Is it time to incorporate Kidney Disease Improving Global Outcomes (KDIGO) bundles into Enhanced Recovery After Surgery (ERAS) protocols for colorectal surgery?

Ripollés-Melchor, J.; Zorrilla-Vaca, A.; Lorente, J.V.; Weiss, R.
doi:10.1016/j.redare.2021.10.008
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Enhanced Recovery &#40;ERAS&#41; programmes emerged as a comprehensive approach to surgical patient care&#44; seeking to standardise multimodal interventions and implement evidence-based multidisciplinary perioperative care elements&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> The original idea of ERAS programmes was based on the benefits produced by the synergistic combination of multiple measures and interventions&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Each intervention individually contributes to an overall benefit&#44; although considered isolated interventions&#44; only a few appear to have a significant benefit&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Because ERAS protocols encompass a range of interventions&#44; the key question is which interventions should be included&#46; These decisions are a major challenge in the era of individualised perioperative medicine&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> especially since they depend on different criteria in a heterogeneous group of patients&#46; Above all&#44; the benefit of an ERAS protocol must respond to a specific issue in the particular patient group&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">ERAS programmes have led to significant improvements in postoperative outcomes in several surgical specialties&#44; although there are still many elements with little evidence &#40;e&#46;g&#46; biomarkers&#44; machine learning&#44; alternative analgesic therapies&#41;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> and some targets remain unaddressed&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Acute kidney injury &#40;AKI&#41; is a controversial target&#44; which has been addressed through different interventions&#44; including goal-directed fluid therapy &#40;GDFT&#41; protocols&#44; however&#44; recent studies highlight a worrying increase in AKI rates following the implementation of enhanced recovery programmes&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">ERAS programmes seek an answer to this question&#58; 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&#63; For patients undergoing colorectal surgery&#44; the general answer is yes&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> although it may be difficult to provide a correct answer&#46; First&#44; many of the interventions included in one-&#43; citation are too general to comprehensively address specific postoperative problems&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Recently&#44; Hollis and Kennedy pointed out that ERAS programmes may increase certain postoperative complications&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> including postoperative AKI&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The incidence of AKI varies greatly depending on the definition used&#46; With the introduction of the unified classification system Kidney Disease&#58; Improving Global Outcomes &#40;KDIGO&#41;&#44; observational studies have shown that even small increases in creatinine or decreases in urine output can significantly impact morbidity and length of stay&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> while the Risk&#44; Injury&#44; Failure&#44; Loss&#44; and End-Stage Renal Disease &#40;RIFLE&#41; classification<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> tends to underestimate the incidence of AKI&#46; Several studies have yielded controversial results regarding the relationship between ERAS and AKI&#46; For example&#44; Horres et al&#46; found no association between AKI and ERAS programmes using the RIFLE classification&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> but subsequent studies have indicated a significant association&#44; especially when using the KDIGO classification&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> Pooling these studies&#44; a recent meta-analysis by Zorrilla-Vaca et al&#46; demonstrated that ERAS programmes tend to have significantly higher rates of postoperative AKI&#44; raising concerns about a potential increase in long-term mortality&#46; This begs the question&#44; why would an intervention aimed at improving outcomes &#40;ERAS&#41; worsen kidney function&#63;</p><p id="par0020" class="elsevierStylePara elsevierViewall">There is no short or easy answer to this question&#46; Firstly&#44; the dogmatisation of ERAS protocols has resulted in the systematic application of various interventions without a clear risk-based stratification approach&#44; some of them overrated&#44; and some tested outside research settings&#44; because ERAS programmes do not necessarily improve outcomes in &#8220;real-world&#8221; settings due to a lack of sufficient compliance with protocols&#46;<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&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;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&#46;<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&#46; So-called &#8220;zero balance&#8221; is recommended for patients at low risk of postoperative complications&#44; while fluid volume &#40;SV&#41; optimisation is recommended for high-risk patients and&#47;or procedures&#46;<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&#46; Brandstrup et al&#46; demonstrated in a low-powered study that zero balance therapy was comparable to GDFT in terms of haemodynamic parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In contrast&#44; a recent study demonstrated that AKI was significantly higher in the zero-balance fluid therapy group compared to the GDFT group &#40;21&#46;4&#37; vs&#46; 13&#46;8&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;040&#41; after colorectal cancer surgery in an ERAS setting&#46;<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&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> therefore some authors recommend an overall positive balance of 1&#8211;2 litres&#46;<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&#46; Probably the message to the clinician should be towards encouraging GDFT&#44; as a restrictive fluid therapy regimen&#44; which should not imply a negative fluid balance&#44; is not the solution for our patients&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It should be made clear that recommendations on perioperative fluid administration should not be taken as &#8220;one size fits all&#8221;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;24</span></a> and misinterpretation of these recommendations may lead to errors in daily practice&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although GDFT has been shown to decrease complications in high-risk patients&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> there are controversial results within the ERAS pathway for many reasons &#40;e&#46;g&#46;&#44; preoperative euvolaemia&#44; reduced inflammatory response&#41;&#46; However&#44; they all have in common that patients with hypotension and&#47;or low cardiac output have an increased risk of postoperative AKI&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> There is strong evidence that patients with adequate blood pressure and cardiac output have a lower incidence of AKI&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> Studies with no difference between control and intervention groups also showed no difference in the incidence of postoperative AKI&#46; Low compliance with ERAS protocols is thought to be directly related to lower adherence to haemodynamic algorithms&#44; leading to greater variability in intraoperative fluid administration and increased risk of adverse renal outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Considering the pathophysiology that leads to postoperative AKI&#44; it seems logical to apply patient-tailored haemodynamic protocols&#46;<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&#46; The authors concluded that the incidence of postoperative AKI is significantly reduced &#40;relative risk &#46;70&#59; 95&#37; CI&#58; &#46;53&#59; to &#46;92&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; when an individualised treatment strategy is used &#40;i&#46;e&#46;&#44; maintaining a perioperative systolic blood pressure within 10&#37; of baseline&#44; together with optimisation of flow and stroke volume&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In addition&#44; decreasing the duration of perioperative hypotension also reduces the incidence of postoperative AKI&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Hatib et al&#46; developed an algorithm that uses machine learning to predict duration of hypotension&#44; known as the Hypotension Prediction Index &#40;HPI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The HYPE study recently demonstrated that the use of the HPI&#44; together with a haemodynamic optimisation algorithm&#44; reduces the severity and duration of intraoperative hypotension&#46;<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&#44; although more evidence is needed to clarify its clinical impact&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As most ERAS protocols do not include specific recommendations for high-risk patients&#44; 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&#46; In the context of ERAS&#44; there are two possible options&#58; &#40;1&#41; to consider all patients to be at high risk of AKI&#44; and to generalise the implementation of bundles to reduce AKI&#44; or &#40;2&#41; to apply appropriate bundles individually to patients at high risk of AKI&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The BigPAK study aimed to test the benefit of the KDIGO bundle of measures &#40;i&#46;e&#46;&#44; discontinuation of all neurotoxic agents when possible&#44; optimisation of haemodynamics and volaemia&#44; consideration of functional haemodynamic monitoring&#44; close monitoring of serum creatinine and diuresis&#44; avoidance of hyperglycaemia&#44; and consideration of hyperglycaemia&#44; avoidance of hyperglycaemia and close monitoring of serum creatinine and diuresis&#41;&#44; avoidance of hyperglycaemia and consideration of alternatives to radiocontrast agents&#41;<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 &#40;&#91;TIMP-2&#93;&#215;&#91;IGFBP-7&#93;&#41; in the early postoperative period&#46; In the renally stressed group of patients&#44; the incidence of AKI was significantly reduced &#91;27&#46;1&#37; intervention vs&#46; 48&#37; control&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;03&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> From these results&#44; one can go a step further and ask why we should wait until the postoperative period&#44; if patients at high risk of AKI could be easily identified before surgery and KDIGO guidelines could be applied from the outset&#46; It makes sense to apply KDIGO measures to all patients at risk of AKI&#44; rather than waiting for renal damage or renal injury to appear&#44; both of which are associated with worse outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In terms of ERAS pathways&#44; stress biomarkers could be used in several ways&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> either to identify patients at high risk of AKI early&#44; or to guide fluid&#47;drug therapies immediately after surgery&#46; The evidence favours KDIGO bundles as a safety feature in cases of high biomarker levels&#46; 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 &#40;i&#46;e&#46;&#44; non-steroidal drugs&#44; zero-balance fluid therapy&#41; to facilitate early discharge&#46;<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&#59; however&#44; based on the evidence summarised above and the alarming rates of AKI reported in ERAS programmes&#44; we would encourage the implementation of KDIGO bundles in conjunction with GDFT in patients at high risk of AKI in ERAS settings&#46;</p></span>"
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