Use of systemic thrombolytic therapy in patients with non-traumatic cardiac arrest: A systematic review and meta-analysis
Abstract
Objective: To better delineate the benefits and risks of systemic thrombolytic therapy in patients with cardiac arrest from non-traumatic etiologies.
Data sources: MEDLINE, EMBASE, and SCOPUS were systematically searched up to November of 2017.
Study Selection: All retrospective and prospective studies in which systemic thrombolytic therapy was used during the sequence of cardiopulmonary resuscitation (CPR) or shortly after achieving return of spontaneous circulation (ROSC) were included.
Data extraction: The following variable results were extracted from intervention and control groups if available: rate of ROSC, survival after 24 hours, survival at discharge, neurological performance at 6 months based on a favorable Cerebral Performance Categories Scale (1 or 2) and major bleeding events.
Data Synthesis: Eight retrospective studies and 6 prospective studies were included in the qualitative analysis. Research synthesis was conducted when at least 4 studies were available for an outcome, which limited the analysis of major bleeding events and neurologic outcomes. Benefit of thrombolytic therapy in survival to discharge showed a moderate beneficial effect (OR = 2.79, 2.11–3.69) in the retrospective study analysis while in the prospective study analysis no statistically significant benefit was found (OR = 1.27, 0.77–2.10). Benefit of thrombolysis in the rate of ROSC was not statistically significant in the prospective analysis (OR = 1.59, 0.92–2.76, p = 0.138) as well as survival at 24 hours (OR = 1.17, 0.72–1.71).
Conclusions: The widespread use of thrombolytics in patients with non-traumatic cardiac arrest does not seem to improve major outcomes, including survival to discharge. However, the modest benefit found in the retrospective study analysis suggests a subgroup of patients that may benefit from this therapy.
Keywords: Thrombolytic therapy, cardiac arrest, advanced cardiac life support, cardiopulmonary resuscitation, tissue plasminogen activator
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References
Silfvast T. Cause of death in unsuccessful prehospital resuscitation.
J Intern Med 1991 Apr;229(4):331–5.
Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary
angiography in survivors of out-of-hospital cardiac
arrest. N Engl J Med 1997 Jun 5;336(23):1629–33.
Renkes-Hegendörfer U, Hermann K. Successful treatment
of a case of fulminant massive pulmonary embolism with
streptokinase. Anaesthesist 1974 Nov;23(11):500–1.
Ballew KA, Philbrick JT, Caven DE, et al. Predictors of survival
following in-hospital cardiopulmonary resuscitation.
A moving target. Arch Intern Med 1994 Nov 14;154(21):
–32.
Bedell SE, Delbanco TL, Cook EF, et al. Survival after cardiopulmonary
resuscitation in the hospital. N Engl J Med 1983
Sep 8;309(10):569–76.
Van Walraven C, Stiell IG, Wells GA, et al. Do advanced cardiac
life support drugs increase resuscitation rates from inhospital
cardiac arrest? The OTAC Study Group. Ann Emerg
Med 1998 Nov;32(5):544–53.
Böttiger BW, Martin E. Thrombolytic therapy during cardiopulmonary
resuscitation and the role of coagulation activation
after cardiac arrest. Curr Opin Crit Care 2001 Jun;
(3):176–83.
Ames A, Wright RL, Kowada M, et al. Cerebral ischemia. II. The
no-reflow phenomenon. Am J Pathol 1968 Feb; 52(2):437–53.
Fischer EG, Ames A, Hedley-Whyte ET, et al. Reassessment
of cerebral capillary changes in acute global ischemia and
their relationship to the “no-reflow phenomenon.” Stroke
Feb; 8(1):36–9.
Safar P. Cerebral resuscitation after cardiac arrest: a review.
Circulation 1986 Dec; 74(6 Pt 2): IV138–153.
Böttiger BW, Motsch J, Böhrer H, et al. Activation of blood
coagulation after cardiac arrest is not balanced adequately
by activation of endogenous fibrinolysis. Circulation 1995
Nov 1;92(9):2572–8.
Gando S, Kameue T, Nanzaki S, et al. Massive fibrin formation
with consecutive impairment of fibrinolysis in patients with
out-of-hospital cardiac arrest. Thromb Haemost 1997 Feb;
(2):278–82.
Fischer M, Böttiger BW, Popov-Cenic S, et al. Thrombolysis
using plasminogen activator and heparin reduces cerebral
no-reflow after resuscitation from cardiac arrest: an
experimental study in the cat. Intensive Care Med 1996 Nov;
(11):1214–23.
Lin SR, O’Connor MJ, Fischer HW, et al. The effect of combined
dextran and streptokinase on cerebral function and
blood flow after cardiac arrest: and experimental study on
the dog. Invest Radiol 1978 Dec;13(6):490–8.
Kim YH, Park JH, Hong SH, et al. Nonproteolytic neuroprotection
by human recombinant tissue plasminogen activator.
Science 1999 Apr 23;284(5414):647–50.
Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC
guidelines on the diagnosis and management of acute pulmonary
embolism. Eur Heart J 2014 Nov 14;35(43):3033–3069,
a–3069k.
Jaff MR, McMurtry MS, Archer SL, et al. Management of massive
and submassive pulmonary embolism, iliofemoral deep
vein thrombosis, and chronic thromboembolic pulmonary
hypertension: a scientific statement from the American Heart
Association. Circulation 2011 Apr 26;123(16):1788–830.
Bailén MR, Cuadra JA, Aguayo De Hoyos E. Thrombolysis
during cardiopulmonary resuscitation in fulminant pulmonary
embolism: a review. Crit Care Med 2001 Nov;29(11):
–9.
Fibrinolytic Therapy Trialists’ (FTT) Collaborative (last).
Indications for fibrinolytic therapy in suspected acute myocardial
infarction: collaborative overview of early mortality and
major morbidity results from all randomised trials of more
than 1000 patients [Internet]. Centre for Reviews and Dissemination
(UK); 1994. Available from: https://www.ncbi.nlm.nih.
gov/books/NBK66304/
O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/
AHA guideline for the management of ST-elevation myocardial
infarction: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice
Guidelines. J Am Coll Cardiol 2013 Jan 29;61(4):e78–140.
Effects of tissue plasminogen activator and a comparison of
early invasive and conservative strategies in unstable angina
and non-Q-wave myocardial infarction. Results of the TIMI
IIIB Trial. Thrombolysis in Myocardial Ischemia. Circulation
Apr;89(4):1545–56.
Anderson HV, Cannon CP, Stone PH, et al. One-year results
of the Thrombolysis in Myocardial Infarction (TIMI) IIIB
clinical trial. A randomized comparison of tissue-type
plasminogen activator versus placebo and early invasive
versus early conservative strategies in unstable angina and
non-Q wave myocardial infarction. J Am Coll Cardiol 1995
Dec;26(7):1643–50.
Neumar RW, Shuster M, Callaway CW, et al. Part 1: Executive
Summary: 2015 American Heart Association Guidelines
Update for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Circulation 2015 Nov 3;132
(18 Suppl 2):S315–367.
Li X, Fu Q, Jing X, et al. A meta-analysis of cardiopulmonary
resuscitation with and without the administration of
thrombolytic agents. Resuscitation 2006 Jul;70(1):31–6.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement
for reporting systematic reviews and meta-analyses of
studies that evaluate health care interventions: explanation
and elaboration. PLoS Med 2009 Jul 21;6(7):e1000100.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting
items for systematic reviews and meta-analyses: the
PRISMA statement. PLoS Med 2009 Jul 21;6(7):e1000097.
Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane
Collaboration’s tool for assessing risk of bias in randomised
trials. BMJ. 2011 Oct 18;343:d5928.
Ottawa Hospital Research Institute [Internet]. [cited 2018
May 6]. Available from: http://www.ohri.ca/programs/
clinical_epidemiology/oxford.asp
Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring
inconsistency in meta-analyses. BMJ 2003 Sep 6;327(7414):
–60.
Borenstein M, Hedges LV, Higgins JPT, et al. Introduction to
Meta-Analysis. John Wiley & Sons;2011.434 p.
Palmer TM, Sterne JAC. Meta-Analysis in Stata: An Updated
Collection from the Stata Journal, Second Edition. Second.
College Station, TX: Stata Press;2015.534p.
Van Campen LC, Van Leeuwen GR, Verheugt FW. Safety
and efficacy of thrombolysis for acute myocardial infarction
in patients with prolonged out-of-hospital cardiopulmonary
resuscitation. Am J Cardiol 1994 May 15;73(13):953–5.
Ruiz-Bailén M, Aguayo de Hoyos E, Serrano-Córcoles MC,
et al. Efficacy of thrombolysis in patients with acute myocardial
infarction requiring cardiopulmonary resuscitation.
Intensive Care Med 2001 Jun;27(6):1050–7.
Lederer W, Lichtenberger C, Pechlaner C, et al. Recombinant
tissue plasminogen activator during cardiopulmonary
resuscitation in 108 patients with out-of-hospital cardiac
arrest. Resuscitation 2001 Jul;50(1):71–6.
Renard A, Verret C, Jost D, et al. Impact of fibrinolysis on
immediate prognosis of patients with out-of-hospital cardiac
arrest. J Thromb Thrombolysis 2011 Nov;32(4):405–9.
Janata K, Holzer M, Kürkciyan I, et al. Major bleeding complications
in cardiopulmonary resuscitation: the place of
thrombolytic therapy in cardiac arrest due to massive pulmonary
embolism. Resuscitation 2003 Apr;57(1):49–55.
Kurkciyan I, Meron G, Sterz F, et al. Pulmonary embolism
as a cause of cardiac arrest: presentation and outcome. Arch
Intern Med 2000 May 22;160(10):1529–35.
Kurkciyan I, Meron G, Sterz F, et al. Major bleeding complications
after cardiopulmonary resuscitation: impact of thrombolytic
treatment. J Intern Me. 2003 Feb;253(2):128–35.
Schreiber W, Gabriel D, Sterz F, et al. Thrombolytic therapy
after cardiac arrest and its effect on neurological outcome.
Resuscitation. 2002 Jan;52(1):63–9.
Böttiger BW, Bode C, Kern S, et al. Efficacy and safety of
thrombolytic therapy after initially unsuccessful cardiopulmonary
resuscitation: a prospective clinical trial. Lancet
Lond Engl 2001 May 19;357(9268):1583–5.
Böttiger BW, Arntz H-R, Chamberlain DA, et al. Thrombolysis
during resuscitation for out-of-hospital cardiac arrest.
N Engl J Med 2008 Dec 18;359(25):2651–62.
Abu-Laban RB, Christenson JM, Innes GD, et al. Tissue
plasminogen activator in cardiac arrest with pulseless
electrical activity. N Engl J Med. 2002 May 16;346(20):
–8.
Stadlbauer KH, Krismer AC, Arntz HR, et al. Effects of
thrombolysis during out-of-hospital cardiopulmonary resuscitation.
Am J Cardiol 2006 Feb 1;97(3):305–8.
Wenzel V, Krismer AC, Arntz HR, et al. A comparison of
vasopressin and epinephrine for out-of-hospital cardiopulmonary
resuscitation. N Engl J Med 2004 Jan 8;350(2):
–13.
Bozeman WP, Kleiner DM, Ferguson KL. Empiric tenecteplase
is associated with increased return of spontaneous
circulation and short term survival in cardiac arrest patients
unresponsive to standard interventions. Resuscitation
Jun;69(3):399–406.
Fatovich DM, Dobb GJ, Clugston RA. A pilot randomised
trial of thrombolysis in cardiac arrest (The TICA trial).
Resuscitation 2004 Jun;61(3):309–13.
