Maurizio Cecconi

A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients

BACKGROUND: Complications from major surgery are undesirable, common, and potentially avoidable. The long-term consequences of short-term surgical complications have recently been recognized to have a profound influence on longevity and quality of life in survivors. In the past 30 years, there have been a number of studies conducted attempting to reduce surgical mortality and morbidity by deliberately and preemptively manipulating perioperative hemodynamics. Early studies had a high control-group mortality rate and were criticized for this as being unrepresentative of current practice and raised opposition to its implementation as routine care. We performed this review to update this body of literature and to examine the effect of changes in current practice and quality of care to see whether the conclusions from previous quantitative analyses of this field remain valid. METHODS: Randomized clinical trials evaluating the use of preemptive hemodynamic intervention to improve surgical outcome were identified using multiple methods. Electronic databases (MEDLINE, EMBASE, and the Cochrane Controlled Clinical Trials register) were screened for potential trials, reference lists of identified trials were examined, and additional sources were sought from experts and industry representatives. Identified studies that fulfilled the entry criteria were examined in full and subjected to quantifiable analysis, subgroup analysis, and sensitivity analysis where possible. RESULTS: There were 29 studies identified, 23 of which reported surgical complications. In total, the 29 trials involved 4805 patients with an overall mortality of 7.6%. The use of preemptive hemodynamic intervention significantly reduced mortality (pooled odds ratio [95% confidence interval] of 0.48 [0.33–0.78]; P = 0.0002) and surgical complications (odds ratio 0.43 [0.34–0.53]; P < 0.0001). Subgroup analysis showed significant reductions in mortality for studies using a pulmonary artery catheter, supranormal resuscitation targets, studies using cardiac index or oxygen delivery as goals, and the use of fluids and inotropes as opposed to fluids alone. By contrast, there was a significant reduction in morbidity for each of the 4 subgroups analyzed. CONCLUSION: The use of a preemptive strategy of hemodynamic monitoring and coupled therapy reduces surgical mortality and morbidity.

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

ObjectiveCirculatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock.MethodsThe European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575–590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? Four types of statements were used: definition, recommendation, best practice and statement of fact.ResultsForty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring.ConclusionsThis consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock.

Bench-to-bedside review: The importance of the precision of the reference technique in method comparison studies – with specific reference to the measurement of cardiac output

Bland-Altman analysis is used for assessing agreement between two measurements of the same clinical variable. In the field of cardiac output monitoring, its results, in terms of bias and limits of agreement, are often difficult to interpret, leading clinicians to use a cutoff of 30% in the percentage error in order to decide whether a new technique may be considered a good alternative. This percentage error of ± 30% arises from the assumption that the commonly used reference technique, intermittent thermodilution, has a precision of ± 20% or less. The combination of two precisions of ± 20% equates to a total error of ± 28.3%, which is commonly rounded up to ± 30%. Thus, finding a percentage error of less than ± 30% should equate to the new tested technique having an error similar to the reference, which therefore should be acceptable. In a worked example in this paper, we discuss the limitations of this approach, in particular in regard to the situation in which the reference technique may be either more or less precise than would normally be expected. This can lead to inappropriate conclusions being drawn from data acquired in validation studies of new monitoring technologies. We conclude that it is not acceptable to present comparison studies quoting percentage error as an acceptability criteria without reporting the precision of the reference technique.

Clinical review: Goal-directed therapy-what is the evidence in surgical patients? The effect on different risk groups

Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery. By augmenting oxygen delivery index (DO2I) with a combination of intravenous fluids and inotropes (goal directed therapy (GDT)), postoperative mortality and morbidity of high-risk patients may be reduced. However, although most studies suggest that GDT may improve outcome in high-risk surgical patients, it is still not widely practiced. We set out to test the hypothesis that GDT results in greatest benefit in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct. We performed a systematic search of Medline, Embase and CENTRAL databases for randomized controlled trials (RCTs) and reviews of GDT in surgical patients. To minimize heterogeneity we excluded studies involving cardiac, trauma, and paediatric surgery. Extremely high risk, high risk and intermediate risks of mortality were defined as >20%, 5 to 20% and <5% mortality rates in the control arms of the trials, respectively. Meta analyses were performed and Forest plots drawn using RevMan software. Data are presented as odd ratios (OR; 95% confidence intervals (CI), and P-values). A total of 32 RCTs including 2,808 patients were reviewed. All studies reported mortality. Five studies (including 300 patients) were excluded from assessment of complication rates as the number of patients with complications was not reported. The mortality benefit of GDT was confined to the extremely high-risk group (OR = 0.20, 95% CI 0.09 to 0.41; P < 0.0001). Complication rates were reduced in all subgroups (OR = 0.45, 95% CI 0.34 to 0.60; P < 0.00001). The morbidity benefit was greatest amongst patients in the extremely high-risk subgroup (OR = 0.27, 95% CI 0.15 to 0.51; P < 0.0001), followed by the intermediate risk subgroup (OR = 0.43, 95% CI 0.27 to 0.67; P = 0.0002), and the high-risk subgroup (OR 0.56, 95% CI 0.36 to 0.89; P = 0.01). Despite heterogeneity in trial quality and design, we found GDT to be beneficial in all high-risk patients undergoing major surgery. The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death. The reduction of complication rates was seen across all subgroups of GDT patients.

Cardiac output monitoring: an integrative perspective.

Cardiac output monitoring in the critically ill patient is standard practice in order to ensure tissue oxygenation [1] and has been traditionally accomplished using the pulmonary artery catheter (PAC). In recent years, however, the value of PAC has been questioned with some suggesting that its use might not only be unnecessary but also potentially harmful [1]. This notion, together with the availability of new less invasive cardiac output measuring devices, has markedly decreased the widespread use of the PAC [2]. Today, various devices are available to measure or estimate cardiac output using different methods. Some of these less invasive devices track stroke volume (SV) continuously and provide dynamic indices of fluid responsiveness, others allow assessment of volumetric preload variables, and some also provide continuous measurement of central venous saturation via the use of proprietary catheters that are attached to the same monitor. All these variables — together with cardiac output — may result in an improved hemodynamic assessment of the critically ill patient. However, it is important to appreciate that each device has its inherent limitations and that no cardiac output monitoring device can change patient outcome unless its use is coupled with an intervention that by itself has been associated with improved patient outcomes. Therefore, the concept of hemodynamic optimization is increasingly recognized as a cornerstone in the management of critically ill patients and has been shown to be associated with improved outcome in the perioperative [3] and in the intensive care unit (ICU) [4] setting.

What is a fluid challenge

Purpose of reviewThe fluid challenge is used in the fluid management of many sick patients. The principle behind the fluid challenge technique is that by giving a small amount of fluid in a short period of time, the clinician can assess whether the patient has a preload reserve that can be used to increase the stroke volume with further fluids. The key components of a fluid challenge are described. Recent findingsDynamic predictors of fluid responsiveness are increasingly used in preference to the central venous and pulmonary artery occlusion pressure. The gold standard to monitor the response to a fluid challenge is using a continuous cardiac output monitoring. Fluid therapy guided by flow monitoring has been shown to reduce hospital stay and postoperative complications. SummaryA fluid challenge identifies and simultaneously treats volume depletion, whilst avoiding deleterious consequences of fluid overload through its small volume and targeted administration.

Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional anaesthesia

IntroductionTotal hip replacement is one of the most commonly performed major orthopaedic operations. Goal-directed therapy (GDT) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia. GDT has never been formally assessed during regional anaesthesia.MethodsPatients undergoing total hip replacement while under regional anaesthesia were randomised to either the control group (CTRL) or the protocol group (GDT). Patients in the GDT group, in addition to standard monitoring, were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system, and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2.ResultsPatients randomised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period (means ± standard deviation (SD): 6,032 ± 1,388 mL vs. 2,635 ± 346 mL; P < 0.0001), and more of the GDT patients received dobutamine (0 of 20 CTRL patients vs. 11 of 20 GDT patients; P < 0.0003). The GDT patients also received more blood transfused during the intraoperative period (means ± SD: 595 ± 316 mL vs. 0 ± 0 mL; P < 0.0001), although the CTRL group received greater volumes of blood replacement postoperatively (CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL; P < 0.001). Overall blood consumption (intraoperatively and postoperatively) was not different between the two groups. There were an increased number of complications in the CTRL group (20 of 20 CTRL patients (100%) vs. 16 of 20 GDT patients (80%); P = 0.05). These outcomes were predominantly due to a difference in minor complications (20 of 20 CTRL patients (100%) vs. 15 of 20 GDT patients (75%); P = 0.047).ConclusionsGDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications. Larger trials are required to confirm our findings.Trial registrationSRCTN11616985

Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND Perioperative mortality after cardiac surgery has decreased in recent years although postoperative morbidity is still significant. Although there is evidence that perioperative goal-directed haemodynamic therapy (GDT) may reduce surgical mortality and morbidity in non-cardiac surgical patients, the data are less clear after cardiac surgery. The objective of this review is to perform a meta-analysis on the effects of perioperative GDT on mortality, morbidity, and length of hospital stay in cardiac surgical patients. METHODS We conducted a systematic review using Medline, EMBASE, and the Cochrane Controlled Clinical Trials Register. Additional sources were sought from experts. The inclusion criteria were randomized controlled trials, mortality reported as an outcome, pre-emptive haemodynamic intervention, and cardiac surgical population. Included studies were examined in full and subjected to quantifiable analysis, subgroup analysis, and sensitivity analysis where possible. Data synthesis was obtained by using odds ratio (OR) and mean difference (MD) for continuous data with 95% confidence interval (CI) utilizing a random-effects model. RESULTS From 4986 potential studies, 5 met all the inclusion criteria (699 patients). The quantitative analysis showed that the use of GDT reduced the postoperative complication rate (OR 0.33, 95% CI 0.15-0.73; P=0,006) and hospital length of stay (MD -2.44, 95% CI -4.03 to -0.84; P=0,003). There was no significant reduction in mortality. CONCLUSION The use of pre-emptive GDT in cardiac surgery reduces morbidity and hospital length of stay.

Tracking changes in cardiac output: methodological considerations for the validation of monitoring devices

BackgroundUntil now, tools for continuous cardiac output (CO) monitoring have been validated as if they were tools for snapshot measurements. Most authors have compared variations in cardiac output between two time-points and used Bland–Altman representations to describe the agreement between these variations. The impacts of time and of repetitive measurements over time are not taken into consideration.PurposeThis special article proposes a conceptual framework for the validation of CO monitoring devices. Four quality criteria are suggested and studied: (1) accuracy (small bias), (2) precision (small random error of measurements), (3) short response time and (4) accurate amplitude response. Because a tolerance is obviously admitted for each of these four criteria, we propose to add as a fifth criterion the ability to detect significant CO directional changes. Other important issues in designing studies to validate CO monitoring tools are reviewed: choice of patient population to be studied, choice of the reference method, data acquisition method, data acceptability checking, data segmentation and final evaluation of reliability.ConclusionApplication of this framework underlines the importance of precision and time response for clinical acceptability of monitoring tools.

Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial

IMPORTANCE Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION clinicaltrials.gov Identifier: ISRCTN 20769191.