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Despite improvements in surgical techniques and perioperative care, cardiac surgery still is burdened by relatively high mortality and frequent major postoperative complications, including myocardial dysfunction, pulmonary complications, neurologic injury, and acute kidney injury. Although the surgeon's skills and volume and patient- and procedure-related risk factors play a major role in the success of cardiac surgery, there is growing evidence that also optimizing perioperative care may improve outcomes significantly. The present review focuses on the aspects of perioperative care that are strictly related to the anesthesia regimen, with special reference to volatile anesthetics and neuraxial anesthesia, whose effect on outcome in adult cardiac surgery has been investigated extensively.

Purpose Perioperative myocardial dysfunction occurs frequently in cardiac surgery, and is a risk factor for morbidity and mortality. Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction. However, long-term outcome data on its efficacy in cardiac surgery are lacking. Materials and methods Cardiac surgery patients with perioperative myocardial dysfunction were randomized to levosimendan or placebo, in addition to standard inotropic care. One-year mortality data were collected. Results We randomized 506 patients (248 to levosimendan 258 to placebo). At 1-year follow-up, 41 patients (16.5%) died in the levosimendan group, while 47 (18.3%) died in the placebo group (absolute risk difference −1.8; 95% CI −8.4 to 4.9; P = .60). Female sex, history of chronic obstructive pulmonary disease, previous myocardial infarction, serum creatinine, hematocrit, mean arterial pressure, and duration of cardiopulmonary bypass were independently associated with 1-year mortality. Conclusions Levosimendan administration does not improve 1-year survival in cardiac surgery patients with perioperative myocardial dysfunction. One-year mortality in these patients is 17%. Six predictive factors for long-term mortality were identified. Study registration number NCT00994825 ( ClinicalTrials.gov ).

Unlike general anaesthesia, neuraxial anaesthesia (NA) reduces the burden and risk of respiratory adverse events in the post-operative period. However, both patients affected by chronic obstructive pulmonary disease (COPD) and chest wall disorders and/or neuromuscular diseases may experience the development or the worsening of respiratory failure, even during surgery performed under NA; this latter negatively affects the function of accessory respiratory muscles, resulting in a blunted central response to hypercapnia and possibly in an exacerbation of cardiac dysfunction (NA-induced relative hypovolemia). According to European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, non-invasive ventilation (NIV) is effective in the post-operative period for the treatment of both impaired pulmonary gas exchange and ventilation, while the intra-operative use of NIV in association with NA is just anecdotally reported in the literature. Whilst NIV does not assure a protected patent airway and requires the patient’s cooperation, it is a handy tool during surgery under NA: NIV is reported to be successful for treatment of acute respiratory failure; it may be delivered through the patient’s home ventilator, may reverse hypoventilation induced by sedatives or inadvertent spread of anaesthetic up to cervical dermatomes, and allow the avoidance of intubation in patients affected by chronic respiratory failure, prolonging the time of non-invasiveness of respiratory support (i.e., neuromuscular patients needing surgery). All these advantages could make NIV preferable to oxygen in carefully selected patients.

In the recently updated international “democracy-based” consensus conference aimed at identifying all nonsurgical strategies which have been shown by sufficiently strong randomized evidence to affect mortality in the perioperative and critical care setting, restrictive inspiratory oxygen fraction (FiO2) was included among interventions reducing mortality. This conclusion was based on the findings of two randomized controlled trials showing a lower intensive care unit (ICU) mortality with a “conservative” FiO2 approach in critically ill patients and an increased long-term mortality in surgical patients receiving high intraoperative FiO2, respectively. However, there is also evidence that high perioperative FiO2 may reduce mortality (possibly through prevention of surgical site infection) among surgical patients, while recent investigations did not confirm (or found a high level of uncertainty about) the survival benefit of restrictive FiO2 strategies in ICU patients. This chapter discusses the main evidences about the topic, the possible mechanisms of the association between FiO2 and mortality, and the implications for clinical practice.

Lung-protective ventilation (LPV) and prone positioning (PP) are currently the two cornerstones of acute respiratory distress syndrome (ARDS) treatment. LPV with low tidal volumes, moderate-to-high levels of positive end-expiratory pressure (PEEP) and, possibly, recruitment maneuvers has been widely shown in randomized controlled trials (RCTs) to reduce mortality in ARDS patients. However, evidence about the favorable effects in terms of survival of PEEP and recruitment maneuvers is not as conclusive as that about low tidal volumes. PP has been shown for over 40 years to improve oxygenation in ARDS patients but only in recent years a large multicenter RCT succeeded in showing improved survival with this strategy.

Geometrical optics, which deals with light as a set of rays traveling in straight lines (according to the so-called ray model of light) is the oldest part of optics, that is the study of light. This chapter discusses some of its laws (such as the law of reflection and the Snell’s law of refraction) and their applications (e.g., lenses and optical fibers), in order to understand how a bronchoscope works. We will also take the opportunity to discuss the physics behind the fogging of a bronchoscope or of personal protective equipment (PPE) such as goggles.

When you are watering a garden, you can reach the most distant areas by simply partially closing the hose with a thumb. In fact, the water speed increases when it flows through a decreased cross-sectional area (continuity equation). According to Bernoulli’s theorem, the pressure of a fluid that travels along a horizontal streamline decreases as its speed increases: the wings of an airplane are built so as to take advantage of this law and make the airplane fly. Both the continuity equation and the Bernoulli’s equation (in a simplified form) have important echocardiographic applications, while they work together in a Venturi mask, allowing the administration of predictable inspiratory oxygen fractions. Moreover, these two physics laws are involved in the pathophysiology of dynamic left ventricle outflow tract obstruction due to systolic anterior motion, which is a possible cause of severe hemodynamic instability in either the operating room or the intensive care unit.

The physics of sound waves has many applications in our everyday lives, from musical instruments to speeding fines, ultrasonography, and radars. This chapter addresses a clinically relevant topic (to anesthesiologists and intensivists) of wave physics: the Doppler Effect and its application to both ultrasonography (e.g., echocardiography) and minimally invasive cardiac output monitoring devices such as the esophageal Doppler.

The part of physics called electricity includes the description of several quantities, phenomena, and devices which are closely related to what anesthesiologists and intensivists daily deal with in their clinical practice. For example, the measurement of a change in the electrical resistance of “something” is involved in invasive pressure monitoring, temperature monitoring, cardiac output estimation, and platelet function testing. Furthermore, body temperature can be measured in clinical practice also using a circuit element, called thermocouple, which relies on a particular thermoelectric effect.

The trajectory of an electromagnetic wave which travels through a transparent medium may be deviated in any direction as a result of the interaction between the wave and some obstacle or “inhomogeneity,” such as the particles that are suspended in the medium. This phenomenon, which is referred to as scattering of the electromagnetic wave, explains why the sky is blue. While nonionizing electromagnetic waves such as visible light and infrared radiation mainly undergo elastic scattering (in which the wavelength of the scattered radiation does not change), scattered ionizing radiations undergo a change in wavelength (inelastic scattering). Both types of scattering may have a role in the daily practice of anesthesia and intensive care medicine. For example, the elastic scattering of infrared radiation is one of the principles on which near-infrared spectroscopy (NIRS) cerebral oximetry is based and, at the same time, represents a major technological challenge which accounts for some limitations of this technique. Moreover, the special kind of (inelastic) scattering which ionizing radiations undergo (Compton scattering) has a key role in radiation protection. Finally, although nonionizing electromagnetic waves mainly undergo elastic scattering, inelastic scattering may also occur: this phenomenon, which is known as Raman scattering, is used in some types of respiratory gas analyzers.

Physics and mathematics are inextricably linked. In fact, for still partly mysterious reasons, the mathematical language is incredibly effective in describing the “physical world.” Accordingly, in Physics for Anesthesiologists and Intensivists we cannot do without a little mathematics to fully understand the physics that lies behind our “clinical” world, namely that of anesthesiology and intensive care medicine. However, some algebra, a bit of geometry and trigonometry, and just a couple of notions of calculus (very rarely), are all we will need, and are briefly brushed up in this chapter. We will also take the opportunity to immediately make some considerations relating to our daily clinical practice, in particular about the use of geometry and trigonometry to help consolidate our ultrasound-guided central venous catheterization technique, especially when it is performed the first few times.

Have you ever tried to open a heavy door by pushing it from a point very close to its hinges? It takes a lot more force (it is not a coincidence that doorknobs are where they are). In fact, considering a body, such as a metal bar, that is free to rotate about an axis, the ability of a force, applied on it at a given point, to rotate this body depends not only on the magnitude (and direction) of the force, but also on how far from the axis the force is applied (moment of a force or torque). The levers we use every day (e.g., pliers, nutcrackers, and tweezers) rely on this principle. In this chapter, the concepts of vector, vector sum, vector component, and moment of a force are applied to the insertion of a central venous catheter and to laryngoscopy.

The pilot balloon palpation (or 'finger-pressure') method is still widely used to assess the endotracheal tube cuff inflation, despite consistent evidence of its poor sensitivity in recognizing cuff overinflation. It was recently speculated that this may be related to the lower wall tension (due to the smaller radius) of the pilot balloon as compared with the cuff, according to Laplace's law. To verify this hypothesis and, secondarily, to assess whether the use of a 'large' pilot balloon (identical to the cuff) increases the reliability of this technique, 62 anesthetists (41 experienced anesthesiologists and 21 residents) were asked to estimate the pressure of a cuff inflated to 88 mmHg into a simulated trachea by feeling both a usual and a modified 'large' pilot balloon. A similar test was repeated at 40 mmHg. After palpation of the usual pilot balloon, only 35% of participants (49% of experienced anesthesiologists and 10% of residents) recognized considerable overinflation (88 mmHg), as compared with 87% of participants (95% of experienced anesthesiologists and 71% of residents) after palpation of the 'large' pilot balloon. Moreover, 89% of participants (85% of experienced anesthesiologists and 95% of residents) believed that pressure was higher in the 'large' balloon than in the normal one. However, only 32% of participants (51% of experienced anesthesiologists and none of residents) recognized slight overinflation (40 mmHg) after feeling the 'large' balloon. The pilot balloon size affects the sensitivity of the 'finger-pressure' technique, but it remains poorly reliable with a larger pilot balloon.

BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P = 0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P = 0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P = 0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P = 0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.).

Objective: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. Design: A systematic review of the literature followed by a consensus-based voting process. Setting: A web-based international consensus conference. Participants: Two hundred fifty-one physicians from 46 countries. Interventions: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. Measurements and main results: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma- derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. Conclusion: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton’s tyrosine kinase—isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress. Searching for novel markers of CLL progression, we analysed the expression of IBTKα in the peripheral blood B-cells of CLL patients, before and after first line therapy causing remission. The expression of IBTKα was significantly increased in disease progression, and decreased in remission after chemotherapy. Consistently with a pro-survival action, RNA interference of IBTKα increased the spontaneous and Fludarabine-induced apoptosis of MEC-1 CLL cells, and impaired the cell cycle of DeFew B-lymphoma cells by promoting the arrest in G0/G1 phase and apoptosis. Consistently, RNA interference of IBTKα up regulated the expression of pro-apoptotic genes, including TNF, CRADD, CASP7, BNIP3 and BIRC3. Our results indicate that IBTKα is a novel marker of CLL progression promoting cell growth and resistance to apoptosis. In this view, IBTKα may represent an attractive cancer drug target for counteracting the therapy-resistance of tumour cells.

Objective: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach. Design: A systematic review of the literature followed by a consensus-based voting process. Setting: A web-based international consensus conference. Participants: More than 400 physicians from 52 countries participated in this web-based consensus conference. Interventions: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide. Measurements and Main Results: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions. Conclusions: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field. Orion Pharma ; Abbott Laboratories ; Pall ; Tenax

Objective: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population. Design: Post hoc analysis of a multicenter randomized trial. Setting: Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries. Participants: The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate

Objective There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. Design Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. Setting Tertiary and University hospitals. Interventions Patients (n = 10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. Measurements and main results The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30 day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. Conclusions The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.

When you open a can of soda or a bottle of sparkling water and you see a lot of bubbles appear, you are observing the effects of Henry’s law: the degree a gas dissolves into a fluid increases proportionally to the increase in partial pressure above the fluid. Moreover, have you ever noticed that warmer is the drink, larger are the bubbles? Or also, that when it’s hot, drinks left in a glass become “flat” more quickly? This too is due to Henry’s law. In fact, the proportionality coefficient of Henry’s law (the so-called Henry’s constant) depends on temperature. In addition to have a key role in both the pathophysiology and treatment of decompression sickness, Henry’s law explains, at least in part, the respiratory alkalosis which develops at low body temperatures (such as during hypothermic cardiopulmonary bypass or deep hypothermic circulatory arrest), which can be managed according to two different strategies (α-stat or pH-stat).

Objective Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality. Design and Setting A web-based international consensus conference. Participants The study comprised 500 clinicians from 61 countries. Interventions A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey. Measurements and Main Results The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted. Conclusions The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality.

The Beer-Lambert law (also known as Beer’s law or Lambert-Beer law) correlates the absorption of light or other electromagnetic waves, as they pass through an object, with the thickness of the object and the amount and absorbing properties of the substances contained therein. This law accounts for the color of the sea and, at the same time, allows anesthesiologists and intensivists to monitor arterial oxygen saturation by means of pulse oximeters. Moreover, capnographers and inhaled anesthetic analyzers rely on it.

The physics of sound waves has many applications in our everyday lives, from musical instruments to speeding fines, ultrasonography, and radars. The first part of this chapter is between serious and humorous: it discusses the origin and propagation of sound in order to explain something “strange” which might (theoretically) occur during a xenon anesthesia. However, the topic also gives us the opportunity to discuss the so-called resonance of invasive pressure monitoring systems. The second part of the chapter briefly addresses another clinically relevant topic (to anesthesiologists and intensivists) of wave physics: the Doppler effect and its application to both ultrasonography (e.g., echocardiography) and noninvasive cardiac output monitoring devices such as the esophageal Doppler.

When you are watering a garden, you can reach the most distant areas by simply partially closing the hose with a thumb. In fact, the water speed increases when it flows through a decreased cross-sectional area (continuity equation). According to Bernoulli’s theorem, the pressure of a fluid that travels along a horizontal streamline decreases as its speed increases: the wings of an airplane are built so as to take advantage of this law and make the airplane fly. Both the continuity equation and the Bernoulli’s equation (in a simplified form) have important echocardiographic applications, while they work together in a Venturi mask, allowing the administration of predictable inspiratory oxygen fractions.

Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression. Electronic supplementary material The online version of this article (10.1186/s12943-017-0730-8) contains supplementary material, which is available to authorized users.

Allogenic blood transfusions (ABTs) are widely used in the perioperative care of patients undergoing major surgery. According to the last available update of the World Health Organization Global Database on Blood Safety, approximately 92 million blood donations are collected annually worldwide, with surgical procedures accounting for consumption of up to 40 % of total blood supply in Western countries.

"OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting.. . DESIGN AND SETTING: Systematic literature review and international web-based survey.. . PARTICIPANTS: More than 300 physicians from 62 countries.. . INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality.. . MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions.. . CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.. . "

Background In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. Methods Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. Results A total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12–48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. Conclusions We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome. Electronic supplementary material The online version of this article (doi:10.1186/s12871-016-0271-5) contains supplementary material, which is available to authorized users.

The use of low-dose dopamine for renal protection has been firstly described more than 50 years ago and has tenaciously resisted until recently. However, it is now clear that this intervention is, on average, not effective for prevention or early treatment of acute kidney injury (AKI) and may even be harmful. Nevertheless, a new enthusiasm has developed during the last decade for a possible nephroprotective action of fenoldopam, a specific dopamine type-1 receptor agonist with a renal action similar to that of low-dose dopamine, but theoretically more favorable and without the adverse effects related to systemic adrenergic stimulation. Fenoldopam remained, until recently, one of the few drugs which were thought to have a potential beneficial effect on renal function, as well as on outcome, in critically ill patients with or at risk for AKI. However, the largest multicenter randomized controlled trial addressing the impact of fenoldopam on the need for renal replacement therapy and on mortality in patients with early cardiac surgery-associated AKI, recently published, seriously questioned the effectiveness (and also the safety) of this strategy.

Noninvasive ventilation (NIV) is increasingly used in cardiac procedures such as percutaneous coronary revascularization in patients with pulmonary edema secondary to acute myocardial infarction, percutaneous cardiac valve procedures, electrophysiological procedures, and transesophageal echocardiography. Although some concerns regarding the use of NIV in these contexts may exist, a team well trained in managing NIV often safely carries out such procedures even in frail or high-risk patients.

Objectives Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. Design and Setting A systematic review of literature followed by web-based voting on findings of a consensus conference. Participants A total of 555 clinicians from 61 countries. Interventions The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents’ agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians’ approach to interventions also were investigated. Measurements and Main Results According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians’ agreement. Conclusions Physicians’ clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.

Obstructive sleep apnea (OSA) is caused by repetitive collapse of the upper airway during sleep. Continuous positive airway pressure (CPAP) is effective for the treatment of OSA, but it is estimated that 29–83 % of patients are nonadherent to this therapy. Transnasal insufflation, consisting of an open nasal cannula system delivering warm and humidified air, has been introduced to treat OSA and may represent an effective and better tolerated alternative to CPAP.

Evidence-based medicine is the gold standard approach in modern medical epistemology. However, there is increasing concern about the low number of evidence-based clinical practices and high-quality multicenter randomized trials in the critical care field. Consensus conferences and guidelines on which physicians base their clinical practice often rely on expert opinions more than on high-quality evidence.

Purpose of review In the last years, the perioperative use of levosimendan in cardiac surgery patients is spreading. Moreover, newer indications have been suggested such as the treatment of sepsis-associated myocardial dysfunction. In the present review, we discuss the most recent evidences in these settings. Recent findings Levosimendan has been seemingly confirmed to reduce mortality in patients undergoing cardiac surgery. In particular, it appears to be the only inotropic drug to have a favorable effect on survival in any clinical setting. Moreover, levosimendan has been shown to exert a cardioprotective action and to reduce acute kidney injury, renal replacement therapy, and ICU stay in cardiac surgery patients. Finally, levosimendan has been suggested to reduce mortality in patients with severe sepsis and to improve renal outcomes in critically ill patients. Summary Although a strong rationale likely exists to use levosimendan in the setting of perioperative and critical care medicine, evidence mainly comes from small and often poor-quality randomized clinical trials, whose results acquire significance only when pooled in meta-analyses. Moreover, some aspects related to which subgroups of patients may derive the most benefits from receiving levosimendan, to the optimal timing of administration, and to the potential adverse effects need to be further clarified. Important insights will be hopefully provided soon by the several large multicenter investigations which are currently ongoing.

Duchenne muscular dystrophy (DMD) is caused by a mutation of the dystrophin gene. The progressive reduction in forced vital capacity predicts the development of respiratory failure, which evolves from nocturnal to daytime hypercapnia until the occurrence of respiratory symptoms. Treatment of pulmonary complications with noninvasive ventilatory support may improve quality of life and reduce the high morbidity, as well as early mortality, associated with DMD.

Background. New imaging tests such as computed tomography [CT], [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning and magnetic resonance imaging (MRI) are not recommended for staging or follow up of asymptomatic patients with EBC according to current guidelines. However, frequently these tests are requested even in the absence of a clinical indication. Variations in practice patterns have significant cost implications and no clear impact on cancer outcomes. Aim. In the present study we analyzed how the availability of novel and more expensive imaging technique has changed staging and follow-up modalities in EBC patients and if these changes affect costs. Methods. Two thousand and five patients with EBC diagnosed between January 2005 and December 2008 were identified using clinical computerized medical records from 639 general practitioners assisting 915,689 inhabitants of the Campania, a southern region of Italy. For each year EBC incidence, the mean number of diagnostic tests per patient (N/Pt) done during the first year after the initial diagnosis and the mean costs per each year were evaluated and compared by Anova test. Results. We identified 576, 489, 474 and 497 newly diagnosed cases of EBC in 2005, 2006, 2007 and 2008 respectively. Table 1 Table 1 describes changes in the mean number of different imaging tests requested per patient in these years. Overall, there was a significant increase of the mean number of imaging tests done per patient from 2005 to 2008 (P Conclusions. TC scan, PET scan and MRI employment for patient with EBC in daily clinical practice has been steadily growing over the past four years. However, there are no data to support their role in routine breast cancer staging or surveillance in asymptomatic patients. More studies are needed to characterize which subset of patients deserve more intensive staging and follow up procedures as costs related to these imaging test prescriptions are relevant. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-09-06.

Objective: To verify the reliability of different markers of fluid-responsiveness during off-pump cardiac surgery (OPCAB). Design: A clinical prospective, nonblinded, nonrandomized study. Setting: A community hospital. Participants: Nineteen patients. Interventions: Pulmonary artery catheter (PAC), LiDCO (LiDCO, London, UK), and transesophageal echocardiography (TEE) parameters were measured before (t0) and after (t1) a fluid challenge was performed 20 minutes after induction of anesthesia, but before sternotomy and without inotropic infusion. A Student t test and Spearman test were performed for statistical analysis. Measurements and Main Results: According to the variation of cardiac index after the fluid challenge (ΔCI%), 2 groups of patients were identified: the responders (Re, ΔCI% > 15%) and the nonresponders (nRe). Mean pulse pressure variation (PPV) and mean stroke volume variation (SVV) before the fluid challenge (t0) were significantly different between the 2 groups. No significant differences were shown in systolic pressure variation (SPV), left ventricular end-diastolic area, left ventricular end-diastolic volume, and peak changes of aortic flow (ΔVAo). A statistically significant correlation was observed between ΔCI% and PPV ( R = 0.793), ΔCI% and SVV ( R = 0.809), and ΔCI% and SPV ( R = 0.766). No correlation with central venous pressure and pulmonary capillary wedge pressure was found. Conclusions: Dynamic parameters of fluid responsiveness by LiDCO are highly sensitive for assessment of intravascular volume status during OPCAB surgery. In contrast, even if static parameters by TEE reflect changes in ventricular diastolic volume, they are poor indicators of fluid responsiveness. Surprisingly, no significant correlation between ΔVAo (TEE) and ΔCI% was found.

Objective Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Design Double-blind, placebo-controlled, multicenter randomized trial. Setting Tertiary care hospitals. Interventions Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. Measurements and main results The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. Conclusions This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

Lung-protective ventilation involves the use of low tidal volumes, moderate-to-high levels of positive end expiratory pressure and, sometimes, recruitment maneuvers (i.e. a transitory increase in transpulmonary pressure aimed at opening atelectatic alveoli). It may prevent or attenuate ventilator induced lung injury and has been widely shown to reduce mortality in patients with acute respiratory distress syndrome. Lung-protective ventilation is, actually, one of the interventions best proven to have an impact on mortality in critically ill patients. In fact, three multicenter randomized controlled trials found that ventilation with low tidal volumes, with or without high positive end expiratory pressure, improves survival in patients with acute respiratory distress syndrome. However, two recent meta-analyses failed to demonstrate a survival benefit of high positive end expiratory pressure. Therefore, evidence about high positive end expiratory pressure is not as conclusive as that about low tidal volumes and further trials are needed in order to define “best” positive end expiratory pressure.

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions.DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references.STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility.DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up.DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions.CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.