Venous Thromboembolic Disease

VENOUS THROMBOEMBOLIC DISEASE
by:R. Duncan Hite, MD
Section on Pulmonary and Critical Care Medicine

Venous Thromboembolic Disease

* Venous thrombosis - ~ 5 million pts yearly
+ Most caused by inadequate prophylaxis in hospitalized pts
* 10 % suffer pulmonary embolism ~ 500,000
* ~ 1% of all hospitalized pts have PE
* Contributes to 6 % of all hospital deaths
* ~ 125,000 deaths annually from PE
+ 3rd most common cardiovascular cause of death (MI, CVA)
+ Most deaths occur early – PREVENTION IS KEY!!
* Diagnosis of PE made in < 30% when contributes to death; < 10% if incidental

Case studies
Venous Thromboembolic Disease
Epidemiology

* 85 - 90% of PE pts have DVT risk factors
* 90-95% of PEs arise from lower ext. DVT
* Defined DVT Risk Factors: (Virchow’s Triad)
o Venous stasis - CHF, Immobility, Age > 70, Travel, Obesity, Recent surgery (4 weeks) or hospitalization (6 mos)
o Venous Injury - Prior DVT/PE, LE Trauma/Surgery
# LE trauma or surgery - Very high (50+%)
# Major surgery - (5 - 8%)
o Hypercoaguability - Cancer, Pregnancy, Nephrotic Syndrome, Hyperhomocysteinemia, Factor V Leyden mutation, Deficiency of Protein C/S or ATIII, Anti Phospholipid Ab, HITTS, Smoking

Pulmonary Hypertension Hemodynamic Effects
Deep Venous Thrombosis
Diagnosis
* Venography - remains the “gold standard”
+ Pitfalls: Difficult to perform, expensive, contrast load, DVT
* Compression Ultrasound (Sonography, Duplex and Color Doppler)
+ Criteria: echogenicity, noncompressibility, distension, free floating thrombus, absence of Doppler waveform, Abnormal color image
+ Accuracy:
# Symptomatic Patients: Sensitivity = 90-100%, Specificity = 95-100%
# High Risk Asymptomatic: Sensitivity = 50-80%, Specificity = 95-100%
* Impedance Plethysmography
* Radionuclide Venography (Indium-111)
* MRI - increasing popularity and utilization, includes deep pelvic veins

Deep Venous Thrombosis Prevention
* Orthopedic Surgery
o LMWH or Coumadin (INR 2.0 - 3.0) beginning preoperatively or immediately postoperatively. Adjusted dose SQ Heparin is an acceptable alternative but more complex.
o Adjuvant use of mechanical devices may add additional benefit. May be sufficient as primary prophylaxis for TKR if used optimally.
o Low dose SQ Hep, Aspirin, IPC alone are not recommended (less effective).
o Duration:
+ minimum of 7-10 days
+ Post Discharge Prophylaxis: 4-6 weeks for high risk patients
* General Surgery (including Urologic)
o Prophylaxis with SQHep, LMWH, ES or IPC
+ Moderate Risk - minor procedure with a risk factor or 40-60 yo, major procedures and <40
+ High Risk - minor procedure with risk factors or >60, major procedures with risk factors or age >40.
+ Increased Risk of Bleeding - use ES or IPC
o Combination therapy: very high risk - multiple risk factors
o Postdischarge Prophylaxis: selected very high risk pts
* Gynecologic Surgery
o Major surgery for benign disease
# SQ Hep BID, LMWH, IPC, continue for several days post op
o Major surgery for malignancy
# SQ Hep TID, Combination AC/Mech, high dose LMWH
* Neurosurgery
o Intracranial Surgery
# IPC or ES, Low dose SQHep or LMWH may be acceptable
# Combination IPC or ES with SQHep or LMWH in high risk

Deep Venous Thrombosis Prevention
* Trauma
o LMWH as soon as possible
o IPC or ES until LMWH started
* Acute Spinal Cord Injury
o LMWH recommended
o Low dose SQHep, ES or IPC are less effective
o Combination Mechanical/anticoagulant may be acceptable
o Continue throughout rehabilatation
* Medical (Cancer, CHF, Bedrest, MI, CVA…)
o Low dose SQ Hep or LMWH
o IPC if anticoagulation contraindicated

PE SIGNS AND SYMPTOMS
Symptoms
* Dyspnea - 80%
* Chest pain - 70%
* Cough - 50%
* Apprehension - 50%
* Hemoptysis - 30%

Signs
* Tachycardia - 60%
* Tachypnea - 70%
* Fever - 60%
* Clinical DVT - 30%

Pulmonary Embolism Diagnosis
* Chest x-ray - nonspecific abnormalities in most; normal early
+ Westermark's sign and Hampton's hump uncommon
* Arterial blood gas – hypoxemia is common
+ 15 - 20% will not manifest hypoxemia (i.e. normal A-a gradient)
* ECG – nonspecific changes typically
+ S1Q3T3 pattern in massive PE with RV strain
+ helpful in evaluating other causes of chest pain

PE – V/Q LUNG SCAN
* Radiolabeled Xenon inhaled for ventilation and radiolabeled Technetium for perfusion
* Safe
* Not very specific
* Not very useful if pre-existing lung disease

Pulmonary Embolism Diagnosis - V/Q Scan
Pulmonary Embolism
Diagnosis - Pulmonary Arteriogram
* Remains “gold standard” for Dx of PE
* Expensive
* Low morbidity and mortality
o Mortality < 0.1%
o Major morbidity < 0.5%
o Pulmonary Hypertension not a contraindication
Pulmonary Embolism
Diagnosis - Pulmonary Arteriogram
Lobar Defect
Segmental Defect
Pulmonary Embolism
Diagnosis - Chest CT
* Accurate for segmental or larger PE
+ Sensitivity 85 - 95% (Overall 50-60%)
+ Specificity 90 - 100%
* Accuracy depends on interpreter
+ Large Inter-interpreter variability
+ Reduced accuracy with less experience
* Significant contrast load ~ 65% of PA gram
* Similar expense to Pulmonary Arteriogram
* Can identify other pulmonary etiologies
Pulmonary Emboli Diagnosis - MRA
Venous Thromboembolism Treatment
Continuous IV Heparin:
Heparin-Induced Antibodies
Venous Thromboembolism Treatment
Low Molecular Weight Heparins:
Venous Thromboembolism Outpatient LMWH
Enoxaparin sodium
Unfractionated heparin
Venous Thromboembolism
Treatment
Synthetic Heparins:
Fondaparinux (Arixtra)
Oral anticoagulation (Coumadin)
Inferior Vena Cava Filter

VENOUS THROMBOEMBOLIC DISEASE.ppt

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Approach to the Jaundiced Patient

Approach to the Jaundiced Patient
Internal Medicine Survivor Series
By:Joel Bruggen, MD

New Onset Jaundice
* Viral hepatitis
* Alcoholic liver disease
* Autoimmune hepatitis
* Medication-induced liver disease
* Common bile duct stones
* Pancreatic cancer
* Primary Biliary Cirrhosis (PBC)
* Primary Sclerosing Cholangitis (PSC)

Jaundiced Emergencies
* Acetaminophen Toxicity
* Fulminant Hepatic Failure
* Ascending Cholangitis

Jaundice Unrelated to Intrinsic Liver Disease
* Hemolysis (usually T. bili < 4)
* Massive Transfusion
* Resorption of Hematoma
* Ineffective Erythropoesis
* Disorders of Conjugation
o Gilbert’s syndrome
* Intrahepatic Cholestasis
o Sepsis, TPN, Post-operation

New Onset Jaundice
* Viral hepatitis
* Alcoholic liver disease
* Autoimmune hepatitis
* Medication-induced liver disease
* Common bile duct stones
* Pancreatic cancer
* Primary Biliary Cirrhosis (PBC)
* Primary Sclerosing Cholangitis (PSC)

HBV Serology
Resolved HBV
HBV vaccinated
Chronic HBV
Acute HBV
HBSAb
HBcAb
IgG
HBcAb
IgM
Acute Hepatitis C
HCV RNA
Anti-HCV
Infection Day 0
HCV RNA Day 12
HCV Antibody Day 70
Plateau phase = 57 days

Alcoholic Liver Disease
* The history is the key – 60 grams/day
* Gynecomastia, parotids, Dupuytren’s
* Lab clues: AST/ALT > 2, MCV > 94

AST < 300
* Alcoholic hepatitis:
o Anorexia, fever, jaundice, hepatomegaly
o Treatment:
+ Abstinence
+ Nutrition
+ Consider prednisolone or pentoxifylline

Alcoholic Liver Disease
Discriminant Function Formula:
DF = [4.6 x (PT – control)] + bilirubin
Consider treatment for DF > 32
* Prednisolone 40 mg/day x 28 days
o contraindications: infection, renal failure, GIB
* Pentoxifylline 400 mg PO tid x 28 days

Autoimmune Hepatitis
* Widely variable clinical presentations
o Asymptomatic LFT abnormality (ALT and AST)
o Severe hepatitis with jaundice
o Cirrhosis and complications of portal HTN
* Often associated with other autoimmune dz
* Diagnosis:
o Compatible clinical presentation
o ANA or ASMA with titer 1:80 or greater
o IgG > 1.5 upper limits of normal
o Liver biopsy: portal lymphocytes + plasma cells

Drug-induced Liver Disease
* Hepatocellular
o acetaminophen, INH, methyldopa, MTX
* Cholestatic
o chlorpromazine, estradiol, antibiotics
* Chronic Hepatitis
o methyldopa, phenytoin, macrodantin, PTU
* Hypersensitivity Reaction
o Phenytoin, Augmentin, allopurinol
* Microvesicular Steatosis
o amiodarone, IV tetracycline, AZT, ddI, stavudine

Acetaminophen Toxicity
* Danger dosages (70 kg patient)
o Toxicity possible > 10 gm
o Severe toxicity certain > 25 gm
o Lower doses potentially hepatotoxic in:
+ Chronic alcoholics
+ Malnutrition or fasting
+ Dilantin, Tegretol, phenobarbital, INH, rifampin
+ NOT in acute EtOH ingestion
+ NOT in non-alcoholic chronic liver disease

Acetaminophen Toxicity
* Day 1:
o Nausea, vomiting, malaise, or asymptomatic
* Day 2 – 3:
o Initial symptoms resolve
o AST and ALT begin to rise by 36 hours
o RUQ pain, tender enlarged liver on exam
* Day 4
o AST and ALT peak > 3000
o Liver dysfunction: PT, encephalopathy, jaundice
o Acute renal failure (ATN)

Acetaminophen Toxicity Treatment
Indications for NAC therapy:
Fulminant Hepatic Failure
* Definition:
o Rapid development of hepatic dysfunction
o Hepatic encephalopathy
o No prior history of liver disease
* Most common causes:
o Acetaminophen
o Unknown
o Idiosyncratic drug reaction
o Acute HAV or HBV (or HDV or HEV)

Fulminant Hepatic Failure
* Close glucose monitoring IV glucose
* Avoid sedatives - give PO lactulose
* Avoid nephrotoxins and hypovolemia
* Vitamin K SQ
o Do not give FFP unless active bleeding, since INR is an important prognostic factor
* GI bleed prophylaxis with PPI
* Transfer all patients with FHF who are candidates to a liver transplant center

Indications:
* Hepatitis C 29%
* Alcoholic Liver Disease 15%
* Cirrhosis of unknown etiology 8%
* Hepatocellular Carcinoma 7%
* Fulminant Hepatic Failure 6%
* Primary Sclerosing Cholangitis 5%
* Primary Biliary Cirrhosis 4%
* Metabolic Liver Disease 4%
* Autoimmune Hepatitis 3%
* Hepatitis B 3%

Liver Transplantation:
Contraindications
* ABSOLUTE
o active alcohol or drug abuse
o HIV positivity
o extrahepatic malignancy
o uncontrolled extrahepatic infection
o advanced cardiopulmonary disease
* RELATIVE
o Age over 65
o poor social support
o poorly controlled mental illness

Obstructive Jaundice
CBD stones (choledocholithiasis) vs. tumor
* Clinical features favoring CBD stones:
o Age < 45
o Biliary colic
o Fever
o Transient spike in AST or amylase
* Clinical features favoring cancer:
o Painless jaundice
o Weight loss
o Palpable gallbladder
o Bilirubin > 10

Ascending Cholangitis
* Pus under pressure
* Charcot’s triad: fever, jaundice, RUQ pain
o All 3 present in 70% of patients, but fever > 95%
o May also present as confusion or hypotension
* Most frequent causative organisms:
o E. Coli, Klebsiella, Enterobacter, Enterococcus
o anaerobes are rare and usually post-surgical
* Treatment:
o Antibiotics: Levaquin, Zosyn, meropenem
o ERCP with biliary drainage

Ascending Cholangitis
Indications for Urgent ERCP
* Persistent abdominal pain
* Hypotension despite adequate IVF
* Fever > 102
* Mental confusion
* Failure to improve after 12 hours of antibiotics and supportive care

Obstructive Jaundice Malignant Causes
* Cancer of the Pancreas
* Cancer of the Bile Ducts (Cholangiocarcinoma)
* Ampullary Tumors
* Portal Lymphadenopathy

Primary Biliary Cirrhosis
* Cholestatic liver disease (ALP)
o Most common symptoms: pruritus and fatigue
o Many patients asx, and dx by abnormal LFT
* Female:male ratio 9:1
* Diagnosis:
o Compatible clinical presentation
o AMA titer 1:80 or greater (95% sens/spec)
o IgM > 1.5 upper limits of normal
o Liver biopsy: bile duct destruction
* Treatment: Ursodeoxycholic acid 15 mg/kg

Primary Sclerosing Cholangitis
* Cholestatic liver disease (ALP)
* Inflammation of large bile ducts
* 90% associated with IBD
o but only 5% of IBD patients get PSC
* Diagnosis: ERCP (now MRCP)
o No autoantibodies, no elevated globulins
o Biopsy: concentric fibrosis around bile ducts
* Cholangiocarcinoma: 10-15% lifetime risk
* Treatment: Liver Transplantation

Diagnosis of Immune-Mediated Liver Disease
Periductal concentric fibrosis
Unusual Causes of Jaundice
* Ischemic hepatitis
* Congestive hepatopathy
* Wilson’s disease
* AIDS cholangiopathy
* Amanita phalloides (mushrooms)
* Jamaican bush tea
* Infiltrative diseases of the liver
o Amyloidosis
o Sarcoidosis
o Malignancy: lymphoma, metastatic dz

Wilson’s Disease
* Autosomal recessive – copper metabolism
* Chronic hepatitis or fulminant hepatitis
* Associated clinical features:
o Neuropsychiatric disease
o Hemolytic anemia
* Physical exam: Kayser-Fleischer rings
* Diagnosis: ceruloplasmin, urinary Cu
* Treatment: d-penicillamine

Critical Questions in the Evaluation of the Jaundiced Patient
* Acute vs. Chronic Liver Disease
* Hepatocellular vs. Cholestatic
o Biliary Obstruction vs. Intrahepatic Cholestasis
* Fever
o Could the patient have ascending cholangitis?
* Encephalopathy
o Could the patient have fulminant hepatic failure?

Evaluation of the Jaundiced Patient HISTORY

* Pain
* Fever
* Confusion
* Weight loss
* Sex, drugs, R&R
* Alcohol
* Medications
* pruritus
* malaise, myalgias
* dark urine
* abdominal girth
* edema
* other autoimmune dz
* HIV status
* prior biliary surgery
* family history liver dz

Evaluation of the Jaundiced Patient PHYSICAL EXAM
* BP/HR/Temp
* Mental status
* Asterixis
* Abd tenderness
* Liver size
* Splenomegaly
* Ascites
* Edema
* Spider angiomata
* Hyperpigmentation
* Kayser-Fleischer rings
* Xanthomas
* Gynecomastia
* Left supraclavicular adenopathy (Virchow’s node)

Evaluation of the Jaundiced Patient LAB EVALUATION
* AST-ALT-ALP
* Bilirubin – total/indirect
* Albumin
* INR
* Glucose
* Na-K-PO4, acid-base
* Acetaminophen level
* CBC/plt
* Ammonia
* Viral serologies
* ANA-ASMA-AMA
* Quantitative Ig
* Ceruloplasmin
* Iron profile
* Blood cultures

Evaluation of the Jaundiced Patient
* Ultrasound:
o More sensitive than CT for gallbladder stones
o Equally sensitive for dilated ducts
o Portable, cheap, no radiation, no IV contrast
* CT:
o Better imaging of the pancreas and abdomen
* MRCP:
o Imaging of biliary tree comparable to ERCP
* ERCP:
o Therapeutic intervention for stones
o Brushing and biopsy for malignancy

Case studies

Approach to the Jaundiced Patient.ppt

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Managing Low Birth Weight and Sick Newborns

Managing Low Birth Weight and Sick Newborns

Advances in Maternal and Neonatal Health

Session Objectives
* To define essential elements of the care of sick newborns, including neonatal resuscitation
* To discuss best practices and technologies

Management of Newborn Illness

* Education of mothers to recognize danger signals
* Working with families to develop complication plan for newborns
* Early recognition and appropriate management of newborn illness

Minimum Preparation for ANY Birth
The following should be available and in working order:
* Heat source
* Mucus extractor
* Self-inflating bag of newborn size
* 2 masks (for normal and small newborns)
* 1 clock
* At least one person skilled in newborn resuscitation present at birth

Essential Care for All Newborns
Most newborns breathe as soon as they are born and only need:
* A clean and warm welcome
* Vigilant observation
* Warmth
* To be observed for breathing
* To be given to the mother for warmth and breastfeeding

Immediate Care of the Newborn: Warmth
* Lay newborn on mother’s abdomen or other warm surface
* Immediately dry newborn with clean (warm) cloth or towel
* Remove wet towel and wrap/cover newborn, except for face and upper chest, with a second towel/cloth

* Blood on newborn is not a risk to newborn, but is a risk to caregiver
* Bathe after 24 hours
* In areas with high HIV prevalence, consider bathing earlier to reduce risk of maternal-fetal transmission, and to reduce risk to caregiver and to other newborns

Immediate Care of the Newborn
* Assess breathing
* Keep head in a neutral position
* IMMEDIATELY assess respirations and need for resuscitation

Signs of Good Health at Birth
Objective measures
* Breathing
* Heart rate above 100 beats/minute
Subjective measures
* Vigorous cry
* Pink skin
* Good muscular tone
* Good reactions to stimulus
* Most important measure is whether newborn is breathing
* Assessing all of above delays resuscitation, if it is necessary.

Birth Asphyxia
* Definition: Failure to initiate and sustain breathing at birth
* Magnitude:
o 3% of 120 million newborns each year in developing countries develop birth asphyxia and require resuscitation
o An estimated 900,000 of these newborns die as a result of asphyxia

Steps in Resuscitation
* Anticipate need for resuscitation at every birth, be prepared with equipment in good condition
* Prevent of heat loss (dry newborn and remove wet clothes)
* Assess breathing
* Resuscitate:
o Open airway
+ Position newborn
+ Clear airway
o Ventilate
o Evaluate

Assess Breathing
Newborn crying?
Provide routine care
* Chest is rising symmetrically
* Frequency >30 breaths/min.
* Not breathing/ gasping
* Breathing < 30 or > 60 breaths/ min.

Immediately start resuscitation
Provide routine care
Open Airway
* Position newborn on its back
* Place head in slightly extend position
* Suction mouth then nostrils

Ventilate
* Select appropriate mask size to cover chin, mouth and nose with a good seal
* Squeeze bag with two fingers or whole hand, look for chest to rise
* If chest not rising:
o Reposition head and mask
o Increase ventilation
o Repeat suctioning

Evaluate
After ventilating for about 1 minute, stop and look for spontaneous breathing
If no breathing, breathing is slow (< 30 breaths/ min.) or is weak with severe indrawing
If newborn starts crying/breathing spontaneously
Continue ventilating until spontaneous cry/ breathing begins

* Stop ventilating
* Do not leave newborn
* Observe breathing
* Put newborn skin-to-skin with mother and cover them both

Harmful and Ineffective Resuscitation Practices
Practices to be avoided include:
* Routine aspiration of the newborn’s mouth and nose as soon as the head is born
* Routine aspiration of the newborn’s stomach at birth
* Stimulation of the newborn by slapping or flicking the soles of her/his feet: only enough stimulation for mildly depressed-delays resuscitation
* Postural drainage and slapping the back: dangerous
* Squeezing the chest to remove secretions from the airway
* Routine giving of sodium bicarbonate to newborns who are not breathing
* Intubation by an unskilled person
* Some traditional practices:
o Putting alcohol in newborn’s nose
o Sprinkling or soaking newborn with cold water
o Stimulating anus
o Slapping newborn

Infection Prevention for Resuscitation
* Handwashing
* Use of gloves
* Careful suctioning if using a mucus extractor operated by mouth
* Careful cleaning and disinfection of equipment and supplies
o Do not reuse bulb—difficult to clean, poses risk of cross infection
* Correct disposal of secretions

Documentation
Details of the re
Post-Resuscitation Tasks: Successful Resuscitation
Post-Resuscitation Tasks: Unsuccessful Resuscitation
Policy Decisions for Resuscitation
Principles of Success
Care of the Low Birth Weight Newborn
Care of the Preterm Newborn
Principles of Management for Low Birth Weight and Preterm Newborns
* Warmth
* Feeding
* Detection and management of complications (e.g., resuscitation, assisted respiration)

As for all newborns:
* Lay newborn on mother’s abdomen or other warm surface
* Dry newborn with clean (warm) cloth or towel
* Remove wet towel and wrap/cover with a second dry towel
* Bathe after temperature is stable

Warmth: Problem with Incubators
* Potential source of infection
* Often temperature controls malfunction
* Often share incubator for more than one newborn

Need alternative method: kangaroo care
Feeding
Early and exclusive breastfeeding
* Breastmilk = best nourishment
* Already warm temperature
* Facilitated by kangaroo care

Definition of Kangaroo Care
* Early, prolonged and continuous skin-to-skin contact between a mother and her newborn
* Could be in hospital or after early discharge

How to Use Kangaroo Care
* Newborn’s position:
o Held upright (or diagonally) and prone against skin of mother, between her breasts
o Head is on its side under mother’s chin, and head, neck and trunk are well extended to avoid obstruction to airways
* Newborn’s clothing:
o Usually naked except for nappy and cap
o May be dressed in light clothing
o Mother covers newborn with her own clothes and added blanket or shawl
* Newborn should be:
o Breastfed on demand
o Supervised closely and temperature monitored regularly
* Mother needs lots of support because kangaroo care:
o Is very tiring for her
o Restricts her freedom
o Requires commitment to continue

Effectiveness of Kangaroo Care
* Randomized controlled trial
* Conducted in three tertiary and teaching hospitals in Ethiopia, Indonesia and Mexico
* Study effectiveness, feasibility, acceptability and cost of kangaroo mother care when compared to conventional methods of care
Benefits of Kangaroo Care
* Is efficient way of keeping newborn warm
* Helps breathing of newborn to be more regular; reduce frequency of apneic spells
* Promotes breastfeeding, growth and extra-uterine adaptation
* Increases the mother’s confidence, ability and involvement in the care of her small newborn
* Seems to be acceptable in different cultures and environments
* Contributes to containment of cost— salaries, running costs (electricity, etc.)

Summary

* Skilled attendant
* Equipment available and working
* Begin resuscitation immediately
o Ventilate
o Reassess frequently
o Kangaroo care once successful

References

Managing Low Birth Weight and Sick Newborns.ppt

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