cardiovascular-agents and Cerebral-Hemorrhage

Persistent patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. Prostaglandin synthetase inhibitors such as indomethacin promote PDA closure but also have potential side effects. The effect of the prophylactic use of indomethacin, where infants who may not have gone on to develop a symptomatic PDA would be exposed to indomethacin, warrants particular scrutiny.. To determine the effect of prophylactic indomethacin on mortality and morbidity in preterm infants.. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 5, 2010), MEDLINE, EMBASE and CINAHL (until April 2010), conference proceedings, and previous reviews.. Randomised or quasi-randomised controlled trials that compared prophylactic indomethacin versus placebo or no drug in preterm infants.. The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two review authors.. Nineteen eligible trials in which 2872 infants participated were identified. Most participants were very low birth weight, but the largest single trial restricted participation to extremely low birth weight infants (N = 1202). The trials were generally of good quality.The incidence of symptomatic PDA [typical relative risk (RR) 0.44, 95% confidence interval (CI) 0.38 to 0.50] and PDA surgical ligation (typical RR 0.51, 95% CI 0.37,0.71) was significantly lower in treated infants. Prophylactic indomethacin also significantly reduced the incidence of severe intraventricular haemorrhage (typical RR 0.66, 95% CI 0.53 to 0.82). Meta-analyses found no evidence of an effect on mortality (typical RR 0.96, 95% CI 0.81 to 1.12) or on a composite of death or severe neurodevelopmental disability assessed at 18 to 36 months old (typical RR 1.02, 95% CI 0.90, 1.15).. Prophylactic indomethacin has short-term benefits for preterm infants including a reduction in the incidence of symptomatic PDA, PDA surgical ligation, and severe intraventricular haemorrhage. However, there is no evidence of effect on mortality or neurodevelopment.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Randomized Controlled Trials as Topic

Patent ductus arteriosus (PDA) and intraventricular haemorrhage (IVH) are both associated with increased mortality and morbidity in preterm infants. Indomethacin has been used successfully to treat symptomatic PDA and may also prevent or limit IVH in the neonatal period. There are however potential unwanted side effects of indomethacin, in particular a potential for reduced organ perfusion that might outweigh any clinical benefits. The prophylactic use of indomethacin, where infants who may not have gone on to develop a symptomatic PDA or IVH would be exposed to indomethacin, warrants particular scrutiny.. This review examines the effectiveness of prophylactic intravenous indomethacin in reducing the mortality and morbidity associated with PDA and IVH in preterm infants.. An initial literature search was conducted in three computerised databases: MEDLINE; EMBASE; and the Oxford Database of Perinatal Trials in October 1994. The search was updated in February 1997 and October 2001.. Strict selection criteria were applied to clinical trials: the population had to be newborn preterm infants (less than 37 completed weeks gestation); the intervention had to be prophylactic intravenous indomethacin; the trial had to be randomised and controlled; and at least one of several prespecified outcomes had to be reported in the results.. The methodological quality of each study was assessed using explicit criteria. Data on relevant outcome measures were extracted and, where appropriate, the results of individual trials were combined using meta-analysis techniques to provide a pooled estimate of effect.. Nineteen eligible trials randomising 2872 infants were identified. There is no evidence of difference in mortality at latest follow-up between infants receiving prophylactic indomethacin and controls, pooled relative risk (RR) = 0.96 [95% CI 0.81 to 1.12]. There is no evidence to suggest prophylactic indomethacin is associated with any reduction in long-term neurosensory impairment, ie no significant difference in rates of cognitive delay, cerebral palsy, blindness or deafness. The incidence of symptomatic patent ductus arteriosus is significantly reduced in treated infants, pooled RR = 0.44 [0.38 to 0.50] but there is no evidence that treatment affects respiratory outcomes. Prophylactic indomethacin reduces the need for surgical PDA ligation [RR = 0.51 (0.37,0.71)]. Prophylactic indomethacin significantly reduces the incidence of Grade 3 and 4 intraventricular haemorrhage, pooled RR = 0.66 [0.53 to 0.82]. There is no evidence of difference in rates of necrotising enterocolitis, excessive clinical bleeding or sepsis. Increased incidence of oliguria is seen with prophylactic indomethacin [RR = 1.90 (1.45,2.47] but this is not associated with major renal impairment.. Prophylactic treatment with indomethacin has a number of immediate benefits, in particular a reduction in symptomatic patent ductus arteriosus, the need for duct ligation and severe intraventricular haemorrhage. There is no evidence to suggest either benefit or harm in longer term outcomes including neurodevelopment. Depending on clinical circumstances and personal preferences, there may be a role for prophylactic indomethacin in some infants on some neonatal units.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic

This section is under preparation and will be included in the next issue.. Indomethacin is used to treat symptomatic patent ductus arteriosus and may prevent or limit intraventricular haemorrhage in the neonatal period. This review examines the effectiveness of prophylactic intravenous indomethacin in reducing the mortality and morbidity associated with these conditions in infants weighing less than 1750 grams at birth.. A literature search from January 1980 to October 1994 was made in three computerised data bases: Medline; Embase; and the Oxford Database of Perinatal Trials. The search was updated in February 1997.. Strict selection criteria were applied to clinical trials: the population had to be newborn infants of birth weight < 1751 grams; the intervention had to be prophylactic intravenous indomethacin; the trial had to be randomised and controlled; and at least one of several prespecified outcomes had to be reported in the results.. The methodological quality of each study was assessed using explicit criteria. Data on relevant outcome measures were extracted on two separate occasions and, where appropriate, the results of individual trials were combined using meta-analysis techniques to provide a pooled estimate of effect.. There is a trend towards reduced neonatal mortality in infants receiving prophylactic indomethacin, pooled relative risk (RR) = 0. 85 [95% CI 0.66 to 1.09]. The incidence of symptomatic patent ductus arteriosus is significantly reduced in treated infants, pooled RR = 0.35 [0.26 to 0.47] but there is no evidence that treatment affects respiratory outcomes. Prophylactic indomethacin significantly reduces the incidence of Grade 3 and 4 intraventricular haemorrhage in treated infants, pooled RR = 0.60 [0.43 to 0.83]. There is no evidence to suggest prophylactic indomethacin is associated with any long term adverse effect although there is a trend in treated infants towards an increased incidence of necrotizing enterocolitis, and some evidence that treatment may transiently impair renal function. There is no evidence that haemostasis is disturbed.. Prophylactic treatment with indomethacin has a number of immediate benefits, in particular a reduction in symptomatic patent ductus arteriosus and severe intraventricular haemorrhage. There is no evidence at present of long-term harm. Further trials are needed to assess more precisely the effects, both beneficial and harmful, on short and long-term outcomes.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic

Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke.. PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization.. The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization.. PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke.

Topics: Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Cerebral Hemorrhage; Cilostazol; Clinical Protocols; Double-Blind Method; Humans; Predictive Value of Tests; Probucol; Prospective Studies; Republic of Korea; Research Design; Risk Factors; Stroke; Tetrazoles; Time Factors; Treatment Outcome

Our multicenter Indomethacin Intraventricular Hemorrhage (IVH) Prevention Trial demonstrated a reduction of IVH in preterm infants. Analysis of our cohort by sex showed indomethacin halved the incidence of IVH, eliminated parenchymal hemorrhage, and was associated with higher verbal scores at 3 to 8 years in boys.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Child; Child, Preschool; Female; Humans; Incidence; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Language Tests; Logistic Models; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sex Characteristics

This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased. Brain water contents and Evans blue extravasation of the right basal ganglia in the ICH group were augmented, and significantly reduced by escin. Escin abated the increases of monocyte counts and serum IL-1β levels induced by ICH. IL-1β administration reversed the effect of escin on Garcia test scores, the brain water contents, and the Evans blue extravasation. Escin ameliorated the increasing levels of RhoA, ROCK1, nuclear NF-κB and the decreasing expression of IκBα, cytosolic NF-κB, occludin, claudin-5 in the ICH group. IL-1β administration blocked not only escin-mediated increases of IκBα, cytosolic NF-κB, occludin, and claudin-5, but also escin-caused decreases of RhoA, ROCK1, and nuclear NF-κB. The results indicate that escin improves neurological outcomes and the BBB function in ICH mice, which is associated with attenuating ICH-induced peripheral system inflammation, and therefore, inhibiting IL-1β/RhoA/NF-κB signaling pathway in BBB, at least in part. These findings suggest that it may be useful to ameliorate brain injury by inhibiting systemic inflammation instead of aiming to target the brain directly after ICH.

Topics: Animals; Blood-Brain Barrier; Body Water; Cardiovascular Agents; Cerebral Hemorrhage; Escin; Interleukin-1beta; Male; Mice; Monocytes; Nervous System Diseases; NF-kappa B; rhoA GTP-Binding Protein; Signal Transduction; Systemic Inflammatory Response Syndrome

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Topics: Blood Pressure; Brain Ischemia; Cardiovascular Agents; Cerebral Hemorrhage; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Stroke; Systematic Reviews as Topic

To compare the effects of prophylactic indomethacin versus expectant management on short-term respiratory outcomes in extremely low-birth-weight (ELBW) infants.. This was a retrospective cohort study of ELBW infants with gestational age less than 28 weeks, born at a level III neonatal intensive care unit from 2004 to 2009. Patients were grouped based on whether they received prophylactic indomethacin or expectant treatment. The key outcome was the cumulative number of days of mechanical ventilation. Other outcomes were cumulative number of days supplemental oxygen and continuous positive airway pressure (CPAP) were required; duration of hospital stay; mortality; and other morbidities such as necrotizing enterocolitis and intraventricular hemorrhage. Multivariable linear regression was performed with treatment group and seven covariates, defined a priori, as predictor variables and cumulative number of days of mechanical ventilation as the outcome.. There were 144 infants in the prophylaxis group and 221 infants in the expectant treatment group. At baseline, the Score for Neonatal Acute Physiology-Perinatal Extension, incidence of respiratory distress syndrome, and usage of antenatal corticosteroids were significantly higher in the prophylaxis group. The cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP were significantly higher in the prophylaxis group. On multivariable linear regression, after adjusting for confounders, use of prophylactic indomethacin (unstandardized β coefficient = 12.4; 95% confidence interval [CI]: 6.6, 18.1; p < 0.001), birth weight (β =  -0.025; 95% CI: -0.05, -0.001; p = 0.043), and gestation (β =  -4.5; 95% CI: -7.24, -1.8; p = 0.001) were the independent predictors of cumulative number of days of mechanical ventilation.. ELBW infants who received prophylactic indomethacin had significantly longer cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP. Prophylactic indomethacin is an independent predictor of cumulative number of days of mechanical ventilation.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Continuous Positive Airway Pressure; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Length of Stay; Male; Oxygen Inhalation Therapy; Respiration, Artificial; Retrospective Studies; Time Factors; Watchful Waiting

Much effort has been made to study first-ever stroke patients. However, recurrent stroke has not been investigated as extensively. It is unclear which risk factors dominate, and whether adequate secondary prevention has been provided to patients who suffer from recurrent stroke. Also, the different types of recurrent stroke need further evaluation.. The study included patients with recurrent stroke admitted to twenty-three Swedish stroke centers. The type of previous and recurrent stroke was determined, as well as evaluation (when applicable) of recurrent ischemic stroke according to the TOAST classification. Presence of vascular risk factors was registered and compared to the type of stroke. Also assessed was ongoing secondary prevention treatment at recurrent stroke onset.. A total of 889 patients with recurrent stroke (mean age 77) were included in the study. Of these, 805 (91%) had ischemic stroke, 78 (9%) had intracerebral hemorrhage and 6 (<1%) stroke of unknown origin. The most frequent vascular risk factors were hypertension (75%) and hyperlipidemia (56%). Among the 889 patients, 29% had atrial fibrillation. Of the patients in the ischemic group with cardiac embolism, only 21% were on anticoagulation treatment. The majority of the patients (75%) had their most recent previous stroke >12 months before admission.. Few patients had a recurrent stroke shortly after the previous stroke in this study. This indicates that it is meaningful to prevent a second event with an adequate long-term treatment strategy for secondary prevention after first-ever stroke. There also seems to be a clear potential for improving secondary prevention after stroke.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antihypertensive Agents; Atrial Fibrillation; Brain Ischemia; Cardiovascular Agents; Cerebral Hemorrhage; Diabetes Complications; Embolism; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Secondary Prevention; Smoking; Stroke; Sweden; Time Factors; Treatment Outcome

Primary intracerebral haemorrhage (ICH) is associated with considerable morbidity and mortality. Local endothelin release following ICH may contribute to the pathophysiology of perilesional ischaemia. In diabetics, endothelin release can be enhanced by hyperglycaemia and cerebrovascular dilation may be inhibited by vascular endothelial dysfunction. To examine the effects of endothelin-mediated vasoconstriction after spontaneous ICH in the normal and diabetic brain, regional cerebral blood flow (rCBF) was examined in insulin dependent BB-rats and non-diabetic BB control rats. These experiments were performed 24 h following experimental ICH in both groups of animals that were either given the endothelin antagonist SB209670 or saline. Perilesional oligaemia was similar in control and SB209670 treated diabetic rats, but SB209670 reduced perilesional oligaemia in normal rats. In brain contralateral to the experimental ICH, rCBF was increased by SB209670 in diabetic rats, but not in non-diabetic rats. These studies show that there are differences in the cerebrovascular effects of endothelin in perilesional and contralateral brain in non-diabetic and diabetic rats following ICH.

Topics: Animals; Cardiovascular Agents; Cerebral Hemorrhage; Cerebrovascular Circulation; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Hematoma; Indans; Rats; Rats, Inbred BB

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Postnatal Care

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Curare; Humans; Language; Muscle Relaxants, Central; Muscle Spasticity; Paralysis; Russia

Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Cardiovascular Agents; Cerebral Hemorrhage; Ergoloid Mesylates; Ergot Alkaloids; Hematoma; Hibernation; Hypothermia, Induced; Norepinephrine