Protocolised personalised peri-operative haemodynamic management

Advanced haemodynamic monitoring should be used to carefully guide therapy with fluids, inotropes and vasopressors in the peri-operative period of high-risk surgery. Titrating fluids and vasoactive agents to achieve predefined target values of haemodynamic variables is referred to as ‘goal-directed therapy’. With this strategy, the haemodynamic targets and therapeutic interventions are usually summarised in a protocol, which usually includes a schematic treatment algorithm. However, this approach contrasts with the growing recognition that haemodynamic management should be tailored to the cardiovascular physiology and the clinical situation of each individual patient – that is what is called personalised haemodynamic management.1 In this Editorial, we discuss the two concepts of protocolised and personalised haemodynamic management and advocate a combined approach, namely Protocolised Personalised Peri-operative Haemodynamic Management (PPPHM). Protocolised peri-operative haemodynamic management Already in 1974, Shoemaker2 stated that ‘protocols, routines and other standards do not insure excellence, but sometimes they prevent disasters. [...] In essence, the development of protocols is the first step in leading from anecdotal to scientific medicine’. In the years since, numerous protocols for peri-operative goal-directed haemodynamic therapy have been suggested. The term ‘goal-directed therapy’, however, is vague and there is considerable variation among the protocols with regard to the variables and values used as treatment goals, the timing and types of therapeutic interventions, and the techniques used for haemodynamic monitoring.3 In general, protocolised haemodynamic management is most effective in patients with a predetermined clinical course,4 and thus is particularly relevant for elective surgery. In high-risk patients having major surgery, peri-operative goal-directed therapy can help to maintain or restore adequate oxygen delivery to the organs. Overall, there is substantial evidence that peri-operative goal-directed therapy can reduce postoperative morbidity and mortality in high-risk patients,5,6 particularly if goal-directed therapy is started in the intra-operative rather than the postoperative period, if a cardiac output (CO) monitor is used, and if the use of vasoactive agents is required per protocol (as opposed to protocolised fluid therapy only).6 Some of the studies on peri-operative goal-directed therapy used rigid treatment algorithms with fixed, predefined target values of haemodynamic variables.7,8 Most currently used algorithms include blood flow optimisation using oesophageal Doppler or pulse wave analysis to estimate stroke volume (SV) and CO, or dynamic cardiac preload variables – such as pulse pressure variation or SV variation – to guide fluid therapy. In the – so far – largest multicentre randomised controlled trial, the pragmatic OPTIMISE trial,5 protocolised haemodynamic treatment using colloid boluses and a fixed dose of the inotrope dopexamine to achieve a maximal value of SV did not result in a statistically significant reduction in the combined primary endpoint of postoperative complications and mortality (although the primary endpoint occurred less frequently in the intervention group). Protocolised haemodynamic management has the advantages of standardising treatment, minimising variability in care within and among institutions, and providing an educational framework. It may, therefore, increase the quality of care by reducing medical errors, especially in settings with poor resources or less experienced doctors. In addition, simple algorithms may facilitate high adherence rates to goal-directed therapy in clinical studies and encourage implementation of such treatment strategies in routine practice. However, despite numerous studies on peri-operative goal-directed therapy in a variety of clinical settings, the optimal peri-operative goal-directed therapy algorithm that will be effective in every patient remains elusive, considering the large variability of patient-related factors.1 From a physiological point of view, it is simplistic to apply the same rigid ‘one size fits all’ treatment protocol to different patients having major surgery. For example, the optimal CO or central venous oxygen saturation (ScvO2) during major surgery may not be the same for a 70-year-old patient with arterial hypertension and coronary artery disease, a 25-year-old patient suffering from ulcerative colitis with no history of cardiovascular disease, and a 50-year-old patient with advanced chronic liver disease. Personalised peri-operative haemodynamic management There is an increasing belief that peri-operative medicine should be based on principles of ‘precision medicine’ or ‘personalised medicine’ considering underlying pathophysiologic mechanisms and specific phenotypes of patients. Personalised haemodynamic management is based on the recognition and specific treatment of individual disease patterns considering the individual patient's personal haemodynamic profile adapted to the clinical situation (instead of applying the same treatment protocol to a group of patients).1 The underlying rationale behind personalised peri-operative haemodynamic management is that haemodynamic variables have large inter-individual variability and are dependent on a variety of biometric, demographic and clinical factors, so that treatment goals should be adapted to the individual patient's cardiovascular dynamics rather than using fixed population-derived normal values for everyone.1 However, personalised peri-operative haemodynamic management still needs to be standardised and kept within certain limits to avoid ‘chaotic care’, that is, excessive variability in care between physicians with different levels of knowledge and experience. Clear definitions of personalised target variables are also needed, for the conduct of clinical trials. Protocolised personalised peri-operative haemodynamic mamagement We should therefore combine protocolised and personalised peri-operative haemodynamic management. By associating the concepts of protocolised and personalised peri-operative haemodynamic management, we could combine the advantages of the two strategies and counterbalance their limitations. We propose to call this approach, PPPHM. Different strategies can be used to achieve PPPHM (Fig. 1). First, functional haemodynamic monitoring could be coupled with protocolised care to titrate therapeutic interventions to patient-specific physiological goals.9 Treatment targets could be adapted to the cardiovascular physiology of the individual patient, the current physiological state, and the clinical context, using functional haemodynamic monitoring instead of fixed targets of static haemodynamic variables.1,9 Functional haemodynamic monitoring is based on evaluating the dynamic response of haemodynamic variables to a therapeutic intervention or defined alteration and includes the prediction and assessment of fluid responsiveness.9 Dynamic cardiac preload variables can help to estimate a patient's position on the cardiac function curve based on heart–lung interactions at any point during surgery and thus be used to assess the probability that a patient will be fluid responsive. It is important, however, to remember that fluid responsiveness does not equal need for fluids and that using fluids to maximise rather than optimise SV may induce further complications. To minimise the risks of excessive fluid administration a ‘mini-fluid challenge’ approach can be used.10 Coupling functional predictors or tests of preload responsiveness with treatment algorithms can help to personalise protocolised goal-directed therapy. Treatment algorithms combining dynamic cardiac preload variables and CO during protocolised peri-operative goal-directed therapy have been proposed in patients having major abdominal surgery.11–13Fig. 1: Schematic illustration of advantages (+) and drawbacks (−) of protocolised and personalised haemodyamic management strategies and how these could be combined.Second, treatment algorithms can be individualised by including adaptive target values of haemodynamic variables instead of fixed target values. For example, different CO targets could be given depending on different ages, comorbidities, haemoglobin concentrations, ScvO2 values and/or microcirculation data, instead of targeting the same CO goal in every patient. Third, coupling treatment protocols with haemodynamic targets based on personal values adapted to the clinical situation instead of using population-derived normal values might enable goal-directed therapy to be personalised.1 Targeting personal normal values seems to be promising in peri-operative medicine where pre-operative baseline values can easily be assessed before elective surgery. For example, individualising blood pressure (BP) management based on pre-operative resting BP values,14 or achieving pre-operative values of oxygen delivery in the postoperative period15 has been associated with less morbidity in high-risk patients. Further research, however, is needed to better understand the relation between baseline pre-operative cardiovascular physiology and peri-operative haemodynamic alterations and metabolic demands. In conclusion, in peri-operative medicine, protocolising haemodynamic management can help to standardise treatment and minimise variability in care. However, rigid protocolised haemodynamic management using treatment algorithms with fixed target values ignores the cardiovascular pathophysiology of the individual patient. In contrast, personalised haemodynamic management is based on the recognition and specific treatment of individual disease patterns, considering the individual patient's cardiovascular dynamics. Nevertheless, to prevent ‘chaotic care’, personalised haemodynamic management needs to be standardised within certain limits to avoid excessive variability in care. By associating the concepts of protocolised and personalised haemodynamic management, we could combine the advantages and counterbalance the limitations of the two strategies. Several strategies could be used to achieve this, including coupling treatment algorithms with functional haemodynamic monitoring and integrating adaptive and personalised target values of haemodynamic variables into goal-directed therapy protocols. Importantly, the knowledge and experience of the clinician remain indispensible for the success of any treatment algorithm, which should augment, but not supplant, a careful clinical evaluation. Acknowledgements relating to this article Assistance with the Editorial: none. Financial support and sponsorship: none. Conflicts of interest: BS collaborates with Pulsion Medical Systems SE (Feldkirchen, Germany) as a member of the medical advisory board, and has received institutional restricted research grants, honoraria for giving lectures and refunds of travel expenses from Pulsion Medical Systems SE, research support and honoraria for giving lectures from Edwards Lifesciences (Irvine, CA, USA), honoraria for giving lectures and refunds of travel expenses from CNSystems Medizintechnik AG (Graz, Austria), institutional restricted research grants, honoraria for consulting, and refunds of travel expenses from Tensys Medical Inc. (San Diego, CA, USA), and has received institutional restricted research grants from Retia Medical LLC. (Valhalla, NY, USA). This article was checked and accepted by the Editors, but was not sent for external peer-review.