency is much higher than in patients with other thrombophilic conditions. The recurrence rate is similarly high. There is no difference in clinical severity between patients with type I defects and type II mutations.
COMPLICATIONS
Recurrent thrombosis (requires indefinite anticoagulation)
PATIENT MONITORING
Warfarin requires periodic (monthly after initial stabilization) monitoring of the INR.
REFERENCES
1. Vinazzer H. Hereditary and acquired antithrombin deficiency. Semin Thromb Hemost. 1999;25(3): 257-263.
2. Dager WE, Gosselin RC, Owings JT. Argatroban therapy for antithrombin deficiency and mesenteric thrombosis: Case report and review of the literature. Pharmacotherapy. 2004;24(5): 659-663.
3. Kottke-Marchant K, Duncan A. Antithrombin deficiency: Issues in laboratory diagnosis. Arch Pathol Lab Med. 2002;126(11):1326-1336.
MISCELLANEOUS
See also: Thrombosis; Deep Vein (DVT); Protein C Deficiency; Protein S Deficiency; Prothrombin 20210 (Mutation); Factor V Leiden
Friday, January 2, 2009
ANTI PHOSPHOLIPID ANTIBODY SYNDROME
ANTI-PHOSPHOLIPID ANTIBODY SYNDROME - Christopher S.Manasseh, MD
BASICS
DESCRIPTION
• An autoimmune thrombotic syndrome characterized by the presence of antiphospholipid antibodies in association with either recurrent venous or arterial thromboembolic events or repeated fetal loss
• Types
- Primary
Occurs in patients without clinical evidence of another autoimmune disease
- Secondary
Occurs in association with another disease such as systemic lupus erythematosus (SLE)
- Catastrophic antiphospholipid syndrome
Differs from primary and secondary types in the caliber of vessels affected. Venous or arterial thrombosis of large vessels is less common, and patients present with acute thrombotic microangiopathy, kidney being the most commonly affected organ.
Disseminated intravascular coagulation which does not occur in primary or secondary forms is seen in up to 25% of patients with the catastrophic type.
• Synonym(s): Hughes syndrome
ALERT
Geriatric Considerations
Atherosclerosis and cancer are more frequent causes of thrombosis than is antiphospholipid antibody syndrome.
Pregnancy Considerations
• Increased frequency of recurrent fetal loss
• Increased risk of premature delivery due to pregnancy related hypertension and uteroplacental insufficiency
GENERAL PREVENTION
In pregnant women with h/o recurrent fetal loss, use low dose unfractionated heparin 5000 U SQ b.i.d.
In all women with the syndrome and previous pregnancy loss, aspirin 325 mg/day may provide protection against future thrombosis.
Modification of secondary risk factors for atherosclerosis include control of hypertension, diabetes, hyperlipidemia, and smoking cessation.
EPIDEMIOLOGY
1/2 of all patients with the syndrome have the primary form of the disease.
Incidence
• 15% of women with recurrent pregnancy loss have this syndrome
• 63% of patients have at least 1 valvular abnormality on echocardiogram
Prevalence
1-5% of otherwise young healthy adults have antiphospholipid antibodies
50-70% of patients with SLE who have the antiphospholipid antibodies may develop this syndrome
RISK FACTORS
• Smoking
• Oral contraceptive use
• Surgery
• Immobilization
• Pregnancy
PATHOPHYSIOLOGY
Any organ can be involved, and the extent of involvement depends on the
• Nature and size of vessel involved
• Acuteness or chronicity of the thrombotic process
ETIOLOGY
Antiphospholipid antibodies promote thrombosis by any of the following hypotheses
• Activation of endothelial cells
• Oxidant-mediated injury of the vascular endothelium
• Interference with the phospholipid binding proteins involved in the regulation of coagulation
ASSOCIATED CONDITIONS
• SLE
• Malignant hypertension
• Nephrotic syndrome
DIAGNOSIS
SIGNS AND SYMPTOMS
• Arthralgia
• Livedo reticularis
History
• Family history of rheumatic illness
• Personal history of thrombosis
Physical Exam
Look for deep vein thrombosis of the legs.
Most common manifestation of the syndrome
TESTS
• ELISA test for anticardiolipin antibodies
• Clotting test for lupus anticoagulant
Lab
• Thrombocytopenia
• Leukopenia
Diagnostic Criteria
• The presence of at least ONE of the following clinical criteria
- Vascular thrombosis
1 or more clinical episodes of arterial, venous, or small vessel thrombosis, occurring within any tissue or organ
- Complications of pregnancy
1 or more unexplained deaths of morphologically normal fetuses at or after the 10th week of pregnancy OR
1 or more premature births of morphologically normal neonates at or before the 34th week of pregnancy OR
3 or more unexplained consecutive spontaneous abortions before the 10th week of pregnancy
• AND presence of at least ONE of the following laboratory criteria
- Anticardiolipin antibodies
Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on 2 or more occasions at least 6 weeks apart
- Lupus anticoagulant antibodies
Detected in the blood on 2 or more occasions at least 6 weeks apart
Pathological Findings
• Acute changes
- Capillary congestion
- Non-inflammatory fibrin thrombi
• Chronic changes
- Ischemic hypoperfusion
- Atrophy and fibrosis
DIFFERENTIAL DIAGNOSIS
• Other conditions that cause thrombotic microangiopathy, such as
- Hemolytic-uremic syndrome
- Thrombotic thrombocytopenic purpura
• Other thrombophilic conditions, such as
- Deficiency of protein C, protein S
- Deficiency of antithrombin III
- Mutation of factor V Leiden
- Prothrombin gene mutation
- Homocysteinemia
MEDICATION (DRUGS)
First Line
Warfarin treatment of moderate intensity (to achieve an international normalized ratio (INR) of 2-2.9) significantly reduces the rate of recurrent thrombosis.
• Duration of treatment is lifelong.
Second Line
Corticosteroids and azathioprine for treatment of symptoms of lupus in patients with secondary form of the syndrome
SPECIAL THERAPY
In patients who develop new thromboses despite moderate intensity anticoagulant therapy and for patients with catastrophic antiphospholipid syndrome
• Plasmapheresis
• IV immune globulin
FOLLOW-UP
PROGNOSIS
• Pulmonary hypertension, neurologic involvement, myocardial ischemia, nephropathy, gangrene of extremities, and catastrophic APS are associated with a worse prognosis.
• Most patients experience recurrences months or years after the initial event.
• Mortality rate is ~50% in patients presenting with the catastrophic type, and death is due to multi-organ system failure.
COMPLICATIONS
Discontinuation of warfarin results in increased risk of thrombosis (even death), particularly in the 1st 6 months after stopping treatment.
PATIENT MONITORING
As warfarin therapy is lifelong, patients need to have regular monitoring to maintain INR in the therapeutic range (between 2 and 2.9).
REFERENCES
1. Lockshin M. Antiphospholipid antibody syndrome. In: Ruddy S, Harris ED, Sledge CB, ed. Kelley's Textbook of Rheumatology. Philadelphia: Saunders Company; 2001;1145-1152.
2. Erkan D, Yazici Y, Sobel R, Lockshin MD. Primary antiphospholipid syndrome. Functional outcome after 10 years. J Rheumatol. 2000;27:2817-2821.
3. Levine JS, Branch DW. The antiphospholipid syndrome. N Eng J Med. 2002;10:752-759.
4. Crowther MA, Ginsberg JS, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with antiphospholipid syndrome. N Eng J Med. 2003;12:1133-1138.
ADDITIONAL READING
The decade of autoimmunity: edited by Y. Shoenfeld, publication date 1999.
ANTHRAX
ANTHRAX - Benjamin L. Sapers, MD
BASICS
DESCRIPTION
• Anthrax is a highly infectious disease of animals, especially ruminants (hooved animals such as cows, goats, sheep, etc.) that is caused by the bacteria Bacillus anthracis. Cutaneous (95% of US cases); inhalational, and gastrointestinal forms can be transmitted to man by contact with the animals or their products.
• Synonym(s) for skin anthrax: Charbon; Malignant pustule; Siberian ulcer; Malignant edema; Splenic fever; Milzbrand; Ragpicker disease
• Synonym(s) for chest anthrax: Woolsorter disease
GENERAL PREVENTION
• Anthrax vaccine protects against all forms of anthrax and is as safe as other vaccines, according to the Food and Drug Administration, the Centers for Disease Control and Prevention, and the National Academy of Sciences. A 2005 review by the Cochrane Infectious Disease Group concluded that the anthrax vaccine is effective in reducing the risk of contracting anthrax and has a low rate of adverse effects (1)[A].
• Vaccine is given in 6 doses (0, 2, and 4 weeks, and 6, 12, and 18 months) plus annual boosters.
- If you get behind schedule, don't start the series over; begin where you left off (delays don't reduce the resulting protection).
- Redness up to 1 inch (1 cm) wide occurs in 30% of men and 60% of women, and redness or other reactions >5 inches (4 cm) occur in ~1% of people (both male and female).
- Anthrax vaccine often causes a nodule under the skin where the vaccine is injected; this can last from 2-3 months. These nodules eventually resolve.
- The Advisory Committee on Immunization Practices recommends vaccination for the following groups
Persons who work directly with the organism in the laboratory
Persons who work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores
Persons who handle potentially infected animal products in high-incidence areas
Military personnel deployed to areas with high risk for exposure to organisms (when used as a biologic warfare weapon)
Pregnant women should be vaccinated for anthrax only if absolutely necessary.
• Patients with a likely exposure history but no symptoms are candidates for postexposure prophylaxis with either ciprofloxacin 500 mg PO b.i.d. or doxycycline 100 mg PO b.i.d.
EPIDEMIOLOGY
• Cutaneous (skin): 95% of cases in the US; cases of cutaneous anthrax without occupational risk should raise concern for a terrorist attack. About 5-20% of untreated cases result in death.
• Gastrointestinal (GI): Very rare in the US (no documented case in the 20th century).
• Inhalational (chest) anthrax is very rare in US; must be considered a bioterrorist event in US until proven otherwise (the last US occupational case occurred in 1976). Death results in 99% of untreated cases, and in 45-80% of patients with severe symptoms who are treated in a state-of-the-art facility.
• Anthrax is most common in agricultural regions, where it occurs in animals. These regions include the Middle East, Asia, Southern and Eastern Europe, Africa, South and Central America, and the Caribbean.
RISK FACTORS
• Contact with infected animals or their products
• Bioterrorist event
PATHOPHYSIOLOGY
• Bacillus anthracis is a spore-forming, gram-positive bacterium found in the soil worldwide. The word anthracis is derived from a Greek word meaning "coal," which is used to describe the cutaneous form of the disease that leads to a characteristic black lesion.
• B. anthracis has 3 known virulence factors: An antiphagocytic capsule and 2 protein toxins (known as edema factor and lethal factor).
- The capsule provides resistance to phagocytosis.
- Lethal factor and edema factor are named for the effects they induce when injected into experimental animals.
- A protein called protective antigen binds to the host cell's surface; when cleaved by a protease on the cell surface it creates a binding site to which the lethal factor and edema factor can bind; protective antigen is required for the action of the 2 protein toxins.
• B. anthracis spores introduced into the host are ingested at the exposed site by macrophages and then germinate into vegetative forms that produce the virulence factors.
ETIOLOGY
• Skin: Occurs when B. anthracis enters the skin through a cut or abrasion during the handling of animal products (such as meat, wool, or hides infected with B. anthracis)
• GI: Ingestion of bacillus-contaminated meat
• Chest: Inhalation of aerosolized B. anthracis spores
DIAGNOSIS
SIGNS AND SYMPTOMS
• Skin: Begins as a pruritic red-brown papule that enlarges with peripheral erythema, vesiculation, and induration, followed by black eschar formation within 7-10 days of the initial lesion. The papule, blister, and eschar are painless, and cutaneous symptoms may be accompanied by fever, malaise, and headache. A black eschar with massive edema is nearly pathognomonic for cutaneous anthrax.
• GI: Presents as 1 of 2 distinct syndromes oropharyngeal and abdominal. Oropharyngeal syndrome presentation can include fever, edema, ulcer, severe sore throat, and lymphadenopathy resulting in marked unilateral or bilateral neck swelling. Abdominal syndrome may present with fever, malaise, hematemesis, anorexia, severe abdominal pain, and hematochezia or melena.
• Chest: Biphasic presentation, with initial phase featuring nonspecific influenzalike symptoms such as low-grade fever, chills, headache, nonproductive cough, diaphoresis, malaise, chest discomfort, nausea, vomiting, diarrhea, and abdominal pain. This initial phase is followed by the 2nd fulminant phase that includes abrupt onset of high fever, severe dyspnea, hypoxia, hypotension, and death.
History
• Skin: Crucial clinical clues are the rapid evolution of symptoms, lack of pain, occasional massive edema, and the near pathognomonic black eschar. Incubation period is usually immediate but may last up to 1 day.
• GI: Incubation period usually 1-7 days; 2-4 days after onset of symptoms, ascites develop as abdominal pain decreases. Shock and death occur within 2-5 days after onset of symptoms.
• Chest: Incubation period is usually 1 week, but may be as long as 2 months. 2nd portion of the biphasic presentation begins 1-5 days after onset of initial symptoms. There may be a 1-3 day period of improvement after the 1st phase and before the 2nd phase begins. Shock and death occur within 24-36 hours after onset of the 2nd phase.
Physical Exam
• Skin: Red-brown papule, vesicles, or black eschar
• GI: Acute abdomen with rebound tenderness may occur. Ascites present later in course
• Chest: Rhonchi may be present.
TESTS
Lab
Gram stain and culture. A presumptive diagnosis can be made if Gram-positive rods are present that are nonmotile, nonhemolytic, and encapsulated (usually seen with India ink). If antibiotics have been given for >24 hours, perform immunohistochemical staining and/or polymerase chain reaction.
Imaging
• Widened mediastinum on chest radiograph may be present in inhalational anthrax.
• Pleural effusions frequently present in chest anthrax; infiltrates are rare.
• GI: Mesenteric adenopathy on CT scan likely.
DIFFERENTIAL DIAGNOSIS
Skin
Cellulitis
Brown recluse spider bite
Cat-scratch disease
Rat bite fever
Rickettsial spotted fever
Carbuncle
Cowpox
Bullous erysipelas
Tularemia vasculitides
Ecthyma gangrenosum
Orf (a transmissible viral disease of goats and sheep)
TREATMENT
GENERAL MEASURES
Chest and GI anthrax is not known to spread from person to person, so communicability concerns are not an issue during management of the patient. For skin anthrax, avoid contact with the wound or wound drainage.
MEDICATION (DRUGS)
First Line
• Skin: Ciprofloxacin 500 mg PO b.i.d. for 60 days or doxycycline 100 mg PO b.i.d. for 60 days. If systemic involvement, massive edema, or lesions on the head or neck, follow treatment recommendation per inhalational anthrax (2)[C].
• Chest and GI: IV ciprofloxacin 400 mg q12h or doxycycline 100 mg q12h AND 1 or 2 additional antimicrobials such as rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. May switch to PO when clinically appropriate. Must complete 60-day course (combined PO and IV) (2)[C].
Second Line
Patients being treated for anthrax may also benefit from vaccination as part of their regimen (3)[C].
FOLLOW-UP
PROGNOSIS
• Skin: Death in 5-20% of untreated cases.
• GI: Mortality rates as high as 50% have been reported.
• Chest: Death in 99% of untreated cases.
PATIENT MONITORING
Must monitor patient for 60 days to ensure completion of the treatment course
REFERENCES
1. Jefferson T, Demicheli V, Deeks J, et al. Vaccines for preventing anthrax. [Systematic Review] Cochrane Infectious Diseases Group. Cochrane Database of Systematic Rev. 1, 2006.
2. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001;50(42):909-919. Erratum in: MMWR Morb Mortal Wkly Rep. 2001;50(43):962.
3. Centers for Disease Control and Prevention. Use of anthrax vaccine in the United States, ACIP Recommendations. MMWR Recommendations Reports. 2000;49(RR-15):1-20.
ADDITIONAL READING
• The anthrax vaccine immunization program. http://www.anthrax.mil
• Centers for Disease Control and Prevention, Emergency Preparedness and Response. http://www.bt.cdc.gov/agent/anthrax/
• Durning SJ, Roy MJ. Anthrax. In: Roy MJ, ed. Physician's Guide to Terrorist Attack. Totowa, NJ: Humana Press Inc.; 2003.
ANOREXIA NERVOSA (AN)
ANOREXIA NERVOSA (AN) - Mary Muscari, PhD, RN, CRNP, CS
BASICS
DESCRIPTION
• Refusal to maintain normal body weight, with associated fear of weight gain, body image disturbance, and amenorrhea
• Restricting and binge-eating/purging subtypes
• System(s) Affected: Cardiovascular; Endocrine; Metabolic; Gastrointestinal; Nervous; Reproductive
GENERAL PREVENTION
Encourage rational attitude about nutrition and weight, minimize weight-related criticism and teasing, moderate overly high self-expectations, enhance self-esteem
EPIDEMIOLOGY
• Predominant age at onset: 13-18 years
• Predominant sex: Female > Male (20:1)
• Global distribution
Incidence
8-19 women, 2 men per 100,000 per year
Prevalence
1% in women, 0.1% in men
RISK FACTORS
• Female gender
• Perceived body image distortions
• Perfectionism, obsessionality, rigidity
• Negative self-evaluation
• Academic and other achievement pressure
• Participation in sports or artistic activities that emphasize leanness or involve subjective scoring
- Ballet, running, wrestling, figure skating, gymnastics, cheerleading, weight lifting
• Parental psychiatric disorder
Genetics
• Underlying genetic vulnerability likely, but not well understood
- 1st-degree female relative with eating disorder increases risk 6- to 10-fold.
PATHOPHYSIOLOGY
Complex relationship between biologic, psychological, and social factors that results in an unrealistic perception of fatness. Subsequent malnutrition leads to disorder of multiple organs.
ETIOLOGY
• Serotonin neuronal systems are implicated.
• Multifactorial withpsychological, biological, genetic, environmental, and social factors
ASSOCIATED CONDITIONS
• Mood disorder
• Social phobia, obsessive-compulsive disorder
• Substance abuse disorder
• High rates of cluster C personality disorders
DIAGNOSIS
SIGNS AND SYMPTOMS
• Onset may be insidious or stress related
• Amenorrhea (primary or secondary)
• Report feeling fat even when emaciated
• Preoccupation with body size, weight control
• Elaborate food preparation and eating rituals
• Extensive exercise
• Weakness, fatigue, cognitive impairment
• Hypothermia, cold intolerance
• Constipation, bloating, early satiety
• Dry skin, scalp hair loss, peripheral edema
• Lanugo hair on extremities, face, and trunk
• Growth arrest, delayed puberty
• Hypotension, bradycardia, murmurs
• Decreased bone density, fractures
History
Ascertain fear of weight gain and/or distorted body image.
Physical Exam
• Often normal
• Vital signs: Bradycardia, orthostatic hypotension, body weight 85% expected
• Cardiac: Dysrhythmias, midsystolic click of mitral valve prolapse
• Skin/extremities: Dry, lanugo, hair loss, edema
• Neurologic and abdominal exams: To rule out other causes of weight loss and vomiting
TESTS
Lab
• No specific test for AN. Most findings are related directly to starvation, dehydration
- All findings may be within normal limits.
• Low serum leuteinizing hormone, follicle-stimulating hormone; low T4 with normal TSH
• Abnormal liver enzymes
• Altered blood urea nitrogen, creatinine clearance; electrolyte disturbances
• Hypoglycemia, hypercholesterolemia, hypercortisolemia, hypophosphatemia
• Low sedimentation rate
• Anemia, leukopenia, thrombocytopenia
• 12-lead ECG to assess for prolonged QT
Imaging
Dual-energy x-ray absorptiometry (DEXA) of bone only if underweight for >6 months to assess for diminished bone density
Diagnostic Procedures/Surgery
• DSM-IV-TR criteria
- Refusal to maintain body weight at or above a minimally normal weight for age, height
- Intense fear of gaining weight even though underweight
- A disturbance in the way body weight/shape is experienced; undue influence of body on self-evaluation or denial of seriousness of low body weight
- Specific types
Restricting: Not engaged in binge-eating or purging behaviors
Binge-eating/purging type: Regularly engages in binge-eating or purging behaviors (see Bulimia information related to these behaviors)
• Screening tools: SCOFF questionnaire, Eating disorder Screen for Primary Care (ESP), Eating Attitudes Test (EAT), Eating Disorder Inventory (EDI)
Pathological Findings
• Osteoporosis/osteopenia, pathologic fractures
• Sick euthyroid syndrome
• Cardiac impairment
DIFFERENTIAL DIAGNOSIS
• Hyperthyroidism,adrenal insufficiency
• Inflammatory bowel disease
• Immunodeficiency, chronic infections
• Malabsorption, diabetes
• CNS lesion
• Bulimia; body dysmorphic disorder
• Depressive disorders with loss of appetite
• Anxiety disorder, food phobia
• Conversion disorder, schizophrenic disorder
ALERT
AN may exist concurrently with chronic medical disorders, such as diabetes, cystic fibrosis.
TREATMENT
GENERAL MEASURES
• Initial treatment goal geared to weight restoration; most are managed as outpatients
• Outpatient treatment
- Interdisciplinary team (primary care physician, mental health professional, nutritionist) (1,2)[B,C]
- Average weekly weight gain goal: 0.5-1.0 kg (1)[C] with stepwise increase in calories
- Cognitive behavioral and/or family-based therapy (2,3)[B]
- Focus on health, not weight gain alone.
- Build trust, treatment alliance,
- Involve patient in establishing diet and exercise goals.
- Challenge fear of uncontrolled weight gain; help the patient to recognize feelings that lead to disordered eating.
- In chronic cases, goal may be to achieve a safe weight rather than a healthy weight.
• Inpatient treatment
- If possible, admit to specialized eating disorders unit (4)[C]
- Monitor vital signs, cardiac function, watch for edema, rapid weight gain (fluid overload)
- Initial bed rest with supervised meals may be necessary.
- Stepwise increase in activity
- Tube feeding or total parental nutrition used only as last resort
- Supportive symptomatic care as needed
Diet
• Goal is stabilization at a healthy weight on a balanced diet with normal eating pattern
• Diminished ruminations about calories, weight; increased enjoyment
Activity
• Monitor activity.
• Stepwise increase as patient gains weight
• Focus on enjoyable activities rather than goal-oriented ones.
MEDICATION (DRUGS)
First Line
• No medications are available that effectively treat patients with AN, but antidepressants may benefit those with comorbid depression (5,6)[C].
• Selective serotonin-reuptake inhibitors such as fluoxetine (Prozac): 10-60 mg may
- Help prevent relapse after weight gain
- Treat comorbid depression or obsessive-compulsive disorder (1,4,6)[C]
- Attend to black box warnings concerning antidepressants and conduct appropriate informed consent if antidepressants are prescribed
Second Line
• Management of osteopenia
- Elemental calcium 1200-1500 mg/d plus MVI containing 800 IU of vitamin D (2,4)[C]
- No indication for bisphosphonates in AN (2)[C]
- Weak evidence for use of HRT (2)[C]
- Psyllium (Metamucil) preparations (1 tbsp) to prevent constipation
FOLLOW-UP
DISPOSITION
Admission Criteria
• Suggested physiologic values: Heart rate 40 bpm, BP 90/60, symptomatic hypoglycemia, potassium 3 mmol/L, temperature 97.0F (36.1C), dehydration, other cardiovascular abnormalities, weight 75% of the expected weight, rapid weight loss, lack of improvement while in outpatient therapy
• Suggested psychological indications: Poor motivation/insight, lack of cooperation with outpatient treatment, inability to eat, need for nasogastric feeding, suicidal plan or intent, severe coexisting psychiatric disease, problematic family environment
ALERT
Pediatric Considerations
• Children often present with nausea, abdominal pain, fullness, and inability to swallow.
• Additional indications for hospitalization: Heart rate 50 bpm, orthostatic BP, hypokalemia or hypophosphatemia, rapid weight loss even if weight not 75% below normal
Geriatric Considerations
Late-onset AN (>50) may be long-term disease, or triggered by death of loved one, marital discord, or divorce.
Discharge Criteria
Lower relapse rate when discharged at expected healthy weights
PROGNOSIS
• Prognosis: ~50% recover; 25% improved; 25% chronically ill
• Mortality: 5-7%
COMPLICATIONS
• Refeeding syndrome
• Cardiac arrhythmia; cardiac arrest
• Cardiomyopathy, congestive heart failure
• Delayed gastric emptying, necrotizing colitis
• Seizures, Wernicke encephalopathy, peripheral neuropathy, cognitive deficits
• Osteopenia, osteoporosis
Pregnancy Considerations
• Fertility may be affected.
• Increased risk for miscarriage, operative delivery, congenital malformations, and low-birth-weight infants; should be managed as high risk
PATIENT MONITORING
• Level of exercise activity
• Weigh weekly until stable, then monthly.
• Depression, self-esteem, suicidal ideation
REFERENCES
1. NICE. Eating disorderscore interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. NICE Clinical Guideline no 9. London: NICE, 2004 (accessed 15 Feb 2006).
2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Eating Disorders, 3rd ed. 2006, June (accessed Dec 10, 2006).
3. Hay P, Bacaltchuk J, Claudino A, Ben-Tovim D, et al. Individual psychotherapy in the outpatient treatment of adults with anorexia. Cochrane Database Syst Rev. 2003;(4):CD003909.
4. Yager J, Anderson AE. Anorexia nervosa. N Engl J Med. 2005;353:1481-1488.
5. Berkman ND, Bulik CM, Brownley KA, et al. Management of eating disorders. Evidence report/technology assessment No. 135. (Prepared by the RTI International-University of North Carolina Evidence-Based Practice Center under Contract No. 290-02-0016.) AHRQ Publication No. 06-E010. Rockville, MD: Agency for Healthcare Research and Quality, April 2006.
6. Claudino A, Hay P, Lima M, et al. Antidepressants for anorexia nervosa. Cochrane Database Sys Rev. 2006;(1):CD04365.
