Effects of Propofol on Intracranial Pressure and Prognosis in Severe Neuropathy Patients Undergoing Endotracheal Suctioning

Background To investigate whether intravenous propofol before endotracheal suctioning (ES) in severe neuropathy patients can reduce the sputum suction response, improve the prognosis, and accelerate recovery. Methods A total of 208 severe neuropathy patients after craniocerebral surgery were enrolled in the study. The subjects were randomly divided into the experimental group (n=104) and the control group (n=104). The experimental group was given intravenous propofol, 0.5-1 mg/kg, before ES, while the control group was subjected to ES only. Changes in vital signs, sputum suction effect, the uctuation range of intracranial pressure (ICP) before and after ES, choking cough response, short-term complications, and length of stay and hospitalization cost were evaluated. Additionally, the Glasgow Outcome Scale (GOS) prognosis score was obtained at six months after the operation.


Background
Severe neuropathy is often accompanied by disorders of consciousness, weak sputum discharge by spontaneous cough, airway obstruction, and hypoxia, which together aggravate secondary damage to brain cells [1,4,5]. To maintain airway patency and avoid airway obstruction and pulmonary infection in patients affected by severe neuropathy, arti cial airways should be established, and endotracheal suctioning (ES) should be timely performed [1][2][3].
ES stimulates airway mucosa, triggers cough re ex, induces bronchospasm, decreases blood oxygen saturation, and increases intracranial pressure. Severe airway stimulation may lead to adverse consequences [1], such as severe cough, increased chest pressure, a sudden rise in blood pressure, increased cerebral perfusion, increased intracranial pressure (ICP) caused by cerebral vasospasm, and increased risk of vascular rupture [12][13][14][15][16]. The stimulation of the airway caused by different suction modes and duration, the amount of negative pressure applied, and the depth of suction tube insertion lead to re exive ICP changes [4-11, 16, 17].
The objective of the present study was to explore whether the administration of propofol before the ES procedure in severe neuropathy patients helps to maintain the respiratory and circulatory stability, reduces the increase of ICP, and suppresses the high-pressure response caused by intense stimulation. (2) with cerebrovascular disease and undergoing craniocerebral surgery; (3) with arti cial airway and ventilator-assisted respiration; (4) equipped with intracranial pressure monitor; and (5) with the initial ICP of ≤ 25 mmHg. The exclusion criteria were: patients with (1) insu cient blood volume or unstable circulation; (2) hypotension; (3) shock; or (4) maternal patients.

Research methods
Patients in both groups were treated by the same team of doctors and nurses. After the operation, both groups were treated with anti-in ammatory medications, ICP-reducing drugs, and nutritional support. All patients were subjected to continuous ECG monitoring, oxygen inhalation, and intracranial pressure monitoring. The control group was given ES directly without prior administration of propofol. The experimental group was sedated with propofol before ES.
The dose of propofol was 0.5-1 mg/kg, and the injection was performed slowly. For the ES procedure, patients were placed in a supine position, and the head of the bed was raised 15-30°. During the operation, No. 12 sputum suction tubes were used, the interval between consecutive ES was more than 30 minutes, and the negative pressure was set to 200 mmHg; the deep ES was performed [4][5][6][32][33]. Each patient had ES applied at least 5 times.

Outcome measures
The changes in vital signs, ES effect, the uctuation range of ICP before and after ES, choking and coughing reaction, recent complications, prognosis score measured by the Glasgow Outcome Scale (GOS) six months after the procedure, the duration of in-hospital stay, and hospitalization expenses were compared between the two groups. 1.3.3 Measurement of ICP uctuation range The ICP uctuation range was evaluated by the peak value of ICP during ES, the time to reach the peak value (seconds), the value of ICP after the recovery to a stable state, and the time to recover to a stable state (seconds).

Assessment of choking cough response
The choking cough response was graded as follows: grade 1, no choking cough; grade 2, slight cough, 1-2 times, without apparent physical movement; grade 3, strong cough, 3-4 times, with neck and chest movement; grade 4, more than four coughs, accompanied by movement of the entire body and retching, and causing extreme pain [34,35].
1.3.5 Auscultation evaluation of the ES effect Three degrees of reduction of the wheeze phlegm were assigned: 1, complete disappearance; 2, signi cant decrease; and 3, partial decrease [6].

Statistical analysis
The baseline measurement data were analyzed using the SPSS 22.0 software and were represented as the mean and standard deviation (x±s). The Student's t-test was used for comparisons between the two groups. The enumeration data were represented as the composition ratio or percentage, and the chi-square test or Fisher's exact probability method was used for inter-group comparison. The rank data comparison was performed using the rank-sum test. The signi cant level was set at α = 0.05 (two-tailed), and P < 0.05 was considered statistically signi cant. SAS software was used for repeated measurement of quantitative data. The mixed program performed data analysis. A random intercept-slope model that included grouping variables and measurement times was established.

Comparison of baseline conditions between the two groups
A total of 206 patients were included in the analysis (2 patients in the control group withdrew from the study). The average age of the 104 patients in the experimental group was 52.45±15.05 years, and the average age of the 102 patients in the control group was 52.68±14.06 years. There was no signi cant difference in age, gender, condition (pupil size, consciousness, tracheal situation), disease classi cation, surgical method, and GOS between the two groups (all P > 0.05) ( Table 1). Before the administration of propofol and ES, the vital signs were comparable between the two groups (P > 0.05). After ES, the systolic pressure in the control group was higher than in the experimental group (P < 0.05), while the values of HR, P, SpO2, and diastolic pressure were similar in both groups (all P > 0.05 (Table 2).   The number of complications in the two groups is listed in Table 5. There were no signi cant differences in the number of cases of cerebral hemorrhage, brain hernia, and pulmonary infection (all P > 0.05).

Comparison of GOS scores between two groups
Six months after the procedure, 51.54% of the patients in the experimental group and 32.64% in the control group had the GOS score of 4 or 5, while 48.46% in the experimental group and 67.36% in the control group had the GOS score of 1-3. The cases of 4-5 and 1-3 points in the experimental group were both signi cantly less than the control group (both P < 0.05) ( Table 6). There was no statistically signi cant difference between the two groups in total hospital expenses and the length of in-hospital stay (both P > 0.05).

Discussion
The results of the present investigation documented that propofol reduces the irritation associated with sputum suction, uctuation of ICP, cough response, and short-term complications, and improves the GOS score. These ndings indicate that propofol should be used before ES to relieve the stress response of the patients undergoing the procedure.
3.1 Propofol sedation before ES helps to stabilize intracranial pressure ES is an effective method for keeping the arti cial airway unobstructed in patients with severe neurologic diseases, and is, therefore, the most common procedure in neurology ICU. However, ES can increase ICP by stimulating the airway mucosa, triggering cough re ex, elevating chest pressure, increasing blood ow into the brain, and decreasing venous return. The variations in the stimulation of the airway caused by the differences in suction methods, suction duration, negative pressure applied, and suction tube insertion depth, are re ected in ICP changes [4-11, 16, 17]. It has been previously demonstrated that ES is an important factor affecting ICP [12][13][14][15][16]. The results of the current work showed that the average peak value of ICP in the experimental group was 15.57 ± 12.31 mmHg, while that in the control group was 18.24 ± 8.99 mmHg. This nding indicates that propofol sedation before ES can effectively reduce the mean peak of ICP. This bene cial action of propofol depends on its ability to activate the GABA receptor chloride complex and decrease the stress response of the body caused by ES. Moreover, propofol can reduce cerebral blood ow, ICP, and CMRO2 [18][19][20][21][22][23][24][25][26].

Propofol sedation ensures ES effect and reduces pain
Patients undergoing major neurosurgery procedures often experience consciousness disorders and reduced ability of the respiratory tract to perform self-cleaning. It is necessary to conduct timely suction of the sputum and clear respiratory secretion to avoid the obstruction of the arti cial airway and pulmonary infection [1][2][3]. The sputum suction tube repeatedly stimulates the respiratory mucosa, resulting in varying degrees of choking and coughing in patients. In severe cases, it causes a decrease in blood oxygen saturation and an increase in ICP, producing discomfort, and even causing pain [4][5][6][7][8][9][10][11][12][13][14][15][16][17][36][37][38][39][40]. Lucchini and coworkers [37] documented that patients subjected to mechanical ventilation recalled that during their stay in the ICU, ES was the most painful process, with 99% of them reporting painful experience during ES [36][37][38][39]. The current study demonstrated that the effect of ES was accomplished successfully in both the experimental and the control group, but the two groups differed in the grade of choking cough response. The number of patients with extremely painful sputum suction (grade 4) was signi cantly smaller in the experimental group, indicating that appropriate propofol injection prior to ES reduces the painful experience of the patients. Propofol is a short-term anesthesia drug, which is rapidly distributed in the entire organism within 40 seconds after intravenous injection. Intravenous injection of propofol before ES produces a sedative effect, inducing patients to enter the sleep state quickly. In addition, propofol can directly dilate bronchial smooth muscles, inhibit the throat re ex, and reduce the airway hyperresponsiveness during sputum suction. These properties of propofol suppress the stress response activated by ES and reduce the discomfort of patients [18,19,29].
3.3 Propofol sedation before ES helps to improve the prognosis of patients undergoing major neurosurgery In the present investigation, we have applied the concept of enhanced recovery after surgery (ERAS) and consulted relevant literature [24][25][26][27][28][29] to determine that an appropriate dose of sedatives was given before ES according to the weight of the patient. The results showed that propofol did not cause adverse reactions and complications. The evaluation of the GOS prognosis score sixth months after the operation revealed a high proportion of patients with 4-5 points on the GOS scale in the experimental group. This result indicates that the prognosis of patients treated with propofol was good. Together, the collected data show that propofol sedation before ES helps to improve the prognosis of patients undergoing major neurosurgery procedures by reducing the incidence of choking cough and spikes in ICP.
Some limitations of this study should be acknowledged. Only the patients admitted to the neurological ICU of the West China Hospital of Sichuan University were included. The subjects were mostly patients with cerebrovascular disease and severe brain injury. Clinical multi-center trials involving a more extensive range of diseases and larger sample sizes are needed to support the conclusions.

Conclusions
Sedation with a proper amount of propofol before ES can reduce the cough response caused by intense stimulation, reduce the patient's painful experience, suppress the increase in ICP, and improve long-term prognosis. The administration of propofol is safe and does not affect vital signs.  (238)).
Consent for publication: Written informed consent for publication was obtained from all participants.
Availability of data and material: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.