Neurogenic pulmonary edema. Pathogenesis, clinical picture and therapy

Neurogenic pulmonary edema (NPE) is a rare but always life-threatening complication in patients with central nervous system lesions. NPE is evident if patients shortly after cerebral lesions suddenly develop pulmonary edema and other causes of the symptoms, such as aspiration of gastric content, congestive heart failure and direct toxic exposure, are ruled out. METHODS: The current body of literature, partially obtained by computer-guided search (Winspirs) regarding epidemiology, pathophysiology and therapy of NPE was reviewed. Additionally, the case of a patient who developed a sudden pulmonary edema after an episode of tonic-clonic seizures is analyzed. We first provide information about history, definition, incidence and mortality of NPE. Second, a case report of a postictal NPE is presented to illustrate the clinical picture of NPE, and the applied therapeutic strategies are discussed. Third, recent pathophysiologic concepts about symptoms and possible therapeutic principles are reviewed. Fourth, a rational therapeutic plan for the prehospital emergency therapy of NPE is outlined. RESULTS: The different etiologies all have one characteristic feature: an acute emergency which causes increased intracerebral pressure (ICP). NPE is known in patients after cerebral trauma, intracranial hemorrhage, stroke, intracranial tumor or seizures. The incidence is estimated at around 1% after cerebral trauma, at 71% after cerebral hemorrhage and at 2% after seizures. Mortality is appraised to lie between 60 and 100%, independent of etiology. There is a definite pathophysiologic sequence leading to NPE: a central nervous system lesion causes a sudden increase in ICP which triggers an upregulation of sympathetic signal transduction to assure brain perfusion. Increased tonus of venous and arterial vessels and of myocardial function are the immediate consequences. However, if systemic vascular resistance (SVR) increases excessively, left ventricular failure and finally pulmonary edema (NPE) may result. Additionally, the protein-rich edema fluid points to an increased endothelial permeability within the pulmonary circuit. This is thought to be caused by the acute pressure increase and by neurohumoral mechanisms, possibly similar to those described for the systemic inflammatory response syndrome (SIRS). The most important central nervous system structures involved in NPE are the medulla oblongata and the hypothalamus. CONCLUSION: NPE is always a life-threatening symptom after increased ICP, where immediate therapeutic interventions are imperative. A rational therapeutic approach needs to be focused on decreasing ICP as primary goal. Additionally, attempts should be made to optimize body oxygenation, decrease pre- and afterload and increase myocardial contractility. Postictal patients suspicious for incipient ventilation problems must be admitted to hospital for further evaluation.     

Neurogenic pulmonary edema in fatal and nonfatal head injuries

Impaired pulmonary function is a frequent but poorly understood complication of acute head injury (HI). A potential early contributor to the pulmonary dysfunction seen in HI patients is neurogenic pulmonary edema (NPE). We hypothesized that NPE would occur early after HI and that it would have a continuum of clinical severity depending on the severity of the HI and associated intracranial hypertension. A large autopsy data base and inpatient HI data base were used to search for cases of NPE. Patients in the autopsy data base were stratified according to injury type and whether they died at the scene or within 96 hours of injury. There were significant (p < 0.0001, analysis of variance) elevations in lung weights in patients dying at the scene and within 96 hours from HI, compared with those dying from other noncentral nervous system injuries. No other organs studied showed significant weight increases. The incidence of NPE in isolated HI patients dying at the scene was 32%. In patients with isolated HI dying within 96 hours, the incidence of NPE was 50%. We found an inverse correlation (r = 0.62; p < 0.0014) between the initial cerebral perfusion pressure and the PaO2/FIO2 ratio despite a normal-appearing chest x-ray film. We conclude that NPE occurs frequently in HI patients. The process of edema formation begins early in the clinical course and is isolated to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait

Case reports of neurogenic pulmonary edema (NPE) often indicate that the edema resolves quickly. Because plasma epinephrine concentration may be elevated in NPE, and epinephrine has been shown to increase the rate of alveolar liquid clearance (ALC), we determined if ALC was increased in a canine model of NPE produced by the intracisternal administration of veratrine. ALC was determined by instilling autologous plasma into a lower lung lobe and using the increase in instillate protein concentration after 4 h to calculate the volume of fluid cleared from the airspaces by mass balance. To prevent pulmonary hypertension and edema, which would confound the mass balance analysis, carotid arterial blood was allowed to drain into a reservoir as pulmonary arterial pressure started to rise after veratrine administration. ALC in animals administered veratrine (n = 6) was 30.4 +/- 1.6 (SE)% of the instilled volume compared with 14.1 +/- 2.1% observed in control animals. The increase in ALC could be inhibited by adrenalectomy, beta2-adrenergic blockade using ICI 118,551, or sodium channel blockade using amiloride and could be duplicated by infusing epinephrine to increase plasma epinephrine concentration to levels observed in NPE. These data indicate that the increased ALC was mediated by adrenal epinephrine and suggest that edema resolution in patients with NPE might be accelerated by endogenous epinephrine.     

Afterload reduction with phentolamine in patients with acute pulmonary edema

Phentolamine in amounts of 10 to 40 microgram/kg/min was infused intravenously for the emergency treatment of acute pulmonary edema due to left ventricular failure. Fourteen patients with arteriosclerotic heart disease, ranging in age from 52 to 87 years, had clinical and roentgenographic signs of pulmonary edema. The pulmonary artery wedge pressure was increased to an average of 24 mm Hg and the cardiac index was decreased to 1.9 liters/min/m2 or less prior to the administration of phentolamine. A reduction in the pulmonary artery wedge pressure to 14 mm Hg and an increase in the cardiac index to 2.5 liters/min/m2 was observed in response to this alpha adrenergic blocking agent. Reduction in peripheral resistance with phentolamine was associated with reversal of pulmonary edema.     

Complications of posterior capsulotomy with the Nd:YAG laser. Study of 226 cases

BACKGROUND: Severe complications are classically described after capsulotomy: ocular hypertension, cystoid macular edema and secondary retinal detachment. PATIENTS AND METHODS: A series of 226 patients having sustained Nd:YAG laser (PC). Posterior capsulotomy has been studied retrospectively in order to determine the rate of early complications (24 hours after PC) and late complications (up to 6 months after the PC). RESULTS: Fifteen patients (6.6%) presented acute temporary intraocular hypertension, 2 patients (0.9%) a retinal detachment, 2 patients (0.9%) a cystoid macular edema (CME). A total number of complications of 8.4% was observed, 1.8% were heavy. CONCLUSIONS: Transient rise of intraocular pressure is seen. Prophylactic treatment with acetazolamide 500 mg (Diamox) and timolol (Timoptic) is necessary.     

Recording effective capillary pressure: a useful technique in post-pneumonectomy edema

Three cases of postpneumonectomy edema, in which hemodynamic stability was monitored with a Swan-Ganz catheter, are described. Measurement of pressure in the pulmonary capillary was based on the pulmonary artery occlusion curve. High capillary pressure and normal wedge pressure were observed in all 3 cases, suggesting that the rise in net filtration pressure as a consequence of excess flow is the pathogenic mechanism that triggers edema after pneumonectomy. We emphasize that measurement of effective pulmonary capillary pressure allows for more accurate assessment of the hemodynamic status of such patients than does the measurement of wedge pressure.     

Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain

OBJECTIVE: To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema. DESIGN: Retrospective chart review. SETTINGS: Neurocritical care unit of a university hospital. PATIENTS: Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n = 8), postoperative edema (n = 5), nontraumatic intracranial hemorrhage (n = 8), and cerebral infarction (n = 6). INTERVENTION: Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L. MEASUREMENTS AND MAIN RESULTS: A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2 = .91, p = .03), and postoperative edema (r2 = .82, p = .06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8 +/- 1.4 to 1.1 +/- 0.9 [SEM]) and in patients with postoperative edema (3.1 +/- 1.6 to 1.1 +/- 0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus. CONCLUSIONS: Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.     

New aspects of the treatment of left ventricular failure: Nitroglycerin (author's transl)

The effectiveness of Nitroglycerin and its derivates in angina pectoris is well-known. One of the main effects is the reduction of left ventricular filling pressure. Therefore in patients with left ventricular failure after acute myocardial infarction or with chronic coronary heart disease the indication for Nitroglycerin has to be proved. In 51 patients with 76 measurements Nitroglycerin sublingual, intravenous Nitroglycerin, Isosorbide-Dinitrate and Myocardon were investigated. All substances decreased pulmonary artery pressure especially left ventricular filling pressure. Cardiac output increased or decreased in dependence to the height of left ventricular enddiastolic pressure. In the patients with myocardial infarction and left ventricular failure with filling pressures over 20 mm Hg a significant increase in cardiac output was observed. On the contrary in patients without left ventricular failure cardiac output decreased slightly. Nitroglycerin sublingual is especially useful in the most severe form of left ventricular failure: in pulmonary oedema. 0.8 mg of Nitroglycerin 3 to 4 times in 5 to 10 minutes distance is necessary dependent on the severity of the pulmonary oedema and the height of the blood pressure. The permanent intravenous infusion of Nitroglycerin (3 to 6 mg per hour) is very efficient in the treatment of congestive failure in acute myocardial infarction. The left ventricular filling pressure decreased from 28 to 16 mm Hg with an increase in cardiac output from 3.5 to 4.01/min. The mean arterial pressure dropped about 10 mm Hg. Also with oral derivates of Nitroglycerin (Isosorbide-Dinitrate and Myocardon) an extensive decrease in left ventricular filling pressure and an increase in cardiac output has been observed in patients with left heart failure.     

The use of nasal CPAP in newborns with respiratory distress syndrome

The efficiency of applying continuous positive airway pressure (CPAP) by the nasal route was retrospectively nalyzed in 32 newborns with RDS (23 uncomplicated HMD with additional cardiac or pulmonary complications and 7 RDS of non-hyaline membrane etiology) who underwent nasal CPAP treatment at the Kinderspital Zurich from 1972--1974. 16 of the 23 infants with uncomplicated HMD were successfully treated with CPAP. They showed a significant rise in PaO2 as well as a significant drop in respiratory frequency during nasal CPAP application, the PaCO2 did not change significantly. The remaining 7 infants in this group (7/23) had to be intubated and mechanically ventilated owing to a persistent high FIO2 (4 infants), technical difficulties (1) or nasal hypersecretion (2). Two of these 23 infants died, one of meningitis, one of cerebral hemorrhage. The two infants with HMD and additional cardiac or pulmonary complications and 3 of 7 infants with RDS of non-hyaline membrane etiology had to be intubated and mechanically ventilated after failure of nasal CPAP. All 9 infants in these two groups survived. The nasal CPAP system as described is a simple, inexpensive and effective method of applying CPTPP in newborns with uncomplicated HMD, except radiological stage IV. In HMD with additional cardiac or pulmonary complications and in RDS of non-hyaline membrane etiology the results of nasal CPAP treatment were not convincing.     

Intravenous nitroglycerin in acute respiratory failure of patients with chronic obstructive lung disease, secondary pulmonary hypertension and cor pulmonale

We have studied the hemodynamic effects of an intravenous single dose of nitroglycerin in 13 patients with secondary pulmonary hypertension and Cor Pulmonale, during the acute course of respiratory failure and under assisted ventilation. We observed a significant decrease in systolic, diastolic and mean pulmonary arterial pressures, and in pulmonary resistance and systolic right ventricular work index, without any change in right or left pre-loads. The systolic arterial pressure decreased slightly, without any change in cardiac index or diastolic pressure. The arterial and mixed venous oxygen contents, and the pulmonary shunting ( Qs/Qt) were unchanged. These results suggest that nitroglycerin may be a useful therapy in patients in the acute stages of pulmonary hypertension resulting from chronic lung disease and under assisted ventilation. In addition, the lack of change in cardiac index, intrapulmonary shunting and oxygen content suggests that this decrease in pulmonary resistance is not linked with any deleterious effect in oxygen transfer.     

Response of the glands of internal secretion to chronic administration of strontium-90

A 64-year-old white man with no history of cardiac or bronchopulmonary disease developed acute pulmonary edema shortly after undergoing diagnostic intravenous fluorescein angiography. The patient responded quickly to a course of oxygen, positive pressure breathing, diuretics, and sedation.     

Monocrotaline model of noncardiogenic pulmonary edema in dogs

Monocrotaline, a plant alkaloid shown histologically to produce pulmonary endothelial damage and edema, was used in dogs to produce an acute model of noncardiogenic pulmonary edema. Following intravenous injection there was no change in pulmonary vascular pressures or heart rate; cardiac output fell and pulmonary vascular resistance increased. After 2 h measurement of lung water demonstrated modest pulmonary edema in all animals. The degree of edema produced was more consistent and reproducible than that following alloxan or alpha-naphthylthiourea.     

Prognostic value of myoclonus status in comatose survivors of cardiac arrest

Generalized myoclonus status is common in comatose patients after cardiac resuscitation, but its prognostic value is uncertain. We studied the clinical, radiologic, and pathologic findings in 107 consecutive patients who remained comatose after cardiac resuscitation. Myoclonus status was present in 40 patients (37%). Features more prevalent in patients with myoclonus status were burst suppression on electroencephalograms, cerebral edema or cerebral infarcts on computed tomography scans, and acute ischemic neuronal change in all cortical laminae. All patients with myoclonus status died. Of 67 patients without myoclonus, 20 awakened. We conclude that myoclonus status in postanoxic coma should be considered an agonal phenomenon that indicates devastating neocortical damage. Its presence in comatose patients after cardiac arrest must strongly influence the decision to withdraw life support.     

Effect of artificial ventilation on pulmonary capillary pressure in acute respiratory insufficiency

To determine the influence of intermittent positive pressure breathing (IPPB), the level of pulmonary capillary wedge pressure (PCWP) was compared during IPPB and after a short period off the respirator in 68 occasions on 42 patients with an acute respiratory failure (ARF) of various etiologies. During IPPB, the average PCWP was in the normal range in patients with toxic or neurologic comas and in cases of increased pulmonary capillary permeability edema (IPCPE), PCWP slightly increased within chronic obstructive pulmonary disease (COPD) complicated with ARF and in hemodynamic acute pulmonary edema (HAPE). During the weaning stage, PCWP decreased in the groups of coma, COPD, and IPCPE, but increased in HAPE. The weaning test demonstrates that IPPB influenced PCWP in all patients. Therefore, PCWP cannot be assumed to represent the left ventricle filling pressure. The weaning test allows differentiation of IPCPE from HAPE. In the event of over-infusion or hypovolemia, PCWP measured under IPPB can lead to misinterpretation if not followed up by a second measurement off the respirator.     

Haemodynamic changes in acute myocardial infarction following high doses of furosemide (author's transl)

Haemodynamic measurements were carried out after administration of furosemide to 10 patients suffering from acute myocardial infarction and congestive heart failure. It was observed that a transient deterioration in cardiac function (decreased cardiac output, increased enddiastolic pulmonary arterial pressure and increased pulmonary and systemic resistance) occured in the pre-diuretic stage in these failing hearts. After the onset of diuresis the haemodynamic parameters showed a reversal of the previous trends (increased cardiac output, decreased enddiastolic pulmonary arterial pressure and pulmonary resistance). The consistently lower enddiastolic pulmonary arterial pressure in the diuretic phase as compared with the pre-diuretic value ensured an improvement in cardiac haemodynamics. An attempt was made to interpret the haemodynamic results in the light of the Frank-Starling's curve.     

Massive verapamil overdose complicated by noncardiogenic pulmonary edema

We describe two cases of pulmonary edema, bradycardia, and hypotension associated with massive verapamil overdose. A noncardiogenic etiology of the pulmonary edema was indicated in one patient by normal thermodilution cardiac output and pulmonary artery occlusion pressure, and in the other patient by a normal echocardiogram. We hypothesize that calcium channel blocker overdose predisposes patients to develop pulmonary edema.     

The influence of cardiac frequency on the hemodynamic consequences of mitral stenosis (author's transl)

In eleven patients with isolated mitral stenosis and regular sinus rhythm a right cardiac catheterization was performed and the wedged pulmonary capillary pressure recorded at rest and during electrical pacing of the right atrium at successive frequencies of 100, 120, 140, and, occasionally, 160 and 180 beats/min, while cardiac output was estimated by the Fick's principle. In all cases a significant elevation of pulmonary capillary pressure with a simultaneous reduction in cardiac output was obtained. The rise of wedged pulmonary pressure was proportional to the increment in cardiac frequency and related also to the calculated area of the mitral valve. The influence of active atrial contraction upon pulmonary pressure and cardiac output is discussed and comparisons with other studies are made. Emphasis is made on the value of atrial pacing as a diagnostic method in mitral stenosis, especially in cases in whom classical effort manoeuvres can not be applied or are insufficient to rise cardiac frequency.     

Acute effects of transjugular intrahepatic portosystemic stent-shunt (TIPSS) procedure on renal blood flow and cardiopulmonary hemodynamics in cirrhosis

OBJECTIVE: An acute increase in portal pressure is associated with an immediate reduction in renal blood flow. It has been suggested that this supports the presence of an hepatorenal reflex. In this study, we used TIPSS placement as a model to investigate the effect of an acute reduction in portal pressure on renal blood flow and cardiopulmonary hemodynamic parameters. METHODS: Eleven cirrhotic patients were studied during elective TIPSS placement for variceal hemorrhage (n = 9) or refractory ascites (n = 2). Unilateral renal blood flow (RBF) was measured before and at 5, 15, 30, 45, and 60 min after shunt insertion. Heart rate (HR), mean arterial pressure (MAP), right atrial pressure (RAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and systemic vascular resistance (SVR) were also measured before and 30 min after TIPSS placement. RESULTS: Despite significant increases in CO (p = 0.001), RAP (p < 0.001), PAP (p < 0.001), and PCWP (p = 0.001), and a fall in SVR (p = 0.003), no change was observed in RBF, HR, or MAP after TIPSS placement. The fall in the portoatrial pressure gradient correlated only with the rise in CO (p < 0.05) and the drop in SVR (p < 0.05). CONCLUSION: Despite the fall in portal pressure and the systemic hemodynamic changes caused by TIPSS placement, there is no immediate effect on RBF. Any improvement in renal function after TIPSS procedure does not appear to be due to an acute increase in RBF.     

Fibroelastolytic papulosis of the neck: a report of 20 cases

BACKGROUND: Reports of pulmonary edema complicating inhaled nitric oxide therapy in patients with chronic heart failure and pulmonary hypertension have raised the concern that inhaled nitric oxide may have negative inotropic effects. METHODS AND RESULTS: We investigated the effect of multiple doses of inhaled nitric oxide (20, 40 and 80 ppm) on left ventricular contractile state in 10 open-chest pigs. Pressure-volume loops were generated during transient preload reduction to determine the end-systolic pressure-volume relationship and the stroke work-end-diastolic volume relation. Inhaled nitric oxide had no effect on systemic vascular resistance, cardiac output, end-systolic pressure volume relationship or stroke work-end-diastolic volume relation under normal conditions. After induction of pulmonary hypertension (intravenous thromboxane A2 analog), inhalation of nitric oxide (80 ppm) resulted in a reduction in pulmonary vascular resistance (mean +/- standard error of the mean) from 10.4 +/- 3 to 6.5 +/- 2 Wood units (p < 0.001) and in pulmonary artery pressure from 44 +/- 4 to 33 +/- 4 mm Hg (p < 0.05). Left ventricular end-diastolic volume rose from 53 +/- 9 ml to 57 +/- 10 ml (p = 0.02). No statistically significant change in cardiac output or systemic vascular resistance was observed. Inhaled nitric oxide had no effect on end-systolic pressure-volume relationship or stroke work-end-diastolic volume relation. CONCLUSIONS: In a porcine model of pulmonary hypertension, inhaled nitric oxide does not impair left ventricular contractile function. Therefore the cause of pulmonary edema observed in some patients receiving inhaled nitric oxide is not due to a negative inotropic action of this therapy.     

Neonates with congenital heart disease, Part II: Congenital cardiac defects with increased pulmonary blood flow

Generally, cardiac lesions with increased pulmonary blood flow demonstrate cardiomegaly, increased pulmonary vascular markings, and pulmonary congestion on the chest x-ray. These findings occur as a result of the following: 1. A left-to-right shunt or mixing lesion in which excess volume of blood flow causes dilation of cardiac chambers, resulting in the appearance of cardiomegaly, and in which increased pulmonary artery blood flow causes increased pulmonary vascular markings 2. Obstruction of blood flow that produces pulmonary venous hypertension and resultant pulmonary edema The next article in this series will address cardiac lesions with decreased pulmonary blood flow.