뇌부종이 있는 뇌경색 환자들에서 만니톨과 신부전의 연관성

추인성,봉정빈,안성환,김후원,김진호,강현구 대한신경집중치료학회 2016 대한신경집중치료학회지 Vol.9 No.2

Background: Renal failure is one of the most common side effects of mannitol. However, very little is known regarding the cause, incidence, risk factors, and outcome of mannitol-induced renal failure. The goal of this study is to determine the predicting factors of mannitol-induced renal failure. Methods: We retrospectively reviewed the medical records of all ischemic stroke patients who were treated with mannitol due to brain edema from January 2008 to December 2010 at Chosun university hospital. From among 125 patients, 25 patients who received mannitol for less than 3 days were excluded and 100 patients were selected. Furthermore, 15% or 25% mannitol was administered intravenously as an intermittent bolus and the maximum dose was less than 200 g/day. Renal failure was defined as an increase in the creatinine level of > 0.5 mg/dL if the baseline value was < 2 mg/dL or an increase in the creatinine level of > 1 mg/dL if the baseline value was > 2 mg/dL. Results: Fourteen patients (14%) were diagnosed as having mannitol-induced renal failure. Glucose level before the use of mannitol and peak osmolality during mannitol treatment were associated with renal failure in univariate analysis. In logistic regression analysis of suspected factors (P<0.1), independent predictive factors of mannitol-induced renal failure were glucose level before the use of mannitol, (odd ratio, 1.01; 95% CI, 1.00–1.03; P<0.043) and peak osmolality (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P=0.01). Conclusions: Strict glucose control before mannitol treatment may reduce the rate of occurrence of renal failure. However, the rate of recovery from renal failure was not confirmed in our study because of the short follow up period.

Mannitol의 주입 경로와 양 및 농도가 혈-뇌 장벽 손상에 미치는 효과

차명훈 ( Myeoung Hoon Cha ),이규홍 ( Kyu Hong Lee ),이철현 ( Chul Hyun Lee ),정명애 ( Myung Ae Chung ),손진훈 ( Jin Hun Sohn ),정재준 ( Chae Joon Cheong ),이배환 ( Bae Hwan Lee ) 한국감성과학회 2008 감성과학 Vol.11 No.4

감성을 비롯한 인간의 뇌 기능은 혈-뇌 장벽을 매개로 약물의 작용에 의해 직접적인 영향을 받을 수 있다. 이 연구는 mannitol의 투여경로와 양, 농도에 의한 혈-뇌 장벽(blood-brain barrier, BBB)의 변화를 알아보고자 수행되었다. 실험동물로서 흰쥐에 20%의 mannitol을 오른쪽 뇌경동맥(internal carotid artery, ICA)을 통하여 주입하였고, 다른 그룹에서는 femoral vein을 통하여 주입하였다. 또한 각기 다른 경로를 이용하여 Evans blue(EB) 염색 시료를 투여한 후 BBB의 변성 정도를 확인하였다. 실험결과 ICA를 통해서 mannitol이 주입된 동물은 동측(ipsilateral side)이 대측(contralateral side)에 비해 EB 염색시료에 의해 영향을 많이 받았으나, femoral vein을 통해서 주입한 경우에는 mannitol의 양과 농도를 증가시켜도 EB 염색시료에 의한 영향이 거의 나타나지 않았다. 이러한 결과는 비록 EB 염색시료의 주입이 ICA를 통해서 또는 정맥경로를 따라서 이루어지더라도, BBB의 변성은 ICA를 통해서 이루어진다고 볼 수 있으며, 이러한 결과는 BBB의 제한적인 조절작용을 통해 인간의 뇌 기능을 이해하는데 좋은 방법을 제공할 수 있다는 것을 시사한다. Functions of human brain including sensibility and emotion may be affected by drugs mediated by the blood-brain barrier (BBB). The present study was performed to evaluate whether injection route, volume and concentration of mannitol could alter the degree of disruption of the BBB. Under urethane anesthesia, female Sprague-Dawley rats were infused with 20% mannitol into the right internal carotid artery (ICA). In the other group, intravenous injection of mannitol through the femoral vein was performed. Evans blue (EB) dye was used as a marker of BBB disruption. When mannitol was injected via the ICA, the content of EB dye in the ipsilateral hemisphere was markedly increased. However, the content of EB in the brain was not increased when mannitol was injected via the femoral vein, even though the volume or concentration of mannitol was increased. These results suggest that the BBB was disrupted only through ICA injection route and this may provide a useful strategy for transient opening of the BBB to control the functions of human brain.

Accumulated Mannitol and Aggravated Cerebral Edema in a Rat Model of Middle Cerebral Artery Infarction

Cho, Jae-Man,Kim, Yeon-Hee,Han, Hyung-Soo,Park, Jae-Chan The Korean Neurosurgical Society 2007 Journal of Korean neurosurgical society Vol.42 No.4

Objective : Repeated administration of mannitol in the setting of large hemispheric infarction is a controversial and poorly defined therapeutic intervention. This study was performed to examine the effects of multiple-dose mannitol on a brain edema after large hemispheric infarction. Methods : A middle cerebral artery was occluded with the rat suture model for 6 hours and reperfused in 22 rats. The rats were randomly assigned to either control (n=10) or the mannitol-treated group (n=12) in which intravenous mannitol infusions (0.8 g/kg) were performed six times every four hours. After staining a brain slice with 2,3,5-triphenyltetrazolium chloride, the weight of hemispheres, infarcted (IH) and contralateral (CH), and the IH/CH weight ratio were examined, and then hemispheric accumulation of mannitol was photometrically evaluated based on formation of NADH catalyzed by mannitol dehydrogenase. Results : Mannitol administration produced changes in body weight of $-7.6{\pm}1.1%$, increased plasma osmolality to $312{\pm}8\;mOsm/L$. It remarkably increased weight of IH ($0.77{\pm}0.06\;gm$ versus $0.68{\pm}0.03\;gm$ : p<0.01) and the IH/CH weight ratio ($1.23{\pm}0.07$ versus $1.12{\pm}0.05$ : p<0.01). The photometric absorption at 340 nm of the cerebral tissue in the mannitol-treated group was increased to $0.375{\pm}0.071$ and $0.239{\pm}0.051$ in the IH and CH, respectively from $0.167{\pm}0.082$ and $0.162{\pm}0.091$ in the IH and CH of the control group (p<0.01). Conclusion : Multiple-dose mannitol is likely to aggravate cerebral edema due to parenchymal accumulation of mannitol in the infarcted brain tissue.

완전뇌허혈후 재관류시에 국소뇌혈류, 체성감각유발전위 및 신경학적 회복에 대한 Mannitol과 Thiopental의 효과

박춘근,이상원,박영섭,최승진,허필우,정동섭,강준기,최창락 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.2

The cardiopulmonary bypass or cerebral circulation arrest is often used in the treatment of complex aneurysm or of arteriovenous malformation to decrease the risk of intraoperative aneurysm rupture. Although experimental studies have suggested that some drugs may protect the brain from ischemic injury, there are limitations in maintaining cerebral perfusion arrest without incurring neurologic deficits due to the initiation of detrimental processes including excitotoxic neuronal injury, activation of phospholipases, influx of calcium, and generation of damaging free radicals. The purpose of this study is to determine wheter mannitol or thiopental has any favorable effects on the recovery of neurologic deficits and on the regional cerebral blood flow(rCBF), somatosensory evoked potential(SEP) and electroencephalogram(EEG) in cats which underwent 15 minutes-complete global ishcemia-reperfusion. The complete global ischemia was produced in 38 cats by temporary intrathoracic occlusion of the innominate artery and the subclavian artery following ligation of bilateral mammary arteries and simultaneous induction of hypotension. The cats were allocated randomly to one of 4 treatment groups : (1) control group, 8 cats received equal volume of saline solution : (2) thiopental group, 10 cats received 45㎎/㎏ thiopental intravenously, (3) mannitol group, 10 cats received 2g/㎏ mannitol intravenously, (4) combined mannitol and thiopental group, 10 cats received equal dose of mannitol and thiopental intravenously. The drugs were administrated in a equally divided dosage before and after the ischemic episode. The results were as follos : 1) Eight animals which received saline showed the severe postischemic hypoperfusion and poor recovery of SEP and EEG, and 6 of them died within 6 hours after the ischemia. 2) Ten thiopental-treated animals also showed the severe postischemic hypoperfusion and poor recovery of SEP and EEG, and 6 of them died within 6 hours the ischemia. 3) Both mannitol-and combined treated groups showed early recovery of EEG, good recovery of SEP and EEG without the severe postischemic hypoperfusion, and 7 of 10 mannitol-treated animals and 8 of 10 combined treated animals were significantly recovered in all parameters. There were not significant differences in all parameters between the mannitol-and combined treated groups. 4) Thirty-four of 38 animals involved in this 15 minutes-ischemia resulted in the severe neurologic deficits inspite of treatment with mannitol, thiopental or both of them. These results suggest that, in cats, mannitol treatment is effective but not thiopental in preventing severe neurologic injury following complete global ischemia and the duration of complete ischemia should be far less than 15 minutes.

급성 뇌허혈증에 있어 만니톨의 효과에 대한 실험적 연구

조경석,홍용길,백민우,김달수,강준기,최창락 대한신경외과학회 1994 Journal of Korean neurosurgical society Vol.23 No.8

The development of postischemic irreversible brain damage depends upon the length of ischemia and its severity during arterial occlusion, although release of the occlusion always leads to restoration of normal or above n o d cerebral blood flow. This experiment was planned to determine the effects of mannitol on cerebral ischemia on subsequential izgional cerebral blood flow(rCBF) and somatosensory evoked potential(SEP) following reperfusion after ischemia and also define the proper time of vascular occlusion without irreversible brain damage. Cerebral ischemia was induced in cat by transorbital occlusion of the left MCA with a Sugita clip for period of 30 minutes and the ischemic brain was reperfused for 180 minutes by removing the clip. Foty adult cats, weighing 25 to 4.0㎏ were divided into 5 groups : control(Gmup Ⅰ, n=8), permanent MCA occlusion(Group Ⅱ, n= 8), permanent MCA occlusion with mannitol infusion (Group Ⅲ, n=8), permanent MCA occlusion with mannitol infUsion(Group Ⅲ, n=8), 30 minutes MCA clipping followed by reperfusion(Gmup Ⅳ, n= 8) and 30 minutes MCA clipping with mannitol infusion followed by reperfusion groups((group Ⅴ, n=8) respedvely. The rCBF and SEP measurents were carried out in each animal immediately, after MCA occlusion, at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and 180 minues followed by reperfusion. The rCBF was measured by the hydrogen clearance technique. Mando1 was given in bolus of l a g body weight as a 25% solution delivered via the femoral vein The results were as follows: 1) Gradual elevation of intracranial pressure(1CP) and systolic blood pressure were observed after MCA occlusion. Treatment with mannitol in MCA occlusion animals(Group Ⅲ & Ⅴ) decreased ICP immediately a k r idusion of mannitol. 2) Normal control rCBF(ml/100g/min) were 51.94±5.05 in the left temporal(LT) and 50.80± 4.87 in the left perietal lobes(LP). 3) The MCA occlusion resulted in a reduction of the blood flows to 72% of the normal control ones(LT : 14.29± 4.81ml/100g/min) at the left temporal area immediately after occlusion and also a reduction of flows to 80.4% of the normal control ones(LT : 1024± 3.69ml/100g/min) at 180 minutes after occlusion in Group Ⅱ. 4) In the mannitol-treated group(group Ⅳ), reperfwd animals, with removal of the clip on MCA had an improved postischemic recovely of blood flow and ipsilateral cerebral blood flows were restored to 42.5% of the normal control ones(LP : 212±4.13ml/100g/min) at 180 minutes after occlusion in Lt parietal CBF. 5 ) In the reperfusion group(group Ⅳ), reperfused animals, with removal of the clip on MCA had an increase in rCBF to the level of 833% of the control value(LT : 45.78± 6.80ml/100g/min) at 180 minutes after reperfusion and also reperfused animals, with treated mannitol had further increase the blood flow up to the level of 92s % of the control value(LT : 49.04± 43.6 ml/100g/min) at 180 minutes after repexfwion. 6) After the MCA occlusion, the SEP was present but markedly altered in shape and particularly the early components of the SEP were suppressed in the ipsilateral occlusion hemisphere. 7) In the mannitol-treated reperfusion group(Group Ⅴ) the amplitude of the SEP was restored to 80% of control value. The SEP was significantly suppressed if the rCBF fell below 10- 14ml/100g/min. These results suggest that provided CBF can be restored to above the 40% threshold well within 30 minutes, prevention of ischemic brain damage can be expected and also the mannitol may of benefit in prolongation of the time threshold for the formation of the cerebral ischemia after vessel occlusion.

흰쥐 하지근육의 허혈-재관류 손상에 Mannitol이 미치는 억제효과

박장상,이경현,최흥식,고용복 大韓脈管外科學會 1995 大韓脈管外科學會誌 Vol.11 No.1

Characterization of Two Mannitol-Producing Leuconostoc Strains from Pa-Kimchi and Their Application for Juice and Yogurt Fermentation

Kang Yun Ji,Kim Min Jae,Kim Tae Jin,Kim Jeong Hwan 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.6

Two mannitol producing lactic acid bacteria were isolated from pa (green onion)- kimchi, identified and named as Leuconostoc mesenteroides SKP 88 and Leuconostoc citreum SKP 92, respectively. Both isolates grew well at 25-30o C, initial pH 6-8, and 3% and lower NaCl concentration. Both isolates converted fructose into mannitol efficiently when grown on MRS broth containing fructose and glucose. Glucose was used as a carbon source and fructose was used as a precursor for mannitol. Mannitol yields were the highest in MRS broth with 3% fructose and 2% glucose. Shine muscat juice fermentation was done using each isolate as a starter. As fermentation progressed, decrease in pH and increases in titratable acidity and viable counts were observed. L. mesenteroides SKP 88 showed better mannitol conversion ability than L. citreum SKP 92, and shine muscat juice fermented with L. mesenteroides SKP 88 showed the mannitol production of 41.6 g/l at 48 h, and juice fermented with L. citreum SKP 92 showed 23.4 g/l at the same time. Yogurt fermentations showed similar patterns, and yogurt fermented with L. mesenteroides SKP 88 showed the mannitol production of 15.13 g/l. These results showed that both strains are useful as starters for healthy fermented foods with reduced fructose contents.

Acute Kidney Injury following Low Dose Mannitol Infusion

You Suk Kim,Yun Jae Kwon,Jin Dong Kim,You Jung Lee,Eun Seo Lee,Yu Ji Lee 조선대학교 의학연구원 2015 The Medical Journal of Chosun University Vol.40 No.2

Mannitol is commonly used to reduce intracranial and intraocular pressures and to prevent dialysis-disequilibrium syndrome. However, intravenous mannitol infusion in various cases has the potential to result in acute kidney injury (AKI). We present a case of mannitol-induced AKI that developed after low dose mannitol infusion and resulted in recovery after hemodialysis. A 66-year-old woman was admitted to the hospital with a diagnosis of left middle cerebral artery infarction. On hospital day 5, cerebral edema was observed on a follow-up MRI. D-mannitol 35 g was given intravenously every 8 hours. Four days later, serum creatinine levels were elevated from 1.2 mg/dL to 3.5 mg/dL. The serum osmolal gap was found to be 52.4 mosm/kg H2O and urine output was reduced from 2.78 mL/kg/h to 0.69 mL/kg/h over three days. Hemodialysis over 2 hours was performed and renal function subsequently improved to baseline function. A potential risk of AKI exists even with low dose mannitol infusion in patients with advanced age, underlying renal impairment, and concomitant use of nephrotoxic agents. Mannitol-induced AKI may be rapidly reversed by short-term hemodialysis.

Mannitol Augments the Effects of Systemical Stem Cell Transplantation without Increasing Cell Migration in a Stroke Animal Model

이상훈,강호영,김종훈,박동혁 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.5

Background: Mannitol increases blood–brain barrier permeability and can improve the efficiency of systemically administered stem cells by facilitating stem cell entry from the periphery into the injured brain. The aim of this study was to elucidate the neuroprotective effects of a combination of mannitol pretreatment and stem cell transplantation on stroke-induced neural injury. Methods: The experimental rats were randomly assigned to three groups 24 h after middle cerebral artery occlusion and reperfusion. One group received intravenous (IV) injections of phosphate-buffered saline (vehicle), another group received IV injections of human adipose-derived stem cells (hADSCs), and the last group received IV injections of hADSCs 10 min after IV mannitol injections. Neurobehavioral functions and infarct volume were compared. Immunohistochemistry (IHC) analyses were performed using antibodies against ionized calcium binding adapter-1 (IBA-1), rat endothelial antigen-1 (RECA-1), and bromodeoxyuridine/doublecortin (BrdU/DCX). Results: PKH-26 labeling revealed no difference in the number of stem cells that had migrated into the injured brain, and hADSC transplantation did not improve the infarct volume. However, neurobehavioral functions improved in the mannitol group. IHC showed higher numbers of RECA-1-positive cells in the peri-infarcted brain and BrdU-/DCX-colocalized cells in the subventricular zone in the mannitol group. IBA-1-positive cell number decreased in the hADSC-only and mannitol-pretreatment groups compared with the vehicle group even though there was no difference between the former two groups. Conclusion: Combinatorial treatment with mannitol and hADSC transplantation may have better therapeutic potential than hADSC monotherapy for ischemic stroke.

백내장 수술 전 안압 하강의 각막 내피세포 보호 효과

안용선,조양경 대한안과학회 2015 대한안과학회지 Vol.56 No.4

목적: 백내장 수술 전 만니톨 정맥주사를 통한 안압 하강 후 백내장 초음파 유화술을 시행하는 것이 수술 후 각막내피 손상을 감소시킬 수 있는지 알아보고자 한다. 대상과 방법: 양안 백내장 수술 환자 중 양안 모두 전방 깊이가 2.50 mm 미만인 36안(A군)과 2.50 mm 이상인 44안(B군)을 대상으로하였다. 각 군내 동일 환자에서 무작위로 한쪽 눈 수술 전에만 만니톨 정맥주사를 시행하고, 반대쪽 눈 수술 전에는 시행하지 않았다.모든 환자들은 수술 후 1일, 2주, 5주에 각막 내피세포 밀도, 세포면적 변이계수(Coefficient of variation, CV), 육각형세포 비율(Hexagonality, HA)과 각막 두께를 측정하였다. 그리고 A군과 B군 각각에서 만니톨 정맥주사를 시행한 군과 시행하지 않은 군의 수술후 시력, 각막 내피세포 그리고 각막 두께를 비교하였다. 결과: A군에서 수술 전 만니톨 정맥주사를 시행한 군이 시행하지 않은 군보다 수술 후 1일, 5주째 각막 내피세포 밀도가 유의하게 더 높았고, 1일째 각막의 두께가 유의하게 얇았으며, 최대 교정 시력도 유의하게 더 좋았다(all p<0.05). 하지만 B군에서는 만니톨 정맥주사를 시행한 군과 시행하지 않은 군 사이의 각막 내피세포 밀도, CV, HA, 각막의 두께, 최대 교정 시력은 모든 경과 관찰 시점에서 유의한 차이가 없었다. 결론: 전방의 깊이가 얕은 환자에서 백내장 초음파 유화술 전 만니톨 정맥주사에 의한 안압 하강은 수술 후 초기 각막 내피세포 보호에 효과가 있고, 초기 시력 회복에 도움이 된다. Purpose: To evaluate whether intraocular pressure reduction by intravenous injection of mannitol before phacoemulsificationcataract surgery can have a protective effect on corneal endothelium. Methods: Patients undergoing sequential bilateral cataract surgery were divided into 2 groups, 36 eyes with anterior chamber depth (ACD) ˂ 2.50 mm (group A) and 44 eyes with ACD ≥ 2.50 mm (group B). In each group, preoperative intravenous injection of mannitol was performed in 1 randomly selected eye of the patient. The specular microscopic examination including cell density(ECD), coefficient of variation (CV), hexagonality (HA) of corneal endothelium, and corneal thickness was performed on postoperative 1 day, 2 weeks, and 5 weeks. In each group, the parameters were compared between the eyes with mannitolization and the contralateral eyes without mannitolization. Results: In group A, eyes with preoperative mannitolization showed significantly higher ECD at postoperative 1 day and 5 weeks and showed a significantly thinner cornea at postoperative 1 day than those without mannitolization (all p < 0.05). However, in group B, there was no significant difference of ECD, CV, HA, and corneal thickness between the eyes with and without mannitolization. Conclusions: Preoperative intraocular pressure reduction by mannitolization before phacoemulsification can protect the corneal endothelial cells and recover the early postoperative period visual acuity in eyes with shallow anterior chamber.