Effect of hyperglycemia at admission on the outcome of surgical evacuation of supratentorial spontaneous intracerebral hemorrhage

Open access: https://ina-jns.org/ Effect of hyperglycemia at admission on the outcome of surgical evacuation of supratentorial spontaneous intracerebral hemorrhage Mohamad Saekhu1*, Hilman Mahyuddin1, Samsul Ashari1, David Tandian1, Hanif G Tobing1, Renindra A Aman1, Syaiful Ichwan1, Wismaji Sadewo1, Setyowidi Nugroho


INTRODUCTION
The case fatality of spontaneous intracerebral hemorrhage (SICH) is high, particularly in low-to middle-income countries. 1,2 The 1-month mortality of such condition is 40%, 3 and no significant change was observed within the last two decades. 4 Aside from hematoma volume, comorbidities are the significant factors that influence mortality and outcome 5-7 , of which hyperglycemia is the most common. 8 Clinical studies have shown that hyperglycemia in the acute phase of ischaemic and hemorrhagic stroke is associated with poor outcome. 8, 9 Meanwhile, other studies have shown that surgical evacuation of hematoma can reduce mortality. 7 Therefore, the detrimental effect of hyperglycemia on the outcome of patients with SICH who are undergoing surgical evacuation of hematoma must be further validated. This study aimed to assess the effect of hyperglycemia on in-hospital mortality and length of hospital stay (LOS) in patients with supratentorial SICH who underwent surgical evacuation of the hematoma.

METHODS
This study is a subanalysis (cohort design) from the previous clinical trial that assessed the neuroprotective effects of tigecycline. 10 The ethical clearance number of the study of the neuroprotective effects of tigecycline was 493/PT02.FK/ETIK/2012. Out of 72 subjects, 68 subjects had the result of blood glucose level at admission to the hospital, and four subjects were missed the blood glucose levels. Only subjects who had blood glucose levels at admission are included in this study.
The blood glucose levels of the subjects were assessed before the administration of prophylactic antibiotics. Based on blood glucose levels, subjects were divided into hyperglycemia and non-hyperglycemia groups. Hyperglycaemia was defined as blood glucose level > 140 mg/dL (7.77 mmol/L). 11 We also collect data that previously believed to affect the outcome of patients with SICH. The outcomes measured included in-hospital mortality and LOS. Data about LOS were dichotomized to < 15 days based on our clinical experience. We assessed for the severity of clinical injury using the Glasgow Coma Scale, and radiologic severity was examined according to hematoma volume, degree of brain midline shift (MLS), and obstruction of the ambient cistern. 12, 13 Midline shift (MLS) was measured at the level of the foramen of Monro using the following equation: MLS = (□/2) − □, where a is the width of the intracranial space through the septum pellucidum (SP), and b is the distance from the bone to the SP. 13 The chi-square test and Fisher's exact test were used to analyze the association between the characteristics of patients, radiological findings, and outcomes. A multivariate analysis using logistic regression was conducted for variables with a p-value < 0.25 in the univariate analysis. A p-value < 0.05 was considered statistically significant.

RESULTS
The mean age of the subjects in this study was 54.5 ± 9 years, the mean volume of hematoma was 51 ± 15 mL, and the mean blood sugar level at admission was 173 ± 64 mg/dL. The proportion of hyperglycemia on various factors that were commonly believed to affect the outcome of SICH seen in Table 1.
A total of 19 (26%) in-hospital mortalities were recorded during the study, and 15 (79%) patients died within the first seven days after surgery. The median LOS was 12.5 (range: 2 -64) days. The effect of hyperglycemia on the outcome of surgical evacuation of supratentorial SICH is shown in Table 2.
Patients with hyperglycemia upon admission did not significantly differ in terms of in-hospital mortality and LOS.

Acknowledgments
We thank all patients and their families who participated in this study, and hospitals were included in this study with their permission.

AUTHOR CONTRIBUTIONS
MS conceived and carried out the experiments, involved in treating patients who are research subjects, and wrote the manuscript. HM conceived the experiments. SA supervised the project. DT involved in treating patients who are research subjects. HGT involved in treating patients who are research subjects. SI involved in treating patients who are research subjects. WS involved in treating patients who are research subjects. SN supervised the project.

DISCUSSION
Hyperglycaemia is a common medical complication in patients with SICH. Pathophysiologically, hyperglycemia is caused by the disruption of blood glucose regulation in the brainstem due to the mass effect of hematoma and brain herniation. 12 Previous studies have shown that the prevalence of hyperglycemia in patients with SICH is 51%. 13 Although a higher cut-off value was used to define hyperglycemia (7.77 mmol/L rather than 6.5 mmol/L), this study showed a higher prevalence of 65%. This phenomenon may be attributed to three reasons. First, one study of traumatic brain injury has shown that patients with more severe injury have significantly higher blood glucose levels. 14 MLS was associated with hyperglycemia in our study, which strengthens the notion that such a condition can reflect the severity of brain injury correlated to SICH. Second, all patients in our study had a hematoma volume > 30 mL, compared with < 30 mL in other studies. 10,13 Third, the prevalence of diabetes in our study was higher than that of previous studies (18% vs. 11%). Following a previous study, 13 our study showed that a history of diabetes was significantly associated with hyperglycemia (OR: 7.667; 95% CI: 0.925 -63.567; p = 0.045).
Considering that hyperglycemia can reflect the severity of brain injury in patients with SICH, such a condition can affect the outcome of patients with SICH. Previous studies have shown that hyperglycemia is associated with mortality after SICH. 13,15, 16 In contrast, our study showed that hyperglycemia upon admission was not associated with mortality and LOS. Indeed, all participants in our study underwent hematoma evacuation, whereas participants in previous studies did not. Hematoma volume is considered a determinant factor for outcome. 5 Hematoma evacuation may negate the influence of other factors. Another study that included both surgical and non-surgical patients has shown that hyperglycemia did not affect mortality. 17 The present study had some limitations. The outcome upon discharge and in-hospital mortality and LOS are challenging to assess. However, after five days of managing patients with supratentorial SICH, early assessment of the prognosis of SICH is feasible, 18 and the adverse effect of hyperglycemia can be observed within the first four weeks after onset. 19 Also, short-term assessments, such as evaluation of in-hospital mortality and LOS, can be used to distinguish patients who may benefit from the surgical evacuation of hematoma and to provide information about recovery expectations to patients and relatives. 20