458
Correspondence
[4] Anonymous. Lawriter—ORC—1337.11. Durable power of attorney for health care definitions. [Internet]. [cited 2014 Aug 14]. Available from: http://codes.ohio.gov/orc/1337.11. [5] Murphy DJ, Burrows D, Santilli S, Kemp AW, Tenner S, Kreling B, et al. The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation. N Engl J Med 1994;330(8):545–9. [6] Gina K, Gill G, Fukushima E, Abu-Laban RB, Sweet DD. Prevalence of advance directives among elderly patients attending an urban Canadian emergency department. CJEM 2012;14(2):90–6. [7] Taylor DM, Ugoni AM, Cameron PA, McNeil JJ. Advance directives and emergency department patients: ownership rates and perceptions of use. Intern Med J 2003;33 (12):586–92.
Louise Falzon, BA, PGDipInf Center for Behavioral Cardiovascular Health, Department of Medicine Columbia University Medical Center, New York, NY E-mail address: [email protected] Daniel K. Nishijima, MD Department of Emergency Medicine University of California, Davis, Sacramento, CA E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.11.009
Tranexamic acid in brain injury: devil in the detail
To the Editor, We appreciate the comments by Piper et al [1] about the low rate of thromboembolic events reported in the trials included in our systematic review, evaluating the use of tranexamic acid in traumatic brain injury [2]. This low rate has generated both reassurance and skepticism at the same time. The trials included in our systematic review were largely conducted in developing countries [3,4], where follow-up and assessment of complications or side effects might have been very difficult. However, a large body of literature, in both injured and noninjured patients [5,6], has shown that the use of tranexamic acid is not associated with significant (clinically or statistically) increase in the risk of thromboembolic events compared with placebo or standard therapy. Therefore, we believe that the findings of these trials are in line with other studies. Dysregulation of the blood coagulation system after trauma (posttraumatic coagulopathy) is complex and involves a mixture of inflammatory, coagulation, and cellular (platelets, leukocytes, and endothelium) dysfunctions [7,8]. Coagulation is a dynamic process. The coagulation status may change rapidly during injury and resuscitation from an anticoagulant to a procoagulant state or vice versa. Numerous processes, including dysfunction of the natural anticoagulant mechanisms (due to release of anticoagulants from the injured tissue and loss of coagulation factors during hemorrhage), platelet dysfunction, fibrinogen consumption, and hyperfibrinolysis, all contribute to posttraumatic coagulopathy. In addition, dilutional coagulopathy resulting from resuscitation fluids, hypothermia, and acidosis can affect clot formation, adding more layers of complexity to posttraumatic coagulopathy [7,8]. The multifaceted nature of posttraumatic coagulopathy and its rapidly changing dynamics impede the prediction of coagulation-related side effects. Administration of antifibrinolytic agents such as tranexamic acid adds to this complexity. The timing of administration and the status of the coagulation system at that very moment (anticoagulation or procoagulation state) would determine whether thromboembolism formation is prevented or facilitated. Administration of blood or other blood products such as fresh frozen plasma or platelets will also impact this process. Therefore, the occurrence of thromboembolic events involves numerous confounders in addition to tranexamic acid. The studies included in our meta-analysis did not intend to study the cause behind the observed low rate of the thromboembolic events. Whether this low rate will be replicated in future trials remains to be seen. Until then, hopefully, the understandable skepticism results in stratifying risk at the level of each individual patient with trauma and thus using clinical judgment to assess the risk-harm balance of tranexamic acid administration.
Shahriar Zehtabchi, MD Samah G. Abdel Baki, MD Department of Emergency Medicine, State University of New York Downstate Medical Center, Brooklyn, NY E-mail addresess: [email protected] [email protected]
References [1] B.J. Piper, Tranexamic acid in brain injury: the devil in the detail. Am J Emerg Med, in press. [2] Zehtabchi S, Abdel Baki SG, Falzon L, Nishijima DK. Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis. Am J Emerg Med (accepted for publication). [3] CRASH-2 Collaborators. Intracranial Bleeding Study. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 2011;343:354–65. [4] Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for patients with traumatic brain injury: a randomized, double- blinded, placebo-controlled trial. BMC Emerg Med 2013;13:20–8. [5] Huang F, Wu D, Ma G, Yin Z, Wang Q. The use of tranexamic acid to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis. J Surg Res 2014;186:318–27. [6] Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg 2012;147:113–9. [7] White NJ. Mechanisms of trauma-induced coagulopathy. Hematology Am Soc Hematol Educ Program 2013;2013:660–3. [8] Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, et al. Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury 2012;43:26–32.
Tranexamic acid in brain injury: the devil in the detail
To the Editor, The use of tranexamic acid in trauma has been well studied, and its application to subgroups as well as nontrauma patients is growing. However, there must be consideration and concern with regard to the tranexamic acid data presented in the recent systematic review and meta-analysis by Zehtabchi et al [1]. The concern is that the safety data that are cited, with regard to thrombotic complications, have an incredibly low event rate. The data presented suggest that of the 510 patients observed, only 3 had thrombotic events documented and none of these were in the tranexamic acid arms of either study. At first glance, this is reassuring. Thrombotic complication rates in this high-risk brain-injured population range from 3.1% to 12% [2–4]. To observe a large high-risk population and observe so few thrombotic complications are unlikely. The probability of such an event can be calculated given its binary nature (thrombosis vs no thrombosis) and its well-documented event rate [2–4]. Assuming that the event rate was low and we take the event rate of 3% in a population of 510, the anticipated event rate would be 15. Thus, it follows that the probability of observing 3 events or less is 0.00014 (b 1 in 7000). This should raise suspicions in the robustness of the literature as it stands and the weight of emphasis and confidence we invest in it. Benjamin J. Piper, MD, MBBS(Hons), BMsc Department of Anaesthesia and Intensive Care, John Hunter Hospital Newcastle, Australia Corresponding author. Tel.: +61 412 251 655 E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.11.008
Correspondence
% of residents among 4131 completed surveys
References
459
[1] Zehtabchi S. Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis. Am J Emerg Med 2014(0) [published ahead of print]. [2] Nickele CM, Kamps TK, Medow JE. Safety of a DVT chemoprophylaxis protocol following traumatic brain injury: a single center quality improvement initiative. Neurocrit Care 2013;18(2):184–92. [3] Jamjoom AA, Jamjoom AB. Safety and efficacy of early pharmacological thromboprophylaxis in traumatic brain injury: systematic review and metaanalysis. J Neurotrauma 2013;30(7):503–11. [4] Dudley RR. Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits. J Neurotrauma 2010;27(12): 2165–72.
65.1
70 60 50 40 30
23.8
20
10.3 10
0.1
0.7
0
Emergency medicine residents' perspectives on patient safety and duty hours
To the Editor,
Fig. 1. Do you work the appropriate number of clinical hours to be competent to practice EM independently at graduation?
In 2003, the Accreditation Council for Graduate Medical Education implemented standards on duty hours, to promote resident learning and patient safety [1]. In 2008, the Institute of Medicine released a report “Resident Duty Hours: Enhancing Sleep, Supervision, and Safety [2].” In 2011, the Accreditation Council for Graduate Medical Education implemented additional regulations on duty hours and supervision [3]. Emergency medicine (EM) has additional duty hour requirements, including a maximum of 12 continuous scheduled hours and a maximum 60 scheduled hours per week in the emergency department [4]. Evidence has not clearly demonstrated whether duty hour requirements improved trainee well-being or patient safety [5-15]. 2. Methods The American Board of EM (ABEM) delivers the annual ABEM in-training examination. This study was approved by the Human Investigations Committee. The survey was administered on a voluntary basis to EM residents, immediately after the 2014 ABEM in-training examination.
% of residents among 4105 completed surveys
1. Introduction
100 90 80 70 60 50
33.3
40 20
20.5
10
5.1
4. Conclusions Emergency medicine residents believe that duty hour standards improve patient safety and that the current standards are appropriate to ensure patient safety. Further research is required to determine if their perception is truly related to patient safety outcomes.
10.6
0
Fig. 2. Do duty hours improve patient safety?
3. Results A total of 4134 EM residents participated (73%) of 5663 total residents who took the in-training examination. Most residents (62.9%; n = 2596; 95% confidence interval [CI], 61.4%-64.4%) were completely satisfied that their residency was preparing them to practice EM independently. Most residents stated that they are working the appropriate number of hours to practice independently at graduation (65%; n = 2691; 95% CI, 63.7%66.6%) (Fig. 1). Most residents (84%; n = 3462) believe that current duty hour regulations improve patient safety (Fig. 2). Most residents (86%; n = 3360; 95% CI, 84.9%-87.1%) agreed that duty hour regulations are currently appropriate to ensure patient safety (Fig. 3). Residents rated the best aspects of being an emergency physician and the biggest challenges facing EM (Tables 1 and 2).
30.6
30
6%
8%
should work fewer hours currently appropriate should work more hours
86%
% of residents among 3908 completed Fig. 3. To ensure patient safety, are current duty hour regulations appropriate?
Correspondence
[4] Anonymous. Lawriter—ORC—1337.11. Durable power of attorney for health care definitions. [Internet]. [cited 2014 Aug 14]. Available from: http://codes.ohio.gov/orc/1337.11. [5] Murphy DJ, Burrows D, Santilli S, Kemp AW, Tenner S, Kreling B, et al. The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation. N Engl J Med 1994;330(8):545–9. [6] Gina K, Gill G, Fukushima E, Abu-Laban RB, Sweet DD. Prevalence of advance directives among elderly patients attending an urban Canadian emergency department. CJEM 2012;14(2):90–6. [7] Taylor DM, Ugoni AM, Cameron PA, McNeil JJ. Advance directives and emergency department patients: ownership rates and perceptions of use. Intern Med J 2003;33 (12):586–92.
Louise Falzon, BA, PGDipInf Center for Behavioral Cardiovascular Health, Department of Medicine Columbia University Medical Center, New York, NY E-mail address: [email protected] Daniel K. Nishijima, MD Department of Emergency Medicine University of California, Davis, Sacramento, CA E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.11.009
Tranexamic acid in brain injury: devil in the detail
To the Editor, We appreciate the comments by Piper et al [1] about the low rate of thromboembolic events reported in the trials included in our systematic review, evaluating the use of tranexamic acid in traumatic brain injury [2]. This low rate has generated both reassurance and skepticism at the same time. The trials included in our systematic review were largely conducted in developing countries [3,4], where follow-up and assessment of complications or side effects might have been very difficult. However, a large body of literature, in both injured and noninjured patients [5,6], has shown that the use of tranexamic acid is not associated with significant (clinically or statistically) increase in the risk of thromboembolic events compared with placebo or standard therapy. Therefore, we believe that the findings of these trials are in line with other studies. Dysregulation of the blood coagulation system after trauma (posttraumatic coagulopathy) is complex and involves a mixture of inflammatory, coagulation, and cellular (platelets, leukocytes, and endothelium) dysfunctions [7,8]. Coagulation is a dynamic process. The coagulation status may change rapidly during injury and resuscitation from an anticoagulant to a procoagulant state or vice versa. Numerous processes, including dysfunction of the natural anticoagulant mechanisms (due to release of anticoagulants from the injured tissue and loss of coagulation factors during hemorrhage), platelet dysfunction, fibrinogen consumption, and hyperfibrinolysis, all contribute to posttraumatic coagulopathy. In addition, dilutional coagulopathy resulting from resuscitation fluids, hypothermia, and acidosis can affect clot formation, adding more layers of complexity to posttraumatic coagulopathy [7,8]. The multifaceted nature of posttraumatic coagulopathy and its rapidly changing dynamics impede the prediction of coagulation-related side effects. Administration of antifibrinolytic agents such as tranexamic acid adds to this complexity. The timing of administration and the status of the coagulation system at that very moment (anticoagulation or procoagulation state) would determine whether thromboembolism formation is prevented or facilitated. Administration of blood or other blood products such as fresh frozen plasma or platelets will also impact this process. Therefore, the occurrence of thromboembolic events involves numerous confounders in addition to tranexamic acid. The studies included in our meta-analysis did not intend to study the cause behind the observed low rate of the thromboembolic events. Whether this low rate will be replicated in future trials remains to be seen. Until then, hopefully, the understandable skepticism results in stratifying risk at the level of each individual patient with trauma and thus using clinical judgment to assess the risk-harm balance of tranexamic acid administration.
Shahriar Zehtabchi, MD Samah G. Abdel Baki, MD Department of Emergency Medicine, State University of New York Downstate Medical Center, Brooklyn, NY E-mail addresess: [email protected] [email protected]
References [1] B.J. Piper, Tranexamic acid in brain injury: the devil in the detail. Am J Emerg Med, in press. [2] Zehtabchi S, Abdel Baki SG, Falzon L, Nishijima DK. Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis. Am J Emerg Med (accepted for publication). [3] CRASH-2 Collaborators. Intracranial Bleeding Study. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 2011;343:354–65. [4] Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for patients with traumatic brain injury: a randomized, double- blinded, placebo-controlled trial. BMC Emerg Med 2013;13:20–8. [5] Huang F, Wu D, Ma G, Yin Z, Wang Q. The use of tranexamic acid to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis. J Surg Res 2014;186:318–27. [6] Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg 2012;147:113–9. [7] White NJ. Mechanisms of trauma-induced coagulopathy. Hematology Am Soc Hematol Educ Program 2013;2013:660–3. [8] Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, et al. Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury 2012;43:26–32.
Tranexamic acid in brain injury: the devil in the detail
To the Editor, The use of tranexamic acid in trauma has been well studied, and its application to subgroups as well as nontrauma patients is growing. However, there must be consideration and concern with regard to the tranexamic acid data presented in the recent systematic review and meta-analysis by Zehtabchi et al [1]. The concern is that the safety data that are cited, with regard to thrombotic complications, have an incredibly low event rate. The data presented suggest that of the 510 patients observed, only 3 had thrombotic events documented and none of these were in the tranexamic acid arms of either study. At first glance, this is reassuring. Thrombotic complication rates in this high-risk brain-injured population range from 3.1% to 12% [2–4]. To observe a large high-risk population and observe so few thrombotic complications are unlikely. The probability of such an event can be calculated given its binary nature (thrombosis vs no thrombosis) and its well-documented event rate [2–4]. Assuming that the event rate was low and we take the event rate of 3% in a population of 510, the anticipated event rate would be 15. Thus, it follows that the probability of observing 3 events or less is 0.00014 (b 1 in 7000). This should raise suspicions in the robustness of the literature as it stands and the weight of emphasis and confidence we invest in it. Benjamin J. Piper, MD, MBBS(Hons), BMsc Department of Anaesthesia and Intensive Care, John Hunter Hospital Newcastle, Australia Corresponding author. Tel.: +61 412 251 655 E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.11.008
Correspondence
% of residents among 4131 completed surveys
References
459
[1] Zehtabchi S. Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis. Am J Emerg Med 2014(0) [published ahead of print]. [2] Nickele CM, Kamps TK, Medow JE. Safety of a DVT chemoprophylaxis protocol following traumatic brain injury: a single center quality improvement initiative. Neurocrit Care 2013;18(2):184–92. [3] Jamjoom AA, Jamjoom AB. Safety and efficacy of early pharmacological thromboprophylaxis in traumatic brain injury: systematic review and metaanalysis. J Neurotrauma 2013;30(7):503–11. [4] Dudley RR. Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits. J Neurotrauma 2010;27(12): 2165–72.
65.1
70 60 50 40 30
23.8
20
10.3 10
0.1
0.7
0
Emergency medicine residents' perspectives on patient safety and duty hours
To the Editor,
Fig. 1. Do you work the appropriate number of clinical hours to be competent to practice EM independently at graduation?
In 2003, the Accreditation Council for Graduate Medical Education implemented standards on duty hours, to promote resident learning and patient safety [1]. In 2008, the Institute of Medicine released a report “Resident Duty Hours: Enhancing Sleep, Supervision, and Safety [2].” In 2011, the Accreditation Council for Graduate Medical Education implemented additional regulations on duty hours and supervision [3]. Emergency medicine (EM) has additional duty hour requirements, including a maximum of 12 continuous scheduled hours and a maximum 60 scheduled hours per week in the emergency department [4]. Evidence has not clearly demonstrated whether duty hour requirements improved trainee well-being or patient safety [5-15]. 2. Methods The American Board of EM (ABEM) delivers the annual ABEM in-training examination. This study was approved by the Human Investigations Committee. The survey was administered on a voluntary basis to EM residents, immediately after the 2014 ABEM in-training examination.
% of residents among 4105 completed surveys
1. Introduction
100 90 80 70 60 50
33.3
40 20
20.5
10
5.1
4. Conclusions Emergency medicine residents believe that duty hour standards improve patient safety and that the current standards are appropriate to ensure patient safety. Further research is required to determine if their perception is truly related to patient safety outcomes.
10.6
0
Fig. 2. Do duty hours improve patient safety?
3. Results A total of 4134 EM residents participated (73%) of 5663 total residents who took the in-training examination. Most residents (62.9%; n = 2596; 95% confidence interval [CI], 61.4%-64.4%) were completely satisfied that their residency was preparing them to practice EM independently. Most residents stated that they are working the appropriate number of hours to practice independently at graduation (65%; n = 2691; 95% CI, 63.7%66.6%) (Fig. 1). Most residents (84%; n = 3462) believe that current duty hour regulations improve patient safety (Fig. 2). Most residents (86%; n = 3360; 95% CI, 84.9%-87.1%) agreed that duty hour regulations are currently appropriate to ensure patient safety (Fig. 3). Residents rated the best aspects of being an emergency physician and the biggest challenges facing EM (Tables 1 and 2).
30.6
30
6%
8%
should work fewer hours currently appropriate should work more hours
86%
% of residents among 3908 completed Fig. 3. To ensure patient safety, are current duty hour regulations appropriate?
