Filippo Sanfilippo

Amiodarone or lidocaine for cardiac arrest: A systematic review and meta-analysis.

BACKGROUND Guidelines for treatment of out-of-hospital cardiac arrest (OOH-CA) with shockable rhythm recommend amiodarone, while lidocaine may be used if amiodarone is not available. Recent underpowered evidence suggests that amiodarone, lidocaine or placebo are equivalent with respect to survival at hospital discharge, but amiodarone and lidocaine showed higher hospital admission rates. We undertook a systematic review and meta-analysis to assess efficacy of amiodarone vs lidocaine vs placebo. METHODS We included studies published in PubMed and EMBASE databases from inception until May 15th, 2016. The primary outcomes were survival at hospital admission and discharge in OOH-CA patients enrolled in randomized clinical trials (RCT) according to resuscitation with amiodarone vs lidocaine vs placebo. If feasible, secondary analysis was performed including in the analysis also patients with in-hospital CA and data from non-RCT. RESULTS A total of seven findings were included in the metanalysis (three RCTs, 4 non-RCTs). Amiodarone was as beneficial as lidocaine for survival at hospital admission (primary analysis odds ratio-OR 0.86-1.23, p=0.40) and discharge (primary analysis OR 0.87-1.30, p=0.56; secondary analysis OR 0.86-1.27, p=0.67). As compared with placebo, survival at hospital admission was higher both for amiodarone (primary analysis OR 1.12-1.54, p<0.0001; secondary analysis OR 1.07-1.45, p<0.005) and lidocaine (secondary analysis only OR 1.14-1.58, p=0.0005). With regards to hospital discharge there were no differences between placebo and amiodarone (primary outcome OR 0.98-1.44, p=0.08; secondary outcome OR 0.92-1.33, p=0.28) or lidocaine (secondary outcome only OR 0.97-1.45, p=0.10). CONCLUSIONS Amiodarone and lidocaine equally improve survival at hospital admission as compared with placebo. However, neither amiodarone nor lidocaine improve long-term outcome.

Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery: a systematic review and meta-analysis

BackgroundPrevious studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan.MethodsWe performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion.ResultsSix RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05).ConclusionsLevosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality

Purpose: We describe an approach for anticoagulation and transfusions in veno-venous–extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. Methods: Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. Results: In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). Conclusion: Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.

Esmolol in septic shock: old pathophysiological concepts, an old drug, perhaps a new hemodynamic strategy in the right patient

During sepsis, sympathetic activation plays a pivotal role in optimizing cardiac output and blood pressure by acting on the interplays between heart rate (HR), contractility and vascular tone. The integrity of baroreflex function is fundamental for the maintenance of hemodynamic homeostasis. Accordingly, in the early phases of sepsis, tachycardia becomes a crucial mechanism for compensating the decrease in stroke volume (SV) and indicates the efficacy of baroreflex activity (1).

Survey on the demand of sicilian physicians for a specific training on human cadavers and animals

Currently, surgical training of physicians in Italy has limited possibilities.Surgical training can be performed on dissection of human bodies as well as in animal laboratories, but experience is very poor. We conducted a survey through an anonymous questionnaire in order to evaluate the opinions of post-graduate physicians on their need for experience training on both human and animal bodies during their medical studies. A total of 165 young Sicilian physicians responded to the survey. Only 14 of them (8.5%) declared they had specific training on a live animal, while 46 (27.9%) reported they already attended cadaver labs. Over 70% assigned the maximum score to the utility of such courses as integration of medical academic offer. Our results showed that the majority of the subjects interviewed expressed a need for training using these practices and that it might be necessary to investigate patterns to promote the opportunity for direct practice on human and animal bodies.

Central venous pressure monitoring via peripherally or centrally inserted central catheters: a systematic review and meta-analysis

Introduction The central venous pressure (CVP) is the most commonly used static marker of preload for guiding fluid therapy in critically ill patients, though its usefulness remains controversial. Centrally inserted central catheters (CICCs) are the gold-standard devices for CVP monitoring but peripherally inserted central catheters (PICCs) may represent a valid alternative. We undertook a systematic review and meta-analysis with the aim to investigate whether the difference between PICC- and CICC-measured CVP is not significant. Methods We searched for clinical studies published in PubMed and EMBASE databases from inception until December 21st 2016. We included studies providing data on paired and simultaneous CVP measurement from PICCs and CICCs. We conducted two analyses on the values of CVP, the first one according to the total number of CVP assessments, the second one considering the number of patients recruited. Results Four studies matched the inclusion criteria, but only three of them provided data for the meta-analyses. Both analyses showed non-significant differences between PICC-measured and CICC-measured CVP: 1489 paired simultaneous CVP assessments (MD 0.16, 95%CI −0.14, 0.45, p = 0.30) on a total of 57 patients (MD 0.22, 95%CI −1.46, 1.91, p = 0.80). Both analyses showed no heterogeneity (I2 = 0%). Conclusions Available evidence supports that CVP monitoring with PICCs is accurate and reproduces similar values to those obtained from CICCs. The possibility to monitor CVP should not be used among clinical criteria for preferring a CICC over a PICC line.

The importance of diastolic dysfunction in the development of weaning-induced pulmonary oedema

The group of Prof. Monnet et al. [1] elegantly described the characteristics of patients failing spontaneous breathing trials (SBTs; n = 128/283, 45%), confirming that a large proportion of weaning failures (59%) are associated with weaning-induced pulmonary oedema (WiPO). Three factors were independently associated with WiPO during SBT: chronic obstructive pulmonary disease, obesity and “structural cardiopathy”. However, we believe this study also deserves comment for the contribution of LV diastolic dysfunction (LVDD) in cases of WiPO. Despite patients with WiPO having similar LV ejection fraction to those without (61 versus 57%, p = 0.76), they had a higher E/E’ ratio (10.5 versus 8.8, p < 0.01), a parameter strongly associated with LVDD [2]. Furthermore, among patients with cardiac output (CO) monitoring in place during the SBT (n = 85/283), those developing WiPO showed a significant increase in global end-diastolic volume (~200 ml, +22% from baseline), while this parameter remained unchanged when WiPO did not occur. Interestingly, the vast majority of patients experiencing WiPO (n = 28/30) had preload-independence after a passive leg rising (PLR) test and, on the contrary, the PLR test showed preload-dependence in all the patients that did not experience WiPO (n = 55/55). The authors also reported that when preload-independence persisted despite fluid removal, most of the patients again showed WiPO on the following SBT, while a change to a preloaddependence condition was associated with a high rate of successful weaning. Taken together, such findings emphasize the importance of LVDD as a contributor to WiPO. The higher venous return during the shift from positive to negative pressure ventilation determines unfavourable LV loading conditions, which may be poorly tolerated in the context of LVDD. The importance of LVDD is not surprising since it has been associated with weaning failure [3, 4] and also with mortality in sepsis [5]. Of note, the authors report a higher incidence of septic-related cardiomyopathy in patients with WiPO (17 versus 2%, p = 0.01) [1]. We ask the authors to share their opinion on this aspect and to provide the E’ values comparing patients with or without WiPO, since the recently published guidelines have emphasized also the role of E’ when assessing LVDD [2]. On a separate note, another interesting finding that may deserve further comment is that patients with CO monitoring had a trend towards lower SBT failure (n = 45/85) compared to those with no CO monitoring (n = 83/198; p = 0.09, not reported). Was the CO monitoring intentionally used to keep the patient in a “safely dry” condition?