Neurogenic Pulmonary Edema Due to Traumatic Brain Injury: Evidence of Cardiac Dysfunction

Mabrouk Bahloul, Anis N. Chaari, Hatem Kallel, Abdelmajid Khabir, Adnne Ayadi, Hanne Charfeddine, Leila Hergafi, Adel D. Chaari, Hedi E. Chelly, Chokri Ben Hamida, Noureddine Rekik and Mounir Bouaziz
Am J Crit Care 2006;15:462-470
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NEUROGENIC PULMONARY EDEMA DUE TO TRAUMATIC BRAIN INJURY: EVIDENCE OF CARDIAC DYSFUNCTION
By Mabrouk Bahloul, Anis N. Chaari, Hatem Kallel, Abdelmajid Khabir, Adnne Ayadi, Hanne Charfeddine, Leila Herga, Adel D. Chaari, Hedi E. Chelly, Chokri Ben Hamida, Noureddine Rekik, and Mounir Bouaziz. From Service de Ranimation Mdicale (MB, ANC, HK, LH, ADC, HEC, CBH, NR, MB), Service dAnatomopathologie (AK), and Service de Mdecine Lgale (AA), Centre Hospitalier Universitaire Habib Bourguiba, Sfax, Tunisia, and Service de Cardiologie, Centre Hospitalier Universitaire Hdi Chaker, Sfax, Tunisia (HC).

BACKGROUND Acute neurogenic pulmonary edema, a common and underdiagnosed clinical entity, can occur after virtually any form of injury of the central nervous system and is a potential early contributor to pulmonary dysfunction in patients with head injuries. OBJECTIVE To explore myocardial function in patients with evident neurogenic pulmonary edema after traumatic head injury. METHODS During a 1-year period in a university hospital in Sfax, Tunisia, information was collected prospectively on patients admitted to the 22-bed intensive care unit because of isolated traumatic head injury who had neurogenic pulmonary edema. Data included demographic information, vital signs, neurological status, physiological status, and laboratory ndings. All of the patients had computed tomography and plain radiography of the neck and determination of cardiac function. RESULTS All 7 patients in the sample had cardiac dysfunction. Evidence of myocardial damage was confirmed by echocardiography in 3 patients, pulmonary artery catheterization in 3 patients, and/or postmortem myocardial biopsy in 4 patients. Echocardiography studies, repeated 7 days after the initial study in one patient and 90 days afterward in another, showed complete improvement in wall motion, with a left ventricular ejection fraction of 0.65. CONCLUSION All patients who had neurogenic pulmonary edema due to traumatic head injury had myocardial dysfunction. The mechanisms of the dysfunction were multiple. The great improvement in wall motion seen in 2 patients indicated the presence of a stunned myocardium. Further studies are needed to understand the mechanisms of this cardiac dysfunction. (American Journal of Critical Care. 2006;15:462-470)

A
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cute neurogenic pulmonary edema (NPE) is a common and underdiagnosed clinical entity that can occur after virtually any form of injury of the central nervous system. NPE has been described in patients with seizures, stroke, several
Corresponding author: Mabrouk Bahloul, Service de Ranimation Mdicale, Hpital Habib Bourguiba, Route el Ain Km 1, 3029 Sfax, Tunisia (e-mail: bahloulmab@yahoo.fr) To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints@aacn.org.

types of intracranial hemorrhage, infection, and drug use, among other conditions.1 In patients with traumatic acute head injury, impaired pulmonary function is a common but poorly understood complication. NPE is a potential early contributor to the pulmonary dysfunction that occurs in patients with head injuries.1 Although NPE is a frequent complication of traumatic head injury, its occurrence in this specic condition is rarely described. In addition, despite clinical and experimental studies, the mechanisms leading to NPE are not fully understood.
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In this article we report 7 typical cases of NPE associated with traumatic head injury. The aim of this study was to explore myocardial function in patients with evident NPE after traumatic head injury. The study was approved by an internal review board.

Acute neurogenic pulmonary edema

can occur after any form of central nervous system injury.

Materials and Methods

Sample

The sample consisted of nonconsecutive patients admitted to the 22-bed intensive care unit (ICU) of Centre Hospitalier Universitaire Habib Bourguiba, Sfax, Tunisia, during a 1-year period because of NPE due to isolated traumatic head injury. Patients were admitted directly from the scene of the injury within 1 hour of injury. All were examined, and the score on the Glasgow Coma Scale (GCS) was determined at arrival. Patients underwent cerebral computed tomography (CT) as soon as feasible. Excluded from the study were all patients with extracranial injury, patients with other causes of respiratory distress (eg, pulmonary contusion, vomiting, gastric aspiration), and patients with a history of cardiorespiratory disease. The diagnosis of pulmonary edema was based on the presence of clinical and radiological features of pulmonary edema and on the presence of arterial hypoxemia.
Methods

The following information was collected on hospital admission, at ICU admission, and during ICU stay: age, sex, vital signs (heart rate, respiratory rate before mechanical ventilation, systolic and diastolic blood pressure), body temperature, GCS score and neurological manifestations before the use of mechanical ventilation and before patients were sedated, Simplied Acute Physiology Score II (for adult patients) or Pediatric Risk of Mortality score (for children) calculated within 24 hours after admission, the use of mechanical ventilation, the use of inotropic drugs, the occurrence of shock, the occurrence of cardiac arrest, volume of uid intake, and urinary output. Biochemical parameters measured on admission and during the ICU stay were arterial blood gases and acid-base state (pH and bicarbonate level); hemoglobin concentrahttp://ajcc.aacnjournals.org

tion; platelet counts; serum levels of glucose, sodium, and urea; and plasma protein concentration. All patients underwent cranial CT and plain radiographic study of the neck. The CT results were simplied to the presence or absence of hematoma (whether extradural, subdural, or intracerebral), meningeal hemorrhage, cerebral edema, cerebral contusion, pneumocephalus, intracranial mass lesion, and herniation. Neurological status was assessed by using the GCS score at the scene of the accident and the GCS score at hospital arrival after resuscitation but before the use of sedative. All patients with a GCS score of 8 or less, respiratory distress, or shock were intubated, treated with mechanical ventilation, and sedated with midazolam and fentanyl as necessary. Corticosteroids were not used. When an extracranial abnormality was suspected, appropriate investigations were done. The diagnosis of pulmonary edema was established by a medical committee of 5 ICU physicians at the time of admission to the ICU or a few hours later. Pulmonary edema was diagnosed if the patient had clinical and radiological features of pulmonary edema and arterial hypoxemia (arterial oxygen saturation measured while the patient was breathing room air if possible). In patients receiving mechanical ventilation, arterial hypoxemia was dened as present when the ratio of PaO2 to the fraction of inspired oxygen was less than 300. The medical committee took particularly into account the presence of signs of respiratory distress (cyanosis, inspiratory retraction of intercostal spaces) and the presence of lung crackles on auscultation of one or both lungs. In addition, the committee looked for signs of interstitial and/or alveolar pulmonary edema on the chest radiographs. Manifestations of interstitial pulmonary edema on radiographs included the loss of the normal sharp denition of pulmonary vascular markings, haziness, loss of demarcation of hilar shadows, thickening of interlobular septa, and peribronchial cuffing. Radiographic manifestations of alveolar pulmonary edema included unilateral or bilateral conuent acinar shadows creating irregular patchy increases in parenchymal density in the lower two thirds of the lung.2 Cardiac dysfunction was dened by the presence of cardiogenic pulmonary edema and/or cardiogenic shock. In all patients included, cardiac function was explored. In 3 patients, left ventricular ejection fraction (LVEF) was measured by means of echocardiography as soon as feasible (within 24 hours after ICU admission). In addition, in 3 patients, the measurements of pulmonary artery wedge pressure, cardiac index, stroke volume index, and systemic vascular resistance were obtained by using a pulmonary artery catheter inserted a few hours after admission to the
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Table 1 Demographic and clinical parameters of the study population at admission

Patient Parameter Age, y Sex Simplied Acute Physiology Score II Time between accident and admission to intensive care unit, h Score on Glasgow Coma Scale Body temperature, C Heart rate, beats per minute Blood pressure, mm Hg Systolic Diastolic Respiratory rate before mechanical ventilation, breaths per minute Arterial oxygen saturation while breathing air, % Glucose level, mmol/L (mg/dL) Shock pH PaCO2, mm Hg Bicarbonate, mmol/L PaO2 during mechanical ventilation, mm Hg Fraction of inspired oxygen Creatine phosphokinase, U/L Alanine aminotransferase, U/L Aspartate aminotransferase, U/L Mechanical ventilation Urea, mmol/L (mg/dL) Hemoglobin, g/L Hospital stay, d Use of catecholamines Type of catecholamine Outcome 1 23 Male 31 2 12 Male ND 3 6 Male ND 4 14 Male ND 5 12 Male ND 6 49 Male 32 7 38 Male 31

1 3 35 112 92 43

1 4 37.6 120 100 60

1 7 37 130 100 50

1 7 36.5 84 100 50

1 5 ND 120 50 20

1 8 37.8 35 200 80

1 10 38.2 123 140 70

28 ND 5.5 (99) No 7.43 33 26 177 1.00 695 ND ND Yes 5.5 (15) 106 7 Yes Dobut/epin Died

24 ND 6.5 (117) No 7.42 27.7 18.1 153 0.60 ND 32 77 Yes 10 (28) 110 5 Yes Dobut Survived

27 ND 8.7 (157) No 7.11 34.8 11.2 78 0.50 ND ND ND Yes 6.2 (17) 72 3 Yes Dobut Survived

35 75

8 54

33 79 7.9 (142) No 7.45 21.8 15.4 251 1.00 ND ND ND Yes 7.7 (22) 139 15 Yes

34 ND 9.4 (169) No 7.27 38.5 24.6 109 0.60 270 ND ND Yes 5.3 (15) 95 5 Yes Epin Died

6.7 (121) ND No 7.32 35.2 18.6 175 0.60 ND 20 40 Yes 3 (8) 94 4 Yes Epin Died Yes ND ND ND ND ND ND ND ND Yes ND ND 1 Yes

Dobut/norepin Dobut Died Survived

Abbreviations: Dobut, dobutamine; Epin, epinephrine; ND, not determined; Norepin, norepinephrine.

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Table 2 Results of cerebral computed tomography scans

Patient Parameter Extradural hematoma Subdural hematoma Intracerebral hematoma Meningeal hemorrhage Cerebral edema Cerebral contusion Pneumocephalus Mass lesion Herniation 1 No No No No Yes No No No No 2 No Yes No No No No No Yes Yes 3 No Yes No No No No No Yes No 4 Yes No No Yes No Yes Yes No No 5 No No No Yes Yes No No No No 6 No Yes No Yes Yes Yes Yes No No 7 Yes No No No No No No Yes Yes

Clinical Information

All 7 patients had hyperpnea and tachycardia at the time of hospital admission. Cardiogenic shock developed in 1 patient (patient 5, treated with dobutamine and norepinephrine) on hospital admission. The mean GCS score was 6 (range 3-10). All patients had already received mechanical ventilation before the ICU admission. All 7 patients had clinical manifestations of respiratory distress at the scene of the accident. The demographic and clinical parameters of the sample at admission are shown in Table 1. All patients had received catecholamines on ICU admission to treat the pulmonary edema (dobutamine at a mean dose of 10 g/kg per minute plus or minus epinephrine or norepinephrine).
Brain CT

Figure 1 Computed tomography scan of cerebrum of patient 6 shows a subdural hematoma, meningeal hemorrhage, cerebral edema, cerebral contusion, and a pneumocephalus.

All patients had brain CT upon admission. The most common abnormalities were meningeal hemorrhage, subdural hematoma, and mass lesion, observed in 3 patients each (Table 2). Figure 1 shows the cerebral CT scan for patient 6.
Chest Radiography

ICU. In 2 patients, myocardial echocardiography was repeated. Finally, a myocardial biopsy and/or pulmonary biopsy was done for all patients who died.

The chest radiographs obtained upon admission showed signs of alveolar pulmonary edema in all cases (eg, patient 2, Figure 2). In addition, a chest CT scan obtained on ICU admission in patient 5 (Figure 3) clearly shows signs of alveolar pulmonary edema.
Echocardiography

Results
During the study period, 202 patients were admitted with traumatic head injury. Only 7 patients were nally included in this study. The mean time between traumatic head injury and ICU admission was 1 hour. The traumatic head injury was caused by a trafc accident in all cases.

Echocardiographic studies in 3 patients showed global hypokinesia with a decrease in LVEF (to 0.40) in 2 patients (patients 2 and 6). In 1 patient (patient 4), however, a diastolic dysfunction with a reduced velocity of early lling (E wave), an increase in the velocity associated with atrial contraction (A wave), and a ratio

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Figure 2 Chest radiograph of patient 2 shows pulmonary edema.

of E to A of less than 1 was observed. For 2 patients (patients 2 and 6), echocardiography performed 7 and 90 days after the initial study showed complete recovery, with an LVEF of 0.65.
Electrocardiography

Figure 3 Computed tomography scan of the chest of patient 5 obtained on admission to the intensive care unit shows alveolar pulmonary edema.

Summary
The electrocardiograms showed some abnormalities in all patients. The most common abnormality was tachycardia, with heart rates exceeding 122/min. Other abnormalities also were observed, including STsegment depression in 1 patient and right bundle branch block in 2 patients. Table 3 shows the changes observed for each patient on admission.
Pulmonary Artery Catheterization

Pulmonary artery catheterization was done for 3 patients (patients 1, 3, and 7). The ndings indicated a low stroke volume index in all 3 patients. Pulmonary artery wedge pressure was higher in all patients except patient 3. In patient 3, who had pulmonary edema evident on a chest radiograph, the mixed venous oxygen saturation was low (<70%), and the arteriovenous difference in oxygen content was higher than in the other patients (Table 4).
Histological Findings

Postmortem myocardial biopsies were done in 4 cases (patients 1, 4, 5, and 7), and a pulmonary biopsy was done in 1 case (patient 5). Myocardial biopsy showed an interstitial edema in all cases without a focus of necrotic muscle ber or myocardial inltration by inammatory cells. Figure 4 shows the histological findings on myocardial biopsy specimen for patient 5. Examination of the pulmonary biopsy specimen from patient 5 showed marked alveolar edema without signs of inammatory lesions (Figure 5).

In all patients included in the study, the diagnosis of cardiac dysfunction was suspected because of the signs of acute respiratory distress (cyanosis, inspiratory retraction of intercostal spaces), the presence of crackles on auscultation of one or both lungs, and the evidence of pulmonary edema on the chest radiograph. In patients who underwent echocardiography, the cardiogenic part was conrmed by a low LVEF (at 0.40 with catecholamine) in 2 patients and by a reduced velocity of early filling (E wave), an increase in the velocity associated with atrial contraction (A wave), and a ratio of E to A of less than 1 in 1 patient (patient 4). In patients who underwent pulmonary artery catheterization, cardiac dysfunction was indicated by a pulmonary artery wedge pressure greater than 18 mm Hg in 2 patients, and in another patient cardiac dysfunction was indicated by the low mixed venous oxygen saturation (<70%) and the low stroke volume index when treated with catecholamines. Finally, in patient 5, who was admitted for isolated traumatic head injury with acute respiratory distress associated with a refractory shock, the diagnosis of NPE was made by the medical committee on the basis of clinical manifestations (respiratory distress), ndings on chest radiographs, and postmortem biopsy ndings.

All subjects with neurogenic pulmonary

edema had cardiac dysfunction.

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Table 3 Electrocardiographic changes observed in all patients

Patient 1 2 3 4 5 6 7 Sinus tachycardia (beats per minute) Yes (125) Yes (140) Yes (130) Yes (122) Yes (120) Yes (150) Yes (150) T-wave change (localization) No Inversion of T wave (V1 and V2) No No No No No Depression or elevation of RST conguration No No No No No ST-segment depression (V4-V6) No Branch block Yes (right) No Yes (right) No No No No

Table 4 Hemodynamic parameters recorded

Patient Parameter Delay before hemodynamic study, hours after admission to intensive care unit Heart rate, beats per minute Mean arterial pressure, mm Hg Pulmonary artery wedge pressure, mm Hg Cardiac index* Stroke volume index Systemic vascular resistance, dynes seconds cm-5 Arterial hemoglobin concentration, g/L Arterial oxygen saturation, % Mixed venous oxygen saturation, % Arteriovenous oxygen content difference Oxygen extraction ratio, % Arterial carbon dioxide tension, mm Hg Mixed venous carbon dioxide tension, mm Hg Venoarterial carbon dioxide tension difference, mm Hg 1 3 7

4 99 94 26 3.30 30 2089 106 99.8 67.4 3.78 32.0 31.1 34.2 3.1

7 120 73 6 3.01 25 1833 137 97.1 67.8 5.68 31.4 37.3 39.3 2.0

8 133 87 20 5.35 40 1121 95 97.8 62.2 2.55 27.2 40.9 42.9 2.0

Figure 4 Photomicrograph of histological examination of myocardial biopsy specimen from patient 5 shows interstitial myocardial edema (arrows) with no myocyte injury and inammatory inltrate (hematoxylin-eosin, original magnication x200).

*Calculated as cardiac output in liters per minute divided by body surface area in square meters. Calculated as stroke volume in milliliters per beat divided by body surface area in square meters.

Discussion
In this study we conrmed the presence of cardiac dysfunction in patients with NPE due to traumatic brain injury. Pulmonary dysfunction after acute brain

injury is a common but poorly understood phenomenon. 1,3 Causes of pulmonary dysfunction in patients with head injury include pneumonia, aspiration, and pulmonary embolus, but seldom NPE.4,5 NPE is a form of pulmonary edema that develops rapidly after a cerebral injury.1,6 It has been described in trauma patients as parenchymal edema, hemorrhage, and congestion without evidence of chest trauma in patients with isolated head injury.1,7 The true incidence of NPE after acute head injury is difcult to estimate because much of the information comes from small autopsy series or isolated case reports. Furthermore, the clinical relevance of NPE in patients with nonfatal head injury remains to be elucidated, because NPE seems to be rare in patients who survive. However, according to Rogers et al,1 the incidence

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Figure 5 Photomicrograph of histological examination of pulmonary biopsy specimen from patient 5 shows uniform edematous change in the alveolar septa with dilated lymphatic channels, accumulation of red blood cells, and intraalveolar edema (hematoxylin-eosin, original magnication x400).

of NPE in patients with isolated head injury was 32% in patients who died at the scene and 50% in patients who died within 96 hours of the injury. In Tunisia, nearly 13 000 persons are involved in motor vehicle crashes every year. Approximately 1500 of these patients die.8 However, the incidence of NPE had not previously been established. In the study reported here, we included only patients with isolated traumatic head injury and with the typical signs and symptoms of NPE. In addition, because of a lack of tools, it was not possible to examine all patients admitted to our ICU with typical NPE. For these reasons, patients included were nonconsecutive, and we are not able to establish the incidence of this abnormality. NPE is characterized by an increase in extravascular lung water in patients who have sustained a sudden change in neurological condition.9-12 The mechanism by which NPE occurs is not clear, and 2 divergent theories have been proposed to explain its development: increased lung capillary permeability and increased pulmonary vascular hydrostatic pressures. Increased permeability as a mechanism of NPE is supported by some studies in animals that have shown high interstitial (lung lymphatic) or alveolar protein concentrations9,12 and time-dependent ultrastructural changes in pneumocyte type II cells after brain injury.13 Increased permeability may be caused by damage of the capillary endothelium or by direct neural influences on capillary permeability (the blast theory).14-17 On the other hand, hydrostatically induced pulmonary edema can occur without endothelial damage.
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One possible sequence leading to NPE is an acute increase in sympathetic tone that abruptly increases left ventricular afterload and causes intense venoconstriction, thereby elevating left ventricular lling pressures and inducing elevated pulmonary artery wedge pressures, leading to hydrostatic pulmonary edema. This hypothesis was confirmed by experimental studies18,19 and studies in humans.9,20,21 However, pulmonary edema can occur with normal pulmonary artery wedge pressures,22,23 suggesting a neurally mediated pressure independent of the inuence on capillary permeability. In addition to these 2 hypotheses, NPE can result from a cardiac dysfunction. In fact, the early hemodynamic changes that occur in the setting of NPE may lead to the conclusion that the pulmonary edema is of cardiac origin. Smith and Matthay9 reported, as have others, that early analysis of NPE uid reveals a low uid-serum protein ratio consistent with hydrostatic edema. In addition to the change in vascular resistance described, the pathogenesis of hydrostatic NPE may involve direct negative inotropic effects on the heart.24,25 In a retrospective study26 that included 20 patients with NPE, all 20 required mechanical ventilation; cardiac index and left ventricular stroke work index were markedly depressed in 12 of the 20 patients; mean pulmonary artery wedge pressure was 17 mm Hg; mean pulmonary artery pressure was 30.5 mm Hg; and mean systemic vascular resistance index (calculated as systemic vascular resistance in dynes seconds centimeters-5 divided by body surface area in square meters) was 2852. Patients treated with dobutamine had signicant increases in cardiac index and left ventricular stroke work index and signicant decreases in systemic vascular resistance index and pulmonary artery wedge pressure at 2 and 6 hours after institution of therapy and a significantly increased ratio of PaO2 to fraction of inspired oxygen at 6 hours after the start of therapy. The authors26 concluded that NPE was generally associated with severe depression of myocardial function and elevation of pulmonary vascular pressures. This dysfunction was readily reversed by dobutamine.

Neurogenic pulmonary edema may

result from increased lung capillary permeability, increased pulmonary vascular hydrostatic pressure, or cardiac dysfunction.

This hypothesis of myocardial dysfunction was supported by some echocardiographic studies.25,27 In a

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case series of 5 patients with subarachnoid hemorrhage and no history of heart disease, all with severe NPE, 5 had a low LVEF requiring inotropic support.27 Such cases illustrate that NPE and abnormalities in myocardial wall motion can occur concurrently. The cardiac dysfunction and wall-motion abnormalities are temporary, and cardiac function usually returns to normal.25,28,29 This hypothesis of cardiac dysfunction was conrmed by Connor,30 who found further postmortem evidence of myocytolysis and contraction-band necrosis of the heart in neurosurgical patients with NPE. Our findings confirm the hypothesis of myocardial dysfunction. In fact, in our study, cardiac dysfunction was well documented by echocardiography, hemodynamic changes, and/or postmortem biopsy. In addition, the control echocardiography study done in 2 patients showed a complete recovery of cardiac function. This myocardial dysfunction can be related to the massive release of catecholamines,15,25,31 the hyperglycemia that often occurs after traumatic brain injury,8 and/or the massive liberation of cytokines after severe traumatic brain injury.32 However, we cannot rule out other phenomena, especially permeability edema, on the basis of our ndings. The usually reversible myocardial dysfunction shown by echocardiography is poorly correlated with ECG changes.25 Our study conrms this last hypothesis; in fact, electrocardiographic manifestations of myocardial ischemia were observed in only a single patient. Finally, our study has several limitations. Because echocardiography was not available in our ICU or in our hospital, our patients were not examined in a uniform way (some were examined with echocardiography, some with pulmonary artery catheterization). For echocardiography to be done, the patient had to be transferred to another hospital. All patients included in our study had respiratory distress; in particular, patients 1, 3, and 7 had shock associated with acute respiratory distress with a ratio of PaO2 to fraction of inspired oxygen less than 200. Therefore, we preferred to use pulmonary artery catheterization (performed in our ICU) in these patients. In patient 3, the pulmonary artery wedge pressure was normal. Despite that normal nding, the hemodynamic study of these parameters was performed after administration of a catecholamine (dobutamine). The patients mixed venous oxygen saturation was 67.8% and the stroke volume index (calculated as stroke volume in milliliters per beat divided by body surface area in square meters) was 25, suggesting the presence of cardiac dysfunction.33 The high number of patients who were excluded from the study could be a methodological limitation.

Gastric aspiration and pulmonary contusion, which produce increased permeability and pulmonary edema, are potential confounding factors in clinical cases of NPE. We were careful to exclude any cases of observed aspiration and/or chest trauma in order to study typical cases of NPE (with a sure diagnosis) and to exclude the maximal number of patients with other therapeutic interventions (eg, uid infusion). Our sample included young patients (age <30 years in 70% of cases) with a low risk factor of cardiac dysfunction and no history of cardiorespiratory disease. We therefore believe that the elevated pulmonary artery wedge pressures could not be related to simple cardiogenic pulmonary edema. In addition, hemodynamic parameters determined by using pulmonary artery catheters can be difcult to interpret in patients receiving positive pressure ventilation with or without high levels of positive end-expiratory pressure. However, in our study, all parameters (in particular, cardiac index and pulmonary artery wedge pressure) were measured while the patient was receiving catecholamines, and in all patients mixed venous oxygen saturation was low, suggesting cardiac dysfunction.33 In patient 5, we inferred cardiac dysfunction on the basis of a postmortem biopsy; the results of such biopsies can be unreliable and may reect complications of the primary brain injury as much as the primary process. In this patient, who was admitted for isolated traumatic head injury with acute respiratory distress associated with a refractory shock, the diagnosis of NPE was ascertained by the medical committee on the basis of clinical manifestations (respiratory distress), radiological (chest radiographic) ndings, and results of postmortem biopsy.

Conclusion
Our findings confirmed the presence of myocardial dysfunction in patients with NPE due to traumatic head injury; however, we cannot rule out other phenomena, especially permeability edema. The mechanisms of myocardial dysfunction were multiple. The great improvement in wall motion seen in 2 patients indicated the presence of a stunned but viable myocardium. Further studies are needed to understand the mechanisms of this cardiac dysfunction.
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