Rafael Mañez

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation >48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence >10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50–4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14–0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence >10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0–6.1) and colistin (OR 115.7, 95% CI 6.9–1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p = 0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6–12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence >10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Bacteremia is an independent risk factor for mortality in nosocomial pneumonia: a prospective and observational multicenter study

IntroductionSince positive blood cultures are uncommon in patients with nosocomial pneumonia (NP), the responsible pathogens are usually isolated from respiratory samples. Studies on bacteremia associated with hospital-acquired pneumonia (HAP) have reported fatality rates of up to 50%. The purpose of the study is to compare risk factors, pathogens and outcomes between bacteremic nosocomial pneumonia (B-NP) and nonbacteremic nosocomial pneumonia (NB-NP) episodes.MethodsThis is a prospective, observational and multicenter study (27 intensive care units in nine European countries). Consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of pneumonia or on mechanical ventilation for > 48 hours irrespective of admission diagnosis were recruited.ResultsA total of 2,436 patients were evaluated; 689 intubated patients presented with NP, 224 of them developed HAP and 465 developed ventilation-acquired pneumonia. Blood samples were extracted in 479 (69.5%) patients, 70 (14.6%) being positive. B-NP patients had higher Simplified Acute Physiology Score (SAPS) II score (51.5 ± 19.8 vs. 46.6 ± 17.5, P = 0.03) and were more frequently medical patients (77.1% vs. 60.4%, P = 0.01). Mortality in the intensive care unit was higher in B-NP patients compared with NB-NP patients (57.1% vs. 33%, P < 0.001). B-NP patients had a more prolonged mean intensive care unit length of stay after pneumonia onset than NB-NP patients (28.5 ± 30.6 vs. 20.5 ± 17.1 days, P = 0.03). Logistic regression analysis confirmed that medical patients (odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.93 to 16.99, P = 0.002), methicillin-resistant Staphylococcus aureus (MRSA) etiology (OR = 3.42, 95% CI = 1.57 to 5.81, P = 0.01), Acinetobacter baumannii etiology (OR = 4.78, 95% CI = 2.46 to 9.29, P < 0.001) and days of mechanical ventilation (OR = 1.02, 95% CI = 1.01 to 1.03, P < 0.001) were independently associated with B-NP episodes. Bacteremia (OR = 2.01, 95% CI = 1.22 to 3.55, P = 0.008), diagnostic category (medical patients (OR = 3.71, 95% CI = 2.01 to 6.95, P = 0.02) and surgical patients (OR = 2.32, 95% CI = 1.10 to 4.97, P = 0.03)) and higher SAPS II score (OR = 1.02, 95% CI = 1.01 to 1.03, P = 0.008) were independent risk factors for mortality.ConclusionsB-NP episodes are more frequent in patients with medical admission, MRSA and A. baumannii etiology and prolonged mechanical ventilation, and are independently associated with higher mortality rates.

Impact of non-neurological complications in severe traumatic brain injury outcome

IntroductionNon-neurological complications in patients with severe traumatic brain injury (TBI) are frequent, worsening the prognosis, but the pathophysiology of systemic complications after TBI is unclear. The purpose of this study was to analyze non-neurological complications in patients with severe TBI admitted to the ICU, the impact of these complications on mortality, and their possible correlation with TBI severity.MethodsAn observational retrospective cohort study was conducted in one multidisciplinary ICU of a university hospital (35 beds); 224 consecutive adult patients with severe TBI (initial Glasgow Coma Scale (GCS) < 9) admitted to the ICU were included. Neurological and non-neurological variables were recorded.ResultsSepsis occurred in 75% of patients, respiratory infections in 68%, hypotension in 44%, severe respiratory failure (arterial oxygen pressure/oxygen inspired fraction ratio (PaO2/FiO2) < 200) in 41% and acute kidney injury (AKI) in 8%. The multivariate analysis showed that Glasgow Outcome Score (GOS) at one year was independently associated with age, initial GCS 3 to 5, worst Traumatic Coma Data Bank (TCDB) first computed tomography (CT) scan and the presence of intracranial hypertension but not AKI. Hospital mortality was independently associated with initial GSC 3 to 5, worst TCDB first CT scan, the presence of intracranial hypertension and AKI. The presence of AKI regardless of GCS multiplied risk of death 6.17 times (95% confidence interval (CI): 1.37 to 27.78) (P < 0.02), while ICU hypotension increased the risk of death in patients with initial scores of 3 to5 on the GCS 4.28 times (95% CI: 1.22 to15.07) (P < 0.05).ConclusionsLow initial GCS, worst first CT scan, intracranial hypertension and AKI determined hospital mortality in severe TBI patients. Besides the direct effect of low GCS on mortality, this neurological condition also is associated with ICU hypotension which increases hospital mortality among patients with severe TBI. These findings add to previous studies that showed that non-neurological complications increase the length of stay and morbidity in the ICU but do not increase mortality, with the exception of AKI and hypotension in low GCS (3 to 5).

TNF, pig CD86, and VCAM-1 identified as potential targets for intervention in xenotransplantation of pig chondrocytes.

Xenotransplantation of genetically engineered porcine chondrocytes may benefit many patients who suffer cartilage defects. In this work, we sought to elucidate the molecular bases of the cellular response to xenogeneic cartilage. To this end, we isolated pig costal chondrocytes (PCC) and conducted a series of functional studies. First, we determined by flow cytometry the cell surface expression of multiple immunoregulatory proteins in resting conditions or after treatment with human TNF-α, IL-1α, or IL-1β, which did not induce apoptosis. TNF-α and to a lesser extent IL-1α led to a marked upregulation of SLA I, VCAM-1, and ICAM-1 on PCC. SLA II and E-selectin remained undetectable in all the conditions assayed. Notably, CD86 was constitutively expressed at moderate levels, whereas CD80 and CD40 were barely detected. To assess their function, we next studied the interaction of PCC with human monoblastic U937 and Jurkat T cells. U937 cells adhered to resting and in a greater proportion to cytokine-stimulated PCC. Consistent with its expression pattern, pig VCAM-1 was key, mediating the increased adhesion after cytokine stimulation. We also conducted coculture experiments with U937 and PCC and measured the release of pig and human cytokines. Stimulated PCC secreted IL-6 and IL-8, whereas U937 secreted IL-8 in response to PCC. Finally, coculture of PCC with Jurkat in the presence of PHA led to a marked Jurkat activation as determined by the increase in IL-2 secretion. This process was dramatically reduced by blocking pig CD86. In summary, CD86 and VCAM-1 on pig chondrocytes may be important triggers of the xenogeneic cellular immune response. These molecules together with TNF could be considered potential targets for intervention in order to develop xenogeneic therapies for cartilage repair.

Characterization of immunogenic Neu5Gc in bioprosthetic heart valves.

The two common sialic acids (Sias) in mammals are N‐acetylneuraminic acid (Neu5Ac) and its hydroxylated form N‐glycolylneuraminic acid (Neu5Gc). Unlike most mammals, humans cannot synthesize Neu5Gc that is considered foreign and recognized by circulating antibodies. Thus, Neu5Gc is a potential xenogenic carbohydrate antigen in bioprosthetic heart valves (BHV) that tend to deteriorate in time within human patients.

A randomized clinical trial for the timing of tracheotomy in critically ill patients: factors precluding inclusion in a single center study

IntroductionWe investigated the potential benefits of early tracheotomy performed before day eight of mechanical ventilation (MV) compared with late tracheotomy (from day 14 if it still indicated) in reducing mortality, days of MV, days of sedation and ICU length of stay (LOS).MethodsRandomized controlled trial (RCT) including all-consecutive ICU admitted patients requiring seven or more days of MV. Between days five to seven of MV, before randomization, the attending physician (AP) was consulted about the expected duration of MV and acceptance of tracheotomy according to randomization. Only accepted patients received tracheotomy as result of randomization. An intention to treat analysis was performed including patients accepted for the AP and those rejected without exclusion criteria.ResultsA total of 489 patients were included in the RCT. Of 245 patients randomized to the early group, the procedure was performed for 167 patients (68.2%) whereas in the 244 patients randomized to the late group was performed for 135 patients (55.3%) (P <0.004). Mortality at day 90 was similar in both groups (25.7% versus 29.9%), but duration of sedation was shorter in the early tracheotomy group median 11 days (range 2 to 92) days compared to 14 days (range 0 to 79) in the late group (P <0.02). The AP accepted the protocol of randomization in 205 cases (42%), 101 were included in early group and 104 in the late group. In these subgroup of patients (per-protocol analysis) no differences existed in mortality at day 90 between the two groups, but the early group had more ventilator-free days, less duration of sedation and less LOS, than the late group.ConclusionsThis study shows that early tracheotomy reduces the days of sedation in patients undergoing MV, but was underpowered to prove any other benefit. In those patients selected by their attending physicians as potential candidates for a tracheotomy, an early procedure can lessen the days of MV, the days of sedation and LOS. However, the imprecision of physicians to select patients who will require prolonged MV challenges the potential benefits of early tracheotomy.Trial registrationControlled-Trials.com ISRCTN22208087. Registered 27 March 2014.

Influence of cirrhosis in cardiac surgery outcomes.

Liver cirrhosis has evolved an important risk factor for cardiac surgery due to the higher morbidity and mortality that these patients may suffer compared with general cardiac surgery population. The presence of contributing factors for a poor outcome, such as coagulopathy, a poor nutritional status, an adaptive immune dysfunction, a degree of cirrhotic cardiomyopathy, and a degree of renal and pulmonary dysfunction, have to be taken into account for surgical evaluation when cardiac surgery is needed, together with the degree of liver disease and its primary complications. The associated pathophysiological characteristics that liver cirrhosis represents have a great influence in the development of complications during cardiac surgery and the postoperative course. Despite the population of cirrhotic patients who are referred for cardiac surgery is small and recommendations come from small series, since liver cirrhotic patients have increased their chance of survival in the last 20 years due to the advances in their medical care, which includes liver transplantation, they have been increasingly considered for cardiac surgery. Indeed, there is an expected rise of cirrhotic patients within the cardiac surgical population due to the increasing rates of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, especially in western countries. In consequence, a more specific approach is needed in the assessment of care of these patients if we want to improve their management. In this article, we review the pathophysiology and outcome prediction of cirrhotic patients who underwent cardiac surgery.

Evaluation of Serial Arterial Lactate Levels as a Predictor of Hospital and Long-Term Mortality in Patients After Cardiac Surgery

OBJECTIVES Although hyperlactatemia is common after cardiac surgery, its value as a prognostic marker is unclear. The aim of the present study was to determine whether postoperative serial arterial lactate (AL) measurements after cardiac surgery could predict outcome. DESIGN Prospective, observational study. SETTING Surgical intensive care unit in a tertiary-level university hospital. PARTICIPANTS Participants included 2,935 consecutive patients. INTERVENTIONS AL was measured on admission to the intensive care unit and 6, 12, and 24 hours after surgery, and evaluated together with clinical data and outcomes including in-hospital and long-term mortality. MEASUREMENTS AND MAIN RESULTS In-hospital and long-term mortality (mean follow-up 6.3±1.7 years) were 5.9% and 8.7%, respectively. Compared with survivors, nonsurvivors showed higher mean AL values in all measurements (p<0.001). Hyperlactatemia (AL>3.0 mmol/L) was a predictor for in-hospital mortality (odds ratio = 1.468; 95% confidence interval = 1.239-1.739; p<0.001) and long-term mortality (hazard ratio = 1.511; 95% confidence interval = 1.251-1.825; p<0.001). Recent myocardial infarction and longer cardiopulmonary bypass time were predictors of hyperlactatemia. The pattern of AL dynamics was similar in both groups, but nonsurvivors showed higher AL values, as confirmed by repeated measures analysis of variance (p<0.001). The area under the curve also showed higher levels of AL in nonsurvivors (80.9±68.2 v 49.71±25.8 mmol/L/h; p = 0.038). Patients with hyperlactatemia were divided according to their timing of peak AL, with higher mortality and worse survival in patients in whom AL peaked at 24 hours compared with other groups (79.1% v 86.7%-89.2%; p = 0.03). CONCLUSIONS The dynamics of the postoperative AL curve in patients undergoing cardiac surgery suggests a similar mechanism of hyperlactatemia in survivors and nonsurvivors, albeit with a higher production or lower clearance of AL in nonsurvivors. The presence of a peak of hyperlactatemia at 24 hours is associated with higher in-hospital and long-term mortality.

Outcomes of abdominal surgery in patients with liver cirrhosis.

Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery.

Higher requirements of dialysis in severe lithium intoxication.

Severe lithium poisoning is a frequent condition in the intoxicated intensive care unit population. Dialysis is the treatment of choice, but no clinical markers predicting higher requirement for dialysis have been identified to date. We analyze the characteristics of lithium overdose patients needing dialysis to improve lithium clearance, and identify the ones associated with higher dialysis requirement. This is an observational, retrospective study of 14 patients with lithium poisoning admitted from 2004 to 2009. Median age was 41.8 ± 16.1 years. Poisonings were acute in 7.1%, acute‐on‐chronic in 64.28%, and chronic in 28.5% of cases. Comparing clinical and biochemical data in patients requiring more than one dialysis session with those requiring only one session, the univariate analysis showed differences at admission in creatinine clearance (40.5 ± 23 vs. 73.3 ± 24.9 mL/min, P = 0.025), white blood cells (17528 ± 3530 vs. 11580 ± 3360 cells/L, P = 0.007), and blood sodium concentration (134.8 ± 5.9 vs. 141.8 ± 8.4 mmol/L, P=0.035). We measured the degree of association between the number of sessions and the variables with partial correlations. High lithium levels (P = 0.006, r = 0.69), low creatinine clearance (P = 0.04, r = −0.55), and low blood sodium concentration (P = 0.024, r = −0.59) were associated with a greater number of dialysis sessions. The correlation remained significant for blood sodium concentration (P = 0.016, r = −0.67) after adjustment for creatinine clearance and initial lithium levels. Presence on admission of low creatinine clearance, low blood sodium concentration, and/or high lithium levels correlated with a higher number of dialysis sessions in severe lithium poisoning. These factors, especially low blood sodium concentration, are associated with higher dialysis requirements in severe lithium intoxication.