Thrombolysis with recombinant tissue plasminogen activator during cardiopulmonary resuscitation in fulminant pulmonary embolism. A case series.

OBJECTIVE: To describe our outcomes using thrombolysis during the cardiopulmonary resuscitation (CPR) of patients in cardiorespiratory arrest (CA) caused by fulminant pulmonary embolism (FPE). DESIGN: A case series. SETTING: Intensive care units of a district hospital and a referral centre. PATIENTS: Six patients that suffered CA secondary to an FPE. INTERVENTIONS: Administration of recombinant tissue plasminogen activator during usual CPR manoeuvres when there was a strong suspicion of FPE. Permission for the thrombolytic therapy was sought from family members in all cases. RESULTS: Four out of the six patients survived and remain symptom-free. The thrombolysis was not associated with any fatal complications. CONCLUSIONS: Early thrombolysis during CPR manoeuvres for CA apparently caused by an FPE may reduce the mortality rate among these patients.     

Bolus injection of thrombolytic agents during cardiopulmonary resuscitation for massive pulmonary embolism

Thrombolytic therapy has proved to be efficacious in the treatment of massive and fulminant pulmonary embolism (PE), but thrombolysis has been considered as contraindicated during cardiopulmonary resuscitation (CPR). This review on the administration of thrombolytic agents in patients who have suffered massive PE necessitating CPR summarises 14 anecdotal reports and three case series involving 34 patients. The case series revealed an overall initial survival rate of 55–100% following bolus administration of thrombolytic agents. In general, bleeding complications were managed conservatively. The establishment of the diagnosis may be feasible using echocardiography or bedside angiography during CPR. However, therapeutic measures should be taken without delay; the patient's history and the clinical picture may thus be the only diagnostic criteria. Even where myocardial infarction is misinterpreted as PE during CPR, bolus injection of a thrombolytic agent can be an appropriate therapeutic option. An alternative may be mechanical catheter fragmentation of the thrombus with subsequent local thrombolysis. Surgery may be restricted to hospitals with ready access to extracorporeal circulation. We conclude that early administration of thrombolytic agents during PE necessitating CPR may help to reduce mortality. We favour the administration of urokinase (2– to 3 000 000-U bolus) or rt-PA.     

Prehospital thrombolysis during cardiopulmonary resuscitation

Although prehospital cardiac arrest has an incidence of 40-90/100,000 inhabitants per year, there has been a lack of therapeutic options to improve the outcome of these patients. Of all cardiac arrests, 50-70% are caused by acute myocardial infarction (AMI) or massive pulmonary embolism (PE). Thrombolysis has been shown to be a causal and effective therapy in patients with AMI or PE who do not suffer cardiac arrest. In contrast, experience with the use of thrombolysis during cardiac arrest has been limited. Thrombolysis during cardiopulmonary resuscitation (CPR) acts directly on thrombi or emboli causing AMI or PE. In addition, experimental studies suggest that thrombolysis causes an improvement in microcirculatory reperfusion after cardiac arrest. In-hospital and prehospital case series and clinical studies suggest that thrombolysis during CPR may cause a restoration of spontaneous circulation and survival even in patients that have been resuscitated conventionally without success. In addition, there is evidence for an improved neurological outcome in patients receiving a thrombolytic therapy during during CPR. A large randomized, double-blind multicenter trial that has started recently is expected to show if this new therapeutic option can generally improve the prognosis of patients with cardiac arrest.     

Thrombolysis in cardiopulmonary resuscitation

The prognosis of patients suffering cardiac arrest is still poor. Until today, no drug therapy has shown to improve longterm survival after cardiac arrest. Thrombolysis has been shown to be an effective therapy in patients with acute myocardial infarction (AMI) or massive pulmonary embolism (PE). Since 50-70% of cardiac arrests are caused by AMI or massive PE, the combination of cardiopulmonary resuscitation (CPR) and thrombolytic therapy appears to be sensible. As experimental studies have shown, thrombolytic therapy during CPR may not only be a causal treatment for coronary or pulmonary arterial obstruction by thrombi, but may also improve microcirculatory reperfusion after cardiac arrest. Although numerous small clinical studies have shown the efficacy of thrombolysis during CPR in selected patients, the generalized treatment of patients suffering cardiac arrest with thrombolytics can not be recommended based on current clinical evidence. According to the recent CPR guidelines, thrombolysis may be considered in cardiac arrest patients with suspected massive PE or as a so-called rescue therapy after unsuccessful conventional CPR in patients with a suspected thrombotic cause of cardiac arrest. The risk of severe bleeding complications following thrombolysis during CPR seems to be outweighed by the potential benefit of this therapy in selected patients.     

中危（次大面积）急性肺栓塞患者是否需要溶栓治疗

中危（次大面积）急性肺栓塞患者是否需要溶栓治疗已经争论了很多年。中危肺栓塞患者具有较高的死亡风险。因此,有人建议给予中危肺栓塞患者溶栓治疗,溶栓治疗可以更快地溶解血栓,从而降低中危肺栓塞患者的病死率。但也有研究表明,与单纯抗凝治疗比较,溶栓治疗不能进一步降低中危急性肺栓塞患者的病死率和复发率,且并发出血率较高。该文就中危急性肺栓塞溶栓治疗的有效性及安全性作一综述。     

Is thrombolytic therapy effective for pulmonary embolism?

Pulmonary embolism is a disorder that is associated with significant morbidity and mortality. Right-sided heart failure and recurrent pulmonary embolism are the main causes of death associated with pulmonary embolism in the first two weeks after the embolic event. Thrombolysis is a potentially lifesaving therapy when used in conjunction with standard anticoagulation. However, it has significant side effects and must therefore be used with caution. Indications for thrombolysis are not well defined and are thus controversial. The only current absolute indication is massive pulmonary embolism with hypotension. Other potential indications include right heart dysfunction, recurrent pulmonary embolism and the prevention of pulmonary hypertension. However, no evidence exists to show benefit of thrombolytic therapy over standard anticoagulation therapy for recurrent pulmonary embolism, mortality or chronic complications. Bleeding is the most common complication of thrombolysis and may be fatal.     

Helical CT aids in the emergency department diagnosis of pulmonary thromboembolism

Pulmonary thromboembolism remains a diagnostic challenge for emergency physicians. There is a high mortality from failed diagnosis. Rapid and accurate diagnosis by a readily accessible and minimally invasive technique such as helical computerised tomography (CT) has the potential to reduce mortality and allow early consideration of new treatments such as thrombolysis. There is also potential to reduce the number of procedures required to reach a diagnosis. Current published material is reviewed and a suggested role for helical CT in the emergency department diagnosis of pulmonary thromboembolism is outlined. Three case reports are presented where CT has been utilised in the diagnosis of pulmonary thromboembolism in patients presenting to an emergency department.     

18例老年人肺栓塞临床分析

目的：探讨老年人肺栓塞的临床特征。方法：回顾性分析1995年1月至2004年12月本院18例老年人肺栓塞的临床资料。结果：老年人肺栓塞的基础疾病以慢性心肺疾病为主,临床表现不典型,常规检验缺乏特异性;误诊率83％;溶栓和／或抗凝治疗者和非溶栓和／或抗凝治疗者的死亡率分别为17％（1／6）和75％（9／12）。结论：老年肺栓塞误诊率高,及时溶栓和抗凝可以降低死亡率。     

Thrombolytic therapy for massive pulmonary embolism in a patient with a known intracranial tumor

The objective was to describe and review the use of thrombolytic therapy in a patient with an intracranial tumor and massive pulmonary embolism. This is the first reported case of a patient with a known glioblastoma multiforme and massive pulmonary embolism who was successfully treated with alteplase. Pulmonary embolism was demonstrated by a ventilation-perfusion scan and transthoracic echocardiogram with repeat studies demonstrating resolution of the thromboembolism and reperfusion of pulmonary vasculature. A review of the literature revealed that the incidence of intracranial hemorrhage with thrombolysis is <3% and compares favorably with the much higher mortality rate of 25% to >/=50% in patients with hemodynamically unstable pulmonary emboli. The benefit of thrombolysis may outweigh the risks of intracranial hemorrhage in these patients, and careful consideration for its use in these patients is warranted.     

PaCO(2)/ETCO(2) gradient: early indicator of thrombolysis efficacy in a massive pulmonary embolism

End tidal CO(2) measurement may be helpful in detecting the efficacy of thrombolysis after a massive pulmonary embolism. We report the case of a 76-year-old man with a massive pulmonary embolism, who required early intubation and mechanical ventilation. Thrombolysis with rtpA (total dosage: 60 mg) was initiated. During this procedure, clinical data, arterial blood gases and end-tidal CO(2) with a capnograph were recorded. Before thrombolysis the P(a-ET)CO(2) gradient was raised to 25 mmHg. During thrombolysis, the clinical data improved and the P(a-ET) gradient fell to 14 mmHg. We postulate that the P(a-ET)CO(2) gradient seems to be a reasonable indicator of efficacy of thrombolysis in this setting. However, the gradient did not return to normal values (4-5 mmHg). The possible reasons for this may be that during mechanical ventilation there was a large ventilation-perfusion ratio and the cardiac output may have still reduced. With these limitations, we conclude that the P(a-ET)CO(2) gradient should be evaluated as an indicator of pulmonary reperfusion in massive pulmonary embolism.     

"Brain attack": an indication for thrombolysis?

OBJECTIVE: The primary objective of this article is to introduce the reader to the use of thrombolytics in the acute treatment of ischemic stroke. Theory and experimental evidence to support this approach are emphasized in addition to potential adverse effects of thrombolysis. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: Studies were selected for detailed review if they involved stroke patients and addressed possible toxicities of therapy. Any abstracts concerning ongoing clinical trials also were reviewed. DATA EXTRACTION: Data from animal investigations using tissue plasminogen activator for the acute treatment of several models of cerebral ischemia were used to support the importance of early treatment (within six hours of symptom onset). Also, studies performed in animal models of stroke revealed that thrombolysis could be accomplished safely in acute ischemic stroke. All human studies published to data are anecdotal case reports, but point to the safety of thrombolysis if administered early. Reviews of ongoing multicenter trials are taken from published abstracts and proceedings. DATA SYNTHESIS: Thrombolysis holds promise as a hyperacute therapy for acute stroke; however, the risk of intracerebral hemorrhage remains. Crucial to the success of this and any other therapy for acute stroke is the ability to treat patients within hours of symptom onset. Also, the importance of concomitant medications such as heparin and aspirin has not yet been addressed. CONCLUSIONS: Pharmacists need to be knowledgeable of new treatments of stroke and the risks associated with them. As patient educators, pharmacists can contribute to public awareness by promoting the early recognition of stroke symptoms. As pharmacotherapists, pharmacists need to understand the risks and the important monitoring parameters related to thrombolysis. The results of ongoing multicenter clinical trials are awaited before making a final judgment on the usefulness of thrombolysis in acute ischemic stroke.     

Tenecteplase and return of spontaneous circulation after refractory cardiopulmonary arrest

Even with the benefit of cardiopulmonary resuscitation, the prognosis of cardiac arrest remains poor. Multiple case series describe survival with the use of thrombolytic therapy for refractory cardiac arrest. Presumably thrombolysis treats that subset of cardiac arrest cases resulting from fulminant pulmonary embolism, or perhaps massive myocardial infarctions. Published reports to date have dealt exclusively with streptokinase, urokinase, reteplase, or recombinant tissue plasminogen activator. The authors report the first case of return of spontaneous circulation with the administration of tenecteplase. Tenecteplase is a recently developed reengineered isomer of tissue plasminogen activator that possesses many properties of the ideal cardiac arrest thrombolytic agent. It is bolus dosed, stable at room temperature before reconstitution, and is compatible with most other advanced cardiac life support medications. Because of clinical equivalency and its logistical advantages, tenecteplase should be evaluated as an alternative to other thrombolytics in future trials involving cardiac arrest.     

Massive pulmonary embolism leading to cardiac arrest is associated with consumptive coagulopathy presenting as disseminated intravascular coagulation

See also Levi M. Disseminated intravascular coagulation or extended intravascular coagulation in massive pulmonary embolism. This issue, pp 1475–6; Thachil J. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: a rebuttal. This issue, pp 1657–8; Leitner JM, Janata‐Schwatzek K, Spiel AO, Sterz F, Laggner AN, Jilma B. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: reply to a rebuttal. This issue, pp 1658–9. Summary. Background: A consumptive coagulopathy resembling disseminated intravascular coagulation (DIC) has been seen in patients with massive pulmonary embolism (PE). We hypothesized that a DIC‐like condition is relevant in patients whose pulmonary embolism leads to cardiopulmonary arrest and cardiopulmonary resuscitation (CPR). Methods: This hypothesis was tested by the use of a database consisting of all cases of PE diagnosed at the Department of Emergency Medicine from June 1993 to October 2007. Out of 1018 cases with PE, 113 patients underwent CPR. In this cohort study, the resuscitated patients were compared with those with PE but without CPR. Results: Patients with PE and CPR had 3‐fold higher D‐dimer, prolonged prothrombin time (PT), reduced platelet counts and lower fibrinogen and antithrombin (AT) levels compared with PE patients without cardiac arrest (P < 0.001 for all). Among patients with PE and CPR, D‐dimer was abnormal in 100%, PT in 44%, AT in 53%, fibrinogen in 19% and platelets in 25%. In comparison, PE without CPR was associated with abnormal D‐dimer in 99%, abnormal PT in 15%, low AT in 6%, low fibrinogen in 1% and low platelets in 2%. Nine per cent of the resuscitated patients had a DIC score ≥ 5, indicating overt DIC. The DIC score highly correlated with 1‐year and in‐hospital mortality. Conclusions: Massive PE leading to CPR is associated with consumptive coagulopathy and overt DIC. In resuscitated patients, DIC markers may indicate pulmonary embolism as the underlying cause of arrest.     

Bolus thrombolytic infusion during prolonged refractory cardiac arrest of undiagnosed cause

Acute myocardial infarction (AMI) and pulmonary embolism (PE) account for about 70% of cardiac arrest. Although thrombolytic therapy is an effective therapy for both AMI and PE, it is not routinely recommended during cardiopulmonary resuscitation (CPR) for fear of life threatening bleeding complications. Numerous case reports and retrospective studies have suggested a beneficial effect of thrombolytics in cardiac arrest secondary to AMI and PE; however, we present a case of successful use of bolus thrombolytics during CPR in a patient with undifferentiated cardiac arrest (undiagnosed cause) after prolonged conventional resuscitation without success.     

Volumetric capnography as a bedside monitoring of thrombolysis in major pulmonary embolism

Objective To describe the use of volumetric capnography, a plot of expired CO₂ concentration against expired volume, in monitoring fibrinolytic treatment of major pulmonary embolism.Design and setting Two case reports in the emergency department of a teaching hospital.Patients Two conscious and spontaneously breathing patients (69- and 31-year-old women) with major pulmonary embolism requiring thrombolysis. Decision for thrombolysis was based on the association of right ventricular afterload on echocardiography, with respiratory failure and hypotension in the first patient, and dyspnea and hemodynamically stable parameters in the second one.Interventions Successive capnographic measurements were performed before, during, and after thrombolysis. Curves of volumetric capnography were obtained from a sidestream gas monitor with flow sensor and an arterial blood gas analysis for CO₂ partial pressure.Measurements and results We calculated late deadspace fraction, previously suggested as the most effective capnographic parameter in the diagnosis of pulmonary embolism. Late deadspace fraction decreased in the two patients, respectively, from 64.4% to 1.1% and from 25.6% to 5.7% after thrombolysis, with a concomitant disappearance of right heart dysfunction signs on echocardiography.Conclusions Volumetric capnography can monitor thrombolysis in major pulmonary embolism. Differences between volumetric capnography technology and the more traditional arterial to end-tidal CO₂ gradient are important to take into account for clinical application.     

急性肺栓塞患者应用rt-PA溶栓8例护理体会

目的：总结护理在急性肺栓塞患者应用rt-PA溶栓疗法中的作用。方法：应用rt-PA为急性肺栓塞8例进行溶栓治疗。结果：8例溶栓均获成功。结论：急性肺栓塞早期应用rt-PA溶栓，效果优于其他溶栓药物。溶栓疗法专业性强，护士不但要熟练掌握护理基础理论及技术操作，而且要认识和掌握rt-PA溶栓的要点和操作步骤，加强对病情的监护，促进急性肺栓塞患者早日康复。     

Association of mechanical chest compression and prehospital thrombolysis

Pulmonary embolism (PE) is a common cause of sudden death; the use of prehospital thrombolysis is currently a last-resort option and requires a prolonged cardiopulmonary resuscitation (CPR). Novel mechanical devices have recently been introduced that provides automatic mechanical chest compression (AMCC) according to the guidelines and continually without decrease efficiency throughout prolonged resuscitation. A 54 year-old woman with a history of breast cancer experienced sudden chest pain and severe dyspnea. A mobile intensive care unit was dispatched to her home. During physical examination, she suddenly collapsed with pulseless electrical activity as the initial rhythm. Prehospital thrombolysis during CPR combined with use of AMCC was performed based on a strongly suspected diagnosis of massive PE. After 75 minutes of effective CPR, return of spontaneous circulation was attained. After admission to an intensive care unit, computed tomographic scan confirmed bilateral PE. The patient was discharged 3 weeks after CPR in good neurologic condition. To our knowledge, this is the first case describing combined use of thrombolysis and AMCC in out-ofhospital cardiac arrest. However, for the time being, prehospital thrombolysis in CPR continues to be a measure that should only be performed on a case-by-case basis based on informed decision. Further studies are needed to evaluate the efficacy and safety of AMCC with thrombolysis and thus prolonged CPR.     

Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies.

Current reimbursement policy of health insurance for therapeutic plasmapheresis requires proof of efficacy using the concept of evidence-based medicine. The aim of this paper is to review the outcome of plasmapheresis used to treat thrombotic microangiopathy (TMA)-associated syndromes in the last decade to provide scientific evidence to back up reimbursement applications. The strength of evidence of each reviewed study was assessed using the five levels of evidence criteria as defined by the American Society of Hematology in 1996 for assessment of the treatment of immune thrombocytopenia. The level Experimental indication was added for situations where only case reports or small series supported by pathophysiological reasoning are available. The definitions of evidence used in this paper are as follows: Level I, randomized clinical trial with low rates of error (p < 0.01); Level II, randomized clinical trial with high rates of error (p < 0.05); Level III, nonrandomized studies with concurrent control group; Level IV, nonrandomized studies with historical control group; Level V, case series without a control group or expert opinion; and Experimental, case reports and pathophysiological reasoning. The results of this analysis based on the published data is summarized as follows: The indication of plasmapheresis is assigned to Level IV evidence for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); cancer/chemotherapy-associated TTP/HUS is assigned to Level V evidence; and TTP/HUS refractory to standard plasma exchange and post-bone marrow transplantation TTP/HUS are assigned to Experimental indication. For both subsets, protein A immunoadsorption is reportedly successful. The other TMA-associated syndromes, hemolysis elevated liver enzymes low platelets and HUS in early childhood, are no indication of plasmapheresis. Two randomized clinical trials were performed in order to demonstrate the superiority of plasma exchange/fresh frozen plasma (PEX/FFP) over plasma transfusion in the management of TTP/HUS. The results prove the greater clinical success of the latter type of plasma administration. Standard PEX/FFP has reduced the mortality of TTP/HUS from 94.5% to 13%.     

Saddle pulmonary embolism in a pediatric patient with nephrotic syndrome and recent COVID-19 pneumonia: A case report

The pediatric population accounts for a small portion of those with severe disease related to COVID-19. There are few published reports of hypercoagulable states in children with COVID-19. We describe an 11-year-old male with nephrotic syndrome who required inpatient treatment for COVID-19 pneumonia eight weeks prior. He returned to the emergency department with vomiting, tachypnea and was found to have a pulmonary embolism. In this case report, we discuss the risk factors for, presentation and evaluation of hypercoagulable state and its relation to COVID-19 in a pediatric patient.     

Neurologically normal survival after fibrinolysis during prolonged cardiac arrest: case report and discussion

Cardiac arrest secondary to pulmonary embolism is a devastating condition with a high mortality rate. It is currently unclear whether fibrinolysis (thrombolysis) is beneficial in this setting. We report the case of a 28-year-old woman with a pulmonary embolism who developed return of pulses following the administration of tissue plasminogen activator after 38 minutes of pulseless electrical activity cardiac arrest. She went on to make a full neurologic and cardiopulmonary recovery. This case is discussed with reference to the current literature on the subject.