|Year : 2018 | Volume
| Issue : 3 | Page : 183-202
Prognostic factors of patients requiring ventilatory support in the neuro-intensive care unit
Ahmed S Alkotami1, Khaled H Rashed1, Mohamed A Ragab2, Hassan G Nassar1
1 Department of Neuropsychiatry, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||17-Mar-2018|
|Date of Acceptance||23-Jul-2018|
|Date of Web Publication||28-Feb-2019|
Ahmed S Alkotami
Kafr El-Sheikh – Doctors’ Division No. 2, Kafr El-Sheikh, 33511
Background and aim Among ICU admitted patients, primary indication for mechanical ventilation is neurologic in 20%. This is much higher in a dedicated neuro-ICU. The purpose of this study was to assess the clinical predictors for outcome of patients requiring ventilatory support in the neuro-ICU.
Patients and methods This was a prospective cohort study done at Neuropsychiatry Department and Center of Psychiatry, Neurology and Neurosurgery, Tanta University, from May 2016 to May 2017. All patients requiring ventilatory support after admission in our ICU, who were more than or equal to 18 years, and did not die before mechanical ventilation introduction were considered for the study.
Results Of 63 patients, 30 (47.6%) died after mechanical ventilation introduction. Analysis of variables showed that all the following were significant predictors for mortality: old age, Acute Physiology and Chronic Health Evaluation-II score on admission, maximum Sequential Organ Failure Assessment score, National Institutes of Health Stroke Scale, Intracerebral Hemorrhage score on admission, ventilation strategy, main cause for ventilation, stroke type, and association of hypertension and cardiac diseases. Main cause of ventilation also significantly influenced modified Rankin scale among survivors.
Conclusion Old age is associated with higher mortality, although mechanical ventilation can influence mortality among younger age groups. Early introduction of noninvasive positive pressure ventilation can improve in-hospital mortality. Outcome of ventilated patients is closely related to the main cause of ventilation, indicating mechanical ventilation is not essentially a therapeutic measure, however, a crucial supportive one. Application of Acute Physiology and Chronic Health Evaluation-II and Sequential Organ Failure Assessment scores and other prognostic and disability scores as National Institutes of Health Stroke Scale, Intracerebral Hemorrhage score and modified Rankin scale can monitor progression and significantly influence outcome of ventilated patients, especially when related to the main cause of ventilation.
Keywords: mechanical ventilation, neurocritical care, neuro-ICU, prognosis, prospective study
|How to cite this article:|
Alkotami AS, Rashed KH, Ragab MA, Nassar HG. Prognostic factors of patients requiring ventilatory support in the neuro-intensive care unit. Tanta Med J 2018;46:183-202
|How to cite this URL:|
Alkotami AS, Rashed KH, Ragab MA, Nassar HG. Prognostic factors of patients requiring ventilatory support in the neuro-intensive care unit. Tanta Med J [serial online] 2018 [cited 2019 Oct 16];46:183-202. Available from: http://www.tdj.eg.net/text.asp?2018/46/3/183/253198
| Introduction|| |
Mechanical ventilation introduction represents an advanced era in the overall life support of critically ill patients. It is estimated that among patients admitted to ICUs, either medical or surgical, the primary indication for mechanical ventilation is neurologic in 20%. This percentage is much higher in a dedicated neurocritical care unit, where as many as 80% of patients are intubated for a primary neurologic injury ,.
Continuous evolution of mechanical ventilators has been taking place since the introduction of the first noninvasive mechanical ventilation in 1780 by Chaussier. The wide clinical application of the mechanical ventilators in critical care medicine helps in the continuous development, not only of these devices, but also the development of the critical care medicine and, therefore improving the overall outcome of the critically ill patients ,.
Examples for primary neurologic conditions requiring mechanical ventilation include the following: different types of stroke, status epilepticus, encephalitis, neuromuscular weakness as in myasthenia gravis, Guillain–Barre syndrome, amyotrophic lateral sclerosis, acute inflammatory myopathy, intoxications and poisoning, etc. There are special considerations for mechanical ventilation regarding dealing with such patients, and the clinicians must be aware of such issues and be prepared to introduce appropriate strategies to enhance neurologic recovery and facilitate extubation .
For any patient requiring ventilatory support, early detection of the possible risk factors can improve outcome, thus modulation of these risk factors will make management evolve from rehabilitation to prevention. Assessing these possible risk factors can clinically predict the outcome of mechanically ventilated patients admitted in the neuro-ICU. Moreover, carefully choosing the appropriate ventilation strategy and proper management can also influence patients’ outcome, to decide who will benefit and to what extent.
| Patients and methods|| |
This hospital-based cohort prospective study was carried out at Department of Neuropsychiatry and Center of Psychiatry, Neurology and Neurosurgery, Tanta University Hospitals. A total of 63 patients were included in the study during a 12-month period, started from May 2016. This study was approved by the ethics committee of our institution; informed consent was obtained from all patients after full explanation of the procedure. It was approved by the Research Ethical Committee, Faculty of Medicine, Tanta University.
Patients selection criteria
The inclusion criteria included patients with age equal or more than 18 years and any patient requiring ventilatory support owing to either neurologic or non-neurologic causes.
Patients already intubated at the time of admission, patients who were decided to be ventilated before transfer to our ICU, and patients who died before the introduction of mechanical ventilation were excluded from the study.
The studied patients were categorized into five groups according to the main cause of intubation and/or ventilation:
- Group I: patients intubated for airway protection or ventilated for suppression of epileptic activity with no respiratory failure.
- Group II: patients ventilated for central cause for respiratory failure.
- Group III: patients ventilated for failure in respiratory mechanics secondary to the neurological insult (e.g. aspiration pneumonia, stunned myocardium, neurogenic pulmonary edema, and pulmonary embolism).
- Group IV: patients ventilated for respiratory failure caused by peripheral nervous disorder.
- Group V: patients ventilated for causes unrelated to the neurological insult (e.g. chronic obstructive pulmonary disease, and acute renal failure).
Baseline and follow-up assessment: all included patients were subjected to the following:
- History taking including the personal history and comorbid conditions.
- Neurological and general clinical examination.
- Radiological studies according to each case included nonenhanced computed tomography brain, MRI brain, chest imaging, nerve conduction studies, electromyography, and echocardiography.
- Routine laboratory investigations including arterial blood gases, complete blood picture, prothrombin time and activity, international normalized ratio, liver and renal functions, lipid profile, and further laboratory investigations were ordered for each case individually (e.g. D-Dimer, lactic acid dehydrogenase, and cerebrospinal fluid analysis).
- ICU prognostic scores: Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission , and Sequential Organ Failure Assessment (SOFA) score every 2–3 days .
- Neurological disability scale: modified Rankin scale (mRS) ,,.
- Other prognostic/outcome disease-specific scores: National Institutes of Health Stroke Scale (NIHSS) on admission of patients with stroke ,, modified Erasmus Guillain–Barré Outcome Score (mEGOS) for patients with Guillain–Barre, on admission and after 7 days from admission , Intracerebral Hemorrhage (ICH) score on admission of patients with ICH , and Hess and Hunt classification of subarachnoid hemorrhage (SAH) on admission of patients with SAH .
Outcome during hospital stay (died or discharged alive) was considered for the analysis. The outcome of discharged alive patients was determined by assessing the neurological disability, and it was interpreted by mRS.
The collected data were organized, tabulated, and statistically analyzed using statistical package for the social sciences, version 19 created by IBM (Chicago, Illinois, USA). The following statistical methods were used for analysis of results.
Data were expressed as number and percentage.
For numerical values, the range, mean and SD were calculated. The differences between two mean values were tested using Mann–Whitney test (Z score) owing to small sample size of studied categories which did not guarantee normal distribution.
For categorical variable, the number and percentage were calculated, and differences between subcategories were tested by χ2 test. When χ2 was not appropriate, Fisher’s exact test and Monte Carlo exact test were used.
Correlation between data sets was done using Pearson’s correlation (r).
For all statistical tests done, the threshold of significance was fixed at 5% level (P value), that is, when less than 0.05, significant results are indicated.
| Results|| |
Of 63 patients included, 30 (47.6%) died after mechanical ventilation introduction. The age of studied patients ranged from 18 to 82 years, with a mean age 59.70±15.68 years. Overall, 52.4% of patients (33 patients) survived and 47.6% (30 patients) died after introduction of mechanical ventilation. Ischemic stroke cases represented 34.9% of all cases, and hemorrhagic stroke cases represented 28.6% of all cases.
Most cases (76.2%) used invasive positive pressure ventilation (IPPV) alone, whereas the rest used either noninvasive positive pressure ventilation (NPPV) alone (11.1%) or both strategies (12.7%). Diabetes mellitus and hypertension were the most common comorbid conditions found among the studied patients, with a percentage each of 42.9% of all cases, whereas the least common were renal diseases and thyroid dysfunction, with a percentage of 9.5% each.
In relation to patient mortality, no statistically significant difference was found regarding different age subgroups, with increasing percentage of death, from 25% in patients less than 45 years to 66.7% in patients more than or equal to 75 years. When we used a cutoff age at 65 years to define old aged patients, we had found statistically significant influence on patient mortality (P=0.003). No statistically significant difference was found between both sexes, where 50% of males died and 45.2% of females died.
A statistically significant difference (P=0.001) was found regarding ventilator strategy used, where 56.3% of IPPV alone ventilated patient died, none of patients ventilated with NPPV alone died, and 37.5% of the patients died using both strategies.
There was a statistically significant difference (P=0.018) when relating patient mortality to duration of stay, where duration in dead cases ranged from 1 to 27 with a mean of 9.11±5.86, and ranged from 3 to 67, with a mean of 14.15±11.59, in survived cases. No significance was found when relating patient mortality to duration of ventilation, where duration in dead cases ranged from 1 to 14 with a mean of 6.68±3.84, and ranged in survived cases from 1 to 45, with a mean of 8.21±8.12.
We also had found a statistically significant difference among different groups in relation to mortality (P=0.001), where the highest death percentage (80%) was seen in group II, and no death occurred in group V. Moreover, death occurred in 61.9% of group III patients, 28.6% of group IV patients and 14.3% of group I patients. Regarding type of stroke, most patients with hemorrhagic stroke died (83% of cases), whereas only 45.5% of patients with ischemic stroke died. Cause of death among patients with stroke was significantly related to the main cause of ventilation, where 83.4% of patients died from the neurological insult when ventilated owing to the neurological insult itself (group II), whereas 92.3% of patients died from chest condition when ventilated owing mechanical failure related to neurological insult (group III).
Regarding associated comorbid conditions, association of hypertension and cardiac disease significantly influenced mortality of studied patients (P=0.002 and 0.017, respectively).
There was a statistically significant difference (P=0.001) when relating patient grouping according to main cause of ventilation to main cause of in-hospital mortality of patients with stroke, where cause of death was significantly related to the main cause of ventilation, as 83.4% of patients died from the neurological insult when ventilated owing to the neurological insult itself (group II), whereas 92.3% of patients died from chest condition when ventilated owing mechanical failure related to neurological insult (group III) (including most importantly aspiration pneumonia). Only 8.3 and 7.7% of patients died from cardiac condition in group II and group III, respectively.
With application of ICU scores, we had found a statistically significant difference when relating mean APACHE II and maximum SOFA scores to mortality (P=0.003 and 0.001, respectively). APACHE II score on admission was not significantly correlated with duration of stay and ventilation, among neither all cases nor survivors.
When assessing mRS among survivors in relation to patient groups, we found a statistically significant difference among difference groups (P=0.020), where all group I patients were associated with favorable outcome. Moreover, group V patients were the second least disabled, where 66.7% of patients in this group had favorable outcome. In relation to type of stroke, we did not find any significant difference statistically, where 75% of patients with ischemic stroke had unfavorable outcome, whereas 66.7% of patients with hemorrhagic stroke had unfavorable outcome, with a percentage of 66.7%.
A statistically significant difference (P=0.041) was found when assessing NIHSS on admission of patients with stroke and in relation to mortality, where the higher score was associated with a more risk of mortality. The scores of all the dead patients with stroke ranged from 4 to 32, with a mean of 19±7.92, compared with scores ranging from 3 to 21, with a mean score 13±6.22, in survived patients with stroke. Moreover, a significant difference was found between dead and survived patients regarding ICH score on admission (P=0.044), where dead patients’ mean score was 2.9±1.1 and survived patients’ mean score was 1.33±0.58. There was no significant influence of interpreted mEGOS score on the mortality of patients with GBS ([Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7]).
|Table 2 Clinical characteristics of studied patients and their relation to mortality|
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|Table 3 Prognostic/outcome scores, duration of stay and duration of ventilation in relation to mortality|
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|Table 4 Mortality among subarachnoid hemorrhage cases in relation to Hunt and Hess grade on admission|
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|Table 5 Correlation between Acute Physiology and Chronic Health Evaluation-II score on admission and duration of stay and duration of ventilation|
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|Table 6 Assessment of the degree of neurological disability by modified Rankin scale on survivors’ discharge in relation to main cause of ventilation (patient groups) and type of stroke (either ischemic or hemorrhagic)|
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|Table 7 Main cause of death among stroke cases in relation to patient groups and stroke type|
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| Discussion|| |
There has been a huge evolution in the neurological ICU over the past decades, and this had led to a decrease in both in-hospital mortality and length of hospital stay without associated effects on readmission rates and long-term mortality .
Introduction of mechanical ventilation in our ICU represented a step-up in the quality of care delivered to our patients. Mechanical ventilation is an essential supportive measure, and this study was conducted to reveal possible clinical predictors and outcome of the studied patients who required ventilatory support during the setting of admission in our ICU. We applied certain measures and different assessment tools owing to the great case diversity.
We tried to correlate and compare different applied parameters with patients’ mortality and disability, to assess what is a significant predictor for poor outcome and what is not.
Regarding age as a predictor for mortality, we had found no statistically significant difference regarding different age subgroups applied, with increasing percentage of death in patients less than 45 years of age at 25 to 66.7% in patients more than or equal to 75 years of age. We used the same age subgroups applied in APACHE II score for better age discrimination .
When we used a cutoff age at 65 years to define old age, we found a statistically significant difference (P=0.003), where 75% of old aged patients (i.e. >65 years) died compared with 34.9% of patients who were not old (i.e. ≤65). Some studies used this cutoff at 65 years to define old age, and significant difference was reported regarding age of admitted ICU patients, whether ventilated or not ,. This discrepancy may be owing to the effect of mechanical ventilation on younger age groups.
Regarding sex of the studied patients, no statistically significant difference was found between both sexes, where 50% of males died and 45.2% of females died. This was consistent with several studies of sex on outcome of critically ill patients ,. This finding was not consistent with a previous study, which suggested that sex significantly influenced mortality, where mortality rates were significantly higher in females than males. This discrepancy may be owing to different patient populations, as this previous study was performed at two academic referral hospitals where women had less access to basic health care compared with men .
Regarding ventilator strategy used, we had found a statistically significant difference (P=0.001). Overall, 56.3% of IPPV alone ventilated patients died, none of patients ventilated with NPPV alone died, and 37.5% of the patients died who were ventilated by both strategies in the setting of admission in our ICU. This was consistent with Amri Maleh et al.  and Brochard , who suggested that NPPV, especially when early delivered to patients, significantly lowered in-hospital mortality in general, and lowered need for intubation to avoid the harmful hazards of IPPV. However, combining NPPV with IPPV especially when the former is used with caution immediately after extubation for high-risk selected patients had improved weaning outcome and reduced need for re-intubation, as stated by Lin et al. .
Regarding mortality in patient grouping according to main cause of ventilation, we had found a statistically significant difference among different groups (P=0.001). We had found the highest death percentage (80%) in patients ventilated owing to a central impairment of respiratory drive (group II), and no death occurred in patients ventilated owing to a cause not directly related to the neurological insult (group V). Moreover, death occurred in 61.9% of group III patients, 28.6% of group IV patients, and 14.3% of group I patients.
When relating type of stroke to different patient groups, we did not find any statistically significant difference. Most patients with stroke ventilated owing to a cause not directly related to neurological insult (group V) were ischemic in nature (83.3%), whereas most patients ventilated owing to central impairment of respiratory drive (group II) were hemorrhagic in nature.
Regarding mortality in relation to type of stroke, either ischemic or hemorrhagic, we had found a statistically significant difference (P=0.014). Most patients with hemorrhagic stroke died (83% of cases), whereas only 45.5% of patients with ischemic stroke died. This was not consistent with Mayer et al. , where stroke subtype did not significantly influence mortality. This discrepancy may be owing to larger population size in this study (510) in comparison with our study.
In our study, stroke cases were the majority. Causes of in-hospital mortality can be related or unrelated to stroke itself. Some studies denoted that the main cause of in-hospital mortality was related to the neurologic process itself damaging the central nervous system, and other causes included cardiovascular insult, chest conditions, and introduction of mechanical ventilation ,.
When assessing the main cause of in-hospital mortality in mechanically ventilated stroke patients and relating it to the main cause of ventilation, there was a statistically significant difference (P=0.001) regarding patient grouping according to main cause of ventilation, where cause of death was significantly related to the main cause of ventilation, as 83.4% of patients died from the neurological insult when ventilated owing to the neurological insult itself (group II), whereas 92.3% of patients died from chest condition when ventilated owing mechanical failure related to neurological insult (group III) (including most importantly aspiration pneumonia). Only 8.3 and 7.7% of patients died from cardiac condition in group II and group III, respectively.
Regarding comorbid conditions in studied patients, association of hypertension and cardiac diseases significantly influenced mortality of studied patients (P=0.002 and 0.017, respectively). This was consistent with several studies that revealed the major influence of hypertension on mortality rates despite lower incidence of hypertension-related diseases, and also the high mortality rates among patients with cardiovascular diseases ,.
When relating patients’ mortality to duration of stay, we had found a statistically significant difference regarding duration of stay (P=0.018), with a range of 1–27 days and a mean of 9.11±5.86 days in dead cases, and a range of 3–67 days and a mean of 14.15±11.59 days in survived cases. Introduction of mechanical ventilation itself, especially the invasive strategy, can be a predictor of mortality and decreased hospital stay owing to possible associated hazards, although some of these hazards may be overwhelmed ,.
When relating patients’ mortality to duration of ventilation, we had not found a significant relation, with a range of 1–14 days and a mean of 6.68±3.84 days in dead cases, and a range of 1–45 days and a mean of 8.21±8.12 days in survived cases. Figueroa-Casas et al.  had tried to accurately predict the duration of ventilation using different clinical measures, with quite limited results. Some other studies had found a significant influence of prolonged mechanical ventilation on patients’ outcome, where prolonged ventilated patients had poor outcome ,,. This discrepancy may be owing to the nature of studied patients.
With application of several scoring systems, we focused on comparing these scores mainly to mortality of ventilated patients, to assess validity and reliability of these scores in our ICU.
Regarding APACHE II score on admission and maximum SOFA score, we had found a statistically significant difference among different score subgroups in relation to mortality (P=0.003 and 0.001, respectively). In APACHE II score, death percentage increased ascendingly from 22.2% in 5–9 subgroup to 75% in 35–100 subgroup of APACHE II score, with a mean score of 22.37±8.87, and from 0% in 0–6 subgroup to 100% in 15–24 subgroup of SOFA score, with a mean score of 13.10±7.92. This was consistent with Naved et al.  and Bian et al. . Ho  stated that combining APACHE II and maximum SOFA scores may improve the accuracy of risk adjustment in outcome studies of critically ill patients.
Rapsang and Shyam  doubted the sensitivity and specificity of APACHE II score in terms of mortality prediction and stated that it has major limitations such as the presence of comorbid conditions and the dynamic physiological variables that can be influenced by multiple factors, including ongoing resuscitation and treatment.
When we correlated APACHE II score on admission with duration of stay, we found a weak nonsignificant negative association. This was not consistent with Naved et al. , who found a significant negative correlation regarding duration of stay in ICU. They correlated the score among all cases, not only ventilated ones, and also the nature of studied cases differed, as their study was not performed in a dedicated neurological ICU. We also correlated the score with duration of ventilation and found a weak nonsignificant positive correlation. Moreover, this was the finding when we correlated the score among survivors to both duration of stay and ventilation.
When assessing disability by comparing mRS among survivors in relation to patient groups, we had found a statistically significant difference among difference groups (P=0.020), where all group I patients were associated with favorable outcome. Moreover, group V patients were the second least disabled, where 66.7% of patients in this group had favorable outcome. Various degrees of disability were found among the other groups, and the most disabled patients belonged to group III, where 87.5% of patients had unfavorable outcome. Thus, the degree of disability was closely related to the main aim of ventilation ‘patient groups.’ It is to be noted that 54.5% of all survivors had favorable outcome and 45.5% had unfavorable one.
When comparing mRS among survivors in relation to type of stroke, we did not find any significant difference statistically, where 75% of patients with ischemic stroke had unfavorable outcome, whereas 66.7% of patients with hemorrhagic stroke had unfavorable outcome. Overall, 73.3% of all patients with stroke had unfavorable outcome.
The assessment of NIHSS on admission of patients with stroke and comparing it with stroke patients’ mortality revealed a statistically significant difference (P=0.041), where the higher score was associated with a more risk for mortality. The scores of all dead patients with stroke ranged from 4 to 32, with a mean of 19±7.92, compared with 3–21, with a mean score 13±6.22, in survived patients with stroke. This was consistent with Fonarow et al. , indicating that the index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information. Moreover, in agreement with these results, Eskioglou et al.  considered that NIHSS was a good predictor of stroke outcome, where NIHSS score of less than or equal to 6 predicted a good recovery, whereas a score more than or equal to 16 was associated with a high probability of death or severe disability.
Regarding mEGOS on admission and after 7 days for patients with Guillain–Barre, we found no significant influence of the score on patients’ mortality. The mEGOS was used to accurately detect long-term disability of patients with Guillain–Barre at 4 weeks, 3 and 6 months .
Regarding the ICH score an assessing its influence on mortality, when interpreted within 24 h of admission, we had found a significant difference between dead and survived patients (P=0.044), where the mean score of dead patients was 2.9±1.1 and of survived patients was 1.33±0.58. This was consistent with Meyer et al.  and Panchal et al. , where ICH score significantly influenced patient mortality. Panchal et al.  also observed more significance when the score was interpreted 72 h after admission.
When assessing mortality among SAH cases in relation to Hunt and Hess grade on admission, we did not find any statistically significant difference, where 66.7% of cases with grades less than or equal to three died, and all cases with grades more than three died. This was not consistent with Lantigua et al.  and Lee et al. . This may be because our study focused on mechanically ventilated patients and also owing to the limited number of the studied SAH cases.
| Conclusion|| |
Old age is associated with more mortality rates despite no significant difference among the different age groups, thus mechanical ventilation can influence survival among younger age groups. Early introduction of NPPV, when indicated, can improve in-hospital mortality rates and avoid the hazards of intubation and IPPV. Outcome of ventilated patients is closely related to the main cause of intubation and ventilation, where most ventilated patients with central causes of respiratory failure died, indicating mechanical ventilation is not a therapeutic intervention, but essentially a supportive measure, though a crucial one. Association of hypertension and cardiac diseases can be a good predictor factor for mortality of ventilated patients in our ICU. Application of general ICU scores like APACHE II and SOFA scores and other prognostic and disability scores for specific disease such as NIHSS, ICH score, and mRS can monitor case progression and significantly influence outcome of ventilated patients, especially when related to the main cause of ventilation.
Further multicentered studies should be performed in our locality to highlight the role of mechanical ventilation in the neurocritical care unit, focusing on the appropriate strategies and proper troubleshooting of the ventilated patients, and determining the effect of prolonged ventilation on the neurological state.
There is a need of a protocol for evaluation of neurological ICU patients and application of further ICU scores, and combining the results of the applied scores with each other and with each disease-specific prognostic scores to acquire the best interpreted prediction for ventilated patients’ outcome.
Further evaluation of the correlation between duration of ventilation and hospital stay and patient clinical characteristics, with its effect on patient outcome, should be done.
This is a single-center experience and represents a limited number of patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]