Arzu Topeli

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies

BACKGROUND Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). INTERPRETATION The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING None.

Spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European intensive care units.

Objectives:Information on clinical practice regarding the diagnosis of pneumonia in European intensive care units is limited. The aim of this study was to describe the spectrum of actual diagnostic practices in a large sample of European intensive care units. Design:Prospective, observational, multicenter study. Setting:Twenty-seven intensive care units of nine European countries. Patients:Consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of pneumonia or receiving mechanical ventilation for >48 hrs irrespective of admission diagnosis. Interventions:None. Measurements and Main Results:A total of 2,436 patients were evaluated; 827 were admitted with or developed nosocomial pneumonia (hospital-acquired pneumonia [HAP], 27.1%; ventilator-associated pneumonia [VAP], 56.2%; very early onset VAP, 16.7%). Mean age was 59.4 ± 18.1 yrs, 65.0% were men, and mean admission Simplified Acute Physiology Score II was 46.7 ± 17.1. Worsening oxygenation (76.8%), purulent/changing respiratory secretions (72.1%), and new temperature elevation (69.2%) were the most frequent clinical signs of nosocomial pneumonia. Etiological diagnosis was based on noninvasive respiratory specimens in 74.8% of episodes. Bronchoscopy was performed in 23.3% of episodes. Bronchoscopy performance, after adjustment by severity of illness, age, and type of hospital, were predicted by worsening oxygenation (odds ratio 2.03; 95% confidence interval, 1.27–3.24) and male sex (odds ratio 1.77; 95% confidence interval, 1.19–2.65). Definite cause was documented in 69.5% of nosocomial pneumonia cases. The most common isolates were Staphylococcus aureus (16.3% methicillin-sensitive S. aureus and 16.0% methicillin-resistant S. aureus), Pseudomonas aeruginosa (23.1%), and Acinetobacter baumannii (19.1%). Presence of nosocomial pneumonia significantly prolonged mean length of mechanical ventilation (10.3 days, p < .05) and mean intensive care unit length of stay (12.2 days, p < .05) in intensive care unit survivors. Mortality rate was 37.7% for nosocomial pneumonia vs. 31.6% for patients without pneumonia (p < .05). Conclusions:Etiological diagnosis of nosocomial pneumonia in a large sample of European intensive care units was based mainly on noninvasive techniques. However, there was high variability in bronchoscopy use between the participating intensive care units.

Transfusion-associated graft-versus-host disease in immunocompetent patients: case series and review of the literature

BACKGROUND: Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a fatal complication of transfusion of blood products that usually affects immunocompromised patients. Articles reporting this condition in immunocompetent recipients are usually from countries that still have problems in irradiation of blood products.

Rhabdomyolysis in a Patient Treated with Colchicine and Atorvastatin

Objective: To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. Case Summary: A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50–fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. Discussion: Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatins proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. Conclusions: We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.

Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish University Hospital

A total of 101 episodes of Staphylococcus aureus bacteraemia were evaluated for the factors influencing prognosis. The overall episode mortality rate and the mortality rate due to bacteraemia were 43.6 and 21.8%, respectively. Episodes with methicillin-resistant S. aureus (MRSA) bacteraemia had a significantly higher overall mortality rate (58.7 vs. 30.9%, P<0.01) and mortality rate due to bacteraemia (32.6 vs. 12.7%, P=0.02) when compared with episodes caused by methicillin-sensitive S. aureus (MSSA). The multivariate analysis revealed that the underlying disease, presence of infective endocarditis, septic shock and central intravascular catheter and methicillin resistance of S. aureus were the five independent risk factors associated with a higher mortality rate.

Patient to Nurse Ratio and Risk of Ventilator-Associated Pneumonia in Critically Ill Patients

OBJECTIVE To determine how the patient to nurse ratio affects risk for ventilator-associated pneumonia. METHODS Data from an earlier study in 27 intensive care units in 9 European countries were examined in a secondary analysis. The initial cohort included 2585 consecutive patients who had mechanical ventilation (1) after admission for treatment of pneumonia or (2) for more than 48 hours irrespective of the diagnosis at admission. In units with variable staffing levels, the highest patient to nurse ratio in a 24-hour period was considered. Patients from 6 units that did not provide data on nurse staffing levels were excluded from the analysis. RESULTS Ventilator-associated pneumonia developed in 393 of the 1658 patients (23.7%) in the secondary cohort. In units with patient to nurse ratios of 1 to 1, 2 to 1, 2.5 to 1, and 3 to 1, rates were 9.3%, 25.7%, 18.7%, and 24.2%, respectively (P = .003). Rates were significantly lower (P = .002) in units with a ratio of 1 to 1 (9.3%) than in units with a ratio of more than 1 patient to 1 nurse (24.4%). After adjustments for confounding covariates, ratios of more than 1 patient to 1 nurse were no longer associated with increased risk for ventilator-associated pneumonia. CONCLUSIONS A patient to nurse ratio of 1 to 1 appears to be associated with a lower risk for ventilator-associated pneumonia, but after adjustments for confounding covariates, the difference is not significant.

The voluntary drive to breathe is not decreased in hypercapnic patients with severe COPD

How do the respiratory centres of patients with chronic obstructive pulmonary disease (COPD) and hypercapnia respond to acute increases in inspiratory load? A depressed respiratory motor output has long been postulated, but studies on this issue have yielded inconsistent results, partly due to limitations of investigative techniques. Many of these limitations can be overcome by the twitch interpolation technique, which is capable of accurately quantifying the degree of diaphragmatic activation, termed the voluntary drive to breathe. The hypothesis that patients with COPD and hypercapnia compensate for an acute increase in mechanical load on the inspiratory muscles with a lower voluntary drive to breathe than is the case with normocapnic patients was tested. Measurements were obtained in 15 patients with COPD, six of whom displayed hypercapnia and nine normocapnia. The maximum degree of diaphragmatic activation, expressed as a voluntary activation index (mean +/- SEM), was higher in hypercapnic than in normocapnic patients (98.7 +/- 0.7 versus 94.5 +/- 0.9% (p = 0.006)), as was the mean value (94.5 +/- 0.7 versus 88.5 +/- 1.9% (p = 0.01)). Within-patient values of the index were also less variable in the hypercapnic patients (coefficients of variation, 3.4 +/- 0.3 versus 6.1 +/- 0.9%, p = 0.01). Multiple regression analysis revealed the ratio of dynamic elastance to maximum transdiaphragmatic pressure, an index of inspiratory muscle loading, and pH as the only variables that correlated with maximum voluntary activation index (r2 = 0.69, p = 0.02 for each variable). Contrary to the hypothesis, it was concluded that voluntary activation of the diaphragm was greater and less variable in hypercapnic patients than normocapnic patients with severe chronic obstructive pulmonary disease during an acute increase in inspiratory mechanical load. Whether greater diaphragmatic recruitment during episodes of a severe exacerbation of chronic obstructive pulmonary disease provides a survival advantage for hypercapnic patients with chronic obstructive pulmonary disease remains to be determined.

Effect of enteral versus parenteral nutrition on outcome of medical patients requiring mechanical ventilation.

BACKGROUND Early enteral nutrition (EN) in patients receiving mechanical ventilation commonly has been advocated, based mainly on studies conducted in mixed populations of trauma and surgery patients. In this study, ventilator-associated pneumonia rates and outcomes were compared in mechanically ventilated medical intensive care unit (ICU) patients receiving enteral versus parenteral nutrition. METHODS Patients fulfilling inclusion criteria between February 1, 2004, and January 31, 2006, were included. Patients were randomized to enteral or parenteral nutrition (PN) within 48 hours of intubation. Development of ventilator-associated pneumonia, assessment as to whether day feeding goal was attained, duration of mechanical ventilation, ICU and hospital length of stay (LOS), and mortality rates were recorded. RESULTS Of 249 consecutive patients receiving mechanical ventilation, 71 patients were included. Thirty (42.3%) patients received EN, and 41 (57.7%) received PN. There was no difference between groups for age, sex, body mass index, and scores on the Acute Physiology and Chronic Health Evaluation II. Ventilator-associated pneumonia rate, ICU and hospital LOS, and mortality rates were similar for both groups. In the parenterally fed group, duration of mechanical ventilation was longer (p = .023), but the feeding goal was attained earlier (p = .012). CONCLUSIONS In mechanically ventilated patients in the medical ICU, ventilator-associated pneumonia rates, ICU and hospital lengths of stay, and ICU and hospital mortality rates of patients receiving PN are not significantly different than those in patients receiving EN, and feeding goals can more effectively be attained by PN. Yet, duration of mechanical ventilation is slightly longer in patients receiving PN.

Triage decisions for ICU admission: Report from the Task Force of the World Federation of Societies of Intensive and Critical Care Medicine.

Demand for intensive care unit (ICU) resources often exceeds supply, and shortages of ICU beds and staff are likely to persist. Triage requires careful weighing of the benefits and risks involved in ICU admission while striving to guarantee fair distribution of available resources. We must ensure that the patients who occupy ICU beds are those most likely to benefit from the ICUs specialized technology and professionals. Although prognosticating is not an exact science, preference should be given to patients who are more likely to survive if admitted to the ICU but unlikely to survive or likely to have more significant morbidity if not admitted. To provide general guidance for intensivists in ICU triage decisions, a task force of the World Federation of Societies of Intensive and Critical Care Medicine addressed 4 basic questions regarding this process. The team made recommendations and concluded that triage should be led by intensivists considering input from nurses, emergency medicine professionals, hospitalists, surgeons, and allied professionals. Triage algorithms and protocols can be useful but can never supplant the role of skilled intensivists basing their decisions on input from multidisciplinary teams. Infrastructures need to be organized efficiently both within individual hospitals and at the regional level. When resources are critically limited, patients may be refused ICU admission if others may benefit more on the basis of the principle of distributive justice.

Long-term simvastatin attenuates lung injury and oxidative stress in murine acute lung injury models induced by oleic Acid and endotoxin.

BACKGROUND: 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have several pleiotropic effects, including anti-inflammatory properties, and are reported to improve endothelial functions. Pathophysiologically, acute lung injury (ALI) is caused by a severe inflammatory response and endothelial dysfunction. OBJECTIVE: To investigate the effects of simvastatin (an HMG-CoA reductase inhibitor) on oxidative stress and lung histopathology in 2 murine models of ALI, induced by oleic acid and endotoxin. METHODS: The mice were randomly divided into 2 groups: one received 2 mg/kg/d intraperitoneal simvastatin for 15 days. Then the groups were further divided into 3, which received saline, oleic acid, or endotoxin. Four hours after inducing ALI we obtained lung samples for histopathology analysis, myeloperoxidase, glutathione, and malondialdehyde measurement, and blood samples for malondialdehyde measurement. RESULTS: Endotoxin and oleic acid lung injury increased tissue myeloperoxidase (P = .009 for both), decreased tissue glutathione (P = .02 and P = .009, respectively), and increased tissue malondialdehyde (P = .009 for both), compared to the control group. Simvastatin decreased myeloperoxidase only in the oleic acid group (P = .01). Simvastatin increased glutathione (P = .005 and P = .003, respectively) and lowered malondialdehyde in both the endotoxin and oleic acid groups (P = .003 for both). Histopathology revealed that simvastatin protected the lung tissue in both ALI models, but the protection was greater in the endotoxin group. CONCLUSIONS: Pretreatment with simvastatin decreased the severity of ALI in oleic acid and endotoxin ALI models, by decreasing inflammation and oxidative stress.