Prevalence of neurogenic pulmonary edema among patients who died from head injury – a retrospective chart review

Introduction

Neurogenic pulmonary edema (NPE) is an age-old clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system (CNS) insult¹. NPE can occur after virtually any form of injury of the CNS, and is a potential early contributor to pulmonary dysfunction in patients with head injuries². A myriad of CNS events, including spinal cord injury, subarachnoid hemorrhage, traumatic brain injury (TBI), intracranial hemorrhage, status epilepticus, meningitis, and subdural hemorrhage, have been associated with this syndrome^3–6.

The exact mechanism is unknown as it is believed to be multi-pronged and data is sparse. The connection between CNS injury and hemodynamic dysfunction was first described by Harvey Williams Cushing in 1903¹. This was followed by reports of cases in which acute pulmonary edema developed after CNS insult resultant from status epilepticus^1,7 and isolated head bullet wounds³. The etiology is thought to be a surge of catecholamines following the head injury that results in cardiopulmonary dysfunction^8,9. Several cardiovascular events are likely to result from this stimulation resulting in capillary leak and eventual pulmonary edema¹. Bahloul et al. identified features of left ventricular myocardial dysfunction in an echocardiographic study performed on previously healthy traumatic brain injury patients presenting with neurogenic pulmonary edema⁵.

TBI is one of the world’s major causes of mortality and morbidity, particularly in the developing world, where motor vehicle and cyclist crashes are largely due to human error and poor roads^10–13. With increasing industrialization of the developing world, there is a proportional increase in motorized trauma. Uganda is currently ranked second in the world in road traffic accidents after Ethiopia¹⁴. These in a country with a limited health budget, mean resources are stretched to the limit by the burden of care required by trauma patients. TBI forms the majority of trauma cases occurring, either in isolation or as part of multiple trauma^14,15.

The neurosurgery Unit of Mulago NRH admits at least ten critically ill patients per day, while the intensive care unit (ICU) can only admit a maximum of four patients. The national critical care bed capacity is significantly limited for the enormous population in need¹⁶. An in-hospital mortality of 25% following severe TBI was reported in a retrospective study in Mulago NRH¹³ while Kwizera et al. found an ICU mortality rate of 45.3% from head injury nationally. Mortality was commonly due to hemorrhagic shock, respiratory failure and sepsis¹. The majority of survivors are left with gross disabilities while out-of-hospital mortality post-discharge remains largely unknown¹⁶.

Awareness of NPE may lead to early intervention in brain-injured patients. However, although NPE was identified over 100 years ago, it is still underappreciated in the clinical arena. Its sporadic and relatively unpredictable nature, and a lack of etiologic-specific diagnostic markers and treatment modalities, may in part be responsible for its poor recognition at the bedside¹. Worse still, there is very little data on the subject. Current data estimate the prevalence of NPE following severe brain insults, like trauma, stroke, status epilepticus etc., to be about 50%¹⁷, rising up to 92% in fatal subarachnoid hemorrhage¹⁸, being directly related to duration since insult⁴. Most data were, however, based on reviews of hospital records and case studies.

In this study, we determined the prevalence of neurogenic pulmonary edema through postmortem studies of head injured patients and sought to establish its relationship to the different patterns of organ dysfunction in head injured patients. This study also indirectly assessed quality of care of neurosurgery patients in the hospital. There are no published data on a similar study to the best of our knowledge.

Methods

Results

During the study period, twenty-six patients were enrolled in this study. No patient had a premorbid diagnosis of renal, liver or lung disease. Only one patient had preexisting hypertension and obesity but with no documented cardiac disease. No drug or transfusion reactions were noted during the patients’ treatment. Only one patient (3.9%) had aspiration pneumonia. Intracranial abnormalities including raised intracranial pressure had been detected by brain Computed Tomography (CT) scan in 18/26 of the patients. One patient’s brain CT scan showed no acute intracranial pathology while 26.9% (7/26) of patients did not have a brain CT scan performed (Table 1). Autopsy showed features consistent with pulmonary edema in 76.9% of patients, being bilateral in 85% of these. All the 15% in whom edema was unilateral had involvement of the right lung (Table 2).

Brain CT findings included intracranial edema and hemorrhage in 69.2%. 14 (53.9%) of patients had concomitant brain contusions while only one did not reveal any radiological features of intracranial pathology. Only three (11.5%) patients had had chest x-rays performed which revealed features consistent with bilateral airspace disease (Table 1). All patients admitted to ICU received invasive artificial ventilation. Average daily total fluid input was 2 liters with an average overall measured fluid balance (total IV and oral fluid input minus outputs from drains (urine, GI) (Table 1) of +560 mL at time of death. No transfusion reactions were recorded. None of the patients required instrumentation of the chest wall. Five patients (30.8%) had received orthopedic surgical care, two (7.7%) had received surgical toilet for soft tissue injuries while an additional two patients had undergone exploratory laparotomy for blunt abdominal trauma (ruptured spleen and ruptured liver, respectively) (Table 1).

Features of pulmonary edema were noted in 76.9% of patients. 85% of these showed evidence of pulmonary edema bilaterally. Additional injuries noted at autopsy included liver and splenic contusion in one patient each, musculoskeletal injuries (degloving injuries (7.7%), long bone fractures (30.8%). There was no evidence of spinal trauma at autopsy (Table 2). Organs from one patient aged 9 years were not weighted against the European standard to which organ weights were referenced.

Discussion

The true incidence of NPE after acute head injury is difficult to estimate because much of the information comes from small autopsy series or isolated case reports. In this postmortem study, we found prevalence of neurogenic pulmonary edema of 76.9%. In an autopsy and in-patient database study, Rogers et al. found a prevalence of neurogenic pulmonary edema of 32% in patients dying within the first 24 hours and up to 50% in 96 hours².

Pulmonary dysfunction after acute brain injury is a common but poorly understood phenomenon. In classic medical literature, the causes of pulmonary dysfunction in patients with head injury include pneumonia, aspiration, and pulmonary embolus, while NPE is seldom recognized. NPE is a form of pulmonary edema that develops rapidly after a cerebral injury²⁰. It has been described in trauma patients as parenchymal edema, hemorrhage, and congestion without evidence of chest trauma in patients with isolated head injury^18,21.

In Uganda, over 20,000 road traffic crashes occur annually claiming many lives through multiple trauma, head injury being one of the leading causes of death^14,15,22,23. However, the incidence of NPE had not previously been established. In the study reported here, we included only patients with traumatic head injury who died after admission and treatment in the hospital. In addition, because of a shortage of resources, it was not possible to carry out several specialized tests on the patients before death.

Pulmonary edema was bilateral in most patients studied and was predominantly right sided in those with unilateral edema. This relates closely with the theory of a generalized pulmonary vascular disorder in head injured patients which is related to the severity of insult²⁴. The study by Rogers et al., however, describes a predominantly right sided edema presentation². This difference could be related to the difference in severity of illness and quality of initial management instituted. Furthermore, our study applied an European standard to organ weight measurement which was validated in a different population and only gross lung examination was performed for evidence of pulmonary edema which could have contributed to disparity in measurements and findings.

Studies on the other organs showed no significant weight increases. In addition, no significant structural abnormalities indicative of preexisting chronic conditions could be found on anatomical examination of these organs. This correlates well with the definition of neurogenic pulmonary edema in which there is no other significant organ injury in a patient with severe brain injury^1,24,25. Edema was, however, seen in some dissections of the heart and kidneys that could be a result of multi-organ dysfunction as a result of critical illness. In addition, Bahloul et al. described myocardial dysfunction in neurogenic injury which could in part explain the pathophysiology of NPE⁵

Severe TBI frequently presents with significant depression in level of consciousness compromising adaptive protective reflexes. Standard management for severe TBI patients includes ICU admission for intensive monitoring, interventions and supportive care such as invasive mechanical ventilation, among other therapies. Moreover permissive hypercapnia and tight control of blood carbondioxide tension forms an integral part of neurocritical care^26,27. In our study however, only 26.9% of patients were managed in ICU. Consequently, only 26.9% of patients in this study had received mechanical ventilatory support despite 76.9% having potentially developed respiratory dysfunction due to pulmonary edema among other causes. This is partly explained by the shortage of ICU capacity nationally¹⁶ and underscores the pressing need for critical care services in the care of TBI patients.

Brain CT scan is a minimum diagnostic tool. In our study, 26.9% of patients never had a brain CT scan performed. This in addition to limited surgical capacity leads to delay and missed opportunities. As a result, the mortality of head injury patients is very high, resulting perhaps in complications such as neurogenic pulmonary edema. Absence of complete antemortem investigation of the patients before death for pulmonary edema plus associated conditions as well as the small sample size makes it difficult to deduce statistically significant causal relationships in our study. However, strong inferences can be derived from association between severity of brain injury (as shown by need for ICU admission, type of injury) with NPE.

Conclusion

We conclude that NPE occurs frequently in head injury patients. The process of edema formation begins early in the clinical course and is isolated to the lung. NPE thus needs to be critically recognized early in the formulation of a management plan. The contribution of NPE to mortality and morbidity in these patients cannot be deduced from this study, as a causal association between pulmonary edema and mortality was not studied.

Data availability

Dataset 1: Extracted medical data from patients with neurogenic pulmonary edema following head injury 10.5256/f1000research.13750.d202806²⁸