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Thrombolysis following pre-hospital cardiopulmonary resuscitation
International Journal of Cardiology, 37 (1992) 195-198 0 1992 Elsevier Science Publishers B.V. All rights reserved
CARD10
19s 0167-5273/92/$05.00
01557
Thrombolysis following pre-hospital cardiopulmonary resuscitation Clive F.M. Weston a,b and Philip Avery a Departments of a Cardiology and h Epidemiology, lJnir>ersityHospital of Wales, Cardiff; Wales, UK (Received
12 April 1992; accepted
29 June 1992)
Weston CFM, Avery P. Thrombolysis following pre-hospital cardiopulmonary 1992;37:195-198.
resuscitation.
Int J Cardiol
Forty-eight patients were discharged from hospital following successful resuscitation from out-ofhospital ventricular fibrillation. Sixteen of these patients received intravenous thrombolytic therapy on admission to hospital. There were 3 significant bleeding complications and 2 cases of inappropriate administration of streptokinase. One of the patients that did not receive thrombolysis also had a significant bleeding complication of cardiopulmonary resuscitation. Patients admitted to hospital following resuscitation should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, and even then with caution. Key words: Thrombolysis;
Resuscitation;
Complications
Introduction Recent studies have suggested that cardiopulmonary resuscitation, especially for less than 10 min, is not a contraindication to thrombolytic therapy [l-3]. However, a case of fatal intrathoracic haemorrhage has been reported following cardiopulmonary resuscitation and treatment with streptokinase and heparin [4], and we have reported a case of extensive facial and thoracic subcutaneous bruising in a patient given anistreplase following successful resuscitation [5].
Correspondence to: Dr. C.F.M. Weston, University tal of Wales, Cardiff CF4 4XN, Wales, UK.
Hospi-
We have examined the in-hospital management of 48 patients admitted to four local hospitals between July 1989 and January 1992 who were resuscitated by ambulance crew from prehospital ventricular fibrillation, and who were later discharged home. By a description of selected case histories we demonstrate that thrombolytic therapy should be used with caution in these patients. Results Sixteen of the 48 patients received thrombolytic therapy on admission to hospital. All had received defibrillatory shocks and a precordial thump, yet only 7 had received chest compressions for more than 2 min. There were significant
196
bleeding complications in 3 patients (cases l-3). In 10 patients the cardiac arrest was associated with acute myocardial infarction, in 4 with coronary artery disease but no definite evidence of myocardial infarction and in 2 patients (cases 5 and 6) the aetiology of the arrest was not coronary disease. Case histories
commenced cardiopulmonary resuscitation. Within 5 min cardiac output had been restored following two defibrillations. The admission ECG showed ST segment elevation in the inferior leads and the patient received 1.5 MU streptokinase. Within 6 h he became hypotensive and had haematemesis which was treated with blood transfusions and intravenous cimetidine. He was discharged with a diagnosis of acute myocardial infarction.
Bleeding complications Case I [.5/ A 59-yr-old woman collapsed after complaining of chest pain. Cardiopulmonary resuscitation was started by a general practitioner and a non-paramedic ambulance crew before advanced life support was provided by a paramedic. The prolonged resuscitation (greater than 15 min) required defibrillation, intubation and drug administration before cardiac output and breathing was restored. The electrocardiogram (ECG) on admission showed marked ST segment elevation and intravenous anistreplase and heparin were given. Gross subcutaneous bruising developed around the mouth and anterior chest wall and the patient experienced haemoptysis. Transfusions of whole blood and fresh frozen plasma were required. The patient was later discharged with a diagnosis of inferior myocardial infarction. Case 2 An 87-yr-old woman had chest pain for 12 h. She developed ventricular fibrillation whilst in the ambulance and received a precordial thump and chest compressions and was defibrillated twice. Cardiac output was restored within 3 min. The ECG on admission showed changes of acute infero-posterior myocardial infarction and 1.5 MU streptokinase was administered. Within 12 h she developed haemoptysis and obvious periorbital bruising. The haemoglobin fell from 11.4 g/d1 to 9.8 g/d& but no transfusion was given. The lady was later discharged home with a diagnosis of acute myocardial infarction. Case 3 A 59-yr-old man complained of chest pain and called his general practitioner. Approximately 2 min before the arrival of the ambulance the patient collapsed and the general practitioner
Case 4 A 65-yr-old man collapsed in the presence of a general practitioner who commenced cardiopulmonary resuscitation. Ten min later a paramedic arrived and after prolonged attempts, including defibrillations, intubation and drug administration, succeeded in restoring cardiac output. On arrival at hospital the ECG showed atria1 fibrillation and a left bundle branch block pattern. Neither thrombolytic therapy nor aspirin was given. However, the patient had a haematemesis of about 120 ml of fresh blood 4 h later, and subsequently manifest pronounced periorbital petechiae. Investigations of the upper gastrointestinal tract were not performed because of left ventricular failure, and a blood transfusion was not required. This man was felt to have suffered an acute myocardial infarction by virtue of raised cardiac enzymes. Inappropriate therapy Case 5 A 58-yr-old man collapsed in the street without warning. A neighbour commenced cardiac massage. An ambulance attended and there was prolonged resuscitation involving defibrillations, intubation and drug administration. In the Accident and Emergency Department the ECG showed pronounced lateral ST segment depression and 1.2 MU streptokinase was given without complication. Serial ECG’s showed no evidence of acute myocardial infarction and coronary angiography was later shown to be normal. The left ventricle was hypertrophied and there was mitral valve prolapse. Case 6 An 80-yr-old woman collapsed without warning. Resuscitation was commenced by a bystander, an ambulance attended and she was
197
soon defibrillated and cardiac output restored. She was admitted to an intensive care unit where an admission ECG showed non-specific ST changes. The potassium level on admission was 2.9 mmol/l. 1.5 MU streptokinse was infused without any complication. The creatine kinase was only marginally elevated and there was no progression of the ECG abnormalities. This woman was felt to have suffered ventricular fibrillation, without acute myocardial infarction, possibly related to electrolyte abnormalities. Discussion Increasing deployment of defibrillators and paramedic ambulance crew will lead to an increased number of patients surviving pre-hospital ventricular fibrillation and being admitted to hospital [6]. Whilst the majority of these patients will have coronary artery disease 171, and 70% will have angiographic evidence of coronary thrombus formation immediately after resuscitation [8], as few as 20% will show evidence of acute, Q-wave, myocardial infarction [9]. Most patients have either no ECG changes, or ST/T wave changes during the days following resuscitation from outof-hospital cardiac arrest [9]. The benefit of thrombolytic therapy in these remaining surviving patients is questionable. Cardiopulmonary resuscitation, particularly chest compressions, may lead to trauma of a number of organ systems, most commonly rib and sternal fractures [lo]. Lesions within the gastrointestinal tract are not uncommon and gastric haemorrhage or rupture and mesenteric lacerations have been reported [ll]. Both patients who had haematemesis (cases 3 and 4) may well have experienced such trauma, though ischaemic stress ulceration cannot be ruled out. Experience of administering thrombolytic therapy to patients who have already been resuscitated from out-of-hospital cardiac arrest is limited. Cross et al. reported no bleeding complications in ten patients who received thrombolytic therapy following resuscitation, four of whom had had chest compressions 111. A study of patients entered into the first three Thrombolysis and Angioplasty in Myocardial Infarction trials
showed no direct complications of cardiopulmonary resuscitation in 22 patients who received chest compressions before or within 6 h of thrombolytic treatment. However, patients who received cardiopulmonary resuscitation for greater than 10 min were specifically excluded from these trials and the 95% confidence interval for no complications was 0 to 14% [2]. Scholz et al. reported three patients with bleeding complications out of 16 patients who received thrombolysis soon after successful resuscitations [3]. Only 4 of these patients received intravenous thrombolysis. In all there were 8 bleeding complications in 43 patients who underwent prolonged cardiopulmonary resuscitation and received thrombolytic therapy within a time interval of less than 24 h. Not only was the rate of bleeding complications in these patients similar to that seen in patients who did not require resuscitation (18.6% vs 16.1%), but there were felt to be no cases of bleeding that were directly related to cardiac compressions despite 17 cases of rib fracture. Of the 16 patients in our present series there were 3 cases of significant bleeding complications, not necessarily related to the duration of the resuscitation attempt, and 2 cases of inappropriate therapy. Because these patients were selected by virtue of the fact that they were discharged from hospital alive, there are obviously no cases of fatality in the series. We are unaware of any cases of patients admitted to our local hospitals who have died in hospital following resuscitation and the subsequent administration of thrombolytic agents. To our knowledge the only reported case of such a fatality is that of Haugeberg [4]. We believe that such patients should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, namely marked ST segment elevation or new left bundle branch block, and even then with caution. References 1 Cross SJ, Lee HS, Rawles JM, Jennings K. Safety of thrombolysis in association with cardiopulmonary resuscitation. Br Med J 1991;303:1242.
98 2 Tenaglia: AN, Califf RM, Candela RJ et al. Thrombolytic therapy m patients requiring cardiopulmonary resuscitation. Am J Cardiol 1991;68:1015-19. 3 Scholz KH, Tebbe V, Herrmann C et al. Frequency of complications of cardiopulmonary resuscitation after thrombolysis during acute myocardial infarction. Am J Cardiol 1992;69:724-728. 4 Haugeberg G, Bonarjee V, Dickstein K. Fatal intrathoracic haemorrhage after cardiopulmonary resuscitation and treatment with strepokinase and heparin. Br Heart J 1989;62:157-158. 5 Wong SS, Lazarus JH, Weston CFM. Extensive subcutaneous bleeding after cardiopulmonary resuscitation and thrombolytic therapy. Arch Emerg Med 1991;8:140-143. 6 Cobb LA, Weaver WD, Fahrenbruch CE, Hallstrom AP, Copass MK. Community-based interventions for sudden cardiac death. Circulation 1992;85(suppl I):98-102.
7 Perper JA, Kuller LH, Cooper M. Arteriosclerosis of coronary arteries in sudden, unexpected deaths. Circulation 1975;52(suppl 111)27-33. 8 DeWood MA, Leimgruber PP, Shields JP, Kunkel RM, Hensley GR, Reisig AH. Thrombosis in acute myocardial infarction and sudden death: angiographic aspects. Cardiovasc Clinic 1987;18:195-211. 9 Cobb LA, Werner JA, Trobaugh GR. Sudden cardiac death. I. A decade’s experience with out-of-hospital resuscitation. Med Concepts Cardiovasc Dis 1980;19:31-36. 10 Nagel EL, Fine EG, Krischer JP, Davis JH. Complications of CPR. Crit Care Med 1981;9:424. 11 Leadbeatter S, Knight B. Resuscitation artefact. Med Sci Law 1988;28:200-204.
CARD10
19s 0167-5273/92/$05.00
01557
Thrombolysis following pre-hospital cardiopulmonary resuscitation Clive F.M. Weston a,b and Philip Avery a Departments of a Cardiology and h Epidemiology, lJnir>ersityHospital of Wales, Cardiff; Wales, UK (Received
12 April 1992; accepted
29 June 1992)
Weston CFM, Avery P. Thrombolysis following pre-hospital cardiopulmonary 1992;37:195-198.
resuscitation.
Int J Cardiol
Forty-eight patients were discharged from hospital following successful resuscitation from out-ofhospital ventricular fibrillation. Sixteen of these patients received intravenous thrombolytic therapy on admission to hospital. There were 3 significant bleeding complications and 2 cases of inappropriate administration of streptokinase. One of the patients that did not receive thrombolysis also had a significant bleeding complication of cardiopulmonary resuscitation. Patients admitted to hospital following resuscitation should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, and even then with caution. Key words: Thrombolysis;
Resuscitation;
Complications
Introduction Recent studies have suggested that cardiopulmonary resuscitation, especially for less than 10 min, is not a contraindication to thrombolytic therapy [l-3]. However, a case of fatal intrathoracic haemorrhage has been reported following cardiopulmonary resuscitation and treatment with streptokinase and heparin [4], and we have reported a case of extensive facial and thoracic subcutaneous bruising in a patient given anistreplase following successful resuscitation [5].
Correspondence to: Dr. C.F.M. Weston, University tal of Wales, Cardiff CF4 4XN, Wales, UK.
Hospi-
We have examined the in-hospital management of 48 patients admitted to four local hospitals between July 1989 and January 1992 who were resuscitated by ambulance crew from prehospital ventricular fibrillation, and who were later discharged home. By a description of selected case histories we demonstrate that thrombolytic therapy should be used with caution in these patients. Results Sixteen of the 48 patients received thrombolytic therapy on admission to hospital. All had received defibrillatory shocks and a precordial thump, yet only 7 had received chest compressions for more than 2 min. There were significant
196
bleeding complications in 3 patients (cases l-3). In 10 patients the cardiac arrest was associated with acute myocardial infarction, in 4 with coronary artery disease but no definite evidence of myocardial infarction and in 2 patients (cases 5 and 6) the aetiology of the arrest was not coronary disease. Case histories
commenced cardiopulmonary resuscitation. Within 5 min cardiac output had been restored following two defibrillations. The admission ECG showed ST segment elevation in the inferior leads and the patient received 1.5 MU streptokinase. Within 6 h he became hypotensive and had haematemesis which was treated with blood transfusions and intravenous cimetidine. He was discharged with a diagnosis of acute myocardial infarction.
Bleeding complications Case I [.5/ A 59-yr-old woman collapsed after complaining of chest pain. Cardiopulmonary resuscitation was started by a general practitioner and a non-paramedic ambulance crew before advanced life support was provided by a paramedic. The prolonged resuscitation (greater than 15 min) required defibrillation, intubation and drug administration before cardiac output and breathing was restored. The electrocardiogram (ECG) on admission showed marked ST segment elevation and intravenous anistreplase and heparin were given. Gross subcutaneous bruising developed around the mouth and anterior chest wall and the patient experienced haemoptysis. Transfusions of whole blood and fresh frozen plasma were required. The patient was later discharged with a diagnosis of inferior myocardial infarction. Case 2 An 87-yr-old woman had chest pain for 12 h. She developed ventricular fibrillation whilst in the ambulance and received a precordial thump and chest compressions and was defibrillated twice. Cardiac output was restored within 3 min. The ECG on admission showed changes of acute infero-posterior myocardial infarction and 1.5 MU streptokinase was administered. Within 12 h she developed haemoptysis and obvious periorbital bruising. The haemoglobin fell from 11.4 g/d1 to 9.8 g/d& but no transfusion was given. The lady was later discharged home with a diagnosis of acute myocardial infarction. Case 3 A 59-yr-old man complained of chest pain and called his general practitioner. Approximately 2 min before the arrival of the ambulance the patient collapsed and the general practitioner
Case 4 A 65-yr-old man collapsed in the presence of a general practitioner who commenced cardiopulmonary resuscitation. Ten min later a paramedic arrived and after prolonged attempts, including defibrillations, intubation and drug administration, succeeded in restoring cardiac output. On arrival at hospital the ECG showed atria1 fibrillation and a left bundle branch block pattern. Neither thrombolytic therapy nor aspirin was given. However, the patient had a haematemesis of about 120 ml of fresh blood 4 h later, and subsequently manifest pronounced periorbital petechiae. Investigations of the upper gastrointestinal tract were not performed because of left ventricular failure, and a blood transfusion was not required. This man was felt to have suffered an acute myocardial infarction by virtue of raised cardiac enzymes. Inappropriate therapy Case 5 A 58-yr-old man collapsed in the street without warning. A neighbour commenced cardiac massage. An ambulance attended and there was prolonged resuscitation involving defibrillations, intubation and drug administration. In the Accident and Emergency Department the ECG showed pronounced lateral ST segment depression and 1.2 MU streptokinase was given without complication. Serial ECG’s showed no evidence of acute myocardial infarction and coronary angiography was later shown to be normal. The left ventricle was hypertrophied and there was mitral valve prolapse. Case 6 An 80-yr-old woman collapsed without warning. Resuscitation was commenced by a bystander, an ambulance attended and she was
197
soon defibrillated and cardiac output restored. She was admitted to an intensive care unit where an admission ECG showed non-specific ST changes. The potassium level on admission was 2.9 mmol/l. 1.5 MU streptokinse was infused without any complication. The creatine kinase was only marginally elevated and there was no progression of the ECG abnormalities. This woman was felt to have suffered ventricular fibrillation, without acute myocardial infarction, possibly related to electrolyte abnormalities. Discussion Increasing deployment of defibrillators and paramedic ambulance crew will lead to an increased number of patients surviving pre-hospital ventricular fibrillation and being admitted to hospital [6]. Whilst the majority of these patients will have coronary artery disease 171, and 70% will have angiographic evidence of coronary thrombus formation immediately after resuscitation [8], as few as 20% will show evidence of acute, Q-wave, myocardial infarction [9]. Most patients have either no ECG changes, or ST/T wave changes during the days following resuscitation from outof-hospital cardiac arrest [9]. The benefit of thrombolytic therapy in these remaining surviving patients is questionable. Cardiopulmonary resuscitation, particularly chest compressions, may lead to trauma of a number of organ systems, most commonly rib and sternal fractures [lo]. Lesions within the gastrointestinal tract are not uncommon and gastric haemorrhage or rupture and mesenteric lacerations have been reported [ll]. Both patients who had haematemesis (cases 3 and 4) may well have experienced such trauma, though ischaemic stress ulceration cannot be ruled out. Experience of administering thrombolytic therapy to patients who have already been resuscitated from out-of-hospital cardiac arrest is limited. Cross et al. reported no bleeding complications in ten patients who received thrombolytic therapy following resuscitation, four of whom had had chest compressions 111. A study of patients entered into the first three Thrombolysis and Angioplasty in Myocardial Infarction trials
showed no direct complications of cardiopulmonary resuscitation in 22 patients who received chest compressions before or within 6 h of thrombolytic treatment. However, patients who received cardiopulmonary resuscitation for greater than 10 min were specifically excluded from these trials and the 95% confidence interval for no complications was 0 to 14% [2]. Scholz et al. reported three patients with bleeding complications out of 16 patients who received thrombolysis soon after successful resuscitations [3]. Only 4 of these patients received intravenous thrombolysis. In all there were 8 bleeding complications in 43 patients who underwent prolonged cardiopulmonary resuscitation and received thrombolytic therapy within a time interval of less than 24 h. Not only was the rate of bleeding complications in these patients similar to that seen in patients who did not require resuscitation (18.6% vs 16.1%), but there were felt to be no cases of bleeding that were directly related to cardiac compressions despite 17 cases of rib fracture. Of the 16 patients in our present series there were 3 cases of significant bleeding complications, not necessarily related to the duration of the resuscitation attempt, and 2 cases of inappropriate therapy. Because these patients were selected by virtue of the fact that they were discharged from hospital alive, there are obviously no cases of fatality in the series. We are unaware of any cases of patients admitted to our local hospitals who have died in hospital following resuscitation and the subsequent administration of thrombolytic agents. To our knowledge the only reported case of such a fatality is that of Haugeberg [4]. We believe that such patients should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, namely marked ST segment elevation or new left bundle branch block, and even then with caution. References 1 Cross SJ, Lee HS, Rawles JM, Jennings K. Safety of thrombolysis in association with cardiopulmonary resuscitation. Br Med J 1991;303:1242.
98 2 Tenaglia: AN, Califf RM, Candela RJ et al. Thrombolytic therapy m patients requiring cardiopulmonary resuscitation. Am J Cardiol 1991;68:1015-19. 3 Scholz KH, Tebbe V, Herrmann C et al. Frequency of complications of cardiopulmonary resuscitation after thrombolysis during acute myocardial infarction. Am J Cardiol 1992;69:724-728. 4 Haugeberg G, Bonarjee V, Dickstein K. Fatal intrathoracic haemorrhage after cardiopulmonary resuscitation and treatment with strepokinase and heparin. Br Heart J 1989;62:157-158. 5 Wong SS, Lazarus JH, Weston CFM. Extensive subcutaneous bleeding after cardiopulmonary resuscitation and thrombolytic therapy. Arch Emerg Med 1991;8:140-143. 6 Cobb LA, Weaver WD, Fahrenbruch CE, Hallstrom AP, Copass MK. Community-based interventions for sudden cardiac death. Circulation 1992;85(suppl I):98-102.
7 Perper JA, Kuller LH, Cooper M. Arteriosclerosis of coronary arteries in sudden, unexpected deaths. Circulation 1975;52(suppl 111)27-33. 8 DeWood MA, Leimgruber PP, Shields JP, Kunkel RM, Hensley GR, Reisig AH. Thrombosis in acute myocardial infarction and sudden death: angiographic aspects. Cardiovasc Clinic 1987;18:195-211. 9 Cobb LA, Werner JA, Trobaugh GR. Sudden cardiac death. I. A decade’s experience with out-of-hospital resuscitation. Med Concepts Cardiovasc Dis 1980;19:31-36. 10 Nagel EL, Fine EG, Krischer JP, Davis JH. Complications of CPR. Crit Care Med 1981;9:424. 11 Leadbeatter S, Knight B. Resuscitation artefact. Med Sci Law 1988;28:200-204.