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and is legally accepted in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> Knowing its advantages and limitations can help resolve frequent diagnostic problems in the intensive care unit &#40;ICU&#41;&#44; avoid unnecessary resource consumption&#44; and optimize the obtainment of organs for transplantation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Transcranial Doppler and the legal diagnosis of brain death</span><p id="par0015" class="elsevierStylePara elsevierViewall">Spanish Royal Decree &#40;RD&#41; 1723&#47;2012&#44; under Annex 1&#44; <span class="elsevierStyleItalic">Protocols referred to the diagnosis and certification of death for the obtainment of dead donor organs</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> specifies the clinical circumstances in which instrumental tests are obligate&#46; 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and flow persists only during systole&#46; The mean velocity is &#62;10<span class="elsevierStyleHsp" style=""></span>cm&#47;s&#44; and there is still some net flow&#44; with a very high pulsatility index&#46; These findings are recorded in situations of severe intracranial hypertension and may be taken to represent a pre-CCA pattern &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0035" class="elsevierStylePara elsevierViewall">When the ICP is equal to or greater than the systolic blood pressure of the patient&#44; brain perfusion ceases&#46; This phase is characterized by the appearance of a pattern known as <span class="elsevierStyleItalic">reverberant flow</span>&#44; <span class="elsevierStyleItalic">biphasic oscillating flow</span> or <span class="elsevierStyleItalic">inverted diastolic flow</span> &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#44; produced by the elasticity of the arterial wall&#46; It involves anterograde flow in systole&#44; and retrograde or inverted flow in diastole&#8211;both being approximately equal in the same cardiac cycle&#44; and the net brain flow is zero&#46; This pattern has a brief systolic phase&#46; All these observations are correlated to CCA in the arteriographic study&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0040" class="elsevierStylePara elsevierViewall">When the ICP exceeds the systolic blood pressure of the patient we only record <span class="elsevierStyleItalic">systolic spikes</span> or <span class="elsevierStyleItalic">systolic spicules</span>&#44; which are small&#44; anterograde sharp systolic waves with a duration of &#60;200<span class="elsevierStyleHsp" style=""></span>ms and with a systolic peak velocity of &#60;50<span class="elsevierStyleHsp" style=""></span>cm&#47;s&#46; Flow is likewise lacking during the rest of systole and in diastole of the cardiac cycle &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4</span><p id="par0045" class="elsevierStylePara elsevierViewall">In very advanced cases&#44; with great ICP elevations&#44; we observe flow obstruction in the more proximal segments of the arteries of the skull base&#44; causing a <span class="elsevierStyleItalic">total absence of flow signals</span>&#46; In these cases the doubt may arise as to whether the absence of signals is due to CCA or to the lack of an acoustic window&#46; In order to accept the absence of a signal as criterion of CCA&#44; the TCD exploration must be performed under the same clinical conditions and by the same expert explorer as in the previous studies in which flow was still observed&#46;</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">The presence of effective flow in any intracranial artery completely discards CCA &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Doppler study in the extracranial arteries</span><p id="par0055" class="elsevierStylePara elsevierViewall">One of the main limitations of TCD is the absence of an acoustic window&#44; which prevents us from obtaining intracranial signals&#8211;a situation that is found in about 10&#8211;20&#37; of the population<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">17&#44;18</span></a> and which is more common in elderly females&#46; In these cases we can study the internal carotid artery &#40;ICA&#41; and the vertebral arteries &#40;VAs&#41; at extracranial level&#46; When access through the temporal window is not possible&#44; some authors use the ophthalmic window to study the internal carotid artery at carotid siphon level&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19&#44;20</span></a> In this way&#44; Lampl et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> were able to improve the diagnostic performance of the technique by 9&#37;&#46; The use of echo-enhancers also improves exploration in cases of a poor acoustic window&#46; The presence of flow in the carotid siphon is explained by the shunting of blood from the external carotid artery or by CCA occurring distal to it&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The presence of flow in the internal carotid artery and extracranial vertebral arteries does not discard CCA&#46; Consequently&#44; only the transcranial study and the presence of systolic spikes or inverted diastolic flow in the arteries of the skull base are of diagnostic usefulness in relation to BD&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conditions for establishing a diagnosis of cerebral circulatory arrest using transcranial Doppler ultrasound</span><p id="par0065" class="elsevierStylePara elsevierViewall">An adequate system is required&#44; equipped with a 2<span class="elsevierStyleHsp" style=""></span>MHz pulsed-Doppler probe and involving a study sample volume of under 10<span class="elsevierStyleHsp" style=""></span>mm&#44; with the capacity to reach a transmission power of 100<span class="elsevierStyleHsp" style=""></span>mW&#47;cm<span class="elsevierStyleSup">2</span>&#46; The explorer must be an expert&#44; and some guides recommend performing two explorations spaced 30<span class="elsevierStyleHsp" style=""></span>min apart in order to guarantee the irreversibility of CCA&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">6&#44;8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The consensus conference on the diagnosis of CCA&#44; held by a task force of the Neurosonology group dependent upon the World Federation of Neurology&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> together with the recommendations of the Spanish Society of Neurology&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> require the patient to be hemodynamically stable with a mean blood pressure &#40;MBP&#41;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mmHg &#40;blood pressure no lower than 90&#47;50<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#44; and PaCO<span class="elsevierStyleInf">2</span> 35&#8211;45<span class="elsevierStyleHsp" style=""></span>mmHg&#46; Other prerequisites are knowledge of the cause of coma&#44; and the exclusion of hypothermia&#44; metabolic alterations&#44; intoxications and other factors that may alter the neurological findings&#46; Furthermore&#44; two expert physicians are required to determine the absence of brain functions&#46; These conditions seem very restrictive&#44; since one of the main advantages of TCD is its capacity to diagnose CCA in sedated patients or in cases posing clinical diagnostic problems&#46; What advantage could TCD offer if the patient diagnosis has already been confirmed&#63; In our opinion&#44; the requirements of the task force<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> and the recommendations of the Spanish Society of Neurology<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> regarding a complete clinical diagnosis before accepting Doppler ultrasound as a criterion for diagnosing CCA represent unjustified diagnostic demands that deserve to be reconsidered&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In diagnosing CCA&#44; use is made of both TCD&#44; which is a blind technique&#44; and transcranial color-coded duplex sonography&#44;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">21&#8211;23</span></a> which offers more advantages&#44; but which is less widely used in ICUs&#46; Transcranial color-coded duplex sonography allows simultaneous two-dimensional study of the brain &#40;with visualization in color of the arteries and veins of the skull base&#41; and analysis of the vascular Doppler spectra&#46; The transcranial color-coded angioduplex mode&#44; together with the use of echo-enhancers&#44; allows greater percentage vascular identification than conventional TCD&#46; Because of its advantages&#44; it probably will become the most widely used technique in the future&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Transcranial Doppler ultrasound and the diagnosis of brain death</span><p id="par0080" class="elsevierStylePara elsevierViewall">In order to diagnose BD using TCD&#44; we must confirm CCA based on the bilateral recording of reverberant or inverted diastolic flow and systolic spikes in the anterior and posterior circulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;14</span></a> These findings must be demonstrated by exploring through the temporal window &#40;both middle cerebral arteries&#59; anterior circulation&#41; and through the suboccipital window &#40;vertebral arteries and basilar artery&#59; posterior circulation&#41;&#8211;though some authors consider exploration of the basilar artery to be sufficient&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">23</span></a> The advantages and limitations of TCD in diagnosing CCA associated to BD are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">A metaanalysis published in 2006<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a> evaluated a total of 684 patients included in 10 studies covering the period 1980&#8211;2004&#46; Only two of the studies were considered to be of high quality&#44; and these two articles reported a sensitivity of 95&#37; and a specificity of 99&#37;&#46; On including the other 8 studies of lesser quality in the analysis&#44; the sensitivity was seen to decrease to 88&#37;&#44; while specificity remained the same &#40;99&#37;&#41;&#46; Of note in this review is the many studies that did not explore the posterior fossa&#46; This must be criticized&#44; since a diagnosis of BD requires the confirmation of CCA by exploring both the anterior and the posterior circulation&#46; Ultrasound exploration of the posterior circulation in an intubated patient involves some technical difficulty&#44; and therefore the high sensitivity obtained in the mentioned metaanalysis can be explained by the many studies that failed to explore the posterior fossa&#46; The specificity of TCD as a test for confirming BD in the literature varies between 97 and 100&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">6&#44;11&#44;14</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Limitations of transcranial Doppler in diagnosing brain death</span><p id="par0090" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Absence of an acoustic window&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Explorer dependency&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Difficulty exploring the posterior circulation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">False-positive readings in diagnosing BD &#40;patients who do not meet the clinical criteria of BD but present CCA at Doppler exploration&#41;&#58; ultrasound patterns consistent with CCA have been described in the early stage of subarachnoid hemorrhage secondary to aneurysmal rupture with large ICP elevations&#44; and in cardiac arrest&#46; These situations are transient and reversible&#59; some guides therefore recommend repeating the exploration after 30<span class="elsevierStyleHsp" style=""></span>min&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">5&#44;7</span></a> However&#44; this general norm does not appear to be very justified in patients with refractory and progressive intracranial hypertension syndrome&#44; in which daily TCD monitoring is performed&#44; and gradual worsening until reaching criteria of CCA is confirmed&#46; In addition to these transient situations&#44; there have been some exceptional reports of false-positive readings in both open-skull patients and in patients without cranial defects&#46; In all of these cases TCD exploration was complete&#44; comprising both the anterior and the posterior circulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8&#44;24&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">False-negative readings in diagnosing BD &#40;patients with clinical criteria of BD and the presence of flow at Doppler exploration&#41;&#58; open-skull patients may have clinical criteria of BD in the presence of cerebral blood flow&#46; This situation can be seen in patients with a ventricular drain&#44; decompressive craniectomy&#44; skull dome rupture&#44; fractures of the base of the skull&#44; and in infants under 1 year of age with still open fontanelles&#46; In all of these cases the open skull condition allows a certain intracranial decompression that explains the persistence of flow in some of the intracranial arteries&#44; despite clinically confirmed BD&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">26&#8211;28</span></a> It is therefore very important to remember that CCA is not always in synchrony with the clinical exploration of BD&#44; i&#46;e&#46;&#44; CCA is accompanied by clinical data of BD&#44; though the opposite is not always true&#44; since some patients present cerebral blood flow despite a clinically confirmed diagnosis of BD &#40;these being cases of &#8220;flow without function&#8221;&#41;&#46; This same phenomenon has been described in patients with post-cardiac arrest anoxic encephalopathy&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">28&#8211;30</span></a> In such cases&#44; during the interval of cardiac arrest&#44; the neurons suffer irreversible damage&#44; though the recovery of heart beat with cardiopulmonary resuscitation maneuvering produces cerebral reperfusion that explains the ultrasound confirmation of flow despite the existence of neuron death&#46; This mechanism explains the &#8220;flow without function&#8221; phenomenon in anoxia&#46;</p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">In these cases&#44; the use of TCD not only fails to help in diagnosing BD but also may even complicate things by causing a delay in confirming CCA&#46; For this reason the Spanish Neurosonology Society recommends that TCD should not be used as a complementary technique for diagnosing BD in open-skull patients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> However&#44; and since this persistent flow phenomenon does not always occur&#44; we consider that the use of TCD can be defended&#44; bearing in mind these limitations&#44; with a view to avoiding delays in the diagnosis of BD and the certification of patient death&#46; If there are no problems or interferences in establishing a clinical diagnosis of BD&#44; then the clinical exploration should prevail over the TCD findings&#46; The presence of &#8220;flow without function&#8221; in open-skull patients and a clinical diagnosis of BD has also been demonstrated in other flow studies such as cerebral angiography with multislice computed tomography&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#8211;32</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The diagnosis of CCA is time-dependent&#58; some authors have found that CCA documented by TCD &#40;even in closed-skull patients&#41; is not simultaneous to the clinical diagnosis of BD&#59; its diagnostic performance is therefore regarded as being time-dependent&#46; Dosemeci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> reported a sensitivity of 70&#46;5&#37; in a study of 61 patients with a clinical diagnosis of BD&#46; In the first TCD exploration performed 0&#46;5&#8211;4<span class="elsevierStyleHsp" style=""></span>h after confirmation of the clinical diagnosis&#44; the authors recorded persistent flow in 18 patients &#40;29&#37;&#41;&#46; Subsequent follow-up of these patients confirmed CCA in 12 cases at second TCD exploration 12&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;3<span class="elsevierStyleHsp" style=""></span>h after the clinical diagnosis&#46; Two patients required a third exploration&#44; and another required four TCD explorations to confirm BD 96<span class="elsevierStyleHsp" style=""></span>h after the clinical diagnosis&#46; Based on these results&#44; Dosemeci et al&#46; concluded that the need to demonstrate CCA in patients with a clinical diagnosis of BD should be debated&#44; since it can delay the certification of patient death&#46; Kuo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> reported a sensitivity of 77&#46;2&#37; in 44 patients diagnosed with BD&#44; and likewise found the diagnostic sensitivity to increase over time&#46; Specifically&#44; up until 6<span class="elsevierStyleHsp" style=""></span>h after the clinical diagnosis&#44; TCD only confirmed CCA in 58&#46;3&#37; of the patients&#44; while after 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h&#44; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h and 24&#8211;36<span class="elsevierStyleHsp" style=""></span>h the percentage was seen to increase to 76&#46;9&#44; 83&#46;3 and 100&#37;&#44; respectively&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0130" class="elsevierStylePara elsevierViewall">Exploration with TCD is noninvasive&#44; repeatable and readily available&#44; and allows the demonstration of CCA accompanying BD&#46; Thanks to its specificity of close to 100&#37;&#44; the technique is particularly useful in sedated patients or in individuals in which a complete neurological exploration proves difficult&#46; Its limitations comprise the absence of an acoustic window&#44; explorer dependency&#44; and the existence of false-negative readings &#40;patients with blood flow at TCD exploration but with a clinical diagnosis of BD&#41; in the presence of an open skull and anoxia&#46; On the other hand&#44; CCA is not always synchronic to the clinical diagnosis of BD&#59; as a result&#44; its diagnostic performance is time-dependent&#8211;a fact that must be taken into account in order to avoid delays in certifying patient death&#46; Despite its limitations&#44; TCD is an excellent tool for diagnosing BD and can optimize the obtainment of organs for transplantation purposes&#46; An update on the diagnostic criteria of CCA&#44; based on a multidisciplinary consensus conference&#44; would be desirable&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Financial support</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have received no financial support of any kind in relation to this study&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Transcranial Doppler ultrasound is able to demonstrate cerebral circulatory arrest associated to brain death&#44; being especially useful in sedated patients&#44; or in those in which complete neurological exploration is not possible&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Transcranial Doppler ultrasound is a portable&#44; noninvasive and high-availability technique&#46; Among its limitations&#44; mention must be made of the absence of acoustic windows and false-negative cases&#46; In patients clinically diagnosed with brain death&#44; with open skulls or with anoxia as the cause of death&#44; cerebral blood flow can be observed by ultrasound&#44; since cerebral circulatory arrest is not always synchronized to the clinical diagnosis&#46; The diagnostic rate is therefore time-dependent&#44; and this fact must be recognized in order to avoid delays in death certification&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Despite its limitations&#44; transcranial Doppler ultrasound helps solve common diagnostic problems&#44; avoids the unnecessary consumption of resources&#44; and can optimize organ harvesting for transplantation&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El Doppler transcraneal permite demostrar la parada circulatoria cerebral que acompa&#241;a a la muerte encef&#225;lica&#44; siendo especialmente &#250;til en pacientes sedados&#44; o en los que no puede realizarse la exploraci&#243;n neurol&#243;gica completa&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El Doppler transcraneal es una t&#233;cnica port&#225;til&#44; no invasiva y de alta disponibilidad&#46; Entre sus limitaciones est&#225; la ausencia de ventana s&#243;nica y los casos falsos negativos&#46; En pacientes con diagn&#243;stico cl&#237;nico de muerte encef&#225;lica&#44; que tienen cr&#225;neos abiertos o anoxia como causa de la muerte&#44; puede sonorizarse flujo sangu&#237;neo cerebral&#44; ya que la parada circulatoria cerebral no siempre es sincr&#243;nica con el diagn&#243;stico cl&#237;nico&#46; Su rentabilidad diagn&#243;stica es&#44; por tanto&#44; dependiente del tiempo&#44; hecho que debe ser reconocido para no retrasar la declaraci&#243;n de muerte&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A pesar de sus limitaciones&#44; el Doppler transcraneal ayuda a resolver frecuentes problemas diagn&#243;sticos&#44; evita un consumo innecesario de recursos y puede optimizar la obtenci&#243;n de &#243;rganos para trasplante&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Escudero D&#44; Otero J&#44; Quind&#243;s B&#44; Vi&#241;a L&#46; Doppler transcraneal en el diagn&#243;stico de la muerte encef&#225;lica&#46; &#191;Es &#250;til o retrasa el diagn&#243;stico&#63; Med Intensiva&#46; 2015&#59;39&#58;244&#8211;250&#46;</p>"
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Allows monitoring of patient evolution&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Results not interfered with by central nervous system depressor drugs&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Limitations</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Difficulty exploring posterior circulation in critical patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>False-negative results in patients with anoxia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> False-negative results in patients with open skull &#40;decompressive craniectomy&#44; fractures with skull dome rupture&#44; ventricular drainage&#44; and infants with open fontanelles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Time-dependent diagnostic performance &#40;diagnostic sensitivity increases over time&#41;&nbsp;\t\t\t\t\t\t\n
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Review
Transcranial Doppler ultrasound in the diagnosis of brain death. Is it useful or does it delay the diagnosis?
Doppler transcraneal en el diagnóstico de la muerte encefálica. ¿Es útil o retrasa el diagnóstico?
D. Escuderoa,
Corresponding author
, J. Oterob, B. Quindósa, L. Viñaa
a Servicio de Medicina Intensiva, Hospital Universitario Central de Asturias, Oviedo, Spain
b Unidad de Coordinación de Trasplantes y Medicina Regenerativa, Hospital Universitario Central de Asturias, Oviedo, Spain
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and vary according to the legal specifications in force in each individual country&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">3&#44;4</span></a> If the patient is sedated&#44; suffers serious craniofacial damage&#44; or presents intolerance of the apnea test&#44; techniques that study brain circulatory flow&#44; such as angiography with multislice computed tomography &#40;CT&#41;&#44; brain scintigraphy with Tc<span class="elsevierStyleSup">99</span>-HMPAO&#44; or transcranial Doppler &#40;TCD&#41; are advised&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">5&#8211;11</span></a> The diagnosis of BD is a key element in all national transplant programs&#46; In Spain&#44; almost 90&#37; of all transplants are performed with organs obtained from donors that have died under conditions of BD&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Transcranial Doppler ultrasound is one of the most widely used methods for diagnosing BD&#44; and is legally accepted in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> Knowing its advantages and limitations can help resolve frequent diagnostic problems in the intensive care unit &#40;ICU&#41;&#44; avoid unnecessary resource consumption&#44; and optimize the obtainment of organs for transplantation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Transcranial Doppler and the legal diagnosis of brain death</span><p id="par0015" class="elsevierStylePara elsevierViewall">Spanish Royal Decree &#40;RD&#41; 1723&#47;2012&#44; under Annex 1&#44; <span class="elsevierStyleItalic">Protocols referred to the diagnosis and certification of death for the obtainment of dead donor organs</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> specifies the clinical circumstances in which instrumental tests are obligate&#46; In its Section 4&#44; and among the &#8220;tests evaluating cerebral blood flow&#8221;&#44; TCD is described as one of the techniques that can be used&#44; though the Decree does not specify which cerebral arteries are to be explored&#44; or what type of ultrasound findings are needed to confirm CCA&#46; As specified in Section 3 of the mentioned Decree&#44; TCD allows abbreviation or even suppression &#40;according to medical criterion&#41; of the recommended 6-h observation period in destructive brain damage and 24<span class="elsevierStyleHsp" style=""></span>h of anoxia&#44; thereby facilitating things in the event of organ donation&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Transcranial Doppler in cerebral circulatory arrest</span><p id="par0020" class="elsevierStylePara elsevierViewall">Patients with serious brain damage and refractory intracranial hypertension syndrome suffer a gradual decrease in brain perfusion pressure and cerebral blood flow&#44; which finally causes CCA&#46; The use of TCD for the diagnosis of CCA was first described in 1974&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> and since then many publications have warranted its usefulness in this context&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;14&#44;15</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The study of cerebral blood flow velocity with TCD during the development of CCA distinguishes four evolutive stages&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> each with its own characteristic flow pattern&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0030" class="elsevierStylePara elsevierViewall">When the ICP exceeds the diastolic blood pressure&#44; the cerebral blood flow velocity at the end of diastole is zero&#44; and flow persists only during systole&#46; The mean velocity is &#62;10<span class="elsevierStyleHsp" style=""></span>cm&#47;s&#44; and there is still some net flow&#44; with a very high pulsatility index&#46; These findings are recorded in situations of severe intracranial hypertension and may be taken to represent a pre-CCA pattern &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0035" class="elsevierStylePara elsevierViewall">When the ICP is equal to or greater than the systolic blood pressure of the patient&#44; brain perfusion ceases&#46; This phase is characterized by the appearance of a pattern known as <span class="elsevierStyleItalic">reverberant flow</span>&#44; <span class="elsevierStyleItalic">biphasic oscillating flow</span> or <span class="elsevierStyleItalic">inverted diastolic flow</span> &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#44; produced by the elasticity of the arterial wall&#46; It involves anterograde flow in systole&#44; and retrograde or inverted flow in diastole&#8211;both being approximately equal in the same cardiac cycle&#44; and the net brain flow is zero&#46; This pattern has a brief systolic phase&#46; All these observations are correlated to CCA in the arteriographic study&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0040" class="elsevierStylePara elsevierViewall">When the ICP exceeds the systolic blood pressure of the patient we only record <span class="elsevierStyleItalic">systolic spikes</span> or <span class="elsevierStyleItalic">systolic spicules</span>&#44; which are small&#44; anterograde sharp systolic waves with a duration of &#60;200<span class="elsevierStyleHsp" style=""></span>ms and with a systolic peak velocity of &#60;50<span class="elsevierStyleHsp" style=""></span>cm&#47;s&#46; Flow is likewise lacking during the rest of systole and in diastole of the cardiac cycle &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4</span><p id="par0045" class="elsevierStylePara elsevierViewall">In very advanced cases&#44; with great ICP elevations&#44; we observe flow obstruction in the more proximal segments of the arteries of the skull base&#44; causing a <span class="elsevierStyleItalic">total absence of flow signals</span>&#46; In these cases the doubt may arise as to whether the absence of signals is due to CCA or to the lack of an acoustic window&#46; In order to accept the absence of a signal as criterion of CCA&#44; the TCD exploration must be performed under the same clinical conditions and by the same expert explorer as in the previous studies in which flow was still observed&#46;</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">The presence of effective flow in any intracranial artery completely discards CCA &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Doppler study in the extracranial arteries</span><p id="par0055" class="elsevierStylePara elsevierViewall">One of the main limitations of TCD is the absence of an acoustic window&#44; which prevents us from obtaining intracranial signals&#8211;a situation that is found in about 10&#8211;20&#37; of the population<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">17&#44;18</span></a> and which is more common in elderly females&#46; In these cases we can study the internal carotid artery &#40;ICA&#41; and the vertebral arteries &#40;VAs&#41; at extracranial level&#46; When access through the temporal window is not possible&#44; some authors use the ophthalmic window to study the internal carotid artery at carotid siphon level&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19&#44;20</span></a> In this way&#44; Lampl et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> were able to improve the diagnostic performance of the technique by 9&#37;&#46; The use of echo-enhancers also improves exploration in cases of a poor acoustic window&#46; The presence of flow in the carotid siphon is explained by the shunting of blood from the external carotid artery or by CCA occurring distal to it&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The presence of flow in the internal carotid artery and extracranial vertebral arteries does not discard CCA&#46; Consequently&#44; only the transcranial study and the presence of systolic spikes or inverted diastolic flow in the arteries of the skull base are of diagnostic usefulness in relation to BD&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conditions for establishing a diagnosis of cerebral circulatory arrest using transcranial Doppler ultrasound</span><p id="par0065" class="elsevierStylePara elsevierViewall">An adequate system is required&#44; equipped with a 2<span class="elsevierStyleHsp" style=""></span>MHz pulsed-Doppler probe and involving a study sample volume of under 10<span class="elsevierStyleHsp" style=""></span>mm&#44; with the capacity to reach a transmission power of 100<span class="elsevierStyleHsp" style=""></span>mW&#47;cm<span class="elsevierStyleSup">2</span>&#46; The explorer must be an expert&#44; and some guides recommend performing two explorations spaced 30<span class="elsevierStyleHsp" style=""></span>min apart in order to guarantee the irreversibility of CCA&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">6&#44;8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The consensus conference on the diagnosis of CCA&#44; held by a task force of the Neurosonology group dependent upon the World Federation of Neurology&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> together with the recommendations of the Spanish Society of Neurology&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> require the patient to be hemodynamically stable with a mean blood pressure &#40;MBP&#41;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mmHg &#40;blood pressure no lower than 90&#47;50<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#44; and PaCO<span class="elsevierStyleInf">2</span> 35&#8211;45<span class="elsevierStyleHsp" style=""></span>mmHg&#46; Other prerequisites are knowledge of the cause of coma&#44; and the exclusion of hypothermia&#44; metabolic alterations&#44; intoxications and other factors that may alter the neurological findings&#46; Furthermore&#44; two expert physicians are required to determine the absence of brain functions&#46; These conditions seem very restrictive&#44; since one of the main advantages of TCD is its capacity to diagnose CCA in sedated patients or in cases posing clinical diagnostic problems&#46; What advantage could TCD offer if the patient diagnosis has already been confirmed&#63; In our opinion&#44; the requirements of the task force<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> and the recommendations of the Spanish Society of Neurology<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> regarding a complete clinical diagnosis before accepting Doppler ultrasound as a criterion for diagnosing CCA represent unjustified diagnostic demands that deserve to be reconsidered&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In diagnosing CCA&#44; use is made of both TCD&#44; which is a blind technique&#44; and transcranial color-coded duplex sonography&#44;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">21&#8211;23</span></a> which offers more advantages&#44; but which is less widely used in ICUs&#46; Transcranial color-coded duplex sonography allows simultaneous two-dimensional study of the brain &#40;with visualization in color of the arteries and veins of the skull base&#41; and analysis of the vascular Doppler spectra&#46; The transcranial color-coded angioduplex mode&#44; together with the use of echo-enhancers&#44; allows greater percentage vascular identification than conventional TCD&#46; Because of its advantages&#44; it probably will become the most widely used technique in the future&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Transcranial Doppler ultrasound and the diagnosis of brain death</span><p id="par0080" class="elsevierStylePara elsevierViewall">In order to diagnose BD using TCD&#44; we must confirm CCA based on the bilateral recording of reverberant or inverted diastolic flow and systolic spikes in the anterior and posterior circulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;14</span></a> These findings must be demonstrated by exploring through the temporal window &#40;both middle cerebral arteries&#59; anterior circulation&#41; and through the suboccipital window &#40;vertebral arteries and basilar artery&#59; posterior circulation&#41;&#8211;though some authors consider exploration of the basilar artery to be sufficient&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">23</span></a> The advantages and limitations of TCD in diagnosing CCA associated to BD are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">A metaanalysis published in 2006<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a> evaluated a total of 684 patients included in 10 studies covering the period 1980&#8211;2004&#46; Only two of the studies were considered to be of high quality&#44; and these two articles reported a sensitivity of 95&#37; and a specificity of 99&#37;&#46; On including the other 8 studies of lesser quality in the analysis&#44; the sensitivity was seen to decrease to 88&#37;&#44; while specificity remained the same &#40;99&#37;&#41;&#46; Of note in this review is the many studies that did not explore the posterior fossa&#46; This must be criticized&#44; since a diagnosis of BD requires the confirmation of CCA by exploring both the anterior and the posterior circulation&#46; Ultrasound exploration of the posterior circulation in an intubated patient involves some technical difficulty&#44; and therefore the high sensitivity obtained in the mentioned metaanalysis can be explained by the many studies that failed to explore the posterior fossa&#46; The specificity of TCD as a test for confirming BD in the literature varies between 97 and 100&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">6&#44;11&#44;14</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Limitations of transcranial Doppler in diagnosing brain death</span><p id="par0090" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Absence of an acoustic window&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Explorer dependency&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Difficulty exploring the posterior circulation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">False-positive readings in diagnosing BD &#40;patients who do not meet the clinical criteria of BD but present CCA at Doppler exploration&#41;&#58; ultrasound patterns consistent with CCA have been described in the early stage of subarachnoid hemorrhage secondary to aneurysmal rupture with large ICP elevations&#44; and in cardiac arrest&#46; These situations are transient and reversible&#59; some guides therefore recommend repeating the exploration after 30<span class="elsevierStyleHsp" style=""></span>min&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">5&#44;7</span></a> However&#44; this general norm does not appear to be very justified in patients with refractory and progressive intracranial hypertension syndrome&#44; in which daily TCD monitoring is performed&#44; and gradual worsening until reaching criteria of CCA is confirmed&#46; In addition to these transient situations&#44; there have been some exceptional reports of false-positive readings in both open-skull patients and in patients without cranial defects&#46; In all of these cases TCD exploration was complete&#44; comprising both the anterior and the posterior circulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8&#44;24&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">False-negative readings in diagnosing BD &#40;patients with clinical criteria of BD and the presence of flow at Doppler exploration&#41;&#58; open-skull patients may have clinical criteria of BD in the presence of cerebral blood flow&#46; This situation can be seen in patients with a ventricular drain&#44; decompressive craniectomy&#44; skull dome rupture&#44; fractures of the base of the skull&#44; and in infants under 1 year of age with still open fontanelles&#46; In all of these cases the open skull condition allows a certain intracranial decompression that explains the persistence of flow in some of the intracranial arteries&#44; despite clinically confirmed BD&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">26&#8211;28</span></a> It is therefore very important to remember that CCA is not always in synchrony with the clinical exploration of BD&#44; i&#46;e&#46;&#44; CCA is accompanied by clinical data of BD&#44; though the opposite is not always true&#44; since some patients present cerebral blood flow despite a clinically confirmed diagnosis of BD &#40;these being cases of &#8220;flow without function&#8221;&#41;&#46; This same phenomenon has been described in patients with post-cardiac arrest anoxic encephalopathy&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">28&#8211;30</span></a> In such cases&#44; during the interval of cardiac arrest&#44; the neurons suffer irreversible damage&#44; though the recovery of heart beat with cardiopulmonary resuscitation maneuvering produces cerebral reperfusion that explains the ultrasound confirmation of flow despite the existence of neuron death&#46; This mechanism explains the &#8220;flow without function&#8221; phenomenon in anoxia&#46;</p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">In these cases&#44; the use of TCD not only fails to help in diagnosing BD but also may even complicate things by causing a delay in confirming CCA&#46; For this reason the Spanish Neurosonology Society recommends that TCD should not be used as a complementary technique for diagnosing BD in open-skull patients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> However&#44; and since this persistent flow phenomenon does not always occur&#44; we consider that the use of TCD can be defended&#44; bearing in mind these limitations&#44; with a view to avoiding delays in the diagnosis of BD and the certification of patient death&#46; If there are no problems or interferences in establishing a clinical diagnosis of BD&#44; then the clinical exploration should prevail over the TCD findings&#46; The presence of &#8220;flow without function&#8221; in open-skull patients and a clinical diagnosis of BD has also been demonstrated in other flow studies such as cerebral angiography with multislice computed tomography&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#8211;32</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The diagnosis of CCA is time-dependent&#58; some authors have found that CCA documented by TCD &#40;even in closed-skull patients&#41; is not simultaneous to the clinical diagnosis of BD&#59; its diagnostic performance is therefore regarded as being time-dependent&#46; Dosemeci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> reported a sensitivity of 70&#46;5&#37; in a study of 61 patients with a clinical diagnosis of BD&#46; In the first TCD exploration performed 0&#46;5&#8211;4<span class="elsevierStyleHsp" style=""></span>h after confirmation of the clinical diagnosis&#44; the authors recorded persistent flow in 18 patients &#40;29&#37;&#41;&#46; Subsequent follow-up of these patients confirmed CCA in 12 cases at second TCD exploration 12&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;3<span class="elsevierStyleHsp" style=""></span>h after the clinical diagnosis&#46; Two patients required a third exploration&#44; and another required four TCD explorations to confirm BD 96<span class="elsevierStyleHsp" style=""></span>h after the clinical diagnosis&#46; Based on these results&#44; Dosemeci et al&#46; concluded that the need to demonstrate CCA in patients with a clinical diagnosis of BD should be debated&#44; since it can delay the certification of patient death&#46; Kuo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> reported a sensitivity of 77&#46;2&#37; in 44 patients diagnosed with BD&#44; and likewise found the diagnostic sensitivity to increase over time&#46; Specifically&#44; up until 6<span class="elsevierStyleHsp" style=""></span>h after the clinical diagnosis&#44; TCD only confirmed CCA in 58&#46;3&#37; of the patients&#44; while after 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h&#44; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h and 24&#8211;36<span class="elsevierStyleHsp" style=""></span>h the percentage was seen to increase to 76&#46;9&#44; 83&#46;3 and 100&#37;&#44; respectively&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0130" class="elsevierStylePara elsevierViewall">Exploration with TCD is noninvasive&#44; repeatable and readily available&#44; and allows the demonstration of CCA accompanying BD&#46; Thanks to its specificity of close to 100&#37;&#44; the technique is particularly useful in sedated patients or in individuals in which a complete neurological exploration proves difficult&#46; Its limitations comprise the absence of an acoustic window&#44; explorer dependency&#44; and the existence of false-negative readings &#40;patients with blood flow at TCD exploration but with a clinical diagnosis of BD&#41; in the presence of an open skull and anoxia&#46; On the other hand&#44; CCA is not always synchronic to the clinical diagnosis of BD&#59; as a result&#44; its diagnostic performance is time-dependent&#8211;a fact that must be taken into account in order to avoid delays in certifying patient death&#46; Despite its limitations&#44; TCD is an excellent tool for diagnosing BD and can optimize the obtainment of organs for transplantation purposes&#46; An update on the diagnostic criteria of CCA&#44; based on a multidisciplinary consensus conference&#44; would be desirable&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Financial support</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have received no financial support of any kind in relation to this study&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Transcranial Doppler ultrasound is able to demonstrate cerebral circulatory arrest associated to brain death&#44; being especially useful in sedated patients&#44; or in those in which complete neurological exploration is not possible&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Transcranial Doppler ultrasound is a portable&#44; noninvasive and high-availability technique&#46; Among its limitations&#44; mention must be made of the absence of acoustic windows and false-negative cases&#46; In patients clinically diagnosed with brain death&#44; with open skulls or with anoxia as the cause of death&#44; cerebral blood flow can be observed by ultrasound&#44; since cerebral circulatory arrest is not always synchronized to the clinical diagnosis&#46; The diagnostic rate is therefore time-dependent&#44; and this fact must be recognized in order to avoid delays in death certification&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Despite its limitations&#44; transcranial Doppler ultrasound helps solve common diagnostic problems&#44; avoids the unnecessary consumption of resources&#44; and can optimize organ harvesting for transplantation&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El Doppler transcraneal permite demostrar la parada circulatoria cerebral que acompa&#241;a a la muerte encef&#225;lica&#44; siendo especialmente &#250;til en pacientes sedados&#44; o en los que no puede realizarse la exploraci&#243;n neurol&#243;gica completa&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El Doppler transcraneal es una t&#233;cnica port&#225;til&#44; no invasiva y de alta disponibilidad&#46; Entre sus limitaciones est&#225; la ausencia de ventana s&#243;nica y los casos falsos negativos&#46; En pacientes con diagn&#243;stico cl&#237;nico de muerte encef&#225;lica&#44; que tienen cr&#225;neos abiertos o anoxia como causa de la muerte&#44; puede sonorizarse flujo sangu&#237;neo cerebral&#44; ya que la parada circulatoria cerebral no siempre es sincr&#243;nica con el diagn&#243;stico cl&#237;nico&#46; Su rentabilidad diagn&#243;stica es&#44; por tanto&#44; dependiente del tiempo&#44; hecho que debe ser reconocido para no retrasar la declaraci&#243;n de muerte&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A pesar de sus limitaciones&#44; el Doppler transcraneal ayuda a resolver frecuentes problemas diagn&#243;sticos&#44; evita un consumo innecesario de recursos y puede optimizar la obtenci&#243;n de &#243;rganos para trasplante&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Escudero D&#44; Otero J&#44; Quind&#243;s B&#44; Vi&#241;a L&#46; Doppler transcraneal en el diagn&#243;stico de la muerte encef&#225;lica&#46; &#191;Es &#250;til o retrasa el diagn&#243;stico&#63; Med Intensiva&#46; 2015&#59;39&#58;244&#8211;250&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Middle cerebral artery showing a strongly systolic pattern with minimum diastolic flow&#44; consistent with precerebral circulatory arrest&#46; Pulsatility index 2&#46;90&#44; reflecting high intracranial pressure&#46;</p>"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Middle cerebral artery explored through the temporal window with an inverted diastolic flow pattern &#40;A&#41; and systolic spikes &#40;B&#41;&#44; exhibiting a systolic peak of under 50<span class="elsevierStyleHsp" style=""></span>cm&#47;s&#44; characteristic of cerebral circulatory arrest&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Basilar artery explored through the suboccipital window at a depth of 81<span class="elsevierStyleHsp" style=""></span>mm &#40;A&#41; and vertebral artery at 65<span class="elsevierStyleHsp" style=""></span>mm&#44; with inverted diastolic flow &#40;B&#41;&#44; typical of cerebral circulatory arrest&#46;</p>"
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Advantages</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Portable technique allowing patient bedside explorations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Noninvasive method measuring intracranial arterial flow velocity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Allows monitoring of patient evolution&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Results not interfered with by central nervous system depressor drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Limitations</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Explorer dependent technique&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Absence of acoustic window&#44; which prevents ultrasound transmission &#40;10&#8211;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Difficulty exploring posterior circulation in critical patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>False-negative results in patients with anoxia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> False-negative results in patients with open skull &#40;decompressive craniectomy&#44; fractures with skull dome rupture&#44; ventricular drainage&#44; and infants with open fontanelles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Time-dependent diagnostic performance &#40;diagnostic sensitivity increases over time&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Advantages and limitations of transcranial Doppler in diagnosing brain death&#46;</p>"
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