- Email: [email protected]
Molecular and cellular effects of cardiac mechanotransduction during cardiopulmonary resuscitation and postresuscitation period: another piece in the puzzle
250
Correspondence
Table 2 A comparison of transtracheal ultrasonography results with the continuous capnographic waveform Continuous capnographic waveform
A. Transtracheal ultrasonography Tracheal positive Tracheal negative Total B. Lung sliding sign with ultrasonography Present Absent Total
Present
Absent Total
n
n %
%
n
%
62 96.9 1 20.0 63 91.3 2 3.1 4 80.0 6 8.7 64 92.8 5 7.2 69 100.0
63 98.4 1 20.0 64 92.8 1 1.6 4 80.0 5 7.2 64 92.8 5 7.2 69 100.0
[3] Newcombe R. Two-sided confidence intervals for the single proportion: comparison of seven methods. Statist Med 1998;17:857-72. [4] Grmec S. Comparison of three different methods to confirm tracheal tube placement in emergency intubation. Intensive Care Med 2002;28: 701-4. [5] Bozeman WP, Hexter D, Liang HK, Kelen GD. Esophageal detector device versus detection of end-tidal carbon dioxide level in emergency intubation. Ann Emerg Med 1996;27:595-9. [6] Ornato JP, Shipley JB, Racht EM, et al. Multicenter study of a portable, hand-size, colorimetric end-tidal carbon dioxide detection device. Ann Emerg Med 1992;21:518-23. [7] Tanigawa K, Takeda T, Goto E, Tanaka K. The efficacy of esophageal detector devices in verifying tracheal tube placement: a randomized cross-over study of out-of-hospital cardiac patients. Anesth Analg 2001; 92:375-8. [8] Weaver B, Lyon M, Blaivas M. Confirmation of endotracheal tube placement after intubation using the ultrasound sliding lung sign. Acad Emerg Med 2006;13(3):239-44. [9] Sustić A. Role of ultrasound in the airway management of critically ill patients. Crit Care Med 2007;35(5 suppl.):S173-7.
Table 3 Statistical calculations for the diagnostic performance of (A) transtracheal and (B) lung ultrasonography 95% CI A. Sensitivity Specificity Positive predictive value (+ PV) Negative predictive value (− PV) Positive likelihood ratio (+ LR) Negative likelihood ratio (− LR) Area under ROC curve (AUC) B. Sensitivity Specificity + PV − PV + LR − LR AUC
96.9 80.0 98.4 66.7 4.84 0.04 0.884
89.2-99.6 28.4-99.5 91.4-100.0 18.7-96.9 3.1-7.5 0.004-0.4 0.785-0.949
98.4 80.0 98.4 80.0 4.92 0.02 0.892
91.6-100.0 28.4-99.5 91.6-100.0 22.8-99.8 3.2-7.6 0.001-0.30 0.794-0.954
Table 4 Statistical calculations for the diagnostic performance of BED (TUS with LUS) 95% CI Sensitivity Specificity Positive predictive value Negative predictive value Positive likelihood ratio Negative likelihood ratio Area under ROC curve
100.0 80.0 98.5 100.0 5.0 0.0 0.900
94.4-100.0 28.4-99.5 91.6-100.0 29.2-100.0 3.2-7.8 – 0.804-0.959
Molecular and cellular effects of cardiac mechanotransduction during cardiopulmonary resuscitation and postresuscitation period: another piece in the puzzle☆,☆☆ To the Editor, Almost 60 years have passed since major discoveries regarding cardiopulmonary resuscitation (CPR) were made. Until now, several fundamental breakthroughs have been achieved in the field of CPR; however, survival remains low [1]. Our difficulty in resuscitating cardiac arrest patients reflects a limited understanding of the pathophysiology of global ischemia and reperfusion. As such, a better understanding of the molecular pathophysiology of cardiac arrest and postresuscitation period is an essential first step toward increasing survival. Maintaining cell shape and tone is crucial for the function and survival of cells and tissues, whereas mechanical stresses play a central role in the regulation of physiological processes, including the heart [2]. As all organs, the heart consists of billions of cells that function autonomously, as group of cells (eg, sinus node), or as a whole organ, preserving a balance between it and the rest of the organism. Consequently, any disturbances in the surrounding environment can potentially either directly or indirectly disrupt this balance. In keeping with the concepts of stress, any environmental stress will result in disruption of homeostatic equilibrium, resulting, in turn, in various disorders at the organ or cellular level. Mechanotransduction describes the molecular mechanisms by which cells respond to mechanical changes in their physical environment. It reflects the process whereby mechanical forces are converted into biochemical or electrical signals that are able to promote structural and functional remodeling in cells and tissues. Mechanical stimuli can be forces exerted on the cell from the extracellular environment, such as those imposed by compression or tension, or they can be intracellular forces that arise from cellular responses to changes in extracellular matrix quality. Recent focus on mechanotransduction in the heart has been aimed at elucidating the molecular mechanisms by which myocardial structures sense physical loads and transduces ☆
Sources of support: None. Conflicts of interest: None.
☆☆
Correspondence them into biochemical signals to alter gene expression and modify cellular structure and function. However, an important issue that remains to be elucidated is the effect of mechanical signaling due to chest compressions. Generally, the mechanical load transfer from a skin contact area to deeper tissues during CPR involves several tissue layers [3]. However, the continuous bodywide network of loose connective tissue that surrounds organs, nerves, and blood vessels also constitutes a matrix through which molecular signaling exchange takes place [4]. Consequently, the direct contact of this network with the heart may also facilitate the transduction of mechanical signals, initiating intracellular molecular signaling in cardiomyocytes through stretch-activated channels [5]. Cardiac cells recognize mechanical stimulation through forceinduced conformational changes at the molecular level, although these molecular mechanisms remain unclear. There is evidence that the axial compression and recoil of cardiac cells may stimulate stretch sensitive ion channels and result in direct effects on electrical activity by causing changes in intracellular Na+ and Ca2+ [6]. In addition, extracellular forces can alter focal adhesion proteins and modify concentrations and conformation of cytoskeletal cross-linking proteins [7]. Finally, the retrograde and antegrade coronary blood flow during CPR may induce a proinflammatory, prothrombotic state characterized by high cell turnover (resulting in both proliferation and death) relative to cells in static state [5]. Taken together, these recent findings raise the question as to whether chest compressions
251 may exert detrimental effects during CPR, decreasing, thus, the possibility of restoration of spontaneous circulation. Immediately after restoration of spontaneous circulation, the changes in hemodynamic loading, the mechanical disturbation of the ventricles, and the increase of intrathoracic pressure due to mechanical ventilation may cause various electrophysiologic effects [8]. The cyclic increases in intraventricular pressure on the stunned myocardial wall cause a whole myocardial bulging during systole, which is exacerbated by the decreased myocardial compliance of ischemic contracture [8]. Moreover, these conditions may be aggravated by the increased concentration of endogenous and exogenous adrenaline, which increases intraventricular pressure and slows conduction, facilitating arrhythmogenesis [9]. Also, after successful resuscitation, cardiac myocytes may sense increased strain levels (eg, postcardiac arrest myocardial edema or hemodynamic disturbances) through several pathways and respond with an increased intracellular Ca2+ concentration, exacerbating mitochondrial swelling, ischemic contracture, and myocardial compliance (Fig.) [10]. In conclusion, although our research in CPR is currently focused on oxidant stress, inflammation, and ischemia-reperfusion injury, specific attention should be given to the complex area of mechanotransduction and mechanical signaling because there is evidence that it is equally important. In particular, the mechanically induced molecular effects of chest compressions need to be elucidated. Furthermore, arterial shear stress may result in the release of modulatory and signaling molecules,
Fig. Mechanical forces generated via chest compressions and hemodynamic disturbances may exacerbate postcardiac arrest syndrome. CA, cardiac arrest; I/R, ischemia/reperfusion; ATP, adenosine triphosphate; ROS, reactive oxygen species; PRP, postresuscitation period.
252
Correspondence
whereas changes in hemodynamic loading may facilitate arrhythmogenesis. Research on these issues might further help identify the effects of cardiac mechanotransduction during CPR. Athanasios Chalkias PhD Elizabeth O. Johnson PhD Theodoros Xanthos PhD Department of Anatomy, Medical School National and Kapodistrian University of Athens 11527 Athens, Greece E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2012.08.010
References [1] Deakin CD, Nolan JP, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation 2010;81:1305-52. [2] Cook B, Hard RW, McConnaughey WB, et al. Preserving cell shape under environmental stress. Nature 2008;452:361-4. [3] Geerligs M, Peters GW, Ackermans PA, et al. Does subcutaneous adipose tissue behave as an (anti-)thixotropic material? J Biomech 2010;43:1153-9. [4] Banes AJ, Tsuzaki M, Yamamoto J, et al. Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol 1995;73:349-65. [5] Shyu KG. Cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes. Clin Sci (Lond) 2009;116: 377-89. [6] Iribe G, Ward CW, Camelliti P, et al. Axial stretch of rat single ventricular cardiomyocyte causes an acute and transient increase in Ca2+ spark rate. Circ Res 2009;104:787-95. [7] Johnson CP, Tang HY, Carag C, et al. Forced unfolding of proteins with cells. Science 2007;317:663-6. [8] Franz MR, Cima R, Wang D, et al. Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias. Circulation 1992;86:968-78. [9] Chalkias A, Xanthos T. Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev 2012;17: 117-28. [10] Lammerding J, Kamm RD, Lee RT. Mechanotransduction in cardiac myocytes. Ann NY Acad Sci 2004;1015:53-70.
Ultrasound-guided peripheral intravenous placement with standard-length catheters and long cathetersB To the Editor, In a prospective, randomized controlled trial comparing performance of standard-length catheters and long catheters for ultrasound (US)–guided peripheral intravenous cannulation (PIC) in acute hospitalized patients with difficult venous ☆ Statement: All authors have no financial support and potential conflicts of interest for this work.
access, Elia et al [1] showed that compared with standardlength catheter US-guided PIC, long catheter US-guided PIC required a higher time but was associated with a lower risk of catheter failure. Their findings have potential implications for use of long catheters as a solution to low survival of USguided peripheral catheters. Other than the limitations described in the discussion, we feel that several issues of this study require discussion and clarification. First, the authors defined failure of 3 attempts through standard blind insertion techniques as an inclusion criterion of patients with difficult venous access. This is subjective because the standard blind insertion techniques may be performed by junior or inexperienced staffs. Moreover, there may be a bias effect because the operators know that, if 3 blind attempts fail, an US-guided technique will be used. These factors might have made the validity of this study questionable. Second, quite rightly, the primary outcome of this study is catheter failure rate. However, comparing cannulation times with standard-length catheters and long catheters may not be an entirely appropriate comparison because the time requirements for cannulation procedures of long catheters include the additional times needed for aseptic technique, local anesthesia of cannulation site, insertion of guide wire via the initial catheter, removal of the initial catheter, insertion of long catheter over the wire, removal of guide wire, and fixation of long catheter with suture to the skin. Moreover, we note that cannulation times with standard-length catheters and long catheters are significantly longer in this study than in the previous studies in emergency department (ED) patients with difficult intravenous access [2-5]. Because this study does not exactly define the cannulation time in the method, it is difficult to compare results of their and previous studies. Third, in the method, the authors stated that all US-guided PIC procedures were performed by nurses, attending physicians, or resident physicians, and all the operators received a suitable training on US-guided PIC. In discussion, they further explained that procedures were performed by experienced and inexperienced operators. It would be interesting to know how they defined experienced and inexperienced operators. More importantly, the authors should explain if they attempted to define proficiency with US-guided PIC before initiation of the study. The basic skill required for US-guided PIC can be acquired in a suitable training, but attainment of expert performance with a high success rate needs practice and experience. Resnick et al [6] observed that the operators required more than 15 procedures to achieve a high success rate of US-guided PIC in ED patients. Moreover, the rate of success is directly proportional to the number of previous US-guided PIC performed by the ED technician [7]. In this study, it is unclear whether the 2 groups are comparable with respect to distribution of experienced and inexperienced operators. We believe that addressing these factors would further clarify the transparency of this study with a diverse group of emergency staffs. Fourth, we agree that the short-axis approach is faster than the long-axis approach in obtaining vascular access with US-
Correspondence
Table 2 A comparison of transtracheal ultrasonography results with the continuous capnographic waveform Continuous capnographic waveform
A. Transtracheal ultrasonography Tracheal positive Tracheal negative Total B. Lung sliding sign with ultrasonography Present Absent Total
Present
Absent Total
n
n %
%
n
%
62 96.9 1 20.0 63 91.3 2 3.1 4 80.0 6 8.7 64 92.8 5 7.2 69 100.0
63 98.4 1 20.0 64 92.8 1 1.6 4 80.0 5 7.2 64 92.8 5 7.2 69 100.0
[3] Newcombe R. Two-sided confidence intervals for the single proportion: comparison of seven methods. Statist Med 1998;17:857-72. [4] Grmec S. Comparison of three different methods to confirm tracheal tube placement in emergency intubation. Intensive Care Med 2002;28: 701-4. [5] Bozeman WP, Hexter D, Liang HK, Kelen GD. Esophageal detector device versus detection of end-tidal carbon dioxide level in emergency intubation. Ann Emerg Med 1996;27:595-9. [6] Ornato JP, Shipley JB, Racht EM, et al. Multicenter study of a portable, hand-size, colorimetric end-tidal carbon dioxide detection device. Ann Emerg Med 1992;21:518-23. [7] Tanigawa K, Takeda T, Goto E, Tanaka K. The efficacy of esophageal detector devices in verifying tracheal tube placement: a randomized cross-over study of out-of-hospital cardiac patients. Anesth Analg 2001; 92:375-8. [8] Weaver B, Lyon M, Blaivas M. Confirmation of endotracheal tube placement after intubation using the ultrasound sliding lung sign. Acad Emerg Med 2006;13(3):239-44. [9] Sustić A. Role of ultrasound in the airway management of critically ill patients. Crit Care Med 2007;35(5 suppl.):S173-7.
Table 3 Statistical calculations for the diagnostic performance of (A) transtracheal and (B) lung ultrasonography 95% CI A. Sensitivity Specificity Positive predictive value (+ PV) Negative predictive value (− PV) Positive likelihood ratio (+ LR) Negative likelihood ratio (− LR) Area under ROC curve (AUC) B. Sensitivity Specificity + PV − PV + LR − LR AUC
96.9 80.0 98.4 66.7 4.84 0.04 0.884
89.2-99.6 28.4-99.5 91.4-100.0 18.7-96.9 3.1-7.5 0.004-0.4 0.785-0.949
98.4 80.0 98.4 80.0 4.92 0.02 0.892
91.6-100.0 28.4-99.5 91.6-100.0 22.8-99.8 3.2-7.6 0.001-0.30 0.794-0.954
Table 4 Statistical calculations for the diagnostic performance of BED (TUS with LUS) 95% CI Sensitivity Specificity Positive predictive value Negative predictive value Positive likelihood ratio Negative likelihood ratio Area under ROC curve
100.0 80.0 98.5 100.0 5.0 0.0 0.900
94.4-100.0 28.4-99.5 91.6-100.0 29.2-100.0 3.2-7.8 – 0.804-0.959
Molecular and cellular effects of cardiac mechanotransduction during cardiopulmonary resuscitation and postresuscitation period: another piece in the puzzle☆,☆☆ To the Editor, Almost 60 years have passed since major discoveries regarding cardiopulmonary resuscitation (CPR) were made. Until now, several fundamental breakthroughs have been achieved in the field of CPR; however, survival remains low [1]. Our difficulty in resuscitating cardiac arrest patients reflects a limited understanding of the pathophysiology of global ischemia and reperfusion. As such, a better understanding of the molecular pathophysiology of cardiac arrest and postresuscitation period is an essential first step toward increasing survival. Maintaining cell shape and tone is crucial for the function and survival of cells and tissues, whereas mechanical stresses play a central role in the regulation of physiological processes, including the heart [2]. As all organs, the heart consists of billions of cells that function autonomously, as group of cells (eg, sinus node), or as a whole organ, preserving a balance between it and the rest of the organism. Consequently, any disturbances in the surrounding environment can potentially either directly or indirectly disrupt this balance. In keeping with the concepts of stress, any environmental stress will result in disruption of homeostatic equilibrium, resulting, in turn, in various disorders at the organ or cellular level. Mechanotransduction describes the molecular mechanisms by which cells respond to mechanical changes in their physical environment. It reflects the process whereby mechanical forces are converted into biochemical or electrical signals that are able to promote structural and functional remodeling in cells and tissues. Mechanical stimuli can be forces exerted on the cell from the extracellular environment, such as those imposed by compression or tension, or they can be intracellular forces that arise from cellular responses to changes in extracellular matrix quality. Recent focus on mechanotransduction in the heart has been aimed at elucidating the molecular mechanisms by which myocardial structures sense physical loads and transduces ☆
Sources of support: None. Conflicts of interest: None.
☆☆
Correspondence them into biochemical signals to alter gene expression and modify cellular structure and function. However, an important issue that remains to be elucidated is the effect of mechanical signaling due to chest compressions. Generally, the mechanical load transfer from a skin contact area to deeper tissues during CPR involves several tissue layers [3]. However, the continuous bodywide network of loose connective tissue that surrounds organs, nerves, and blood vessels also constitutes a matrix through which molecular signaling exchange takes place [4]. Consequently, the direct contact of this network with the heart may also facilitate the transduction of mechanical signals, initiating intracellular molecular signaling in cardiomyocytes through stretch-activated channels [5]. Cardiac cells recognize mechanical stimulation through forceinduced conformational changes at the molecular level, although these molecular mechanisms remain unclear. There is evidence that the axial compression and recoil of cardiac cells may stimulate stretch sensitive ion channels and result in direct effects on electrical activity by causing changes in intracellular Na+ and Ca2+ [6]. In addition, extracellular forces can alter focal adhesion proteins and modify concentrations and conformation of cytoskeletal cross-linking proteins [7]. Finally, the retrograde and antegrade coronary blood flow during CPR may induce a proinflammatory, prothrombotic state characterized by high cell turnover (resulting in both proliferation and death) relative to cells in static state [5]. Taken together, these recent findings raise the question as to whether chest compressions
251 may exert detrimental effects during CPR, decreasing, thus, the possibility of restoration of spontaneous circulation. Immediately after restoration of spontaneous circulation, the changes in hemodynamic loading, the mechanical disturbation of the ventricles, and the increase of intrathoracic pressure due to mechanical ventilation may cause various electrophysiologic effects [8]. The cyclic increases in intraventricular pressure on the stunned myocardial wall cause a whole myocardial bulging during systole, which is exacerbated by the decreased myocardial compliance of ischemic contracture [8]. Moreover, these conditions may be aggravated by the increased concentration of endogenous and exogenous adrenaline, which increases intraventricular pressure and slows conduction, facilitating arrhythmogenesis [9]. Also, after successful resuscitation, cardiac myocytes may sense increased strain levels (eg, postcardiac arrest myocardial edema or hemodynamic disturbances) through several pathways and respond with an increased intracellular Ca2+ concentration, exacerbating mitochondrial swelling, ischemic contracture, and myocardial compliance (Fig.) [10]. In conclusion, although our research in CPR is currently focused on oxidant stress, inflammation, and ischemia-reperfusion injury, specific attention should be given to the complex area of mechanotransduction and mechanical signaling because there is evidence that it is equally important. In particular, the mechanically induced molecular effects of chest compressions need to be elucidated. Furthermore, arterial shear stress may result in the release of modulatory and signaling molecules,
Fig. Mechanical forces generated via chest compressions and hemodynamic disturbances may exacerbate postcardiac arrest syndrome. CA, cardiac arrest; I/R, ischemia/reperfusion; ATP, adenosine triphosphate; ROS, reactive oxygen species; PRP, postresuscitation period.
252
Correspondence
whereas changes in hemodynamic loading may facilitate arrhythmogenesis. Research on these issues might further help identify the effects of cardiac mechanotransduction during CPR. Athanasios Chalkias PhD Elizabeth O. Johnson PhD Theodoros Xanthos PhD Department of Anatomy, Medical School National and Kapodistrian University of Athens 11527 Athens, Greece E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2012.08.010
References [1] Deakin CD, Nolan JP, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation 2010;81:1305-52. [2] Cook B, Hard RW, McConnaughey WB, et al. Preserving cell shape under environmental stress. Nature 2008;452:361-4. [3] Geerligs M, Peters GW, Ackermans PA, et al. Does subcutaneous adipose tissue behave as an (anti-)thixotropic material? J Biomech 2010;43:1153-9. [4] Banes AJ, Tsuzaki M, Yamamoto J, et al. Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol 1995;73:349-65. [5] Shyu KG. Cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes. Clin Sci (Lond) 2009;116: 377-89. [6] Iribe G, Ward CW, Camelliti P, et al. Axial stretch of rat single ventricular cardiomyocyte causes an acute and transient increase in Ca2+ spark rate. Circ Res 2009;104:787-95. [7] Johnson CP, Tang HY, Carag C, et al. Forced unfolding of proteins with cells. Science 2007;317:663-6. [8] Franz MR, Cima R, Wang D, et al. Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias. Circulation 1992;86:968-78. [9] Chalkias A, Xanthos T. Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev 2012;17: 117-28. [10] Lammerding J, Kamm RD, Lee RT. Mechanotransduction in cardiac myocytes. Ann NY Acad Sci 2004;1015:53-70.
Ultrasound-guided peripheral intravenous placement with standard-length catheters and long cathetersB To the Editor, In a prospective, randomized controlled trial comparing performance of standard-length catheters and long catheters for ultrasound (US)–guided peripheral intravenous cannulation (PIC) in acute hospitalized patients with difficult venous ☆ Statement: All authors have no financial support and potential conflicts of interest for this work.
access, Elia et al [1] showed that compared with standardlength catheter US-guided PIC, long catheter US-guided PIC required a higher time but was associated with a lower risk of catheter failure. Their findings have potential implications for use of long catheters as a solution to low survival of USguided peripheral catheters. Other than the limitations described in the discussion, we feel that several issues of this study require discussion and clarification. First, the authors defined failure of 3 attempts through standard blind insertion techniques as an inclusion criterion of patients with difficult venous access. This is subjective because the standard blind insertion techniques may be performed by junior or inexperienced staffs. Moreover, there may be a bias effect because the operators know that, if 3 blind attempts fail, an US-guided technique will be used. These factors might have made the validity of this study questionable. Second, quite rightly, the primary outcome of this study is catheter failure rate. However, comparing cannulation times with standard-length catheters and long catheters may not be an entirely appropriate comparison because the time requirements for cannulation procedures of long catheters include the additional times needed for aseptic technique, local anesthesia of cannulation site, insertion of guide wire via the initial catheter, removal of the initial catheter, insertion of long catheter over the wire, removal of guide wire, and fixation of long catheter with suture to the skin. Moreover, we note that cannulation times with standard-length catheters and long catheters are significantly longer in this study than in the previous studies in emergency department (ED) patients with difficult intravenous access [2-5]. Because this study does not exactly define the cannulation time in the method, it is difficult to compare results of their and previous studies. Third, in the method, the authors stated that all US-guided PIC procedures were performed by nurses, attending physicians, or resident physicians, and all the operators received a suitable training on US-guided PIC. In discussion, they further explained that procedures were performed by experienced and inexperienced operators. It would be interesting to know how they defined experienced and inexperienced operators. More importantly, the authors should explain if they attempted to define proficiency with US-guided PIC before initiation of the study. The basic skill required for US-guided PIC can be acquired in a suitable training, but attainment of expert performance with a high success rate needs practice and experience. Resnick et al [6] observed that the operators required more than 15 procedures to achieve a high success rate of US-guided PIC in ED patients. Moreover, the rate of success is directly proportional to the number of previous US-guided PIC performed by the ED technician [7]. In this study, it is unclear whether the 2 groups are comparable with respect to distribution of experienced and inexperienced operators. We believe that addressing these factors would further clarify the transparency of this study with a diverse group of emergency staffs. Fourth, we agree that the short-axis approach is faster than the long-axis approach in obtaining vascular access with US-