Alberto Corona

Predictors of prolonged mechanical ventilation in a cohort of 5123 cardiac surgical patients.

Background Prolonged mechanical ventilation (PMV) after heart surgery is associated with increased patient morbidity and mortality. Methods In this prospective observational cohort study the aim was to assess PMV predictors and its impact on ICU, hospital length of stay and survival in cardiac surgical patients admitted to our eight-bed ICU from January 2000 to December 2006. All perioperative patient variables were put into an electronic database. Five thousand one hundred and twenty-three patients were divided into two cohorts: early extubation, undergoing a successful extubation for 12 h or less, and delayed extubation, needing a mechanical ventilation for more than 12 h. Results A logistic regression model identified the following as PMV predictors: age more than 65 years [odds ratio (OR), 1.296; 95% confidence interval (CI), 1.017–1.069; P = 0.016], chronic renal failure (OR, 1.571; 95% CI, 1.566–2.466; P = 0.011), chronic obstructive pulmonary disease (OR, 1.453; 95% CI, 1.695–2.454; P = 0.006), redo surgery (OR, 2.010; 95% CI, 1.389– 2.114; P = 0.001), emergency surgery (OR, 1.622; 95% CI, 1.515–2.494; P = 0.016), New York Heart Association/Canadian Cardiovascular Society class higher than 2 (OR, 1.491; 95% CI, 1.704–2.321; P = 0.001), left ventricular ejection fraction of 30% or less (OR, 2.125; 95% CI, 1.379–1.991; P = 0.000), red blood cell (OR, 5.430; 95% CI, 3.636–8.130; P = 0.000) and fresh frozen plasma transfusion units more than four (OR, 3.019; 95% CI, 1.808–5.050; P = 0.000) and cardiopulmonary bypass time more than 77 min (OR, 2.030; 95% CI, 1.248–2.174; P = 0.002). Early extubation group patients showed a higher probability of being discharged from ICU to cardiac surgical ward (log-rank = 1108.951; P = 0.000) and from cardiac to rehabilitation ward (log-rank = 598.005; P = 0.000) and higher hospital survival (log-rank = 53.215; P = 0.000). Conclusion This review allowed us to assess predictors, helping us to identify ‘a priori’ patients more likely to undergo PMV.

Caring for HIV-Infected Patients in the ICU in The Highly Active Antiretroviral Therapy Era

The use of intensive care units (ICU) resources for HIV-Infected patients has been controversial since the first reported cases, raising practical ethical and economic issues about aggressive treatment. The aim of this review of the literature is to provide current information on the epidemiology of human immunodeficiency virus (HIV)-infected patients admitted to ICU during the era of highly active antiretroviral therapy (HAART) and to highlight issues related to HAART that are relevant to the intensivist. Overall mortality of critically ill HIV-infected patients in ICU has decreased in the HAART era and patients are more commonly admitted with non-HIV-related illnesses. Use of HAART in ICU is problematic, however it may be associated with improved outcomes. More HIV-infected patients surviving ICU admission are more likely to need critical care for problems unrelated to HIV infection or for conditions related to HAART toxicity. Intensivists need to be familiar with HAART (i) to recognize life-threatening toxicities unique to these drugs; (ii) to avoid drug interactions, which are extremely common and potentially life-threatening; (iii) to avoid enhancing HIV drug resistance, an occurrence that could have devastating consequences for the patient following ICU discharge.

Bacteraemia incidence, causative organisms and resistance patterns, antibiotic strategies and outcomes in a single university hospital ICU: continuing improvement between 2000 and 2013

OBJECTIVES The optimal duration of antibiotic treatment in patients with bloodstream infections remains contentious, with concerns regarding both undertreatment and the encouragement of antibiotic resistance. In our ICU we traditionally use short-course antibiotic monotherapy as the mainstay of treatment. We sought to document the impact of this strategy on pathogen type, resistance patterns and patient outcomes. A comparison was made against data collected during a similar exercise in 2000. METHODS We retrospectively reviewed data on all patients with community-, hospital- and ICU-acquired bacteraemia over a 6 month period (1 December 2012 to 31 May 2013) in a general medical-surgical ICU in a London university hospital. Causative pathogens, resistance patterns, use and duration of monotherapy or combination therapy, breakthrough and relapse rates, and patient outcomes were assessed. RESULTS The 2013 cohort comprised 113 episodes in 87 patients. Short-course monotherapy (median course 4-5 days) was used in 65.7% of episodes (73.5% in 2000). As with the 2000 cohort, the incidence of antimicrobial resistance, fungaemia, bacteraemia breakthrough and relapse remained low. Of note, there was a decreasing incidence of ICU-acquired MRSA, MDR Gram-negative bacteraemia and fluconazole-resistant candidaemia. Hospital mortality was 32% (45% in 2000). CONCLUSIONS Our strategy predominantly utilizing short-course antibiotic monotherapy remains effective in achieving good clinical outcomes among patients with bloodstream infections, with low rates of antibiotic resistance and clinical relapse. Prospective trials of short-course monotherapy are warranted to assess clinical efficacy and antimicrobial resistance.

Comparison of the Surgical Pleth Index with autonomic nervous system modulation on cardiac activity during general anaesthesia: A randomised cross-over study.

BACKGROUND Surgical plethysmographic index (SPI) has been proposed as a tool to measure the nociception/antinociception balance during general anaesthesia. Untreated nociception may increase sympathetic tone, but the relationship between SPI and the autonomic nervous system (ANS) is poorly understood. OBJECTIVE We hypothesised that two different levels of SPI might be associated with differences in ANS modulation, measured by the frequency domain analysis of heart rate variability (HRV). DESIGN A randomised, cross-over group study, conducted between February and November 2009. SETTING University tertiary referral hospital in Milan, Italy. PATIENTS Forty-two adult patients undergoing scheduled laparoscopic abdominal surgery. INTERVENTIONS ECG, noninvasive arterial blood pressure and SPI were recorded during balanced general anaesthesia with inhaled sevoflurane and intravenous remifentanil. After pneumoperitoneum induction, the remifentanil infusion rate was set to obtain two different levels of SPI (>50, HI-SPI, and <50, LO-SPI) for each patient. MAIN OUTCOME MEASURES Arterial pressure, heart rate (HR), low-frequency and high-frequency spectral components, the low frequency/high frequency ratio (measure of sympathovagal balance) and whole power spectrum density of HRV were measured at the two different levels of SPI. RESULTS Thirty-nine patients were included in the final analysis. During LO-SPI, HR and systolic and mean blood pressures were significantly lower than HI-SPI. The median low frequency/high frequency ratio was reduced during LO-SPI [1.29 interquartile range (IQR) 0.66 to 2.05) vs. 2.36 (1.30 to 3.62), P = 0.008]. The sensitivity analysis revealed a significant correlation between SPI changes and changes of all ANS indices, arterial pressure and HR, with a slightly better correlation for low frequency/high frequency (Spearman &rgr; = 0.70, IQR 0.484 to 0.834, P < 0.001). CONCLUSION In the context of a balanced general anaesthesia in healthy patients undergoing laparoscopic abdominal surgery, ANS modulation seems to correlate with changes in SPI. Further studies are warranted to assess whether this may reflect a change in nociception/antinociception balance or a pharmacodynamic effect of remifentanil.

Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae

Background Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

Pulse photoplethysmographic amplitude and heart rate variability during laparoscopic cholecystectomy: A prospective observational study

BACKGROUND Surgical stress affects the autonomic nervous system by increasing sympathetic outflow. One method of monitoring sympathetic activity is pulse photoplethysmographic analysis. From this two indices can be derived – autonomic nervous system state (ANSS) and ANSS index (ANSSi). It has recently been claimed that these indices can be used to measure sympathetic activity in anaesthetised patients, but their validity has not yet been demonstrated. OBJECTIVE To measure changes in pulse photoplethysmographic indices and determine any agreement with autonomic nervous system modulation of the cardiovascular system in healthy study participants during surgery under general anaesthesia. DESIGN Prospective observational study. SETTING Single-centre study based at a tertiary care centre in Milan, Italy. PATIENTS Healthy patients undergoing general anaesthesia for elective laparoscopic cholecystectomy. INTERVENTIONS ANSS, ANSSi, and heart rate variability (HRV) were analysed at three main times: baseline, after induction of general anaesthesia, and after pneumoperitoneum insufflation. MAIN OUTCOME MEASURES The magnitude of changes in photoplethysmographic and HRV indices was measured. The agreement between pulse photoplethysmographic and HRV-derived indices was assessed by Bland–Altman plots. RESULTS In total, 52 patients were enrolled and their data analysed. Both pulse photoplethysmographic and HRV indices changed during the study phases. An agreement was found between ANSSi and low frequency spectral components of HRV [bias 10.2nu, 95% confidence interval (CI) −13 to 33.4], high frequency spectral components of HRV (bias 6.1 nu, 95% CI −16.3 to 28.6), and low frequency/high frequency ratio (bias 16.1nu, 95% CI −1.4 to 33.5). The agreement was weaker between ANSSI and HRV indices. CONCLUSION The study endorses the use of pulse photoplethysmographic indices ANSS and ANSSi as surrogates to estimate changes of autonomic modulation of the cardiovascular system in healthy adults during surgery under general anaesthesia. Orcid ID: orcid.org/0000–0002–9616–803X.

Pulse Photoplethysmographic Analysis Estimates the Sympathetic Activity Directed to Heart and Vessels.

Background:Novel pulse photoplethysmographic–derived indices have been proposed as tools to measure autonomic nervous system (ANS) modulation in anesthetized and awake patients, but nowadays their experimental validation is lacking. The authors aimed to investigate the ability of pulse photoplethysmographic amplitude (PPGA), ANS state (ANSS), and ANSS index (ANSSi) to measure changes of ANS modulation in response to sympathetic stimulation. Methods:Ten awake healthy volunteers underwent two passive head-up tilts at 45° and 90°. The heart rate variability (HRV) and systolic arterial pressure variability were analyzed in the frequency domain as a measure of ANS modulation directed to the heart and the vessels. HRV, baroreflex sensitivity, and pulse photoplethysmographic indices were measured at baseline and after tilt maneuvers. The agreement between HRV-derived indices and pulse photoplethysmographic indices was assessed using Bland–Altman plots. Results:PPGA, ANSS, and ANSSi changed significantly during the study protocol. Head-up tilt decreased PPGA and ANSS and increased ANNSi. There was a good agreement between ANSSi and baroreflex sensitivity explored in the high-frequency band (bias, 0.23; 95% CI, −22.7 to 23.2 normalized units) and between ANSSi and the sympathovagal modulation directed to the heart (bias, 0.96; 95% CI, −8.7 to 10.8 normalized units). Conclusions:In controlled experimental conditions, novel pulse plethysmographic indices seem to estimate the changes of the sympathetic outflow directed to the vessels and the sympathovagal balance modulating heart rate. These indices might be useful in the future to monitor the fluctuation of sympathetic activity in anesthetized patients.

Antifungal therapy in the critically ill: In medio stat virtusc Is a preemptive approach correct?

2737 inactive forms, believed to be linked to the N-terminal domain of C1INH (4). C1INH downregulated activated neutrophil and elastase release in patients with severe sepsis (5). Inhibition of thrombin activity by C1INH may contribute to diminishing of vascular permeability (6). Furthermore, the suppressive effect of C1INH on bradykinin-mediated vascular leakage has been long used in the treatment of hereditary angioedema. C1INH administration appears to be safe in terms of treatment and prevention protocol in hereditary angioedema. There have been no reports of serious adverse events related to immunosuppression since introduction of this regime several years ago. Dr. Herscu consulted for ViroPharma, a C1INH maker. Dr. Igonin has employment with Scientific Advisor and BioGenius LLC and holds a patent with BioGenius LLC.

Timely selection of adequate antifungal therapy for candidemia in the critically ill: Don't let the yeast rise!

I n this issue of Critical Care Medicine, Labelle et al. (1) examine the impact of treatment-related variables for Candida species bloodstream infection on hospital mortality. They undertook a retrospective cohort study on all candidemic patients at their hospital receiving antifungal therapy over a two and half year period. Patients admitted to the intensive care unit were analyzed as a separate subgroup. Clinical and microbiologic data were obtained from separate databases. In total, they identified 245 candidemic patients, of whom 111 (45.3%) needed intensive care unit management. Crude mortality was 29.4% in the hospital cohort and 36% in those admitted to intensive care unit. Binary logistic regression analysis identified as independent predictors of hospital mortality: 1) increments in Acute Physiology and Chronic Health Evaluation II score; 2) corticosteroid use at the time a positive blood culture was drawn; 3) inadequate initial fluconazole dosing; and 4) central venous catheter retention. They concluded that optimization of initial antifungal therapy and central venous catheter removal were important management steps to improve outcomes. Epidemiologic data collected over the past two decades show the increasing incidence of Candida species bloodstream infection in nonimmunocompromised critically ill patients and recognition of its associated mortality (2). In the United States, invasive candidiasis now accounts for 17% of all hospital-acquired infection (3). Candidemia, representing 10% to 20% of all candidiasis, is considered merely the tip of the iceberg (2). Data from National Nosocomial Infections Surveillance system showed that Candida species are responsible for 5% to 10% of all bloodstream infections and are the fourth leading microorganism only preceded by coagulase-negative staphylococci, Staphylococcus aureus, and enterococci (3). Candidemia rates and attributable mortality range respectively from 1 to 94 cases/1000 admissions and from 6% to 48% according to case mix and type of Candida species (2). The current article by Labelle et al. is a further useful addition to the literature. The data were collected from two apparently complete data registries, one demographic and the other infection-based, thus supporting the representativeness of their sample. The recommendation of optimizing first-line antifungal therapy, both in terms of timely institution and appropriateness of agent and dose, is an important message to improve outcomes and reduce the rate of related early and late complications (4–6). Delay in initiating antifungal treatment in the critically ill is associated with a worse outcome (4, 7, 8). Endophtalmitis, endocarditis, and other severe disseminated forms of candidiasis can complicate candidemia (6). Candida species have the ability to produce virulence factors that, by disrupting host cell membranes through complex sugar molecules, enhance their capacity to colonize mucosal and synthetic surfaces as a preparatory step to host tissue invasion. Removal of intravenous catheters, whenever feasible, would logically complement optimization of drug therapy (3, 4, 9). However, the literature is inconsistent, with a number of studies demonstrating no outcome improvement through central line removal, regardless of the patient’s immune status (9, 10, 11). As with most retrospective database interrogations, some biases and limitations are intrinsically present, especially with respect to direct assessment of any outcome differences. Nonsurvivors had significantly higher levels of comorbidity and severity of illness, and the association with corticosteroid use and nonremoval of catheters could also be a reflection of their illness acuity (e.g., presence of shock, severe coagulopathy). As is so often the case with hospitalacquired infections, directly attributable mortality is difficult to precisely tease out. Indeed, in the current article, 57% to 72% of the hospital and intensive care unit cohorts had concurrent (presumably bacterial) infection, and this may have also impacted outcome. In their logistic regression model, they did not consider the presence of previous Candida species patient colonization, which has been previously documented to be a leading risk factor for infection (2, 12). Colonization or superficial infection with a genotypically identical strain usually precedes bloodstream infections. Sequential spread from the abdominal cavity to other body sites before candidemia occurred was shown by Solomkin et al. (13) in the early 1980s. Heavy or increasing growth of Candida species in peritoneal cavity specimens is also predictive of subsequent candidemia (2, 14). Likewise, the severity of sepsis was not entered into their multivariate model and this will clearly influence outcome. As Harbarth et al. (15) recently suggested, the detrimental effects of delayed and/or inadequate antimicrobial therapy weaken in the most severely ill patients with short life expectancies. The duration of antifungal therapy is also not reported, nor the clinical and/or microbiological parameters on which therapy was discontinued (or even escalated). For example, a decision to withdraw lifeprolonging therapy may have been taken on the basis of the patient’s underlying illness. Finally, they did not report on either recurrence rates or episodes of breakthrough candidemia, other useful markers of the efficacy of treatment. A final point worth making is on the difficulty of rapid speciation of the infecting organism. Many studies report a rise in Candida glabrata infection which requires higher doses of fluconazole (16). C. glabrata was responsible for one sev*See also p. 2967.

Effects of laparoscopic radical prostatectomy on intraoperative autonomic nervous system control of hemodynamics

BACKGROUND Laparoscopic radical prostatectomy induces hemodynamic changes that have been supposed due to autonomic nervous system activity. The aim of this study is to measure the sympathetic and vagal modulation on hemodynamic response to steep Trendelenburg and pneumoperitoneum for laparoscopic surgery. METHODS Autonomic nervous system modulation was assessed noninvasively through heart rate variability and arterial pressure variability analysis in patients undergoing elective laparoscopic radical prostatectomy and in awake volunteers during head-down tilt. RESULTS Forty patients and 14 awake volunteers were studied. The induction of general anesthesia significantly decreased the heart rate, arterial pressure, vagal modulation, and sympathetic modulation. Steep Trendelenburg increased vagal and sympathetic modulation both in anesthetized and awake subjects. Pneumoperitoneum increased arterial pressure without effect on autonomic nervous system control in anesthetized patients. CONCLUSIONS Hemodynamic changes occurring during laparoscopic radical prostatectomy reveal autonomic response to the challenges (i.e. general anesthesia and head down position), and non-neurally mediated increase of arterial pressure caused by pneumoperitoneum. This study supports the notion that during laparoscopic radical prostatectomy the association between the vagal stimulation due to Trendelenburg positioning and sympathetic withdrawal caused by general anesthesia could lead to severe bradycardia and cardiac arrest in risky patients.