Editorial article
Is it time to incorporate Kidney Disease Improving Global Outcomes (KDIGO) bundles into Enhanced Recovery After Surgery (ERAS) protocols for colorectal surgery?
¿Es el momento de incorporar el paquete de medidas Kidney Disease Improving Global Outcomes (KDIGO) a los Programas de Recuperación Intensificada para cirugía colorrectal?
J. Ripollés-Melchora,b,c,
, A. Zorrilla-Vacad,e, J.V. Lorentec,f, R. Weissf,g,h
Corresponding author
a Department of Anesthesia and Critical Care, Hospital Universitario Infanta Leonor, Madrid, Spain
b Spanish Perioperative Audit and Research Network (REDGERM)
c Fluid Therapy and Hemodynamic Group of the Hemostasis, Transfusion Medicine and Fluid Therapy Section, Spanish Society of Anesthesia and Critical Care (SEDAR)
d Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
e Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
f Department of Anesthesia and Critical Care, Juan Ramón Jiménez Hospital, Huelva, Spain
g Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
h Renal Protection Network, RAPNET
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These decisions are a major challenge in the era of individualised perioperative medicine,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> especially since they depend on different criteria in a heterogeneous group of patients. Above all, the benefit of an ERAS protocol must respond to a specific issue in the particular patient group.</p><p id="par0010" class="elsevierStylePara elsevierViewall">ERAS programmes have led to significant improvements in postoperative outcomes in several surgical specialties, although there are still many elements with little evidence (e.g. biomarkers, machine learning, alternative analgesic therapies)<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> and some targets remain unaddressed.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Acute kidney injury (AKI) is a controversial target, which has been addressed through different interventions, including goal-directed fluid therapy (GDFT) protocols, however, recent studies highlight a worrying increase in AKI rates following the implementation of enhanced recovery programmes.</p><p id="par0015" class="elsevierStylePara elsevierViewall">ERAS programmes seek an answer to this question: Will the implementation of a set of perioperative measures within these programmes reduce length of hospital stay and postoperative morbidity in patients undergoing surgery compared to a traditional approach? For patients undergoing colorectal surgery, the general answer is yes,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> although it may be difficult to provide a correct answer. First, many of the interventions included in one-+ citation are too general to comprehensively address specific postoperative problems.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Recently, Hollis and Kennedy pointed out that ERAS programmes may increase certain postoperative complications,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> including postoperative AKI.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The incidence of AKI varies greatly depending on the definition used. With the introduction of the unified classification system Kidney Disease: Improving Global Outcomes (KDIGO), observational studies have shown that even small increases in creatinine or decreases in urine output can significantly impact morbidity and length of stay,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> while the Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) classification<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> tends to underestimate the incidence of AKI. Several studies have yielded controversial results regarding the relationship between ERAS and AKI. For example, Horres et al. found no association between AKI and ERAS programmes using the RIFLE classification,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> but subsequent studies have indicated a significant association, especially when using the KDIGO classification.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a> Pooling these studies, a recent meta-analysis by Zorrilla-Vaca et al. demonstrated that ERAS programmes tend to have significantly higher rates of postoperative AKI, raising concerns about a potential increase in long-term mortality. This begs the question, why would an intervention aimed at improving outcomes (ERAS) worsen kidney function?</p><p id="par0020" class="elsevierStylePara elsevierViewall">There is no short or easy answer to this question. Firstly, the dogmatisation of ERAS protocols has resulted in the systematic application of various interventions without a clear risk-based stratification approach, some of them overrated, and some tested outside research settings, because ERAS programmes do not necessarily improve outcomes in “real-world” settings due to a lack of sufficient compliance with protocols.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Both hypo- and hypervolaemia are associated with higher rates of postoperative complications,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> and therefore ERAS recommendations may carry the risk of shifting a perioperative fluid strategy towards one of these two opposing extremes if not administered with caution.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The initial recommendations were constructed based on a matrix that considered surgical and patient risk factors. So-called “zero balance” is recommended for patients at low risk of postoperative complications, while fluid volume (SV) optimisation is recommended for high-risk patients and/or procedures.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Different fluid strategies have been compared in terms of postoperative renal outcomes. Brandstrup et al. demonstrated in a low-powered study that zero balance therapy was comparable to GDFT in terms of haemodynamic parameters.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In contrast, a recent study demonstrated that AKI was significantly higher in the zero-balance fluid therapy group compared to the GDFT group (21.4% vs. 13.8%, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.040) after colorectal cancer surgery in an ERAS setting.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The RELIEF study demonstrated that a restrictive approach increases the incidence of postoperative AKI compared to a liberal fluid strategy,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> therefore some authors recommend an overall positive balance of 1–2 litres.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> This recommendation may support the erroneous generalisation of liberal strategies instead of individualised fluid therapy. Probably the message to the clinician should be towards encouraging GDFT, as a restrictive fluid therapy regimen, which should not imply a negative fluid balance, is not the solution for our patients.</p><p id="par0035" class="elsevierStylePara elsevierViewall">It should be made clear that recommendations on perioperative fluid administration should not be taken as “one size fits all”<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,24</span></a> and misinterpretation of these recommendations may lead to errors in daily practice.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although GDFT has been shown to decrease complications in high-risk patients,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> there are controversial results within the ERAS pathway for many reasons (e.g., preoperative euvolaemia, reduced inflammatory response). However, they all have in common that patients with hypotension and/or low cardiac output have an increased risk of postoperative AKI.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> There is strong evidence that patients with adequate blood pressure and cardiac output have a lower incidence of AKI.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28,29</span></a> Studies with no difference between control and intervention groups also showed no difference in the incidence of postoperative AKI. Low compliance with ERAS protocols is thought to be directly related to lower adherence to haemodynamic algorithms, leading to greater variability in intraoperative fluid administration and increased risk of adverse renal outcomes.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Considering the pathophysiology that leads to postoperative AKI, it seems logical to apply patient-tailored haemodynamic protocols.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The INPRESS study underlines this aspect and successfully demonstrates that individualisation is a reasonable solution. The authors concluded that the incidence of postoperative AKI is significantly reduced (relative risk .70; 95% CI: .53; to .92; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.01) when an individualised treatment strategy is used (i.e., maintaining a perioperative systolic blood pressure within 10% of baseline, together with optimisation of flow and stroke volume).<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In addition, decreasing the duration of perioperative hypotension also reduces the incidence of postoperative AKI.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Hatib et al. developed an algorithm that uses machine learning to predict duration of hypotension, known as the Hypotension Prediction Index (HPI).<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The HYPE study recently demonstrated that the use of the HPI, together with a haemodynamic optimisation algorithm, reduces the severity and duration of intraoperative hypotension.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> This proactive approach appears to prevent periods of hypotension that may lead to hypoperfusion and AKI, although more evidence is needed to clarify its clinical impact.</p><p id="par0050" class="elsevierStylePara elsevierViewall">As most ERAS protocols do not include specific recommendations for high-risk patients, the importance of postoperative AKI is often underestimated<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> and it is still unclear what set of measures can help prevent this complication. In the context of ERAS, there are two possible options: (1) to consider all patients to be at high risk of AKI, and to generalise the implementation of bundles to reduce AKI, or (2) to apply appropriate bundles individually to patients at high risk of AKI.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The BigPAK study aimed to test the benefit of the KDIGO bundle of measures (i.e., discontinuation of all neurotoxic agents when possible, optimisation of haemodynamics and volaemia, consideration of functional haemodynamic monitoring, close monitoring of serum creatinine and diuresis, avoidance of hyperglycaemia, and consideration of hyperglycaemia, avoidance of hyperglycaemia and close monitoring of serum creatinine and diuresis), avoidance of hyperglycaemia and consideration of alternatives to radiocontrast agents)<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> in a subgroup of patients at high risk of AKI identified by elevated levels of two novel stress biomarkers ([TIMP-2]×[IGFBP-7]) in the early postoperative period. In the renally stressed group of patients, the incidence of AKI was significantly reduced [27.1% intervention vs. 48% control, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03].<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> From these results, one can go a step further and ask why we should wait until the postoperative period, if patients at high risk of AKI could be easily identified before surgery and KDIGO guidelines could be applied from the outset. It makes sense to apply KDIGO measures to all patients at risk of AKI, rather than waiting for renal damage or renal injury to appear, both of which are associated with worse outcomes.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In terms of ERAS pathways, stress biomarkers could be used in several ways,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> either to identify patients at high risk of AKI early, or to guide fluid/drug therapies immediately after surgery. The evidence favours KDIGO bundles as a safety feature in cases of high biomarker levels. Patients with low biomarker levels in the immediate postoperative period may be candidates in whom the complex perioperative measures of ERAS programmes could be safely implemented (i.e., non-steroidal drugs, zero-balance fluid therapy) to facilitate early discharge.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Intensified recovery programmes are considered best perioperative practice and should be implemented comprehensively to achieve better patient outcomes; however, based on the evidence summarised above and the alarming rates of AKI reported in ERAS programmes, we would encourage the implementation of KDIGO bundles in conjunction with GDFT in patients at high risk of AKI in ERAS settings.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Restoration of function: the holy grail of peri-operative care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. 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