Objective To investigate the effects of high concentrations of iodide exposure on mitochondrial superoxide production,cell viability and cell damage in the thyroid of metallothionein Ⅰ/Ⅱ knockout (MT-Ⅰ/Ⅱ KO) mice and corresponding wild type (WT) mice.Methods Thyroid cell suspension of six to eight weeks old healthy male MT-Ⅰ/Ⅱ KO mice and WT mice were prepared.The thyroid cells were treated with high concentrations (10-4,10-3,10-2 mol/L) of potassium iodide(KI),or 10-3 mol/L hydrogen peroxide(H2O2) for 2 hours,respectively.Cell viability was evaluated with methyl thiazolyl tetrazolium(MTT) assay.Lactate dehydrogenase (LDH) level in cell culture medium was detected by enzyme-linked immunosorbent assay(ELISA).Mitochondrial superoxide production in the thyroid cells was measured by flow cytometry using a fluorescent probe,mitochondrial superoxide(MitoSOX).Results Compared to the control group[(100.00 ± 0.00)％,(100.00 ± 0.00)％],the cell viability of 10-4,10-3,10-2 mol/L KI and 10-3 mol/L H2O2 exposure groups were significantly decreased in the thyroid cells of both WT [(73.63 ± 2.05)％,(72.41 ± 2.26)％,(69.63 ± 2.29)％,(44.90 ± 2.93)％] and MT-Ⅰ/Ⅱ KO mice[(65.40 ± 2.39)％,(64.51 ± 2.27)％,(61.48 ± 2.33)％,(40.80 ± 2.76)％,all P＜ 0.05].Compared to the control group [(1 995.28 ± 30.52),(2 004.96 ± 19.71)U/L],significantly increased LDH activities were detected in the thyroid cells of WT [(2 809.22 ± 156.53),(2 850.80 ± 137.83),(2 920.45 ± 152.92),(4 487.49 ± 130.67)U/L] and MT-Ⅰ / Ⅱ KO mice [(3 261.06 ± 120.44),(3 474.19 ± 142.15),(3 597.08 ± 150.86),(4 706.64 ± 148.57)U/L,all P ＜ 0.05].Compared to the control group (26.49 ± 7.66,37.11 ± 8.48),the MitoSOX red fluorescence intensities of 10-2 mol/L KI and 10-3 mol/L H2O2 groups were significantly increased in WT mice(58.96 ± 5.11,87.95 ± 4.25) and MT-Ⅰ/ⅡKO mice(71.21 ± 5.55,99.76 ± 4.42) by flow cytometry (all P ＜ 0.05).Compared to the thyroid cells in WT mice,significantly decreased cell viability (all P ＜ 0.05),significantly increased LDH activity(all P ＜ 0.05) and significantly increased MitoSOX red fluorescence intensity by flow cytometry (all P ＜ 0.05) were detected in the thyroid cells of MT-Ⅰ/Ⅱ KO mice following treatment with KI or H2O2.Conclusions High concentrations of iodide (10-2 mol/L) and 10-3 mol/L H2O2 may lead to significant increase of mitochondrial superoxide production and LDH activity,decrease of cell viability in both WT and MT-Ⅰ / Ⅱ KO mice.More significant increase of superoxide production is detected in MT-Ⅰ / Ⅱ KO mice,indicating the potential protective role of metallothionein in the thyroid cells of WT mice.

Objective To investigate the effects of iodine excess on spleen cell viability,lactate dehydrogenase (LDH) leakage,mitochondrial superoxide production and peroxiredoxin (Prx)3 expression in methallothionein Ⅰ / Ⅱ knockout (MT-Ⅰ / Ⅱ KO)mice.Methods Spleen cell suspensions were prepared from six to eight-week old and healthy male MT-Ⅰ / Ⅱ KO mice and wild type (WT) mice; the cell number was adjusted to 5 × 107/L and the cells were plated in 96-well plates (100 μl each well); the cells were exposed to various concentrations of KI (0,10-4,10-3,10-2 mol/L) and 10-3 mol/L H2O2,respectively,for two hours,and control group did not give KI nor H2O2.Cell viability was assayed by methyl thiazolyl tetrazolium (MTT) colorimetric method.Cell damage was detected by chemical colorimetric method.Mitochondrial superoxide production in the spleen cells was measured by flow cytometry.Western blotting technology was used to investigate the expression of Prx3.Results In both MT-Ⅰ/Ⅱ KO and WT mice,the differences of cell viability,LDH leakage,mitochondrial superoxideproduction and the expression of Prx3 of spleen cells among the treatment groups were statistically significant (F =357.92,71.03,130.36,10.36,179.58,26.92,187.43,and 7.16,all P ＜ 0.05).Compared to the control group [(100.00 ± 2.00)％,(100.00 ± 1.63)％,(3 202.22 ± 85.63),(3 161.51 ± 144.49)U/L,43.82 ± 1.56,38.60 ± 2.81,0.61 ± 0.09,0.50 ± 0.08],cell viability of 10-4,10-3,10-2 mol/L KI treatment and 10-3 mol/L H2O2 groups [(80.77 ± 1.86)％,(89.89 ± 2.90)％,(76.08 ± 1.92)％,(87.66 ± 1.74),(73.26 ± 1.86)％,(84.30 ± 2.23)％,(66.22 ± 1.71)％,(70.80 ± 1.49)％] was decreased (all P ＜ 0.05); LDH leakage [(3 880.00 ± 190.62),(3 431.17 ± 170.45),(4 178.33 ± 170.43),(3 598.63 ± 189.09),(4 388.61 ± 123.79),(3 863.72 ± 195.64),(4 615.28 ± 196.17),(4 148.12 ± 195.81)U/L] was increased significantly (all P＜ 0.05); and mitochondrial superoxide production in the spleen cells (53.83 ± 3.22,47.03 ± 1.60,58.92 ± 4.00,50.48 ± 2.59,72.72 ± 2.14,68.53 ± 2.97,80.76 ± 4.11,75.26 ± 3.41) was increased significantly (all P ＜ 0.05); Prx3 expressions in 10-3、10-2 mol/LKI and 10-3 mol/L H2O2 treatment groups (0.82 ± 0.12,0.65 ± 0.12,0.96 ± 0.15,0.73 ± 0.16,1.04 ± 0.13,0.85 ± 0.16) significantly increased (all P ＜ 0.05),the differences of Prx3 expressions between 104 mol/L KI groups (0.73 ± 0.15,0.55 ± 0.09),and control groups were not statistically significant (all P ＞ 0.05).In 104,10-3,10-2 mol/L KI and 10-3 mol/L H2O2 treatment groups,cell viability of MT-Ⅰ/Ⅱ KO mice spleen was lower than that of WT mice (t =6.47,10.93,9.30 and 4.96,all P ＜ 0.05); LDH leakage was higher than that of WT mice (t =4.30,5.58,5.56 and 4.13,all P ＜ 0.05); mitochondria superoxide production was higher than that of WT mice (t =4.64,4.33,2.80 and 2.52,all P ＜ 0.05); Prx3 expression was higher than that of WT mice (t =2.54,2.37,2.59 and 2.27,all P ＜ 0.05).Conclusions KI may decline the cell viability,increase the leakage of LDH and increase the production of mitochondrial superoxide production and Prx 3 expression,which are much more significant in MT-Ⅰ /Ⅱ KO mice,suggesting that MT Ⅰ /Ⅱ has some antioxidative effect in high concentration of iodide induced oxidative stress in the spleen.

Objective To evaluate the diagnostic value of cerebrospinal lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation (PNBM) with blood-contaminated cerebrospinal fluid (CSF). Methods A prospective observational study was conducted. 101 patients underwent neurosurgical operation and clinically suspected PNBM admitted to neurosurgical intensive care unit (NSICU) of the First Affiliated Hospital of Sun Yat-sen University from October 2015 to December 2016 were enrolled. Based on red blood cell quantitative test in CSF, the patients were divided into blood-contaminated and non blood-contaminated CSF groups. According to the PNBM diagnostic criteria of 2008 Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN), all patients were divided into PNBM group and non-PNBM group. The biochemical indexes levels in CSF were compared among the groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of CSF lactate for PNBM in blood-contaminated patients.Results A total of 101 suspected PNBM patients were enrolled. In 77 blood-contaminated CSF patients, 39 patients were diagnosed as PNBM (account for 50.6%); in 24 non-blood-contaminated patients, 12 patients were diagnosed as PNBM (account for 50.0%). ① In non-PNBM patients, the lactate level in blood-contaminated CSF was significantly higher than that of non-blood-contaminated CSF (mmol/L: 3.5±1.3 vs. 2.3±1.1,P < 0.01). In PNBM patients, there was no significant difference in lactate level between blood-contaminated CSF and non blood-contaminated CSF (mmol/L: 6.8±2.1 vs. 6.9±2.5,P > 0.05). ② In both blood-contaminated and non blood-contaminated CSF, white blood cell (WBC), protein and lactate levels in PNBM group were significantly higher than those in non-PNBM group [WBC (×106/L): 660.0 (67.5, 1105.0) vs. 41.0 (15.0, 142.5) in blood-contaminated CSF,168.0 (86.5, 269.5) vs. 34.5 (7.0, 83.5) in non-blood-contaminated CSF; protein (mg/L): 4757.8 (2995.2, 10219.8) vs. 1292.8 (924.2, 1936.2) in blood-contaminated CSF, 39247.3 (14900.6, 62552.2) vs. 1441.6 (977.3, 2963.9) in non blood-contaminated CSF; lactate (mmol/L): 6.8±2.1 vs. 3.5±1.3 in blood-contaminated CSF, 6.9±2.5 vs. 2.3±1.1 in non blood-contaminated CSF, allP < 0.05], and glucose and CSF glucose/blood glucose ratio in PNBM group were significantly lower than those in non-PNBM group [glucose (mmol/L): 2.5±1.2 vs. 4.4±1.6 in blood-contaminated CSF, 1.9±1.4 vs. 3.4±0.9 in non blood-contaminated CSF; CSF glucose/blood glucose ratio: 0.28±0.15 vs. 0.46±0.16 in blood-contaminated CSF, 0.24±0.16 vs. 0.45±0.11 in non blood-contaminated CSF, allP < 0.01]. ③ It was shown by ROC curve analysis that CSF lactate level was a good diagnostic parameter for PNBM both in blood-contaminated and non blood-contaminated CSF, and the area under ROC curve (AUC) was 0.91 and 0.97, respectively. When the cutoff value of lactate in non blood-contaminated CSF was 3.35 mmol/L, the sensitivity was 100%, and the specificity was 91.7%. When the cutoff value of lactate in blood-contaminated CSF was 4.15 mmol/L, the sensitivity was 92.3%, and the specificity was 71.1%, and the combination of CSF lactate and glucose achieved better diagnostic specificity (AUC = 0.96, sensitivity was 97.4%, specificity was 84.2%).Conclusions Blood in CSF led to the elevation of CSF lactate as compared with that in non-blood-contaminated CSF of patients with PNBM. CSF lactate was still a good diagnostic parameter for PNBM both in blood-contaminated patients, and the combination of CSF lactate and glucose achieved better diagnostic specificity.

Objective:To investigate the pathophysiology,clinical manifestation and neuroimaging characteristics and therapeutic experiences for hemichore associated with non-ketotic hyperglycemia (HC-NH).Methods:Clinical data of three patients with HC-NH from Xiangya Hospital,Central South University were analyzed retrospectively,and the related literature was reviewed.Results:The core clinical features of HC-NH were characterized by acute/subacute onset of hemichorea with non-ketotic hyperglycemia in the elderly females.Radiologic findings associated with HC-NH were characterized by hyperattenuation on computed tomographic (CT) scans and hyperintensity on Tl-weighted magnetic resonance imaging (MRI) at unilateral basal ganglion region.Blood glucose control was the foundation of treatment.Dopamine receptor antagonists and benzodiazepine sedative were helpful in controlling hemichorea.Conclusion:Hemichorea-hemiballismus is a rare complication of nonketotic hyperglycaemia in elderly type 2 diabetes.It is associated with contralateral striatal radiological abnormality and typically T1 hyperintensity on MRI.The pathophysiology of HC-NH is not clear.The prognosis of HC-NH is favorable.Antidiabetic drugs combined with dopamine receptor antagonists can effectively relieve the hemichorea symptoms.

OBJECTIVETo analyze potential mutations of the NOTCH3 gene in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL).

METHODSThe two probands and related family members and 100 healthy controls were recruited. Potential mutations of the NOTCH3 gene were screened by PCR and direct sequencing. PolyPhen-2 and SIFT software were used to predict the protein function.

RESULTSThe conditions of both probands were adult-onset, with main clinical features including recurrent transient ischemic attacks and/or strokes, cognitive impairment. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A heterozygous mutation c.328C>T (p.Arg110Cys), which was located in exon 3 of the NOTCH3 gene and known as a causative mutation, was identified in proband 1. A novel heterozygous mutation c.1013 G>C (p.Cys338Ser) located in exon 6 of the NOTCH3 gene was identified in the proband 2, which was not reported previously. The same mutations were not detected among the 100 unrelated healthy controls. Function analysis suggested that heterozygous mutation c.1013G>C can severely affect the functions of NOTCH3 protein.

CONCLUSIONTwo heterozygous missense mutations in the NOTCH3 gene have been identified in two families affected with CADASIL. The novel heterozygous Cys338Ser mutation in exon 6 of the NOTCH3 gene probably underlies the CADASIL.

Adult ; Brain ; diagnostic imaging ; CADASIL ; diagnostic imaging ; genetics ; Female ; Heterozygote ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; Receptor, Notch3 ; genetics

Objective: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. Methods: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol, diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. Results: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. ① The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. ② The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). ③ There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. Conclusions Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.

Objective To investigate the dynamic changes in early gastric antrum contraction in patients with craniocerebral injury. Methods The patients with craniocerebral injury admitted to neurosurgery intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from July to November in 2018 were enrolled. The changes in antral contraction frequency (ACF), antral contraction amplitude (ACA) and antral motility index (MI) were dynamically observed at 1-6 days after injury by ultrasonography. According to Glasgow coma score (GCS), the patients were divided into moderate to severe craniocerebral (GCS ≤ 11) and mild craniocerebral injury groups (GCS > 11). The differences in ACF, ACA and MI between the two groups were compared to observe the effect of craniocerebral injury on gastric antral motility. The patients were divided into simple supratentorial and supratentorial combined infratentorial lesion groups according to the lesion location of craniocerebral injury. The differences in ACF, ACA and MI between the two groups were compared to analyze the influence of lesion location on gastric antrum activity. Results A total of 68 patients with craniocerebral injury were screened during the study period, 50 patients were in accorded with the admission criteria, 17 patients were withdrawn from the observation because they could not tolerate the ultrasonography of gastric antrum or discharged from ICU. Finally, 33 patients were enrolled in the analysis. ① The ACF, ACA and MI at 1 day after injury were lower [ACF (times/min): 1.67 (0.00, 2.00), ACA: 42.06 (0.00, 44.45)%, MI: 0.70 (0.00, 0.87)], and then gradually increased, till 6 days after injury, ACF was 1.83 (1.25, 2.79) times/min, ACA was 56.80 (33.25, 60.77)%, and MI was 0.89 (0.50, 1.70), which showed no differences among all time points (all P > 0.05). ② The contractile function of gastric antrum in two groups of patients with different degrees of craniocerebral injury was decreased, especially ACA in patients with moderate to severe craniocerebral injury (n = 22), which showed significant differences at 3 days and 5 days after injury as compared with mild craniocerebral injury [n = 11; 3 days: 35.05 (0.00, 53.69)% vs. 58.51 (49.90, 65.45)%, 5 days: 39.88 (0.00, 77.01)% vs. 56.94 (41.71, 66.66)%, both P < 0.05], indicating that the degree of craniocerebral injury affected the contractive function of gastric antrum. However, there was no significant difference in ACF or MI between the two groups at different time points after injury. ③ The contractile function of gastric antrum was decreased after craniocerebral injury in both groups of patients with different lesion locations of craniocerebral injury. The ACF, ACA, and MI at 3-4 days in patients with supratentorial combined infratentorial lesion (n = 12) were slightly lower than those in patients with simple supratentorial lesion [n = 21; 3 days: ACF (times/min) was 0.83 (0.00, 2.00) vs. 2.25 (0.00, 3.00), ACA was 35.05 (0.00, 53.60)% vs. 49.93 (0.00, 63.44)%, MI was 0.29 (0.00, 1.07) vs. 1.23 (0.00, 1.61); 4 days: ACF (times/min) was 1.42 (0.50, 2.63) vs. 2.00 (1.63, 2.63), ACA was 30.45 (21.69, 60.61)% vs. 43.29 (38.41, 53.35)%, MI was 0.50 (0.15, 1.45) vs. 0.97 (0.66, 1.28)] without statistical differences (all P > 0.05), indicating that the lesion location might not affect the contractive function of gastric antrum. Conclusion In the early stage of craniocerebral injury, the contractile function of gastric antrum was decreased, and the more severe the craniocerebral injury, the worse contractive function of gastric antrum.[Key words] Craniocerebral injury; Antral contraction; Enteral nutrition; Antral ultrasonography

OBJECTIVE: To study the influential factor of hyperlactatemia after the brain tumor craniotomy. METHODS: Patients who underwent selective brain tumor (including glioma, meningioma and acoustic schwannoma) craniotomyin the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital, Sun Yat-sen University from December 1st 2018 to May 20th 2019 were enrolled. The incidence of hyperlactatemia after the brain tumor craniotomy was investigated. Univariate and multivariate linear regression analysis were performed to identify the association of initial artery lactate with the operation duration, the intraoperative blood loss, the total intraoperative fluid infusion, intraoperative ringer lactate fluid infusion, intraoperative urine volume, intraoperative fluid balance, the total intraoperative corticosteroids dosage and the tumor type. Pearson method was used to analyze the correlation between lactate in arterial blood and independent related factors. RESULTS: A total of 148 patients were enrolled including 45 patients (30.41%) with glioma, 64 patients (43.24%) with meningioma, and 39 patients (26.35%) with acoustic schwannoma. The initial lactate level in arterial blood increased significantly in 148 patients, with a median of 4.80 (3.68, 5.90) mmol/L. Among them, 78 patients (52.70%) had mild elevation of lactate in arterial blood (2 mmol/L < lactate ≤ 5 mmol/L), 61 patients (41.22%) had significant elevation of lactate in arterial blood (5 mmol/L < lactate ≤ 10 mmol/L), and 2 patients (1.35%) had serious elevation of artery lactate (> 10 mmol/L). And only 7 patients (4.73%) had normal level of lactate in arterial blood (≤ 2 mmol/L). Univariate analysis showed that initial postoperative artery lactate was positively correlated with the operation duration [β = 0.556, 95% confidence interval (95%CI) was 0.257-0.855, P < 0.001] and the total intraoperative corticosteroids dosage (β = 0.477, 95%CI was 0.174-0.779, P = 0.002). There was no significant correlation between the initial postoperative artery lactate and tumor types, the intraoperative blood loss, the total fluid infusion, the ringer lactate fluid infusion, urine volume, and the fluid balance. Further multivariate linear regression analysis showed that the operation duration (β = 0.499, 95%CI was 0.204-0.795, P = 0.001) and the total intraoperative corticosteroids dosage (β = 0.407, 95%CI was 0.111-0.703, P = 0.008) were independent risk factors affecting the initial postoperative artery lactate. The correlation analysis showed that there was a significant positive correlation between lactate in arterial blood and operation time and total hormone dosage during operation (r₁ = 0.289, r₂ = 0.248, both P < 0.01). CONCLUSIONS Initial artery lactate after brain tumor craniotomy is associated with surgery duration and exogenous administration of corticosteroids.
Adrenal Cortex Hormones/therapeutic use* ; Arteries ; Brain Neoplasms ; Craniotomy ; Humans ; Retrospective Studies

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.
Adult ; Anti-Bacterial Agents/cerebrospinal fluid* ; Drug Monitoring ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/cerebrospinal fluid*

OBJECTIVE: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. RESULTS: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. (1) The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. (2) The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). (3) There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. CONCLUSIONS Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.
Adult ; Anti-Bacterial Agents/blood* ; Critical Illness ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/blood*