Review Article Neurogenic pulmonary edema

1. Review ArticleNeurogenic pulmonary edema ActaAnaesthesiol Scand 2007; 51: 447-445 R4 이동현

2. Neurogenic pulmonary edema(NPE) • Defined as acute pulmonary edema occurring shortly after a central neurologic insult • Often present without pre-existing cardiovascular or pulmonary pathology that could explain the edema • But, dose not exclude a coexisting effect of neurologic insult on myocardial function • Cause of confusion in reported incidence of NPE

3. Epidemiology • Cases reported in • Subarachnoid hemorrhage(SAH) • Traumatic brain injuries • Cervical medulla injuries • Cerebral thrombosis • Cerebral gas embolism • Intracerebral hemorrhage • Intracranial tumors • Epilepsy • Postoperative intracranial surgery • Enterovirus encephalitis(hand, foot, mouse disease) • Meningitis • Multiple sclesosis • Brambrink and Dick • Cerebral hemorrhage(71%), seizure activity(2%), cerebral trauma(1%)

4. Epidemiology • SAH • Main cause of NPE • Pulmonary edema after SAH : 23% • Friedman et al : NPE in 2% of 305 SAH pts • Between D1 and D7 after SAH • Most important risk factors • Clinical and radiological severity of SAH • Vertebral artery origin • Positive correlation • Age • Delay to surgery • Intentional hypervolemia • Early detection and treatment of NPE minimize mortality associated with SAH.

5. Epidemiology • Head injury • Up to 20% of severe head injury • In autopsy database • Incidence of NPE : 32% • 50% in victims dying within 96 hrs. • Status epilepticus • 1/3 of status epilepticus patients • Major cause of NPE in children • Occurs mainly during post-ictal period • Can be recurrent

6. Pathophysiology • Hemodynamic mechanism • Adrenergic response to cerebral insult • Intense pulmonary vasoconstriction • Increase in pulmonary hydrostatic pressure • Increase in permeability of pulmonary capillaries • Inflammatory mechanism • Also induce an increase in permeability of pulmonary capillaries • NPE trigger zones • Hypothalamus • Medulla oblongata

7. Pathophysiology • Hemodynamic mechanism • Sudden increase in ICP induce • α-adrenergic response • Increase in pulmonary and systemic vasoconstriction • Subsequent fluid shift into pulmonary alveoli and and interstitial space • Pulmonary vasoconstriction increase cardiac workload • Severe myocardial depression • Even stunned myocardium • Cf) patients with hypertensive cardiomyopathy • Less sensitive to catecholamine • Some protection against this acute effect

8. Pathophysiology • Norepinephrine and neuropeptide Y • Located in sympathetic nerve ending • Play important role in NPE • Vasoconstrictive action • Increasing pulmonary vascular permeability • Endothelin-1 • One of the most potent vasoconstrictor • Time dependent increase in rats with NPE • Intrathecal injection in rats 22-fold increase in pulmonary vascular permeability • Activation of medullaryendothelin receptors • Stimulate norepinephrine release • Nitric oxide • Endothelial-mediated vasodilatation • In rats with cerebral trauma, injection of nitric oxide synthase inhibitor increase mortality

9. Pathophysiology • Inflammatory mechanism • Cerebral insult cause local inflammatory reaction • Brain cytokines and chemokines • Produced by astrocytes and microglial cell • TNF-α, IL-1β, IL-6 • Diffuse into systemic circulation after BBB disruption • Cause peripheral organ inflammation • Cause expression of substance P, neurokinin A • Bronchoconstriction • Edema of bronchial mucosa • Increase of pulmonary capillary permeability • Increase leukocyte activation

10. Diagnosis • Clinical presentation • No specific clinical presentation • Signs of acute pulmonary edema • Usually lack of signs of LV failure • Tachypnea, tachycardia, basal pulmonary crackles, respiratory failure and lack of cardiac gallop • Unilateral NPE seems to be possible • Complementary investigations • CXR : bilateral pulmonary infiltrates • Echocardiogram, TE Doppler, CVP : normal • ECG : unchanged • No specific biologic marker • Troponin Ic, brain natriuretic peptide(BNP) elevation • Blood C-reactive protein, IL-6 level can be increased

11. Differential diagnosis • Aspiration pneumonia and ventilator-associated pneumonia • Complications associated with impairment of consciousness • Blood level of pro-calcitonin : evidence of invasive bacterial infection • Ventilation-induced lung injury • Decreased tolerance to alveolar stretching • Over-inflation injury • Increased susceptibility to reperfusion injury

12. Treatment/management • May resolve in 48-72 h with appropriate Mx • Prognosis is dependent on neurologic injury. • Acute neurologic insult • Control of triggering CNS insult • Decrease ICP, evacuate hematoma, treat convulsion • Classical pulmonary edema therapy • Ventilation • Patients with serious NPE : must be intubated early, sedated and ventilated with PEEP • PEEP < 15 cmH2O : not impede cerebral perfusion pr. • Permissive hypercapnia and prone position • Direct tracheal insufflation • Nitric oxide inhalation

13. Treatment/management • Hemodynamic function • Reduce preload and afterload • Increase myocardial contractility • Hypotensive agent without cerebral vasodilatory effects : urapidil, clonidine • Dobutamine • Epinephrine and norepinephrine • Diuretics • Neurologic care • Decreasing high ICP • Optimizing cerebral perfusion pressure • Mannitol or hypertonic saline

14. Treatment/management • Brain death • Permissive hypercapnia, nitric oxide inhalation • Optimize V/Q ratio • Decrease pulmonary vascular pressure • Vasoactive drugs • Maintain peripheral organ hypoperfusion • Prevent multiorgan failure

15. Conclusion • NPE should be considered when patients with central neurologic injury suddenly become dyspneic or present with decreased PaO2/FiO2 ratio. • Associated mortality is high. • Recovery is usually rapid with appropriate management. • Early treatment of underlying neurologic cause is cornerstone of NPE Mx. • Most patients should be intubated, sedated, ventilated with PEEP and maintained with normal hemodynamic stability. • NPE in brain death is major cause of graft dysfunction and even of transplantation failure.