Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine

An international team of 12 experts in the field of shock was invited by the European Society of Intensive Care Medicine to form a Task Force to evaluate new evidence and to revise the guidelines as judged appropriate. Four types of statements were used for the consensus—statements of facts, recommendations, best practice and definitions (for example, definition of shock).

Statements of facts are used to summarize an important topic discussed in the consensus when facts, rather than actions, are discussed and agreed.

Indications to act or not to act on a specific issue are written in the form of a “recommendation” or “best practice statement”. Although the formal GRADE (Grading of Recommendations Assessment, Development and Evaluation) system of evidence review with the generation of evidence profiles was not conducted, in making their recommendations the Task Force members took into account the principles of the GRADE system. This system classifies recommendations as strong (Level 1) or weak (Level 2) [2] based on the certainty of Task Force members that following given recommendation will result in more good than harm. Panelists were also aware that strength of the GRADE system recommendation depends on the quality of underlying evidence (certainty in the estimates of effects), balance of benefits and harms, costs and values and preferences of the interested parties. When the panel judged that a specific recommendation should be issued, but there was either no reasonable alternative or sufficient indirect reasoning not to commit time and resources to formal evidence review, best practice statements were issued.

A modified Delphi approach was used to achieve consensus. For each of the five questions included in the 2006 guidelines [1], five pairs of experts of the consensus group were assigned the task of reviewing the new clinical trial data and presenting their findings at a consensus conference. During the conference, held in Brussels in March 2014, the evidence and recommendations were reviewed and discussed by the entire group and consensus reached.

A medical writer (Sophie Rushton-Smith) was present at the conference in Brussels and recorded the minutes of the discussion. These were used to complete the contributions of the authors and to draft the first version of the manuscript.

A conference call was held in August 2014. To complete the process by taking into account the latest papers published (up to 1 October 2014), members of the Task Force communicated with each other via emails and telephone conversations. The findings are presented in this report. While the same five questions of 2006 were used as the basis to search and discuss available literature, the present report has been written without retaining the order of the answers to the five questions of the 2006 consensus. This decision was based on the obvious overlap between answers to the different questions and to provide a more readable manuscript. The main differences between the 2007 report of Antonelli et al. [1] and this consensus are summarized in Tables 1 and 2. The statements issued in 2014 by the Task Force are summarized in Tables 3, 4, 5 and 6.

The three main reasons for monitoring cardiac function in circulatory shock are for:

Optimal fluid management is one of the cornerstones of hemodynamic management in shock. Both hypovolemia and hypervolemia are harmful states, and attempts have to be made to administer the fluids in the best possible way. Therefore, the first questions physicians should ask themselves are: (1) whether the clinical problem at hand can be (partially) resolved by increasing cardiac output and (2) whether fluid resuscitation will be effective to achieve this target.

Preload, along with afterload and cardiac contractility, is an important determinant of cardiac output. Preload has been defined as myocardial stretch imposed by ventricular filling at the end of the diastole. While fluid resuscitation should not be delayed, efforts should be made to assess if a patient will respond to fluids. Ideally, in cases of shock, a clinician should be able to use a measure of preload to determine whether a patient requires additional fluids to increase cardiac output. CVP and pulmonary artery occlusion pressure (PAOP) are the most commonly used estimates of right ventricular (RV) and LV preloads, respectively. Volumetric parameters, assessed by transpulmonary thermodilution, and end-diastolic ventricular volumes, determined by echocardiography, are also used to evaluate preload [72]. However, each of these pressure and volume measurements has their limitations. Dynamic measures of assessing whether a patient requires additional fluid to increase stroke volume (i.e. assessing fluid responsiveness) have been proposed in an effort to improve fluid management. The principle behind dynamic measures is that changes in intrathoracic pressure imposed by mechanical ventilation impact on venous return and subsequent cardiac output. During a positive pressure breath, RV filling has been shown to decrease by 20–70 %, leading to a decrease in stroke volume that can be amplified by an increasing degree of hypovolemia [85, 86]. This finding indicates that dynamic measures allow the discrimination of preload-dependent and preload-independent hemodynamic situations (i.e. these measures identify the position of a patient’s individual Frank–Starling curve). Different dynamic measures are currently available and can be routinely assessed at the bedside using standard and minimally invasive hemodynamic monitoring systems. These include the assessment of pulse pressure variation (PPV) and stroke volume variation (SVV) via the arterial line or non-invasively by plethysmography, as well as of aortic flow variation and vena cava collapsibility or distensibility determined by Doppler and other modalities of echocardiography [87‐89]. The need for additional fluid may also be evaluated by observing the response to a volume challenge. Following the rapid administration of a bolus of intravenous fluid (i.e. 500 mL in <30 min) or a passive leg-raising test (which is akin to a fluid load, as venous return increases), cardiac output immediately increases in patients who are fluid-responsive [3, 77, 90].

Despite the fact that current guidelines as well as important clinical trials have used measures of preload to guide fluid resuscitation, clinicians should be cautious when using such measures. Importantly, any measure of preload, particularly if it is a one-time measurement, should not be taken out of context with respect to the measures of other variables and the patient’s overall clinical condition. For example, a normal individual with a normal vascular volume has a very low CVP and does not require additional fluid; alternatively, some patients with high measures of preload pressure may benefit from additional fluids. Thus, changes in these parameters following interventions may be much more useful than a single measurement. Unfortunately, poor correlations between estimates of preload (whether pressures or volumes) and predictions of fluid responsiveness have been widely reported. For example, in normal healthy volunteers, both CVP and PAOP are poor predictors of preload, cardiac performance and changes in cardiac performance following fluid loading compared with measurements of end-diastolic ventricular volumes. End-diastolic ventricular volumes have also been found to provide superior estimates of preload compared with CVP and PAOP in diverse groups of critically ill patients [91]. Nonetheless, there may be clinical settings, such as severe congestive heart failure or hypovolemia, where titration of fluid therapy based on CVP and PAOP may be helpful [92]. Notably, measurements of ventricular volumes are not always easy to obtain (especially on the right side of the heart), are associated with costs and time delays and are operator-dependent. A number of studies have shown that dynamic measures of fluid responsiveness are better predictors of fluid responsiveness than static parameters in mechanically ventilated patients. PPV and SVV, for example, have proven to be good predictors of fluid responsiveness in sedated mechanically ventilated patients without spontaneous breathing activities and in sinus rhythm. Dynamic measures do have several limitations, however. Importantly, patients must be on fully controlled mechanical ventilation without spontaneous efforts, which is seldom the case in ICU patients. In addition, these parameters are affected by the magnitude of the employed tidal volume. Finally, most of the evaluations involving dynamic measures have included relatively stable patients, such as post-cardiac surgery patients, and the extent to which these measures are useful in other potentially unstable populations is uncertain. Few studies evaluating measures of fluid responsiveness have specifically focused on the spontaneously breathing patient. Not surprisingly, the measurement of PPV had no predictive value in the subgroup of patients with spontaneous breathing activity [93]. However, reductions in right atrial pressures by at least 1 mmHg during a spontaneous inspiration have been shown to be a reasonable predictor of fluid responsiveness [94‐96]. Passive leg-raising (e.g. 45° elevation for 4 min while maintaining the trunk supine) results in an increase in RV and LV preload. Such a test may help in predicting individual fluid responsiveness during spontaneous and positive pressure breaths while avoiding the hazards of unnecessary fluid loading [97, 98].

Several techniques are available to evaluate the microcirculation in critically ill patients. These show some relation between altered microcirculation and poor outcome. In experimental conditions, shock states have been associated with a decrease in perfused capillary density and an increase in the heterogeneity of microcirculatory perfusion, with non-perfused capillaries in close vicinity to perfused capillaries [140].

The use of metabolic parameters for the assessment of regional microcirculatory perfusion is promising. Tissue CO₂ represents the balance between local production and removal; thus, a rising value likely reflects a decrease in local blood flow rather than an increased local production of CO₂. When associated with arterial CO₂, tissue CO₂ allows determination of the gradient or the PCO₂ gap, which is inversely related to the proportion of perfused capillaries [141]. An occlusion test with near-infrared spectroscopy may help to evaluate indirectly the dynamic response of the microcirculation to an occlusion, even if the link between vasoreactivity, microcirculation and tissue oxygenation is still not clearly established. The evaluation of StO₂ [tissue (muscle) oxygen saturation] changes in response to a vascular occlusion test provides two additional parameters: the StO₂-deoxygenation rate (DeOx), which has been related to the local metabolic rate and local blood flow distribution, and the StO₂-reoxygenation rate (ReOx). In a population of septic shock patients with restored MAP, decrements in DeOx and ReOx were found to be associated with a longer ICU stay, and impaired DeOx was associated with no improvement in organ failures after 24 h [142]. The ReOx rate seen on reperfusion is an measure of both the limb’s oxygen content and the capacity to recruit arterioles and venules (‘microvascular reserve’) [143].

Microvideoscopic techniques, such as orthogonal polarization spectral and sidestream dark field imaging, can directly evaluate microvascular networks covered by a thin epithelium, such as the sublingual microcirculation. They take into account the heterogeneity of microvascular perfusion. The following parameters have been suggested [144]: (1) a measure of vessel density (total or perfused vessel density); (2) two indices of vascular perfusion (proportion of perfused vessels and microcirculatory flow index); (3) a flow heterogeneity index. These indices evaluate how many vessels are perfused, the quality of the flow and whether non-perfused areas are located next to well-perfused areas. Using these techniques, microvascular alterations, similar to those reported in experimental conditions, have been observed in patients with septic [145], cardiogenic [146], and hemorrhagic [147] shock.

One goal of the management of patients with shock within the first hours after admission is to ensure adequate tissue perfusion and cellular metabolism. In a prospective observational study, early improvement in microvascular perfusion in response to goal-directed therapy was associated with an improvement in organ function [148]. These data strongly suggest that microcirculatory alterations are implicated in the development of organ failure. In a randomized, double-blind, crossover study by Hernandez et al. [149] in patients with pressor-dependent septic shock and hyperlactatemia, increasing oxygen delivery for 90 min by infusion of dobutamine did not alter lactate clearance, regional flow (measured by gastric tonometry PCO₂) or microcirculatory flow (measured by sublingual imaging

The use of microcirculatory markers of tissue perfusion will require further large-scale studies to assess their potential benefit in microcirculation-oriented or microcirculation-guided management and/or therapy of early shock resuscitation. In summary, these techniques need further exploration and are not presently recommended as targets for resuscitation.