Carlos Corredor

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 complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

Cerebral oximetry and return of spontaneous circulation after cardiac arrest: A systematic review and meta-analysis

AIM The prediction of return of spontaneous circulation (ROSC) during resuscitation of patients suffering of cardiac arrest (CA) is particularly challenging. Regional cerebral oxygen saturation (rSO2) monitoring through near-infrared spectrometry is feasible during CA and could provide guidance during resuscitation. METHODS We conducted a systematic review and meta-analysis on the value of rSO2 in predicting ROSC both after in-hospital (IH) or out-of-hospital (OH) CA. Our search included MEDLINE (PubMed) and EMBASE, from inception until April 4th, 2015. We included studies reporting values of rSO2 at the beginning of and/or during resuscitation, according to the achievement of ROSC. RESULTS A total of nine studies with 315 patients (119 achieving ROSC, 37.7%) were included in the meta-analysis. The majority of those patients had an OHCA (n=225, 71.5%; IHCA: n=90, 28.5%). There was a significant association between higher values of rSO2 and ROSC, both in the overall calculation (standardized mean difference, SMD -1.03; 95%CI -1.39,-0.67; p<0.001), and in the subgroups analyses (rSO2 at the beginning of resuscitation: SMD -0.79; 95%CI -1.29,-0.30; p=0.002; averaged rSO2 value during resuscitation: SMD -1.28; 95%CI -1.74,-0.83; p<0.001). CONCLUSIONS Higher initial and average regional cerebral oxygen saturation values are both associated with greater chances of achieving ROSC in patients suffering of CA. A note of caution should be made in interpreting these results due to the small number of patients and the heterogeneity in study design: larger studies are needed to clinically validate cut-offs for guiding cardiopulmonary resuscitation.

Long-Term Consequences of Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES To determine the effect of acute kidney injury (AKI) associated with cardiac surgery on long-term mortality. DESIGN Systematic review and meta-analysis of 9 observational studies extracted from the MEDLINE and EMBASE electronic databases. SETTING Hospitals undertaking cardiac surgery. PARTICIPANTS The study included 35,021 cardiac surgery patients from 9 observational studies. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Nine studies including 35,021 patients reported incidence of AKI data. The median incidence of AKI was 27.75% (IQR, 16.3%-38.86%). There was significant variation in the reported incidence (range, 11.97%-54%), which can be explained by the different AKI definitions used in the included studies. Eight studies provided adjusted effect size data with 95% confidence intervals on the impact of the occurrence of postoperative AKI and long-term mortality outcomes. Occurrence of postoperative AKI is associated with a significantly increased risk of long-term mortality (HR, 1.68; 95% CI, 1.45-1.95; p<0.00001). Recovery of renal function before hospital discharge is associated with a lower long-term mortality risk (HR, 1.31; 95% CI, 1.16-1.47; p<0.00001) compared with patients who experienced persistent abnormal renal function on hospital discharge (HR, 2.71; 95% CI, 1.26-5.82; p = 0.01). CONCLUSIONS There is wide variation in the reported incidence of AKI after cardiac surgery, reflecting the different AKI classification systems used. AKI after cardiac surgery is associated with an increased risk of long-term mortality. Patients with persistent renal dysfunction after hospital discharge carry a higher risk of AKI.

Simulation-based learning of transesophageal echocardiography in cardiothoracic surgical trainees: A prospective, randomized study.

OBJECTIVES The Intercollegiate Surgical Curriculum now recommends that cardiac surgical trainees should be able to understand and interpret transesophageal echocardiography images. However, cardiac surgical trainees receive limited formal transesophageal echocardiography training. The objective of this study was to assess the impact of simulation-based teaching versus more traditional operating room teaching on transesophageal echocardiography knowledge in cardiac surgical trainees. METHODS A total of 25 cardiac surgical trainees with no formal transesophageal echocardiography learning experience were randomly assigned by computer to a study group receiving simulation-based transesophageal echocardiography teaching via the Heartworks (Inventive Medical, London, UK) simulator (n = 12) or a control group receiving transesophageal echocardiography teaching during elective cardiac surgery (n = 13). Each subject undertook a video-based test composed of 20 multiple choice questions on standard transesophageal echocardiography views before and after teaching. RESULTS There was no significant difference in the pretest scores between the 2 groups (P = .89). After transesophageal echocardiography teaching, subjects within each group demonstrated a statistically significant improvement in transesophageal echocardiography knowledge. Although the subjects within the simulation group outperformed their counterparts in the operating room teaching group in the post-test scores, this difference was not significant (P = .14). CONCLUSIONS Despite the familiarity with transesophageal echocardiography images during surgery, subjects in the simulation group performed at least as well as those in the operating room group. Surgical trainees will benefit from formal transesophageal echocardiography teaching incorporated into their training via either learning method.

Hemodynamic optimization in severe trauma: a systematic review and meta-analysis.

Objective Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. Methods The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized, controlled trials of goal-directed therapy in severe trauma patients. Mortality was the primary outcome of this review. Secondary outcomes included complication rates, length of hospital and intensive care unit stay, and the volume of fluid and blood administered. Meta-analysis was performed using RevMan software, and the data presented are as odds ratios for dichotomous outcomes and as mean differences (MDs) and standard MDs for continuous outcomes. Results Four randomized, controlled trials including 419 patients were analyzed. Mortality risk was significantly reduced in goal-directed therapy-treated patients, compared to the control group (OR=0.56, 95%CI: 0.34-0.92). Intensive care (MD: 3.7 days 95%CI: 1.06-6.5) and hospital length of stay (MD: 3.5 days, 95%CI: 2.75-4.25) were significantly shorter in the protocol group patients. There were no differences in reported total fluid volume or blood transfusions administered. Heterogeneity in reporting among the studies prevented quantitative analysis of complications. Conclusion Following severe trauma, early goal-directed therapy was associated with lower mortality and shorter durations of intensive care unit and hospital stays. The findings of this analysis should be interpreted with caution due to the presence of significant heterogeneity and the small number of the randomized, controlled trials included.

Dynamic Assessment of the Heart: Echocardiography in the Intensive Care Unit

Echocardiography provides useful information for the diagnosis and management of haemodynamically unstable patients in the intensive care unit (ICU). Simultaneous visualisation of structure and function of the heart, coupled with the ability to monitor in real time the results of therapeutic intervention makes echocardiography an instrumental tool for the critical care physician. The last few years have seen giant leaps on the diagnostic quality of new portable devices and digital storage management systems, improving the reliability of bedside echo studies.

Influence of Thrombolysis and Mechanical Ventilation on Echocardiographic Predictors of Survival after Acute Pulmonary Embolism

To the Editor: Khemasuwan et al. retrospectively evaluated a cohort of 211 patients admitted to intensive care units (ICUs) with acute pulmonary embolism (PE). The investigators examined the correlation between echocardiographic parameters and clinical outcomes, in particular ICU, hospital, and long-termmortality. Several simple echocardiographic parameters were associated with ICU, hospital, and long-termmortality in this group of patients, while right ventricular (RV) strain analysis was not, although optimal data were available for only 54% of the patients. However, the study findings are partly flawed. The investigators performed adjusted analyses for Acute Physiology and Chronic Health Evaluation score (ICU mortality), Pulmonary Embolism Severity Index score (hospital mortality), or age and gender (longterm mortality), but they did not consider two important issues. First, intravenous thrombolytic therapy was administered to 9% of the study population. Thrombolytic therapy has been previously associated with significant early improvements in echocardiographic parameters of RV function compared with heparin alone in patients with acute massive or submassive PE. Therefore, patients receiving thrombolysis may have had more pronounced improvement in all or some of the parameters that were positively correlated with clinical outcomes in this study. Unfortunately, the investigators did not present a subgroup analysis of the echocardiographic findings in the subgroup of patients who received thrombolysis, and thrombolysis was not considered in the regression analysis. Second, absence of

Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis

50% inferior vena cava (IVC) collapsibility was correlated with ICU and hospital mortality. Nonetheless, 26% of the patients in this study required mechanical ventilation, which in turn significantly influences changes in IVC diameter (IVC distensibility for ventilated patients) and its value as an indicator of RV preload. The investigators did not adjust for this variable in the binary logistic regression analyses, and this can introduce a degree of bias when considering IVC collapsibility as predictor of outcome. Therefore, before the data can be correctly interpreted, an adjustment of the analysis for such variables (thrombolysis and mechanical ventilations) is needed. Finally, it would be interesting if the investigators could look into the echocardiographic follow-up of survivors, evaluating both early (within weeks) and late (after a few months) improvements in RV function and looking for predictors of good functional RV recovery. By reporting these data, the investigators would greatly contribute in providing further valuable insight on this interesting topic.