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thus&#44; patients&#160;with haemodynamic instability are usually treated with&#160;CRRT and more stable patients are with IHD&#46; The second factor&#160;is determined by where the patient is to receive treatment&#160;or by logistic criteria&#46; In cases in which patients have been&#160;admitted to hospital wards or acute nephrology units&#44; they are&#160;treated using IHD and patients admitted to critical care units&#160;are subjected to CRRT&#46; This was demonstrated in the largescale epidemiological study by Uchino et al&#46;<span class="elsevierStyleSup">1</span><span class="elsevierStyleSup"> </span>However&#44; it is&#160;not the aim of this &#8220;Editorial comment&#8221; to opt in favour of&#160;one or other of these therapeutic alternatives&#46; Recent studies&#44;&#160;such as the multi-centre French study&#44;<span class="elsevierStyleSup">2</span><span class="elsevierStyleSup"> </span>have shown that&#44; if&#160;they are carefully applied&#44; either of the two variants can produce&#160;equivalent results in terms of survival&#44; and properly conducted&#160;meta-analyses have not resulted clearly in favour of&#160;one or other modality&#46;<span class="elsevierStyleSup">3</span><span class="elsevierStyleSup"> </span>The IHD used three decades ago&#160;shows no resemblance whatsoever to the technique applied&#160;today&#46; Nowadays the generalized use of bicarbonate concentrates&#160;in the dialysis fluid&#44; together with better water treatment&#160;and the control of conductivity&#44; pH and the temperature&#160;of the monitors used&#44; as well as the fact that the membranes&#160;are becoming increasingly biocompatible and permeable&#44;&#160;have made IHD a highly effective tool&#44; even in the haemodynamically&#160;unstable patient&#46;</p><p class="elsevierStylePara">Generally speaking&#44; in order to measure the dose in the case&#160;of IHD&#44; extrapolating the knowledge acquired from patients&#160;with end-stage or stage 5 CRF&#44; the calculation of the urea&#160;Kt&#47;V value has been used &#40;where K is clearance&#44; t effective&#160;dialysis time and V the urea distribution volume&#41;&#46; The Daugirdas&#160;mathematical formula has become widely used for&#160;such calculations&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">In the Schiffl et al&#8217;s study&#44;<span class="elsevierStyleSup">5</span><span class="elsevierStyleSup"> </span>daily IHD&#44; compared to classic&#160;HD schedules applied every 2 days&#44; improved the 2-week&#160;survival&#44; which was 72 as opposed to 54&#37; respectively&#46; In&#160;the former treatment schedule&#44; the clearance dose adjusted for&#160;time and urea volume distribution &#40;Kt&#47;V&#41; virtually duplicated&#160;its conventional regime counterpart&#44; although in both groups&#160;the results were distinctly lower than the expected&#46;</p><p class="elsevierStylePara">Another major problem&#44; apart from not being able to achieve&#160;the proposed dose&#44; lies in the fact that the total proportion of&#160;body water &#40;urea distribution volume&#41; varies much more&#160;widely in the acute than in the chronic patient&#44; a&#160;phenomenon which is especially important in the critical patient&#46; Furthermore&#44; methods designed to determine body&#160;water &#40;e&#46;g&#46; vectorial bioimpedance&#41;&#44; which are used more&#160;and more frequently in the patient with end-stage CRF&#44; are&#160;rarely applied in the critical patient&#46; This is why&#44; and with&#160;the primary aim of not introducing inaccurate factors&#44; the&#160;calculation of Kt is being recommended&#44; in other words the&#160;absolute &#8220;clearance over time&#8221; value which has not been&#160;adjusted to the volume of body water&#46; Reference values&#44;&#160;which only show differences for sex&#44; are then established&#46; In&#160;the latest models of monitors the implementation of the&#160;calculation of ionic dialysance allows the dialysis dose to be&#160;constantly measured&#44; as well as the accumulated dose for&#160;each IHD session&#44; reliably and in real time&#46; In the current&#160;issue of the journal NEFROLOG&#205;A two studies&#44; which show&#160;us the results and its reliability compared with other calculations&#44; have been published&#46;<span class="elsevierStyleSup">6&#44;7</span><span class="elsevierStyleSup"> </span>Beforehand<span class="elsevierStyleSup">8&#44;9 </span>another&#160;two studies of excellent design had laid the groundwork for&#160;these two studies&#46; The first study<span class="elsevierStyleSup">6</span><span class="elsevierStyleSup"> </span>includes an evaluation of&#160;Kt by ionic dialysance and demonstrates an optimal&#160;correlation without significant differences in the values&#160;obtained with respect to the reference methods&#46; In this study&#160;an evaluation of the difference in the dose obtained in&#160;relation to the prescribed dose was not included&#44; but the&#160;authors obtained a Kt value which was lower than values&#160;which are taken as standard in patients with end-stage CRF&#46;</p><p class="elsevierStylePara">The second study<span class="elsevierStyleSup">7 </span>reaches the conclusion that the measurement&#160;of dialysis dose by means of Kt identified a greater&#160;number of inadequate sessions than the standard Kt&#47;V<span class="elsevierStyleSup">UREA&#160;</span>method&#44; these accounting for a total of 71 compared to 31&#37;&#160;of those detected using the classical method&#46;</p><p class="elsevierStylePara">It is true that when we introduce weight and urea distribution&#160;volume &#40;nearly always unknown in patients who are critical&#41;&#44;&#160;we may apply an inaccurate value&#44; but it is also evident that&#44;&#160;when we establish absolute values for males &#40;45-50L&#41; and females&#160;&#40;40-45L&#41;&#44; we are making a simplification which is very&#160;likely to be exaggerated&#46; A patient weighing 50kg is in no way comparable to one who weighs 120kg so&#44; in our opinion&#44; it&#160;would be more sensible to establish scales or intervals which&#160;could correct these discrepancies&#46;</p><p class="elsevierStylePara">The calculation of clearance values in CRRT is simpler&#46; If&#160;we concentrate exclusively on measuring the elimination of&#160;small molecules &#40;the simplest example of which is urea&#41;&#44; we&#160;can adjust clearance to the volume of effluent&#44; albeit plasma&#160;ultrafiltrate &#40;haemofiltration&#41;&#44; dialysis fluid &#40;haemodialysis&#41;&#160;or a mixture of both &#40;continuous haemodiafiltration&#41;&#46; The&#160;flows permitted for the dialysis liquid by CRRT monitors&#160;virtually manage to equate the concentration of the effluent&#160;output with that of the patient&#44; so that clearance &#40;K<span class="elsevierStyleSup">D</span>&#41; will be&#160;the same as the dialysis flow &#40;Q<span class="elsevierStyleSup">D</span>&#41;&#46; The same is true&#160;regarding the ultrafiltrate volume &#40;K<span class="elsevierStyleSup">F </span>&#61; Q<span class="elsevierStyleSup">F</span>&#41;&#44; where the&#160;sieving coefficient &#40;S&#41; will be the unit for small molecules&#160;and will gradually decrease as the Einstein&#8217;s molecular&#160;radius increase&#46; The <span class="elsevierStyleItalic">cut off </span>point will depend very much on&#160;how the membrane is designed and on how its pore sizes are&#160;distributed&#46; However&#44; we need to remember that continuous&#160;techniques are not entirely so&#44; given that their application&#160;involves interruptions&#44;<span class="elsevierStyleSup">10</span><span class="elsevierStyleSup"> </span>owing to problems with blood clots&#160;in the circuit or times when the treatment is not effective &#40;<span class="elsevierStyleItalic">bypass&#41; </span>because of the need for intervention on the part of&#160;nursing personnel &#40;e&#46;g&#46; the changing of bags&#44; emptying of&#160;effluent&#41;&#44; as well as times in which the patient is&#160;disconnected from the circuit in order to perform surgical&#160;interventions or radiological explorations&#46; Occasions when&#160;the dialysis machine demands the attention of nursing&#160;personnel with alarms&#44; which can sometimes be quite&#160;irritating&#44; are relatively frequent &#40;figure 1&#41;&#46; Consequently&#44;&#160;we need to programme a longer regime than we really think&#160;will be needed&#46;</p><p class="elsevierStylePara">In their classic study Ronco et al<span class="elsevierStyleSup">11</span><span class="elsevierStyleSup"> </span>analysed survival 14 days&#160;after finalizing haemofiltration&#44; using a polysulfone membrane&#160;with replacement fluids in post-dilution containing lactate&#160;with 20&#44; 35 and 45ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#44; and a survival rate of 41&#44;&#160;57 and 58&#37;&#44; respectively&#44; was obtained&#46; In this way&#44; an ultrafiltrate&#160;&#8220;magic figure&#8221; &#40;convection&#41; of 35ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>was obtained&#46;&#160;After this level haemofiltration was defined as &#8220;high&#160;volume&#8221;&#46; However&#44; this single centre study included a small&#160;proportion of patients with sepsis &#40;11 to 14&#37; in randomized&#160;groups&#41;&#44; a percentage which was lower than that of other&#160;studies with similar characteristics&#44; and the analysis of this&#160;subgroup of patients was not statistically or clinically significant&#160;when the <span class="elsevierStyleItalic">hazards ratio </span>was applied&#46; The view that convection&#160;at these levels&#44; and even at much higher levels &#40;defended&#160;by certain influential research groups&#41;&#44; could eliminate&#160;mediators of the inflammatory cascade and&#47;or modulate unfavourable&#160;responses was consolidated&#44; inclining the balance&#160;in favour of the patient&#46;</p><p class="elsevierStylePara">In the study by Saudan et al<span class="elsevierStyleSup">12</span><span class="elsevierStyleSup"> </span>an increase in survival was&#160;demonstrated when diffusion &#40;CVVHDF&#41; was added to a normal&#160;dose of ultrafiltrate &#40;not high volume&#41; and it was concluded&#160;that survival improved&#44; no longer as a result of convection&#160;but of the clearance dose for small molecules&#46; The&#160;study was well designed and included over 100 patients in&#160;each randomized group &#40;206 in total&#41;&#46;</p><p class="elsevierStylePara">It is worth stressing that in CRRT we use highly permeable&#160;membranes&#44; so that&#44; although we only work in the context of&#160;dialysis &#40;without haemofiltration&#41;&#44; with transmembrane pressures&#160;&#40;TMP&#41; close to zero a convective clearance effect will&#160;be added to the diffusive clearance&#46; The first is produced as a&#160;result of the interplay of pressures within the dialyser cartridge&#58;&#160;when blood enters the dialyser&#44; it does so at a pressure&#160;which is higher than that of the dialytic compartment so that&#160;internal filtration occurs and&#44; when it is expelled from the dialyser&#44; the opposite takes place and retrofiltration occurs&#46;&#160;As a result&#44; we can obtain up to 30ml&#47;min of convective&#160;clearance&#44; which is not directly controlled when the treatment&#160;regime is prescribed&#46;<span class="elsevierStyleSup">13</span><span class="elsevierStyleSup"> </span>The principle is the same as the one&#160;which is being used to eliminate light chains in the treatment&#160;of myeloma kidney&#46;<span class="elsevierStyleSup">14&#44;15</span><span class="elsevierStyleSup"> </span>An <span class="elsevierStyleItalic">in vitro </span>study has demonstrated&#160;that the clearance of medium-sized molecules in CRRT can&#160;be the same with haemofiltration as with dialysis and it can&#160;even be better when filters with a small surface area are employed&#44;&#160;a phenomenon which has been partly attributed to the&#160;internal polarization of the proteins that block membrane&#160;pores during ultrafiltration&#44; which impedes the elimination of&#160;medium-sized molecules&#46;<span class="elsevierStyleSup">16</span></p><p class="elsevierStylePara">Two large multi-centre studies have attempted to determine&#160;with some degree of accuracy an optimal dose for the treatment&#160;of the AKI patient&#46; The American study&#44; known by its&#160;acronym ATN&#44;<span class="elsevierStyleSup">17</span><span class="elsevierStyleSup"> </span>did not manage to demonstrate advantages at&#160;higher doses &#40;20 as opposed to 35ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>in CRRT with&#160;haemodiafiltration or with IHD&#44; applying 3 compared to 6 sessions&#160;per week&#41;&#44; selecting one or other technique&#44; depending&#160;on the haemodynamic stability of the patient&#46; In other words&#44;&#160;continuous techniques were used for unstable patients and intermittent&#160;techniques for more stable patients &#40;severity score&#160;on the SOFA cardiovascular scale of 3 or 4 points for CRRT&#160;and less than 3 for IHD&#41;&#46; This has already been refuted by different&#160;groups&#44; including the Spanish group&#44; which recommends&#160;a dynamic approach that constantly adjusts the dose&#44;&#160;depending on the condition of the patient&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">More recently the Australian-New Zealand study&#44; RENAL&#44;<span class="elsevierStyleSup">19</span><span class="elsevierStyleSup">&#160;</span>concluded&#46; In this study 60 and 90-day survival rates were&#160;identical if a standard dose was applied &#40;25ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span>&#41;&#160;rather than an intensive dose &#40;40ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span>&#41;&#44; both using&#160;haemodiafiltration in a Q<span class="elsevierStyleSup">D</span>&#58;Q<span class="elsevierStyleSup">F </span>proportion of 1&#58;1 and with postdilution&#160;replacement&#46; As well as CRRT being indicated&#44;&#160;owing to acute kidney injury &#40;AKI&#41;&#44; the inclusion criteria for&#160;patients consisted of at least one of the following&#58; oliguria &#40;diuresis less than 100 ml during a period of 6 hours&#41; with a&#160;lack of response to resuscitation measures using serums&#44;&#160;serum potassium levels higher than 6&#46;5mmol&#47;l&#44; significant&#160;acidaemia &#40;pH less than 7&#46;2&#41;&#44; plasma urea nitrogen levels&#160;&#40;BUN&#41; higher than 70mg&#47;dl &#40;25mmol&#47;l&#41;&#44; serum creatinine&#160;levels higher than 3&#46;4mg&#47;dl &#40;&#62; 300&#956;mol&#47;l&#41; or clinically significant&#160;oedemas &#40;e&#46;g&#46; lung oedema&#41; and over 700 patients&#160;were included in each group &#40;total 1&#44;464 patients&#41;&#46; Survival&#160;was the same for both groups&#46; The group which received&#160;highly intense treatment exhibited more cases of hypophosphataemia&#44;&#160;which is why they insist on the idea of avoiding&#160;problems caused by excessive dosage&#44; which ties in with the&#160;recently coined concept of &#8220;dialtrauma&#8221;&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In conclusion&#44; with respect to the treatment dose in AKI patients&#44;&#160;we believe that it is better to measure the dose than&#160;not to measure it&#44; but that&#44; in terms of quantity&#44; more is not&#160;necessarily better&#46; As we advance in our search for the ideal&#160;minimum dose&#44; we need to concentrate on good clinical practice&#44;&#160;using great care and common sense&#44; and adapting ourselves&#160;to the context and the technological&#44; human and economic&#160;resources at our disposal&#46; Intuitively&#44; we are led to&#160;think that during the initial phases of multi-organ failure more&#160;doses are needed than during phases of recovery or immunological&#160;paralysis&#46; However&#44; as we understand it&#44; this question&#160;still remains unanswered&#46;</p><p class="elsevierStylePara"><a href="grande&#47;1032718078&#95;v30&#95;n2&#95;v&#46;i&#46;2010&#95;f1&#95;pag148&#46;jpg" class="elsevierStyleCrossRefs"><img src="1032718078_v30_n2_v.i.2010_f1_pag148.jpg" alt="Example of how irritating the alarms of continuous technique monitors can be - Result of the reaction of a relative who decided to curtail the persistent sound of monitors by punching the screen&#46;"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Example of how irritating the alarms of continuous technique monitors can be - Result of the reaction of a relative who decided to curtail the persistent sound of monitors by punching the screen&#46;</p>"
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Clearance dose in acute kidney injury
Dosis de aclaramiento en insuficiencia renal aguda
Francisco Javier Gainza de los Ríosa, F.. Liaño Garcíab
a Servicio de Nefrología, Hospital de Cruces, Barakaldo, Universidad del País Vasco, España,
b Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Consorcio de Investigación del FRA en la Comunidad de Madrid (CIFRA). Universidad de Alcalá, España,
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    "textoCompleto" => "<p class="elsevierStylePara">In the last decade substantial efforts have been made towards&#160;defining the dose threshold for renal replacement&#160;therapy in acute kidney injury &#40;AKI&#41;&#44; which would enable&#160;to reduce the high mortality associated with this common&#160;complication in hospitals&#46;&#160;</p><p class="elsevierStylePara">The first problem we came up against was how to measure&#160;the actual dose we applied reliably&#46; The second was to find a&#160;dose range which would prove as beneficial as possible in&#160;terms of patient survival and recovery from AKI&#46;</p><p class="elsevierStylePara">We have the option of treating our patients with severe AKI&#160;by means of intermittent haemodialysis &#40;IHD&#41; or continuous&#160;renal replacements therapies &#40;CRRT&#41;&#46; Our choice of the technique&#160;is conditioned by two factors&#58; the first and most important&#160;of these is the severity of the patient&#8217;s illness&#59; thus&#44; patients&#160;with haemodynamic instability are usually treated with&#160;CRRT and more stable patients are with IHD&#46; The second factor&#160;is determined by where the patient is to receive treatment&#160;or by logistic criteria&#46; In cases in which patients have been&#160;admitted to hospital wards or acute nephrology units&#44; they are&#160;treated using IHD and patients admitted to critical care units&#160;are subjected to CRRT&#46; This was demonstrated in the largescale epidemiological study by Uchino et al&#46;<span class="elsevierStyleSup">1</span><span class="elsevierStyleSup"> </span>However&#44; it is&#160;not the aim of this &#8220;Editorial comment&#8221; to opt in favour of&#160;one or other of these therapeutic alternatives&#46; Recent studies&#44;&#160;such as the multi-centre French study&#44;<span class="elsevierStyleSup">2</span><span class="elsevierStyleSup"> </span>have shown that&#44; if&#160;they are carefully applied&#44; either of the two variants can produce&#160;equivalent results in terms of survival&#44; and properly conducted&#160;meta-analyses have not resulted clearly in favour of&#160;one or other modality&#46;<span class="elsevierStyleSup">3</span><span class="elsevierStyleSup"> </span>The IHD used three decades ago&#160;shows no resemblance whatsoever to the technique applied&#160;today&#46; Nowadays the generalized use of bicarbonate concentrates&#160;in the dialysis fluid&#44; together with better water treatment&#160;and the control of conductivity&#44; pH and the temperature&#160;of the monitors used&#44; as well as the fact that the membranes&#160;are becoming increasingly biocompatible and permeable&#44;&#160;have made IHD a highly effective tool&#44; even in the haemodynamically&#160;unstable patient&#46;</p><p class="elsevierStylePara">Generally speaking&#44; in order to measure the dose in the case&#160;of IHD&#44; extrapolating the knowledge acquired from patients&#160;with end-stage or stage 5 CRF&#44; the calculation of the urea&#160;Kt&#47;V value has been used &#40;where K is clearance&#44; t effective&#160;dialysis time and V the urea distribution volume&#41;&#46; The Daugirdas&#160;mathematical formula has become widely used for&#160;such calculations&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">In the Schiffl et al&#8217;s study&#44;<span class="elsevierStyleSup">5</span><span class="elsevierStyleSup"> </span>daily IHD&#44; compared to classic&#160;HD schedules applied every 2 days&#44; improved the 2-week&#160;survival&#44; which was 72 as opposed to 54&#37; respectively&#46; In&#160;the former treatment schedule&#44; the clearance dose adjusted for&#160;time and urea volume distribution &#40;Kt&#47;V&#41; virtually duplicated&#160;its conventional regime counterpart&#44; although in both groups&#160;the results were distinctly lower than the expected&#46;</p><p class="elsevierStylePara">Another major problem&#44; apart from not being able to achieve&#160;the proposed dose&#44; lies in the fact that the total proportion of&#160;body water &#40;urea distribution volume&#41; varies much more&#160;widely in the acute than in the chronic patient&#44; a&#160;phenomenon which is especially important in the critical patient&#46; Furthermore&#44; methods designed to determine body&#160;water &#40;e&#46;g&#46; vectorial bioimpedance&#41;&#44; which are used more&#160;and more frequently in the patient with end-stage CRF&#44; are&#160;rarely applied in the critical patient&#46; This is why&#44; and with&#160;the primary aim of not introducing inaccurate factors&#44; the&#160;calculation of Kt is being recommended&#44; in other words the&#160;absolute &#8220;clearance over time&#8221; value which has not been&#160;adjusted to the volume of body water&#46; Reference values&#44;&#160;which only show differences for sex&#44; are then established&#46; In&#160;the latest models of monitors the implementation of the&#160;calculation of ionic dialysance allows the dialysis dose to be&#160;constantly measured&#44; as well as the accumulated dose for&#160;each IHD session&#44; reliably and in real time&#46; In the current&#160;issue of the journal NEFROLOG&#205;A two studies&#44; which show&#160;us the results and its reliability compared with other calculations&#44; have been published&#46;<span class="elsevierStyleSup">6&#44;7</span><span class="elsevierStyleSup"> </span>Beforehand<span class="elsevierStyleSup">8&#44;9 </span>another&#160;two studies of excellent design had laid the groundwork for&#160;these two studies&#46; The first study<span class="elsevierStyleSup">6</span><span class="elsevierStyleSup"> </span>includes an evaluation of&#160;Kt by ionic dialysance and demonstrates an optimal&#160;correlation without significant differences in the values&#160;obtained with respect to the reference methods&#46; In this study&#160;an evaluation of the difference in the dose obtained in&#160;relation to the prescribed dose was not included&#44; but the&#160;authors obtained a Kt value which was lower than values&#160;which are taken as standard in patients with end-stage CRF&#46;</p><p class="elsevierStylePara">The second study<span class="elsevierStyleSup">7 </span>reaches the conclusion that the measurement&#160;of dialysis dose by means of Kt identified a greater&#160;number of inadequate sessions than the standard Kt&#47;V<span class="elsevierStyleSup">UREA&#160;</span>method&#44; these accounting for a total of 71 compared to 31&#37;&#160;of those detected using the classical method&#46;</p><p class="elsevierStylePara">It is true that when we introduce weight and urea distribution&#160;volume &#40;nearly always unknown in patients who are critical&#41;&#44;&#160;we may apply an inaccurate value&#44; but it is also evident that&#44;&#160;when we establish absolute values for males &#40;45-50L&#41; and females&#160;&#40;40-45L&#41;&#44; we are making a simplification which is very&#160;likely to be exaggerated&#46; A patient weighing 50kg is in no way comparable to one who weighs 120kg so&#44; in our opinion&#44; it&#160;would be more sensible to establish scales or intervals which&#160;could correct these discrepancies&#46;</p><p class="elsevierStylePara">The calculation of clearance values in CRRT is simpler&#46; If&#160;we concentrate exclusively on measuring the elimination of&#160;small molecules &#40;the simplest example of which is urea&#41;&#44; we&#160;can adjust clearance to the volume of effluent&#44; albeit plasma&#160;ultrafiltrate &#40;haemofiltration&#41;&#44; dialysis fluid &#40;haemodialysis&#41;&#160;or a mixture of both &#40;continuous haemodiafiltration&#41;&#46; The&#160;flows permitted for the dialysis liquid by CRRT monitors&#160;virtually manage to equate the concentration of the effluent&#160;output with that of the patient&#44; so that clearance &#40;K<span class="elsevierStyleSup">D</span>&#41; will be&#160;the same as the dialysis flow &#40;Q<span class="elsevierStyleSup">D</span>&#41;&#46; The same is true&#160;regarding the ultrafiltrate volume &#40;K<span class="elsevierStyleSup">F </span>&#61; Q<span class="elsevierStyleSup">F</span>&#41;&#44; where the&#160;sieving coefficient &#40;S&#41; will be the unit for small molecules&#160;and will gradually decrease as the Einstein&#8217;s molecular&#160;radius increase&#46; The <span class="elsevierStyleItalic">cut off </span>point will depend very much on&#160;how the membrane is designed and on how its pore sizes are&#160;distributed&#46; However&#44; we need to remember that continuous&#160;techniques are not entirely so&#44; given that their application&#160;involves interruptions&#44;<span class="elsevierStyleSup">10</span><span class="elsevierStyleSup"> </span>owing to problems with blood clots&#160;in the circuit or times when the treatment is not effective &#40;<span class="elsevierStyleItalic">bypass&#41; </span>because of the need for intervention on the part of&#160;nursing personnel &#40;e&#46;g&#46; the changing of bags&#44; emptying of&#160;effluent&#41;&#44; as well as times in which the patient is&#160;disconnected from the circuit in order to perform surgical&#160;interventions or radiological explorations&#46; Occasions when&#160;the dialysis machine demands the attention of nursing&#160;personnel with alarms&#44; which can sometimes be quite&#160;irritating&#44; are relatively frequent &#40;figure 1&#41;&#46; Consequently&#44;&#160;we need to programme a longer regime than we really think&#160;will be needed&#46;</p><p class="elsevierStylePara">In their classic study Ronco et al<span class="elsevierStyleSup">11</span><span class="elsevierStyleSup"> </span>analysed survival 14 days&#160;after finalizing haemofiltration&#44; using a polysulfone membrane&#160;with replacement fluids in post-dilution containing lactate&#160;with 20&#44; 35 and 45ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#44; and a survival rate of 41&#44;&#160;57 and 58&#37;&#44; respectively&#44; was obtained&#46; In this way&#44; an ultrafiltrate&#160;&#8220;magic figure&#8221; &#40;convection&#41; of 35ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>was obtained&#46;&#160;After this level haemofiltration was defined as &#8220;high&#160;volume&#8221;&#46; However&#44; this single centre study included a small&#160;proportion of patients with sepsis &#40;11 to 14&#37; in randomized&#160;groups&#41;&#44; a percentage which was lower than that of other&#160;studies with similar characteristics&#44; and the analysis of this&#160;subgroup of patients was not statistically or clinically significant&#160;when the <span class="elsevierStyleItalic">hazards ratio </span>was applied&#46; The view that convection&#160;at these levels&#44; and even at much higher levels &#40;defended&#160;by certain influential research groups&#41;&#44; could eliminate&#160;mediators of the inflammatory cascade and&#47;or modulate unfavourable&#160;responses was consolidated&#44; inclining the balance&#160;in favour of the patient&#46;</p><p class="elsevierStylePara">In the study by Saudan et al<span class="elsevierStyleSup">12</span><span class="elsevierStyleSup"> </span>an increase in survival was&#160;demonstrated when diffusion &#40;CVVHDF&#41; was added to a normal&#160;dose of ultrafiltrate &#40;not high volume&#41; and it was concluded&#160;that survival improved&#44; no longer as a result of convection&#160;but of the clearance dose for small molecules&#46; The&#160;study was well designed and included over 100 patients in&#160;each randomized group &#40;206 in total&#41;&#46;</p><p class="elsevierStylePara">It is worth stressing that in CRRT we use highly permeable&#160;membranes&#44; so that&#44; although we only work in the context of&#160;dialysis &#40;without haemofiltration&#41;&#44; with transmembrane pressures&#160;&#40;TMP&#41; close to zero a convective clearance effect will&#160;be added to the diffusive clearance&#46; The first is produced as a&#160;result of the interplay of pressures within the dialyser cartridge&#58;&#160;when blood enters the dialyser&#44; it does so at a pressure&#160;which is higher than that of the dialytic compartment so that&#160;internal filtration occurs and&#44; when it is expelled from the dialyser&#44; the opposite takes place and retrofiltration occurs&#46;&#160;As a result&#44; we can obtain up to 30ml&#47;min of convective&#160;clearance&#44; which is not directly controlled when the treatment&#160;regime is prescribed&#46;<span class="elsevierStyleSup">13</span><span class="elsevierStyleSup"> </span>The principle is the same as the one&#160;which is being used to eliminate light chains in the treatment&#160;of myeloma kidney&#46;<span class="elsevierStyleSup">14&#44;15</span><span class="elsevierStyleSup"> </span>An <span class="elsevierStyleItalic">in vitro </span>study has demonstrated&#160;that the clearance of medium-sized molecules in CRRT can&#160;be the same with haemofiltration as with dialysis and it can&#160;even be better when filters with a small surface area are employed&#44;&#160;a phenomenon which has been partly attributed to the&#160;internal polarization of the proteins that block membrane&#160;pores during ultrafiltration&#44; which impedes the elimination of&#160;medium-sized molecules&#46;<span class="elsevierStyleSup">16</span></p><p class="elsevierStylePara">Two large multi-centre studies have attempted to determine&#160;with some degree of accuracy an optimal dose for the treatment&#160;of the AKI patient&#46; The American study&#44; known by its&#160;acronym ATN&#44;<span class="elsevierStyleSup">17</span><span class="elsevierStyleSup"> </span>did not manage to demonstrate advantages at&#160;higher doses &#40;20 as opposed to 35ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>in CRRT with&#160;haemodiafiltration or with IHD&#44; applying 3 compared to 6 sessions&#160;per week&#41;&#44; selecting one or other technique&#44; depending&#160;on the haemodynamic stability of the patient&#46; In other words&#44;&#160;continuous techniques were used for unstable patients and intermittent&#160;techniques for more stable patients &#40;severity score&#160;on the SOFA cardiovascular scale of 3 or 4 points for CRRT&#160;and less than 3 for IHD&#41;&#46; This has already been refuted by different&#160;groups&#44; including the Spanish group&#44; which recommends&#160;a dynamic approach that constantly adjusts the dose&#44;&#160;depending on the condition of the patient&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">More recently the Australian-New Zealand study&#44; RENAL&#44;<span class="elsevierStyleSup">19</span><span class="elsevierStyleSup">&#160;</span>concluded&#46; In this study 60 and 90-day survival rates were&#160;identical if a standard dose was applied &#40;25ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span>&#41;&#160;rather than an intensive dose &#40;40ml &#183; kg<span class="elsevierStyleSup">&#8211;1</span><span class="elsevierStyleSup"> </span>&#183; h<span class="elsevierStyleSup">&#8211;1</span>&#41;&#44; both using&#160;haemodiafiltration in a Q<span class="elsevierStyleSup">D</span>&#58;Q<span class="elsevierStyleSup">F </span>proportion of 1&#58;1 and with postdilution&#160;replacement&#46; As well as CRRT being indicated&#44;&#160;owing to acute kidney injury &#40;AKI&#41;&#44; the inclusion criteria for&#160;patients consisted of at least one of the following&#58; oliguria &#40;diuresis less than 100 ml during a period of 6 hours&#41; with a&#160;lack of response to resuscitation measures using serums&#44;&#160;serum potassium levels higher than 6&#46;5mmol&#47;l&#44; significant&#160;acidaemia &#40;pH less than 7&#46;2&#41;&#44; plasma urea nitrogen levels&#160;&#40;BUN&#41; higher than 70mg&#47;dl &#40;25mmol&#47;l&#41;&#44; serum creatinine&#160;levels higher than 3&#46;4mg&#47;dl &#40;&#62; 300&#956;mol&#47;l&#41; or clinically significant&#160;oedemas &#40;e&#46;g&#46; lung oedema&#41; and over 700 patients&#160;were included in each group &#40;total 1&#44;464 patients&#41;&#46; Survival&#160;was the same for both groups&#46; The group which received&#160;highly intense treatment exhibited more cases of hypophosphataemia&#44;&#160;which is why they insist on the idea of avoiding&#160;problems caused by excessive dosage&#44; which ties in with the&#160;recently coined concept of &#8220;dialtrauma&#8221;&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In conclusion&#44; with respect to the treatment dose in AKI patients&#44;&#160;we believe that it is better to measure the dose than&#160;not to measure it&#44; but that&#44; in terms of quantity&#44; more is not&#160;necessarily better&#46; As we advance in our search for the ideal&#160;minimum dose&#44; we need to concentrate on good clinical practice&#44;&#160;using great care and common sense&#44; and adapting ourselves&#160;to the context and the technological&#44; human and economic&#160;resources at our disposal&#46; Intuitively&#44; we are led to&#160;think that during the initial phases of multi-organ failure more&#160;doses are needed than during phases of recovery or immunological&#160;paralysis&#46; However&#44; as we understand it&#44; this question&#160;still remains unanswered&#46;</p><p class="elsevierStylePara"><a href="grande&#47;1032718078&#95;v30&#95;n2&#95;v&#46;i&#46;2010&#95;f1&#95;pag148&#46;jpg" class="elsevierStyleCrossRefs"><img src="1032718078_v30_n2_v.i.2010_f1_pag148.jpg" alt="Example of how irritating the alarms of continuous technique monitors can be - Result of the reaction of a relative who decided to curtail the persistent sound of monitors by punching the screen&#46;"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Example of how irritating the alarms of continuous technique monitors can be - Result of the reaction of a relative who decided to curtail the persistent sound of monitors by punching the screen&#46;</p>"
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Article information
ISSN: 20132514
Original language: English
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