Effect Of Thrombolytic Treatment Research Articles

Cerebral edema in acute stroke: Effect of thrombolytic treatment

Cerebral edema (CED) is a common complication of ischemic stroke in Intensive Care Unit. Although frequently observed in patients undergoing intravenous thrombolytic (IVT) treatment, the pathogenic role of recombinant tissue plasminogen activator (rtPA) in CED induction has not yet been definitively clarified. The aim of our study is to verify the relationship between CED and rtPA in patients affected by acute ischemic stroke, without reperfusion signs, evaluating the CED growth rate in the first week after stroke onset. In this single-center, retrospective observational study, we included all consecutive patients with acute stroke undergone multi-parameter monitoring of vital signs in the sub-intensive care Unit. We included both patients undergoing systemic IVT and standard medical treatment (n-IVT) with the following time of CT scan: within 4.5 h onset, 24 ± 12 h, 72 ± 24 h and 120 ± 24 h from the stroke onset. Of 1753 with acute ischemic stroke patients screened, 810 patients were included in the study (218 IVT and 592 n-IVT). No significant difference was observed at baseline in age, gender, NIHSS score or infarcted area, while hemorrhagic transformation rate was significantly higher in IVT than in n-IVT group. We observed a significant increase of CED growth rate in IVT patients compared to n-IVT patients only between 24 and 72 h from the ischemic event (respectively 1.85cm3/h and 0.89cm3/h; p = 0.031) regardless of the presence of HT. No significant difference was observed in growth rate between 3 and 5 days following rtPA administration or in overall growth rate. Although the pathogenetic mechanism of rtPA determining CED remains uncertain, our data suggests rtPA can act as a “trigger” of edema onset and progression. Therefore, drugs interfering with specific molecular pathways, such as kallikrein-kinin cascade, could constitute an effective strategy to reduce the risk of development and progression of rtPA-related cerebral edema in patients with acute stroke. Further studies are needed to define the molecular pathways involved in the genesis of CE in humans and to verify the efficacy of specific drugs.

Abstract TP269: Simulation Training Improves Thrombolytic Treatment Logistics

Background: Shorter door-to-needle time (DNT) essentially contributes to the effectiveness of thrombolytic treatment. Simulation-based training could shorten DNTs. Here we present the first results of simulation training, designed to shorten DNT ≤ 20 minutes, conducted in the Czech Republic. Methods: The simulation-training scenario was developed and run by the Comprehensive Stroke Center of St. Anne’s University Hospital in Brno. It has a standard format (intro-simulation-debriefing-conclusion) and includes two rounds of simulation, as well as a video presentation of real thrombolytic cases. Between June 2016 and March 2017, St. Anne’s Hospital staff received this training, followed by 4 of the 5 closest primary stroke centers. The DNTs of hospitals which received training were compared to the DNT of all the other stroke centers in the Czech Republic in the 4-month period pre-training (March - June 2016), as well as post-training (April - July 2017), using data from the SITS registry. Results: In 5 centers participating in simulation training, DNT was 47 minutes (95%CI 45-52; 102 patients) pre-, and 29 minutes (95%CI 24-38; 88 patients) post-training. In 45 stroke centers without training, DNT was 40 minutes (95%CI 40-41; 860 patients) before and 30 minutes (95%CI 28-31; 421 patients) after the simulation period. In trained stroke centers, the percentage of patients that achieved DNT ≤ 20 minutes was 3% pre-training, and increased to 32% post-training (OR=15, 95%CI 4.5-53). In all other stroke centers, 11% and 27% of patients were thrombolyzed with DNT ≤ 20 minutes before and after the simulation period, respectively (OR=3, 95%CI 2.1-4.0). Conclusion: DNT was shortened in all stroke centers. Additionally, training further improved logistics and increased the percentage of patients thrombolyzed within 20 minutes. Simulation training is a powerful tool for improving hospital logistics.

Prevention of early complications and late consequences after acute pulmonary embolism: Focus on reperfusion techniques

Pulmonary embolism (PE) is a major cause of acute cardiovascular mortality and long-term morbidity. Right ventricular (RV) dysfunction is the key determinant of prognosis in the acute phase of PE, and residual RV dysfunction is associated with the development of post-PE functional impairment, chronic thromboembolic disease, and higher costs of treatment over the long term. Patients with clinically overt RV failure, i.e. hemodynamic collapse at presentation (high-risk PE), necessitate immediate thrombolytic treatment to relieve the obstruction in the pulmonary circulation; surgical or catheter-directed removal of the thrombus can be an alternative option. For patients with a high risk of bleeding or active hemorrhage, or for normotensive patients with intermediate-risk PE, systemic (intravenous) standard-dose thrombolysis is not recommended since the risks of treatment outweigh its benefits. In such cases, rescue thrombolysis should be considered only if hemodynamic decompensation develops while on heparin anticoagulation. For survivors of acute PE, little is known on the possible effects of thrombolytic treatment on the risk of chronic functional and hemodynamic impairment. Catheter-directed, ultrasound-assisted, low-dose thrombolysis leads to recovery of RV dysfunction, and its safety profile appears promising. However, adequately powered prospective trials focusing on both short- and long-term clinical outcomes are needed to establish novel interventional techniques in the treatment of PE.

Early neurological improvement after intravenous tissue plasminogen activator infusion in patients with ischemic stroke aged 80 years or older

BackgroundEarly neurological improvement has been observed in patients with stroke receiving treatment with standard intravenous recombinant tissue plasminogen activator. However, the effectiveness of thrombolytic treatment and the risk of hemorrhagic transformation are not well understood in patients aged ≥80 years. In this study, we investigated the influence of age on early neurological improvement and hemorrhagic transformation rates in patients with stroke aged ≥80 years and receiving recombinant tissue plasminogen activator. MethodsThe study included 157 patients who received recombinant tissue plasminogen activator infusion at a teaching hospital. The National Institutes of Health Stroke Scale was used to evaluate stroke severity. Early neurological improvement was defined as an improvement of 8 or more points on this scale (compared with baseline) 24 hours after thrombolytic treatment. Neurological improvement was defined as an improvement of 8 or more points (compared with baseline) at discharge. Neurological deterioration was defined as an increase of 4 or more points (compared with baseline). Multivariate analysis was used to evaluate the associations among age, neurological improvement, and hemorrhagic transformation. ResultsThe rate of early neurological improvement was 36.9% (58/157 patients) and the rate of hemorrhagic transformation was 22.3% (35/157 patients). At discharge, the rate of neurological improvement was 50.9% (80/157 patients) and the rate of neurological deterioration was 13.4% (21/157 patients). There was no statistically significant difference between patients aged ≥80 years and those <80 years of age with respect to rates of early neurological improvement, neurological deterioration, or hemorrhagic transformation. Among patients ≥80 years, the rate of neurological improvement in those receiving thrombolytic treatment was higher than the rate in those patients not receiving thrombolytic treatment (58.8% vs. 14.1%, p < 0.01). We concluded that thrombolysis increases the rate of neurological improvement in patients aged ≥80 years. ConclusionIn older patients, thrombolytic treatment increased the rate of neurological improvement compared with patients not receiving the treatment. The study showed that thrombolytic treatment may be beneficial for patients ≥80 years, but should be performed with extreme care.

Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator (rt-PA) in Acute Lower Limb Ischaemia

For various reasons some patients are unable to undergo intra-arterial thrombolysis for acute limb ischaemia. This interventional case series study prospectively evaluated the effect of thrombolytic treatment with 100 mg recombinant tissue plasminogen activator (rt-PA), administered intravenously, in patients with acute thrombosis of the lower limb arteries and onset of symptoms within 12 h prior to treatment. During a 3-year period (2007-2009), 18 of 86 patients satisfied the inclusion criteria and were included in the study (age range 65-80 years; 11 women). Complete and partial thrombolysis was observed in eight (44.4%) and six (33.3%) patients, respectively. All patients experienced clinical improvement. There were no amputations during the 36-month follow-up period and no haemorrhagic complications in the first 30 days post-treatment. Five patients died (27.8%) during follow-up from unrelated causes. This small study demonstrated that thrombolytic treatment with intravenous rt-PA in selected patients with acute limb ischaemia is feasible.

Angiographic collaterals in acute stroke - relationship to clinical presentation and outcome: The PROACT II trial

113 We studied the relationship between angiographic collateral flow and stroke severity and outcome in patients with MCA occlusion. Patients (180) were randomized 2:1 to 9mg IA r-proUK + subtherapeutic IV heparin or IV heparin alone; 162 were treated as randomized. Angiography at baseline assessed vascular occlusion and collateral flow (no, partial, or complete supply of the ischemic territory). CT was obtained at baseline, 24hrs and 7–10days, and hypodensity volumes were measured. Clinical outcome was assessed at 90days (modified Rankin score≤2). At baseline, collateral flow in 161 cases was: 50 no supply, 100 partial, and 11 complete supply. Patients with complete supply had significantly smaller infarct volumes (2±1cc) on baseline CT than patients with some (13±2cc, p&lt;0.05) or no collaterals (18±4cc, p&lt;0.05). There was a statistically significant difference in the median baseline NIHSS score among the three collateral groups (15 complete vs.16.5 partial vs.18 no). There was no overall relationship between the extent of collaterals and outcome. When considering treatment groups, the effect of r-proUK appears to be (n.s.) greater with increasing degree of collaterals (Table). An analysis of the effect of collaterals and treatment groups on the evolution of hypodensity volumes on 24hrs- and 7–10day CTs was also performed. Collaterals appear to have an effect on baseline CT infarct volume and stroke severity, and on the effect of thrombolytic treatment.

Trombolíticos y neuroprotectores en el tratamiento del paciente con un accidente cerebrovascular isquémico agudo

Cerebrovascular disease occupies second place amongst the causes of mortality in the world. Rapidly after onset of an acute ischemic cerebrovascular accident (CVA) there is irreversible formation of an area affected by the ischemic process (necrotic centre) surrounded by a zone in which reduction of blood flow is less marked. Although the neurons of this region, known as the 'ischemic penumbra', are in a state of 'electrical silence', they may recover if effective treatment is started in time. Treatment of the patient with an acute ischemic CVA should be concentrated in two areas: restoration of blood flow and neuroprotection. In spite of better understanding of the biochemical, genetic and molecular processes which occur during the process of cerebral ischemia, the development of neuroprotector strategies has been largely fruitless. However, restoration of cerebral blood flow is currently possible in a certain group of patients. The fibrinolytic system is formed by an inactive proenzyme, plasminogen, which may be converted to the active form, plasmin, in the presence of specific activators such as tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The effect of thrombolytic treatment is due to dissolution of the fibrin present in the occluding thrombus, with subsequent restoration of the blood flow to the ischemic area. Nevertheless the use of thrombolytic agents has dramatically changed the clinical management of patients with acute ischemic cerebrovascular incidents. Their use involves a significant risk of intracerebral bleeding, which together with the narrow therapeutic window, has made this one of the most controversial fields of current neurology.

Impacto de la trombólisis sobre la supervivencia a corto y largo plazo de una cohorte de pacientes con infarto agudo de miocardio atendidos de forma consecutiva en todos los hospitales de una región sanitaria. Estudio GESIR-5

This study aims to assess the application of thrombolysis in patients with acute myocardial infarction admitted to all the hospitals of a health care area in Catalonia (Spain), and to estimate the effect of thrombolysis on short and long-term survival. From May 1992 to May 1993, all the patients with myocardial infarction admitted to the hospitals of the Costa de Ponent area in the first 72 hours after the initial symptoms were consecutively included in this prospective study. Information on pre-hospital phase, emergency room management and hospitalization was collected. All the patients discharged alive from hospital were followed up by telephone one and four years after hospital admission. 521 patients aged 74 years or less were included. Thrombolytic therapy was applied in 35.3%. There were no statistically significant differences in the proportion of thrombolysis between hospitals with or without intensive care or coronary units. Ten patients died in the emergency room; in the remaining cases, the 28-day case fatality was 10.0%. The effect of thrombolytic treatment on 28-day case fatality was estimated in a logistic regression model, after controlling for age, gender, Killip, ventricular arrhythmia and location of infarction (OR: 0.36; CI 95%: 0.15-0.88). In 28-day survivors, the 4-year cumulated probability of survival was 88.4%, being significantly higher in the group who had received thrombolytic therapy. In the population studied, 28-day case mortality of acute myocardial infarction is similar to that reported in other Mediterranean regions. The benefits of thrombolysis in the acute phase are found to persist after 4 years.

Multiplane transesophageal echocardiography to detect effectiveness of selective pulmonary recombinant tissue-type plasminogen activator thrombolysis in pulmonary embolism and patent foramen ovale

A functionally patent foramen ovale can create a relevant right-to-left shunt during massive pulmonary embolism. This associated feature, although maintaining adequate cardiac output, may explain both the paradoxic embolism and the uneffectiveness of peripherally administered drugs. This case demonstrates the potential of transesophageal echocardiography in monitoring the hemodynamic findings of such patients and, consequently, the effectiveness of thrombolytic treatment. (J Am Soc Echocardiogr 1997;10:384-8.)

P-20 Effect of thrombolytic treatment on occurrence of cardiac arrest during acute myocardial infarction

P-20 Effect of thrombolytic treatment on occurrence of cardiac arrest during acute myocardial infarction

Rapid resolution of new right bundle branch block in acute anterior myocardial infarction patients after thrombolytic therapy.

The objectives of this retrospective study are to describe the effect of thrombolytic treatment on the clinical course of patients with acute anterior myocardial infarction complicated by acute right bundle branch block. Patients admitted to the intensive cardiac care unit within < 4 hours from onset of symptoms, and demonstrating an acute right bundle branch block with, or without left axis deviation, on the qualifying ECG were included. All were given intravenous thrombolytic treatment consisting of: streptokinase (1,500,000 IU/40 min) or recombinant tissue type plasminogen activator (120 mg/6 hours). Following admission, patients were continuously monitored and a 12-lead ECG was recorded during each of the first 3 hours and then every 3 hours over the next 21 hours. Eight patients were included (8/211 = 3.8%). Their mean age was 62 +/- 7 years and time elapse from onset to treatment was 122 +/- 26 minutes. Complete resolution of the right bundle branch block occurred within < 3 hours in all and left axis deviation normalized in two patients. Mean peak creatine kinase was 1214 +/- 604 IU and global left ventricular ejection fraction, measured by isotope ventriculography within 24 hours from admission, was 39% +/- 15%. Only one patient was prophylactically paced. In the others, rapid normalization of the conduction block with reperfusion exceeded the logistics required for the transvenous pacemaker implantation procedure. Coronary angiography performed in six patients during 72 hours from admission revealed high grade stenoses in the proximal portion of the left anterior descending coronary artery in five patients and complete occlusion in one.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost effectiveness of thrombolytic treatment for myocardial infarction: comparison of anistreplase, alteplase and streptokinase in 270 patients treated within 4 hours

Two hundred and seventy patients, under 71 years of age and suffering from a less than 4 h infarction diagnosed according to clinical and electrocardiographic criteria, were included: two 90-patient groups were randomized and then treated with either anistreplase (30 mg iv over 5 min) or alteplase (10 mg bolus injection + 5000 IU heparin bolus injection, followed by 90 mg alteplase over 3 h), and compared with a consecutive control series of 90 patients treated with streptokinase (1.5 million U over 1 h). Intravenous heparin and aspirin (250 mg day-1) were then prescribed routinely. The three groups were comparable as regards age (55.2 +/- 10 years), male/female ratio (10.4), the site of the infarction (42% anterior, 55% inferior) and initial clinical seriousness (Killip I = 90%, II = 8%, III = 2%). The patients were thrombolysed in 17 community hospitals, and then referred to a university hospital with catheterization facilities. An efficacy score was determined, based on four parameters: two obtained from coronary angiography and left ventriculography performed on day 6 +/- 2 (N = 252) (asynergic score and patency of the infarct-related artery), one from Tl-tomography performed at rest (infarct size) and one from radionuclide angiography (global left ventricular ejection fraction) performed between day 15 and day 21 (N = 242). The score (range: 0-24 per patient) was 17.8 +/- 6.4 for alteplase, 17.7 +/- 6.0 for anistreplase and 18.1 +/- 6.0 for streptokinase respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of thrombolytic therapy on the high-resolution electrocardiogram after myocardial infarction

The effects of thrombolytic treatment was studied in 109 consecutive patients 9-11 days after their first acute myocardial infarction by high-resolution electrocardiography (ECG), 24 h Holter monitoring, exercise test and radionuclide ventriculography. Thirty-seven patients were treated with intravenous thrombolytic agents. Thrombolytic treatment was assessed by clinical criteria to be successful in 22 patients and probably successful in 12 patients. Thrombolysis failed in three patients and 72 patients did not receive thrombolytic treatment (control group). Measurements made on the high-resolution and filtered (60 Hz high-pass) vectormagnitude complex included the total duration, the duration of the potential less than 40 microV, the root mean square (RMS) voltage in 10 ms intervals over the first 50 ms and RMS voltage of the last 40, 50 and 60 ms. The filtered QRS duration was significantly shorter in reperfused patients compared with the control group (83 +/- 10 vs 89 +/- 12 ms; P = 0.017). In inferior infarcts (n = 57) the filtered QRS duration was 83 +/- 11 ms in reperfused and 89 +/- 10 ms in non-reperfused patients (P = 0.044), but in anterior infarcts (n = 52) there was no difference. The RMS voltage of the initial 50 ms of the QRS was higher in the reperfused than in non-reperfused anteroseptal infarcts (38 +/- 14 v 23 +/- 10 microV; P = 0.022). Patients successfully treated with thrombolytic agents within the first 2 h had higher RMS voltage of the terminal 40 ms of the QRS than patients treated within 2-4 h (38 +/- 17 vs 27 +/- 17 microV; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolysis in refractory unstable angina

Multiple drug therapy, including nitrates, β blockers, calcium antagonists, aspirin, and heparin, has been advocated as effective in the treatment of unstable angina, a syndrome with a multifactorial pathogenesis. Recently, plaque rupture and thrombosis have been demonstrated as the most important pathogenetic mechanisms. Nevertheless, clear-cut results on the effects of thrombolytic treatment in unstable angina are still lacking. Some possible explanations why the medical treatment of unstable angina has still not yet been standardized, whereas that of myocardial infarction has, are suggested. A review of randomized and nonrandomized studies published on this topic evaluating the role of different thrombolytic agents in unstable angina is presented. In addition the role of coronary angiography is discussed. In view of the disappointing results of coronary artery bypass surgery performed in the acute phase of the disease, one of the goals of clinical research is to identify subsets of patients at high and low risk and who undergo different types of therapeutic interventions. To support published data suggesting that total myocardial ischemia has a significant impact on prognosis, we present our results of a study carried out on patients with refractory unstable angina treated with thrombolytic therapy and evaluated with continuous electrocardiographic monitoring in the attempt to correlate total myocardial ischemia with short-term prognosis. Data in favor of the prognostic role of continuous electrocardiographic monitoring in unstable angina are also revlewed. Finally, we propose some suggestions that might be useful for future studies.

Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment.

Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non-peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it.

Massive pulmonary embolism: short-term effects of thrombolytic treatment.

This study assessed the short-term effects of thrombolytic treatment in 38 patients with massive pulmonary embolism. Thirty-two were treated with streptokinase and six with urokinase. Intrapulmonary artery instillation of fibrinolytic agents was utilized except in 3 patients. There was a marked hemodynamic and arteriographic improvement (p less than 0.0005) in 33 patients (86.8%). Four patients (10.5%) died because of treatment failure. In these cases the fibrinogen concentration remained above 1 gr/liter during therapy. Bleeding was detected in 22 patients (57.8%) but was most often related to puncture or cut-down sites, and only 2 patients (5.2%) had major bleeding. One patient (2.6%) had cerebral hemorrhage. It is concluded that "classic" thrombolytic treatment is to be chosen in life-threatening pulmonary embolism. However, the difficulties sometimes encountered in producing an intense lytic effect and its low fibrinolytic specificity for the thrombus do not permit the obtainment of better results.