BACKGROUND: Dysnatremias are common and prognostically serious in neurocritical care. We studied whether a standardized sodium protocol would improve our neurocritical care of dysnatremias. METHODS: A 5-year prospective study of a standardized sodium protocol for 1,560 patients admitted with various brain diseases in an adult neurologic-neurosurgical intensive care unit (NNICU) was compared with a 5-year retrospective analysis of 1,440 patients without the sodium protocol. Hyponatremia was defined as serum sodium (SNa(+)) < 135 mmol/L and hypernatremia SNa(+ )> 150 mmol/L. The sodium protocol involved measuring SNa(+), serum, and urine osmolality, measured and calculated renal function parameters, fluid intake 40 mL/kg weight/day without hypotonic saline, thiazide, and desmopressin acetate in all normonatremic NNICU patients. RESULTS: In the protocol study, hyponatremia occurred slightly less often (15.7 versus 16.3% of patients; p = 0.684), hypernatremia was significantly higher (respectively 8.5% versus 5.2% of patients; p < 0.001), and no differences were noted in hypo/hypernatremia (p = 0.483). There were no differences in the incidence of hypo-osmolal hyponatremia (respectively 3.5% versus 3.5% of patients; p = 0.987), cerebral salt wasting (CSW; respectively 1.7% versus 1.7% of patients; p = 0.883), syndrome of inappropriate secretion of antidiuretic hormone (SIADH; respectively 0.1% versus 0.3% of patients; p = 0.152), central diabetes insipidus (CDI; respectively 1.0% versus 0.6% of patients; p = 0.149). In hyponatremia there were no differences in the Glasgow Coma Scale (GCS) score upon onset of hyponatremia (p = 0.294), NNICU mortality (respectively 1.0% versus 0.4% patients; p = 0.074), and bad outcome upon discharge from NNICU (respectively 5.1% versus 6.5% of patients; p = 0.101), but in hypernatremia GCS score upon onset (p < 0.001), mortality (respectively 2.8% versus 1.0%; p < 0.001), and bad outcome from NNICU (respectively 6.7% versus 2.7% patients; p < 0.001) were significantly higher. Multivariate logistic regression analysis showed that hypernatremia, compared with hyponatremia, was a significant predictor of mortality during NNICU stay (respectively odds ratio [OR]: 1.14; p = 0.003 versus OR; 5.3; p = 0.002). CONCLUSIONS: The standard sodium protocol lowered the frequency of SIADH, which was encountered in only one patient over 5 years. However, it did not significantly reduce the incidence and improve the outcome of hyponatremia. Hypernatremia occurred more often and had a higher mortality and worse outcome than hyponatremia, but these patients were neurologically worse upon its onset. The prospective study confirmed that CSW, SIADH, and CDI were not common in our neurocritical care.
- MeSH
- desmopresin terapeutické užití MeSH
- diuretika terapeutické užití MeSH
- hypernatremie diagnóza farmakoterapie epidemiologie MeSH
- hyponatremie diagnóza farmakoterapie epidemiologie MeSH
- hypotonické roztoky terapeutické užití MeSH
- iatrogenní nemoci MeSH
- incidence MeSH
- ledvinné látky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci nervového systému komplikace terapie MeSH
- osmolární koncentrace MeSH
- péče o pacienty v kritickém stavu metody MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sodík aplikace a dávkování krev terapeutické užití MeSH
- thiazidy terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- desmopresin MeSH
- diuretika MeSH
- hypotonické roztoky MeSH
- ledvinné látky MeSH
- sodík MeSH
- thiazidy MeSH
Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity.
- MeSH
- antioxidancia terapeutické užití MeSH
- blokátory receptoru 1 pro angiotenzin II terapeutické užití MeSH
- chronická renální insuficience chemicky indukované farmakoterapie patofyziologie MeSH
- doxorubicin MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- imidazoly terapeutické užití MeSH
- inhibitory ACE terapeutické užití MeSH
- kaptopril terapeutické užití MeSH
- krysa rodu Rattus MeSH
- ledvinné látky terapeutické užití MeSH
- melatonin terapeutické užití MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- receptor angiotensinu typ 2 agonisté MeSH
- tetrazoly terapeutické užití MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antioxidancia MeSH
- blokátory receptoru 1 pro angiotenzin II MeSH
- doxorubicin MeSH
- imidazoly MeSH
- inhibitory ACE MeSH
- kaptopril MeSH
- ledvinné látky MeSH
- melatonin MeSH
- olmesartan MeSH Prohlížeč
- reaktivní formy kyslíku MeSH
- receptor angiotensinu typ 2 MeSH
- tetrazoly MeSH
The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.
- MeSH
- amidy aplikace a dávkování MeSH
- fumaráty aplikace a dávkování MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- krysa rodu Rattus MeSH
- ledvinné látky aplikace a dávkování MeSH
- ledviny účinky léků patofyziologie MeSH
- nemoci ledvin farmakoterapie patofyziologie MeSH
- potkani Wistar MeSH
- renální oběh účinky léků MeSH
- renin-angiotensin systém účinky léků MeSH
- renin antagonisté a inhibitory MeSH
- reperfuzní poškození patofyziologie prevence a kontrola MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aliskiren MeSH Prohlížeč
- amidy MeSH
- fumaráty MeSH
- ledvinné látky MeSH
- renin MeSH
Seven cases of cerebral oedema have been observed in enuretic children during low-dose desmopressin (DDAVP) treatment given in a dose of 7-21 microg daily in the Czech Republic between 1995 and 1999, after the drug started to be marketed for this indication and delivered in simple bottles with a dropper. All seven children (age 5-11 years, four boys) experienced a period of unconsciousness but all recovered without sequelae. In most cases, safety measures were underestimated and natraemia was not regularly controlled. Two children developed cerebral oedema after excessive water intake in preparation for uroflowmetry, another one drank much during a hot summer day, in one diabetes insipidus was not recognised and two children were clearly non-compliant with reduced fluid intake on a long-term basis. Only in one child, no risk factor was found. Conclusion. Proper selection and instruction of patients is needed to avert cerebral oedema during treatment with desmopressin for nocturnal enuresis.
- MeSH
- desmopresin škodlivé účinky MeSH
- dítě MeSH
- edém mozku chemicky indukované prevence a kontrola MeSH
- enuréza farmakoterapie MeSH
- hyponatremie chemicky indukované prevence a kontrola MeSH
- intoxikace vodou chemicky indukované prevence a kontrola MeSH
- ledvinné látky škodlivé účinky MeSH
- lidé MeSH
- předškolní dítě MeSH
- spotřebitelská bezpečnost produktů MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- desmopresin MeSH
- ledvinné látky MeSH
BACKGROUND: Desmopressin (an analogue of antidiuretic hormone) holds an important place in the treatment of primary nocturnal enuresis. According to some long-term trials its action is mainly symptomatic. The benefit of treatment and persistence of the effect in relation to the expected decline of enuresis in 15% children/1 year is discussed. METHODS AND RESULTS: The open multicentre trial lasted 42 months. In the first stage 265 patients (164 boys, 101 girls) aged 9.4 +/- 2.8 (5-18 years) were given desmopressin (nasal drops) to achieve a 4-week dry integral. Enuresis stopped in 207/265 (78.1%) children within six (median) weeks of treatment after an effective dose of 10.5 micrograms (median) based on titration. During the second stage 55/265 children (25 boys and 30 girls) proceeded with treatment for 2-30 (median 12) months, one boy did not complete the trial. An effective dose was administered for 3.5 months (median) and then the dose declined depending on the effect by 3.5 micrograms (1 drop) per months (median). In the titration stage enuresis receded in 89.1% (49/55) children. After the first year of the trial there were 72.7% responders (p < 0.001, as compared with the assumed decline), after two years 70.9% (p < 0.01) and after three years 61.1% children (p < 0.05). The trial was completed by 61.1% (33/54) children as respondents. 23 of them 17-38 months after termination of treatment. 29.6% (16/54) patients were relapsing responders on long-term treatment, 5.6% (3/54) patients completed the trial as partial responders and 3.7% (2/54) children as non-responders. Minor side-effects were recorded during the titration stage in 4.5% children, during long-term treatment 5.4% children. The osmolality of morning urine increased during treatment regardless of the final effect (p < 0.01). The authors did not find a significant relationship between age, sex, familial incidence of enuresis, period of treatment and the achieved effect. CONCLUSIONS: The authors provided evidence of a rapid onset of the effect of desmopressin and a high effectiveness throughout the trial. The osmolality of the morning urine was not a reliable predictive factor of the effect. In the authors opinion long-term treatment is important for development of regulation and regression of complaints. During a relapse the authors recommend return to maintenance treatment and gradual discontinuation after 6-12 months. Desmopressin treatment is in the authors' opinion safe, well tolerated and very useful.
- MeSH
- aplikace intranazální MeSH
- desmopresin aplikace a dávkování MeSH
- dítě MeSH
- enuréza farmakoterapie MeSH
- ledvinné látky aplikace a dávkování MeSH
- lidé MeSH
- prospektivní studie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- Názvy látek
- desmopresin MeSH
- ledvinné látky MeSH