Tuberculous meningitis is the most serious form of extrapulmonary tuberculosis and is caused by the invasion of Mycobacterium tuberculosis into the subarachnoid space, causing soft meninges, arachnoid and then cerebral vascular involvement and some parenchymal lesions. Severe TB meningitis combined with respiratory failure is one of the major causes of death in patients with TB meningitis. The use of mechanical ventilation as an important tool in the treatment of respiratory failure is severely limited by its potential effect on intracranial pressure (ICP). A retrospective summary of 28 cases of mechanical ventilation in patients with severe tuberculous meningitis combined with respiratory failure admitted to the intensive care medicine department of our hospital is reported below.
1.1 General information
A total of 28 patients with severe tuberculous meningitis combined with respiratory failure were admitted to the Department of Intensive Care Medicine of our hospital from February 2010 to June 2014, of which, 18 were male and 10 were female; age ranged from 12 to 68 years, with an average of 36.5 years. There were 21 cases of tuberculosis of the brain combined with pulmonary tuberculosis, 5 cases of pleural tuberculosis, 1 case of intestinal tuberculosis, and 1 case of renal tuberculosis. There were 12 cases of acute onset, 14 cases of subacute onset, and 2 cases of chronic onset. Clinical manifestations: all 28 patients showed headache and vomiting, all had fever, malaise and other symptoms of tuberculosis toxicity, and all had symptoms of cranial hypertension. There were 22 cases of meningeal stimulation, 9 cases of drowsiness, 12 cases of coma, 7 cases of delirium, 5 cases of paraplegia, and 1 case of hemiplegia. Pulmonary auscultation could hear wet dumplings in 15 cases, and dry and wet dumplings were not heard in 13 cases. Exclude viral meningitis, septic meningitis, cryptococcal meningitis, acute disseminated encephalomyelitis and other cranio-cerebral disorders.
1.2 Laboratory examination
Cerebrospinal fluid cell count was <100×106/L in 13 cases, (100-1000)×106/L in 14 cases, >1000×106/L in 1 case; neutrophils >0.5 in 7 cases, lymphocytes >0.5 in 21 cases; protein was elevated in 28 cases, sugar was decreased in 20 cases, chloride was decreased in 28 cases; antacid bacillus smear was positive in 3 cases, culture was positive in 4 cases, and mycobacterium tuberculosis PCR was positive in 9 cases. There were 8 cases of routine blood leukocytes (4-10)×109, 2 cases of leukocytes ≤4×109, and 18 cases of leukocytes ≥10×109. Blood gas analysis PH 6.8-7.25 in 11 cases, 7.25-7.35 in 12 cases, 7.35-7.45 in 5 cases; PaO2<40mmHg in 16 cases, 40mmHg≤PaO2<60mmHg in 10 cases, 60mmHg≤PaO2<90mmHg in 2 cases.
1.3 Imaging examination
All patients underwent cranial MRI plain and enhanced scans, and 28 cases were abnormal, including 15 cases of obstructive hydrocephalus with periventricular edema, 2 cases of cerebral infarction, 6 cases of cerebral parenchymal cornual tuberculosis, and 4 cases of massive tuberculosis spheres. 11 cases showed extensive meningeal enhancement in the suprasellar pool, tetrasellar pool, and optic cross pool after enhancement. On chest X-ray, there were 15 cases of multiple lamellar and patchy lung shadows, 2 cases of cavernous shadows, 6 cases of diffuse corn-like shadows, and 5 cases of blunted or absent rib-diaphragm angle.
1.4 Drug treatment
All 28 patients were treated with a standardized anti-tuberculosis regimen, with isoniazid, rifampicin, pyrazinamide, and ethambutol given in quadruple anti-tuberculosis regimens, along with glucocorticoids, as soon as the diagnosis of tuberculous meningitis was highly suspected.
1.5 Mechanical ventilation method
All patients were mechanically ventilated through oral tracheal intubation or tracheotomy with a Vela ventilator, triggered by flow triggering, with a trigger sensitivity of 1 L/rain. The FiO2 was adjusted according to the patient’s condition, and the goal was to maintain SPO2≥90%. Sedation was administered by midazolam injection or propofol injection if the patient was restless.
Results
All patients were given enteral/parenteral nutrition support to maintain water and electrolyte balance, and 12 cases were given lateral ventricular drainage. In this group, 19 patients survived, including 15 cases of self-care, 2 cases of blindness, 1 case of vegetative survival, 1 case of physical activity disorder, 3 cases of automatic discharge and abandonment of treatment, and 5 cases of death.
Discussion.
The treatment of severe tuberculous meningitis is an important element in the field of tuberculosis-related critical care, which often involves the comprehensive treatment capabilities and techniques of tuberculosis, neurology and critical care medicine. Mechanical ventilation is an important tool in the management of severe TB meningitis combined with respiratory failure.
Respiratoryfailure is a clinical syndrome in which different factors cause severe impairment of pulmonary ventilation and/or air exchange, resulting in the inability of the patient to exchange gases effectively, causing hypoxia with (or without) carbon dioxide retention, which leads to a series of physiological and metabolic disorders. Central respiratory failure is caused by damage to the respiratory center due to midbrain, pontine and medulla oblongata disorders, resulting in hypoxia and carbon dioxide retention due to changes in respiratory rhythm, frequency and ventilation. Some patients with severe TB meningitis have central/peripheral respiratory failure that is not relieved by conventional oxygen therapy due to damage to the brain parenchyma or severe pulmonary infections due to prolonged bed rest, coma, or aspiration, and often require invasive mechanical ventilation techniques. However, severe tuberculous meningitis is often combined with cranial hypertension syndrome, and the safety of mechanical ventilation is of great concern.
The use of mechanical ventilation has saved the lives of numerous patients with severe respiratory failure. The relationship between mechanical ventilation and intracranial pressure began to be increasingly studied after the discovery 30 years ago that artificial hyperventilation could reduce intracranial pressure (ICP) in patients with severe craniocerebral injury. In theory, positive pressure mechanical ventilation and positive end-expiratory pressure (PEEP) can induce intrathoracic hypertension, reduce venous return and lower cardiac output, potentially exacerbating intracranial hypertension due to reduced venous return. Elevated intracranial pressure (ICP) and lower blood pressure and cardiac output further reduce cerebral perfusion pressure (CPP), which can induce secondary ischemic and hypoxic injury to the brain. From this perspective, clinicians may face a dilemma when dealing with severe tuberculous meningitis and other central nervous system disorders causing cranial hypertension syndrome combined with respiratory failure.
In clinical practice, how to reduce the possible damage to brain function while having to use mechanical ventilation to save respiratory failure, and how to find the best balance between ensuring oxygenation and brain protection is an important issue to be studied.
PEEP is often applied during mechanical ventilation to promote pulmonary resuscitation, improve pulmonary compliance and oxygenation, and increase oxygenation index in patients with respiratory failure [2], but PEEP simultaneously increases intrathoracic pressure [3-4]. In contrast, it is generally believed that brain tissue cannot be compressed, the volume hardly changes, and there is little regulation of ICP; when intracranial pressure changes, it is mainly regulated by cerebrospinal fluid and cerebral blood volume, especially by cerebral blood volume. The potential effect of mechanical ventilation on cranial hypertension or brain function is mainly reflected in the effect on cerebral blood flow.
The level of ICP can directly affect the cerebrovascular response of patients to MAP [5]. At low ICP, as MAP increases, the cerebral vasculature contracts through self-regulation, which can lead to a decrease in ICP and a corresponding increase in CPP; at increased ICP, vascular self-regulation disappears and the compliance of brain tissue decreases, ICP increases with MAP and the trend of CPP changes is uncertain. Due to significant individual differences in age and respiratory system compliance, and patient age and lung compliance directly affect the response of ICP and CPP to PEEP [6-7].
Integrating existing studies and practices, we believe that mechanical ventilation treatment for patients with severe tuberculous meningitis combined with respiratory failure should be differentiated into two cases.
1, those belonging to central respiratory failure: those with normal or near-normal pulmonary compliance, i.e., those without more serious underlying lung disorders that reduce pulmonary compliance, such as severe tuberculosis, severe pneumonia, ARDS, etc. The increase of PEEP in those with normal pulmonary compliance has only a slight effect on ICP [8], so can we assume that in this case, positive pressure mechanical ventilation has less effect on cranial hypertension, mechanical ventilation can be implemented normally, and the parameters of various mechanical ventilation, especially the setting of PEEP, do not need to consider too much the moderation of cranial hypertension condition;
2, belong to peripheral respiratory failure: there are serious underlying diseases in the lungs, and there are different degrees of decline in pulmonary compliance. Studies on the relationship between positive pressure mechanical ventilation or PEEP and hemodynamics are mostly selected in patients with acute respiratory distress syndrome or acute lung injury [9]. It is commonly believed that PEEP increases intrathoracic pressure, compresses large intrathoracic veins, alveolar septum and pulmonary vessels, reduces venous blood return, decreases both left and right ventricular filling, decreases cardiac expulsion index, and causes a decrease in MAP.
In this case, we believe that the effect of positive pressure mechanical ventilation and PEEP on cranial hypertension may be greater, and the specific implementation of clinical mechanical ventilation should take full account of possible cranial paracranial injuries, and the target treatment of mechanical ventilation should be the low limit of the corrective target of respiratory failure, such as SPO2 maintained at ≥90 can be, while PEEP and support should be reduced as much as possible. When the cranial pressure is very high, obstructive hydrocephalus is severe, and there is a risk of brain herniation, lateral ventricular drainage should be performed promptly to improve respiratory failure while minimizing the cranial impact and saving lives.
At the same time, from another perspective, we should recognize that when severe TB meningitis is combined with severe central or peripheral respiratory failure, timely and effective mechanical ventilation can improve cerebral hypoxia and reduce hypoxic enzymatic hypercapnia in a short time. Hypercapnia can reduce ICP by constricting intracranial arteries to decrease intracranial blood flow (CBF) and reduce cerebrovascular volume (CBV) [11]. Therefore, the benefits of mechanical ventilation during a certain period of time in the emergency phase may far outweigh the possible risk of increased cranial hypertension.
There are no studies on whether to give a “hyperventilation” strategy for mechanical ventilation in severe tuberculous meningitis combined with respiratory failure, and most of the available studies on hyperventilation strategies have focused on craniocerebral trauma. It is generally believed that, on the one hand, hyperventilation causes a decrease in CBF while decreasing ICP, which may lead to ischemic cerebral infarction if artificial hyperventilation is given at this time if the autoregulatory capacity of the cerebrovascular bed is intact; on the other hand, if the primary disease is not cleared in time, cerebral edema will gradually increase and ICP will rise further. The formation of cranial hypertension in tuberculous meningitis is completely different from the mechanism of cranial hypertension caused by craniocerebral trauma, so the author believes that the strategy of “hyperventilation” is not suitable for the treatment of severe tuberculous meningitis combined with respiratory failure.
In conclusion, the relationship between mechanical ventilation and craniocerebral function, especially intracranial pressure, is complex, and it is probably only by fully understanding the dialectical relationship between mechanical ventilation and cerebral function that we can avoid losing sight of one in clinical work. Mechanical ventilation is an important treatment for severe tuberculous meningitis combined with respiratory failure, and it should not be easily abandoned because of the fear of possible damage to the skull and brain from mechanical ventilation.
In the process of mechanical ventilation, the size of the patient’s pulmonary compliance should be determined first, or the classification of respiratory failure should be distinguished, so that the basic mechanical ventilation strategy can be initially determined, and the specific mechanical ventilation strategy that meets the developmental pattern of each patient’s condition can be dynamically improved during monitoring and treatment. This paper only discusses the importance and safety of mechanical ventilation in the treatment of severe tuberculous meningitis combined with respiratory failure from the perspective of the relationship between mechanical ventilation and cranial hypertension or cranio-cerebral function, and the conclusions need to be confirmed by further extensive controlled clinical studies.