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Comment on “Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: Systematic review and meta-analysis”
Comentario sobre “Incidence of Postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis”
Daniel Rivera-Tocancipáa,
, Jesús Hernán Tovar-Cardozob, Luis David Garcésc, Jaime Andrés Salcedoc, Diego Andrés Galeanoc
Corresponding author
riverato@hotmail.com
Corresponding author at: Universidad Surcolombiana, Facultad de Salud, Calle 9 Carrera 14, Neiva, Colombia.
Corresponding author at: Universidad Surcolombiana, Facultad de Salud, Calle 9 Carrera 14, Neiva, Colombia.
a Anesthesiologist, Associate Professor, Faculty of Health, Universidad Surcolombiana, Neiva, Colombia
b Anesthesiologist, Assistant Professor, Faculty of Health, Universidad Surcolombiana, Neiva, Colombia
c Level II Resident in Anesthesiology and Resuscitation. Universidad Surcolombiana, Neiva, Colombia
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Universidad Surcolombiana, Neiva, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author at</span>: Universidad Surcolombiana, Facultad de Salud, Calle 9 Carrera 14, Neiva, Colombia." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Comentario sobre “Incidence of Postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis”" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Description</span><p id="par0005" class="elsevierStylePara elsevierViewall">This article by Gillies et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> attempts to find a response to the use of hydroxyethyl starch (HES) 6% in surgical patients and its possible connection with an increase in mortality at 30 days (primary outcome), the appearance of acute kidney injury (AKI) and the need for dialytic support. These aspects are associated with patients in intensive care, especially with sepsis. To do this, they designed a systematic review of literature since 1946, choosing those essays that compared HES 6% with other resuscitation solutions. Finally, the selected 19 randomized clinical studies, obtaining 1567 patients with whom they carried out a meta-analysis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">No differences were found in surgical patients or in mortality between the use of HES 6% and of other types of fluids in terms of mortality — RD 0.00, CI 95%: 0.02–0.02 — or the need for dialysis support — RD 0.01, CI 95%: 0.04–0.02 — or AKI — RD 0.02, CI 95%: 0.02–0.06.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Finding no additional benefit from the use of HES 6% and taking into account the cost, they do not recommend its use in surgical patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Critical assessment</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="par0020" class="elsevierStylePara elsevierViewall">After applying the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a> criteria, we observed that the authors do not describe the risk of bias of the individual studies. They do not present additional analysis of the results but conclude that 6% HES showed no additional benefit even though this was not the objective of the study. They did not report means of financing, however, in the conflict of interest declaration, they stated that the authors have received honorariums or donations from enterprises related to the debate on the use of HES. The funnel plot for the main outcome shows a low probability of publication bias. The method is clear and is limited to HES at 6% (molar substitution ratio 0.4 and 0.42) and the adult population, thereby eliminating the possibility of other kinds of HES. The definition of Acute Renal Injury was defined differently in the selected studies. Some did not describe any criteria, others used the AKIN (Acute Kidney Injury Network) criteria and others still used the RIFLE (Risk, Injury, Failure, Loss y End Stage Kidney Disease) criteria. In the online version of the article, the clarify that a clinical trial with approximately 19,000 patients would be required to demonstrate any benefits of HES.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">3</span></a> This study excluded neurosurgical, burn, transplant, and obstetric patients.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Mortality</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors describe more than double mortality when HES is not used (5.9% vs. 2.8%) and it is not easy to understand why there is no statistical difference between the two. Applying a contingency table, as if all of the individuals were from the same study (there is minimal heterogeneity according to their descriptions based on the I<span class="elsevierStyleSup">2</span> test), the absolute reduction of risk shows a significant decrease in mortality in the HES group: RD: 0.031, RR 0.47; CI 95%: 0.27–0.79, with a reduction of 53% when HES 6% is used. Thus, there is some doubt about the true value of the results for mortality (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Acute Kidney Injury (AKI)</span><p id="par0030" class="elsevierStylePara elsevierViewall">In the HES group, the incidence of kidney damage was 5.4% versus 3.6% in the group of other fluids. In the HES group, the incidence of kidney damage was 5.4% versus 3.6% in the group of other liquids. When we apply these results in a contingency table, we find that there is a greater incidence of acute kidney injury in the HES group, without statistically significant differences: RD −0.018, RR: 1.51, CI 95%: 0.6–3.8 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Requirement of Renal Replacement Therapy (RRT)</span><p id="par0035" class="elsevierStylePara elsevierViewall">The results between the groups are almost equal and evidently there are no clinical or statistical differences: RD −0.0009, RR 1.0, CI 95%: 0.2–4.15 (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">The debate on the use of colloids vs. crystalloids is not over.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> Studies that defended starches, presented by Boldt et al.,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> ended with methodological errors, duplicity, and fraud. Later, multi-center studies (clinical study 6S – The Crystalloid versus Hydroxyethyl Starch Trial (CHEST)) reignited the debate and lead to the November 2013 alert from the European Medicines Agency (PRAC) recommending the suspension of HES.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The study 6S<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> (Scandinavian Starch in Severe Sepsis and Septic Shock) compared HES 130/0.42 at 6% to Ringer's acetate, reporting greater mortality after 90 days in patients to whom HES was administered along with greater use of RRT, blood transfusions, and greater incidence of severe bleeding. The CHEST<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> study, in critical patients, compared HES 130/0.4 to saline solution at 0.9% and found no differences in mortality at 90 days. However, it did find greater frequency of RRT in the HES group. The studies above present methodological questioning: they included patients after the initial phase of resuscitation and did not include protocols and objectives related to the administration of fluids or a unification of the procedures for initiating RRT.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The CRISTAL (The Colloids Versus Crystalloids for the Resuscitation of the Critically Ill)<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> study, compared colloids (gelatins, dextrans, HES, and albumin) to crystalloids (isotonic or hypertonic saline solution, Ringer's lactate) in septic patients and patients in hypovolemic shock, showing a mortality at 28 days of 25.4% vs. 27% in favor of colloids with no statistically significant difference. The heterogeneity of the evaluated groups is in question.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In surgical patients, we have the analysis by Van Der Linden et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> with 2139 patients comparing HES and other kinds of solutions, finding no adverse effects at the renal level, nor in terms of the transfusion of red blood cells. The heterogeneity of the groups and the variety of HES types is questionable. The meta-analysis of Claude Martin et al.,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> with 17 randomized studies including 1230 patients, found no evidence of renal dysfunction caused by the second generation HES (derived from corn).</p><p id="par0060" class="elsevierStylePara elsevierViewall">The effects of fluid therapy depend on the type of fluid, the quantity administered, and the characteristics of the patients that receive it. Today we know that the basement membrane of the endothelium is covered in proteoglycans and glycoproteins, the so-called “glycocalyx layer”, that act as a second barrier to limit the extravasation of fluids to the interstitial space in addition to filling other roles such as preventing the adhesion of leukocytes and platelets.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> In <span class="elsevierStyleItalic">critical</span> patients this layer tends to be altered by different inflammatory mediators, favoring the extravasation of proteins to the interstitial space. This leads to edema in the tissues and cell aggregation.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> The <span class="elsevierStyleItalic">surgical patient</span>, however, tends to have an initially intact glycocalyx.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The effects of hydroxyethyl starches differ depending on whether they derive from potatoes or corn and on their molecular weight, their molar substitution ratio, and their substitution pattern.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a> Thus the results of the studies on “HES” without specifying what kind can not be extrapolated since clearly the worst results come from HES with high molecular weights and molar substitution ratio.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The characteristics of the patient and the type of HES used may be responsible for the controversial results of the studies.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Shortfalls persist in the methodological designs and especially in the lack of a sufficient sample size to demonstrate statistical differences as clinically significant.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Currently there is no consensus regarding the safety of HES use in surgical patients. However, HES use does represent a high monetary cost when compared to crystalloids. Therefore, the use of HES cannot be recommended until further studies explaining these problems appear.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Financing</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors did not receive any sponsorship to produce this article.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare having no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Description" ] 1 => array:3 [ "identificador" => "sec0010" "titulo" => "Critical assessment" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Methodology" ] ] ] 2 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Mortality" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Acute Kidney Injury (AKI)" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Requirement of Renal Replacement Therapy (RRT)" ] ] ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusion" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Financing" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interests" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rivera-Tocancipá D, Tovar-Cardozo JH, Garcés LD, Salcedo JA, Galeano DA. Comentario sobre “Incidence of Postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis”. Rev Colomb Anestesiol. 2016;44:78–80.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Authors." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Percentage \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total patients: other fluids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">776 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deaths in the other fluids group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total patients in HES group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">685 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deaths in the HES group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab981292.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Results of the outcome of mortality.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Authors." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Percentage \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total patients: other fluids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">197 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with AKI: other fluids group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total patients: HES group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">204 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with AKI: HES group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab981293.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Results of the outcome of Acute Kidney Injury (AKI).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Authors." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Percentage \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total patients: other fluids group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">223 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with RRT: other fluids group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total patients: HES group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">212 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with RRT: HES group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab981294.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Results fro the outcome of Renal Replacement Therapy (RRT).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0075" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Gillies" 1 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 1 | 11 |
| 2024 October | 20 | 3 | 23 |
| 2024 September | 10 | 2 | 12 |
| 2024 August | 10 | 4 | 14 |
| 2024 July | 13 | 1 | 14 |
| 2024 June | 5 | 5 | 10 |
| 2024 May | 10 | 2 | 12 |
| 2024 April | 7 | 9 | 16 |
| 2024 March | 13 | 8 | 21 |
| 2024 February | 10 | 9 | 19 |
| 2024 January | 5 | 6 | 11 |
| 2023 December | 10 | 6 | 16 |
| 2023 November | 4 | 6 | 10 |
| 2023 October | 8 | 3 | 11 |
| 2023 September | 7 | 10 | 17 |
| 2023 August | 17 | 6 | 23 |
| 2023 July | 1 | 5 | 6 |
| 2023 June | 14 | 0 | 14 |
| 2023 May | 26 | 4 | 30 |
| 2023 April | 24 | 3 | 27 |
| 2023 March | 13 | 1 | 14 |
| 2023 February | 15 | 7 | 22 |
| 2023 January | 3 | 7 | 10 |
| 2022 December | 8 | 3 | 11 |
| 2022 November | 12 | 5 | 17 |
| 2022 October | 8 | 7 | 15 |
| 2022 September | 4 | 5 | 9 |
| 2022 August | 9 | 5 | 14 |
| 2022 July | 15 | 10 | 25 |
| 2022 June | 3 | 8 | 11 |
| 2022 May | 7 | 11 | 18 |
| 2022 April | 6 | 4 | 10 |
| 2022 March | 6 | 5 | 11 |
| 2022 February | 14 | 3 | 17 |
| 2022 January | 27 | 5 | 32 |
| 2021 December | 15 | 9 | 24 |
| 2021 November | 5 | 9 | 14 |
| 2021 October | 9 | 9 | 18 |
| 2021 September | 5 | 6 | 11 |
| 2021 August | 8 | 4 | 12 |
| 2021 July | 4 | 4 | 8 |
| 2021 June | 6 | 7 | 13 |
| 2021 May | 7 | 6 | 13 |
| 2021 April | 13 | 9 | 22 |
| 2021 March | 10 | 7 | 17 |
| 2021 February | 5 | 7 | 12 |
| 2021 January | 7 | 6 | 13 |
| 2020 December | 4 | 1 | 5 |
| 2020 November | 5 | 5 | 10 |
| 2020 October | 4 | 2 | 6 |
| 2020 September | 4 | 6 | 10 |
| 2020 August | 5 | 7 | 12 |
| 2020 July | 10 | 5 | 15 |
| 2020 June | 6 | 2 | 8 |
| 2020 May | 2 | 4 | 6 |
| 2020 April | 1 | 2 | 3 |
| 2020 March | 3 | 2 | 5 |
| 2020 February | 2 | 5 | 7 |
| 2020 January | 3 | 4 | 7 |
| 2019 December | 7 | 3 | 10 |
| 2019 October | 0 | 1 | 1 |
| 2019 September | 2 | 4 | 6 |
| 2019 August | 1 | 0 | 1 |
| 2019 July | 2 | 4 | 6 |
| 2019 June | 3 | 4 | 7 |
| 2019 May | 1 | 14 | 15 |
| 2018 October | 1 | 0 | 1 |
| 2018 September | 1 | 0 | 1 |
| 2018 August | 1 | 0 | 1 |
| 2018 June | 5 | 1 | 6 |
| 2018 May | 28 | 7 | 35 |
| 2018 April | 27 | 6 | 33 |
| 2018 March | 15 | 11 | 26 |
| 2018 February | 10 | 7 | 17 |
| 2018 January | 20 | 8 | 28 |
| 2017 December | 11 | 5 | 16 |
| 2017 November | 9 | 9 | 18 |
| 2017 October | 14 | 11 | 25 |
| 2017 September | 14 | 7 | 21 |
| 2017 August | 9 | 9 | 18 |
| 2017 July | 19 | 7 | 26 |
| 2017 June | 16 | 10 | 26 |
| 2017 May | 25 | 13 | 38 |
| 2017 April | 39 | 12 | 51 |
| 2017 March | 16 | 8 | 24 |
| 2017 February | 19 | 6 | 25 |
| 2017 January | 22 | 8 | 30 |
| 2016 December | 34 | 12 | 46 |
| 2016 November | 14 | 9 | 23 |
| 2016 October | 33 | 8 | 41 |
| 2016 September | 23 | 9 | 32 |
| 2016 August | 22 | 6 | 28 |
| 2016 July | 11 | 8 | 19 |
| 2016 June | 1 | 0 | 1 |
| 2016 May | 2 | 0 | 2 |
| 2016 April | 0 | 31 | 31 |
| 2016 March | 2 | 0 | 2 |
| 2016 February | 3 | 24 | 27 |
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