Transcript 50 year old woman with syncope

50 year old woman with hypoxia
and syncope
Mary Pak, MD
Primary Care Conference
August 25, 2004
Objectives
• Clinical presentation of a patient with
pulmonary embolism
• Pathophysiology of hemodynamically
significant pulmonary embolism
• Discussion of the evidence-based role of
thrombolytic therapy in pulmonary embolism
Disclosure
No financial support was provided for this presentation
Case Presentation
50 year old woman was brought to the ER by
her husband after he witnessed her “passing
out”. Starting at 10AM of the morning of
admission, the patient and her husband
report at least 3 episodes of “passing out”,
twice where the patient woke up on the
floor. No seizure activity noted. No bowel
or bladder incontinence. Episodes usually
activity related like walking to the
bathroom.
Case Presentation (con’t)
• Review of Systems:
– Low grade fevers 99.6 to 100.2, ? Chills,
weight loss 10 lbs.
– Dyspnea, worsening x 2 weeks
– ? Chest tightness ? Worse with respirations
– No lightheadedness or dizziness
– No palpitations
Case Presentation (con’t)
• PMH:
Recurrent clear cell CA ovary
(s/p TAH-BSO, carboplatin/taxol)
(s/p partial omentectomy 5/04)
Rosacea
Hypertension
Rheumatic fever as a child
Reactive Airway Disease
DJD
• Allergies:
Amoxicillin
Ibuprofen
Case Presentation (con’t)
• Medications:
Losartan 50 mg daily
HCTZ 50 mg twice daily
hydrocortisone 50 mg po bid
spironolactone 50 mg po bid
ibuprofen 600 mg po q6h
glucosamine
Topical metronidazole
omeprazole
zolpidem PRN
Case Presentation (con’t)
• Social History: Married, former insurance
claims examiner, denies any smoking,
alcohol or drug use.
• Family History:
Father died at age 72, hx HTN
Brother ?blood disorder
No other cancers
Case Presentation (con’t)
• Physical Examination:
Temp 36.4, BP 118/84, pulse 116, resp 20
O2 sat 98% 4L O2
Lungs: bibasilar crackles, no wheezes
CV: Regular rhythm, tachycardic, 2/6 systolic
murmur enhanced by respirations, no rubs or
gallops
Abdomen: soft, obese, NT, well-healed midline
scar with minimal serosanguinous drainage.
Ext: no edema, good pulses, no Homan’s sign
Neuro: nonfocal
Patient Data
Patient Data (con’t)
• Labs:
Creatinine 0.8, K 4.6, CO2 22
WBC 9.2, Hgb 9.8, hct 29
plt 336, INR 1.2
D-Dimer 8.9
CK 30, troponin 0.3
ABG: 7.45/29/80 on 4L O2
Patient Data (con’t)
• EKG
sinus tachycardia ~120, S wave in
lead I, small Q wave in lead III,
T wave inversions in lead III, and
V1 – V3.
• CT Angio
Multiple filling defects including central left
and right main pulmonary arteries, left
subclavian thrombus, markedly dilated right
ventricle. “Extensive and multiple acute
and chronic PE”
Patient Data (con’t)
• Echocardiogram:
RV findings c/w massive acute PE with
markedly dilated RV and severely reduced
systolic function. Findings also notable for
large multilobulated, non-mobile RV
thrombus along the apical wall.
Normal LV systolic function.
Pulmonary Embolism
• PE is a common and often life-threatening
disease.
– Mortality rates reported
• 28% 30-day mortality in Olmsted County
• 17.4% 3-month mortality in the International
Cooperative Pulmonary Embolism Registry (52
institutions in 7 countries)
• 14% in-hospital mortality in a Japanese registry
• On average, 200,000 deaths a year due to PE
Goldhaber SZ Lancet 2004; 363: 1295-1305
Causes of Death in the US
Pulmonary Embolism1
Coronary Heart Disease2
AIDS 2*
Breast Cancer 3#
Highway fatalities 4+
Accidents 2*
1.
2.
3.
4.
Anderson et al Arch Intern Med 1991
AHA. 2001 Heart and Stroke Statistical Update. 2000
ACS. Breast cancer facts and figures.2001
NHTSA. 2001
~200,000
~460,000
13,426
40,200
41,800
97,835
* For the year 1998
# Estimated for the year 2001
+ For the year 2000
Incidence of PE
0.45
0.4
0.35
0.3
0.25
Incidence of acute PE
as admitting diagnosis
(%)
0.2
0.15
0.1
0.05
0
0--9
10--19 20--29 30--39 40--49 50--59 60--69 70--79 80--89
Age (years)
Stein PD. et al. Chest 1999; 116: 909-913.
Pathophysiology of
Hemodynamic Instability in PE
Wood KE Chest 2002; 121: 877-905.
Outcomes in Pulmonary Embolism
Wood KE Chest 2002; 121: 877-905
Thrombolysis in Major
Pulmonary Embolism



Few randomized studies looking at thrombolysis
in PE
Most trials excluded hemodynamically
comprised patients
Largest randomized trial is out of Germany and
enrolled 256 patients.
–
–
Prospective, randomized double-blind, placebocontrolled trial using 100 mg alteplase as study drug
118 patients in the study drug + heparin group, 138
patient in the placebo + heparin group.
Thrombolysis in PE Study
Inclusion Criteria (at least 1 of the following):
1) echocardiographically detected RV dysfunction (RVE +
loss of collapse of IVC without LV or mitral valvular disease) ;
2) Echocardiographically detected pulmonary artery
hypertension defined as tricuspid regurgitant jet > 2.8 m/sec +
confirmation of PE by V/Q, CT angio or PAgram;
3) Precapillary pulmonary hypertension by right heart cath
with PAP > 20 mmHg and PCWP <18 mmHG (to exclude
CHF) + confirmation of PE by V/Q, CT angio or PAgram;
4) New ECG signs of RV strain + confirmation of PE by
V/Q, CT angio or PAgram
a) complete or incomplete RBBB
b) S waves in Lead I combined with Q waves in lead III or
inverted T waves in V1 – V3
Konstantinides S N Engl J Med 2002; 347: 1143-50
Thrombolysis in PE Study (con’t)
Exclusion Criteria:
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
12)
13)
14)
15)
age > 80
Hemodynamic instability (SBP < 90 mmHg) with or without shock;
onset of symptoms > 96 hours prior to diagnosis;
Thrombolytic treatment, major surgery, or biopsy within the previous
7 days;
Major trauma within the preceding 10 days;
Stroke, TIA, craniocerebral trauma or neurologic surgery within the
preceding 6 months;
GI bleeding within the previous 3 months;
Uncontrolled hypertension;
A known bleeding disorder;
Current anticoagulation therapy;
Inability to tolerate alteplase;
pregnancy or lactation;
life-expectancy < 6 months due to underlying disease;
Known diabetic retinopathy;
Planned use of thrombolytics for extensive DVT.
Konstantinides S N Engl J Med 2002; 347: 1143-50
Study Findings
Konstantinides S N Engl J Med 2002; 347: 1143-50
Study Findings (con’t)
P=0.005
Konstantinides S N Engl J Med 2002; 347: 1143-50
Study Findings (con’t)
• Probability of event-free survival during
hospital stay was significantly lower in the
placebo + heparin group.
• Alteplase + heparin may improve the
clinical course of patients with acute
submassive PE (ie, hemodynamically stable
patients) with RV dysfunction/pressure
overload.
Meta-Analysis: Thrombolysis vs
Heparin in PE
• 11 randomized trials identified
– Only 5 trials included patients with major pulmonary
embolism (involving hemodynamic instability)
• No benefit of thrombolytic therapy compared with
heparin for initial treatment of unselected patients
with acute PE.
• Subgroup analysis indicates a benefit of
thrombolysis in those patients with major
pulmonary embolism.
Wan S Circulation 2004; 110: 744-749.
Meta-Analysis (con’t)
• Subgroup analysis:
In patients with major PE with hemodynamic
instability (including syncope), thrombolytic
therapy was associated with significant reduction in
recurrent PE or death (19% in thrombolytic +
heparin vs 9.4% in heparin alone). Number needed
to treat? 10.
Nonmajor bleeding was significantly higher in the
thrombolysis group (22.7%) when compared with
heparin alone (10%). Number needed to harm? 8
Approach to the Patient With
Major Pulmonary Embolism
Wood KE Chest 2002; 121: 877-905
Conclusions
1) Pulmonary embolism is a common disease
with significant potential morbidity and
mortality.
2) Syncope can be an indicator of
hemodynamically significant pulmonary
embolism
3) Thrombolytic therapy in hemodynamically
significant PE has a mortality benefit with a
number needed to treat of 10.
References
1)
2)
3)
4)
5)
Stein PD, et al. Incidence of Acute Pulmonary Embolism in a
General Hospital. Chest 1999; 116: 909 – 913.
Wan S, et al. Thrombolysis Compared With Heparin for the Initial
Treatment of Pulmonary Embolism: A Meta-Analysis of the
Randomized Controlled Trials. Circulation 2004; 110: 744-749.
Agnelli G, Becattini C, Kirschstein T. Thrombolysis vs Heparin in
the Treatment of Pulmonary Embolism: A Clinical Outcome-Based
Meta-Analysis. Arch Intern Med 2002; 162: 2537-2541.
Konstantinides S, et al. Heparin Plus Alteplase Compared With
Heparin Alone in Patients With Submassive Pulmonary Embolism.
N Engl J Med 2002; 347: 1143 – 50.
Goldhaber SZ, Pulmonary Embolism. Lancet 2004; 363: 1295 –
1305.
References
6)
7)
8)
Wood KE. Major Pulmonary Embolism: Review of a
Pathophysiologic Approach to the Golden Hour of
Hemodynamically Significant Pulmonary Embolism. Chest 2002;
121: 877-905 .
Wood KE. The presence of Shock Defines the Threshold to Initiate
Thrombolytic Therapy in Patients with Pulmonary Embolism.
Intensive Care Med 2002; 28: 1537 – 1546.
Anderson FA, Wheeler HB, Goldberg RJ. A Population Based
Perspective of the Hospital Incidence and Case Fatality Rates of
Deep Venous Thrombosis and Pulmonary Embolism: the Worchester
DVT Study. Arch Intern Med 1991; 151: 933-938.