Afternoon Delight

Afternoon Delight Pathophysiology Review August 11, 2010

Case A 54-year-old man is evaluated in the emergency department for a 1-hour history of chest pain with mild dyspnea. The patient had been hospitalized 1 week ago for a colectomy for colon cancer. His medical history also includes hypertension and nephrotic syndrome secondary to membranous glomerulonephritis, and his medications are furosemide, ramipril, and pravastatin. On physical examination, the temperature is 37.5 °C (99.5 °F), the blood pressure is 110/60 mm Hg, the pulse rate is 120/min, the respiration rate is 24/min, and the BMI is 30. Oxygen saturation is 89% with the patient breathing ambient air and 97% on oxygen, 4 L/min. Cardiac examination shows tachycardia and an S4. Breath sounds are normal. Serum creatinine concentration is 1.1 mg/dL (185.6 µmol/L). Chest radiograph is negative for infiltrates, widened mediastinum, and pneumothorax.

EKG

PE protocol CT

What happened? Physical Exam Diagnostic tests History Monitor Treatment

Why? Physical Exam Diagnostic tests History Monitor Treatment

What historical elements increase the pretest probability of PE? 4:45 pm A 54-year-old man is evaluated in the emergency department for a 1-hour history of chest pain with mild dyspnea. The patient had been hospitalized 1 week ago for a colectomy for colon cancer. His medical history also includes hypertension and nephrotic syndrome secondary to membranous glomerulonephritis, and his medications are furosemide, ramipril, and pravastatin. On physical examination, the temperature is 37.5 °C (99.5 °F), the blood pressure is 110/60 mm Hg, the pulse rate is 120/min, the respiration rate is 24/min, and the BMI is 30. Oxygen saturation is 89% with the patient breathing ambient air and 97% on oxygen, 4 L/min. Cardiac examination shows tachycardia and an S4. Breath sounds are normal. Serum creatinine concentration is 1.1 mg/dL (185.6 µmol/L). Chest radiograph is negative for infiltrates, widened mediastinum, and pneumothorax. History

What historical elements increase the pretest probability of PE? 4:45 pm N Engl J Med 2008;358:1037-52. History 1.3% had PE 16.2% had PE 37.5% had PE* 12.1% had PE: +D-dimer 23.2% had PE, -D-dimer 0.5% PE 37.1% had PE** * Ann Intern Med 2001;135:98-107 **JAMA. 2006;295:172-179

What historical elements increase the pretest probability of PE? 4:45 pm A 54-year-old man is evaluated in the emergency department for a 1-hour history of chest pain with mild dyspnea. The patient had been hospitalized 1 week ago for a colectomy for colon cancer. His medical history also includes hypertension and nephrotic syndrome secondary to membranous glomerulonephritis, and his medications are furosemide, ramipril, and pravastatin. On physical examination, the temperature is 37.5 °C (99.5 °F), the blood pressure is 110/60 mm Hg, the pulse rate is 120/min, the respiration rate is 24/min, and the BMI is 30. Oxygen saturation is 89% with the patient breathing ambient air and 97% on oxygen, 4 L/min. Cardiac examination shows tachycardia and an S4. Breath sounds are normal. Serum creatinine concentration is 1.1 mg/dL (185.6 µmol/L). Chest radiograph is negative for infiltrates, widened mediastinum, and pneumothorax. History

What historical elements increase the pretest probability of PE? 4:45 pm N Engl J Med 2008;358:1037-52. History 37.5% had PE* * Ann Intern Med 2001;135:98-107 **JAMA. 2006;295:172-179 37.1% had PE**

Mechanisms of Hypoxemia 6:45 pm • Decreased Inspired Oxygen • Hypoventilation • V/Q mismatch • Shunt • Venous Admixture Physical Exam

Decreased Inspired Oxygen 6:45 pm PIO2= FIO2 x (Patm – PH2O ) PAO2= – PCO2/R FIO2 x (Patm – PH2O ) A decrease in inspired oxygen (PIO2) leads to a decrease in the PAO2. As a result the driving pressure of oxygen through the alveolar- capillary membrane (ie the Aa gradient) is reduced and hypoxemia occurs. Physical Exam Mason: Murray and Nadel's Textbook of Respiratory Medicine, 5th ed.

Hypoventilation 6:45 pm When you hypoventilate, what happens to your PCO2 ? PCO2/R PAO2= FIO2 x (Patm – PH2O ) - Strength Load Drive • CNS Drive • Narcotics • Mass lesions • Metabolic Drive • Alkalosis • Acidosis • Respiratory Muscles • Muscular dystrophy • Myositis • Diaphragm weakness • Hypothyroidism • Neurologic conditions • Myasthenia Gravis • Spinal cord injury • ALS/MS/GBS • Chest wall • Kyphosis, Obesity • Lungs • Fibrosis • Airways • Asthma, COPD • Metabolic demands • Exercise, sepsis Physical Exam

V/Q mismatch Right to Left Shunt: passage of venous blood into the arterial circulation w/o passing ventilated alveoli PaO2≈MvO2 6:45 pm Dead Space: alveolar units are fully ventilated but not perfused PaO2≈ PiO2 Physical Exam Low V/Q: Open alveoli, but low airflow (atelectasis, bronchospasm, partial obstruction of airway) High V/Q: Increasing dead space (PE, hypovolemia) Mason: Murray and Nadel's Textbook of Respiratory Medicine, 5th ed.

Shunt 6:45 pm Hypoxemia caused by shunt is characterized by the failure of Pao2 to rise despite inhalation of pure oxygen (100%). Passage of venous blood into the arterial circulation w/o passing ventilated alveoli Due to deoxygenated blood returning to the left atrium from the thebesian veins and from the bronchial circulation of the airways, there is a normal (anatomic) shunt of 5% in normal individuals. Intrapulmonary Shunt Extrapulmonary Shunt • Pulmonary arteriovenous malformations • hepatopulmonary syndrome • +/- alveolar consolidation or collapse • Atrial septal defect • Ventricular septal defect • Patent ductus arteriosis • Anomalous pulmonary venous circulation Physical Exam Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Venous Admixture 6:45 pm Physical Exam Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Venous Admixture: heart failure 6:45 pm 60% Physical Exam 60% 65% 85% 75% 60%

What is the primary mechanism of Hypoxia for PE? 6:45 pm • V/Q mismatch • Increases the amount of dead space • How can PE cause shunt physiology? • Acquired PFO • Atelectasis in infarcted segment Physical Exam

Comparison of tests 7:05 pm 7:05 pm Diagnostic tests CLEVELAND C.LINIC JOURNAL OF MEDICINE 2002; 69: 721-29.

What about a V/Q scan? 7:05 pm Diagnostic tests JAMA 1990; 263:2753–2759. CLEVELAND C.LINIC JOURNAL OF MEDICINE 2002; 69: 721-29.

Pre-test Probability: important in choosing your next diagnostic test 7:05 pm 7:05 pm Diagnostic tests N Engl J Med 2008;359:2804-13.

Why are PE’s so deadly? 9:10 am • Hypoxemia • RV dysfunction Monitor

S1Q3T3: a sign of acute cor pulmonale EKG DDx: PE, acute bronchospasm, pneumothorax, and other acute lung disorders. − An S wave in lead I signifies a complete or more often incomplete RBBB − In lead III, look for a Q wave, slight ST elevation, and an inverted T wave. These findings are due to the pressure and volume overload over the right ventricle which causes repolarization abnormalities.

How does RV dysfunction cause shock? 9:10 am • As the right ventricle dilates, the interventricular septum shifts toward the left, resulting in left ventricular underfilling and decreased left ventricular diastolic distensibility. • Consequently, systemic cardiac output and systolic arterial pressure decline, thereby impairing coronary perfusion and causing myocardial ischemia. Monitor

How does PE cause Myocardial ischemia? 9:10 am Myocardial ischemia occurs whenever demand exceeds supply… • Elevated right ventricular wall tension reduces right coronary artery blood flow, increases right ventricular myocardial oxygen demand, and causes coronary arterial ischemia. • Hypoxemia further diminishes limited myocardial oxygen supply. • Ultimately, right ventricular infarction, circulatory collapse, and death may ensue. Supply Demand Monitor • Heart Rate • Systolic Blood pressure • Wall Tension • LVEDP/Preload • Wall thickness • Contractility • O2 carrying capacity • PaO2 tension • Hemoglobin • O2 extraction • Coronary blood flow

Terminology 9:10 am • Massive PE: presence of cardiogenic shock, persistent arterial hypotension, or both. • accounts for 5% of all cases of pulmonary embolism • Submassive PE: normotensive patients who may have an elevated risk of death because of right ventricular dysfunction or injury to the myocardium • Among hemodynamically stable PE patients, elevated troponin levels were associated with a 6-fold increased mortality. Monitor

Risk factors for mortality 9:10 am • Age >70 • Cancer • Clinical CHF • COPD • SBP<90 • Tachypnea >20 • RV Hypokinesis Monitor Circulation 2005;112;e28-e32 Lancet 1999;353:1386–1389

Treatment of Acute PE HD #5 Active cancer Unprovoked Pulmonary Embolism Recurrent venous thromboembolism Treatment N Engl J Med 2010;363:266-74.

HD #5 Treatment

Afternoon Delight