Lilibeth A. Pineda

Effect of obesity on intensive care morbidity and mortality: a meta-analysis.

Objective:To evaluate the effect of obesity on intensive care unit mortality, duration of mechanical ventilation, and intensive care unit length of stay among critically ill medical and surgical patients. Design:Meta-analysis of studies comparing outcomes in obese (body mass index of ≥30 kg/m2) and nonobese (body mass index of <30 kg/m2) critically ill patients in intensive care settings. Data Source:MEDLINE, BIOSIS Previews, PubMed, Cochrane library, citation review of relevant primary and review articles, and contact with expert informants. Setting:Not applicable. Patients:A total of 62,045 critically ill subjects. Interventions:Descriptive and outcome data regarding intensive care unit mortality and morbidity were extracted by two independent reviewers, according to predetermined criteria. Data were analyzed using a random-effects model. Measurements and Main Results:Fourteen studies met inclusion criteria, with 15,347 obese patients representing 25% of the pooled study population. Data analysis revealed that obesity was not associated with an increased risk of intensive care unit mortality (relative risk, 1.00; 95% confidence interval, 0.86–1.16; p = .97). However, duration of mechanical ventilation and intensive care unit length of stay were significantly longer in the obese group by 1.48 days (95% confidence interval, 0.07–2.89; p = .04) and 1.08 days (95% confidence interval, 0.27–1.88; p = .009), respectively, compared with the nonobese group. In a subgroup analysis, an improved survival was observed in obese patients with body mass index ranging between 30 and 39.9 kg/m2 compared with nonobese patients (relative risk, 0.86; 95% confidence interval, 0.81–0.91; p < .001). Conclusion:Obesity in critically ill patients is not associated with excess mortality but is significantly related to prolonged duration of mechanical ventilation and intensive care unit length of stay. Future studies should target this population for intervention studies to reduce their greater resource utilization.

Comparison of potentiated and unpotentiated twitches as an index of muscle fatigue.

Recent data suggest that the potentiated twitch is a more sensitive index of contractile fatigue than is the unpotentiated twitch. We hypothesized that after a potentially fatiguing load, the fall in twitch amplitude of the potentiated twitch would be significantly greater than that of an unpotentiated twitch. We compared the response of the potentiated and unpotentiated twitches to a series of potentially fatiguing loads using magnetic stimulation of the femoral nerve in 10 healthy subjects. The baseline unpotentiated quadriceps twitch force (TwQu), potentiated quadriceps twitch force (TwQp), and maximal voluntary contraction (MVC) were 129 ± 6 N, 198 ± 6 N, and 622 ± 25 N, respectively. During a fatigue protocol that was designed to induce a spectrum of fatigue from mild to marked, the percent fall in quadriceps twitch force was significantly greater for the potentiated method than for the unpotentiated method at all levels of fatigue (P < .005). The within‐subject within‐day coefficient of variation was 7.5 ± 0.5% for TwQu and 5.6 ± 0.9% for TwQp. Thus, TwQp is reproducible and is superior to TwQu for detecting early muscle fatigue.

Effect of oral decontamination with chlorhexidine on the incidence of nosocomial pneumonia: a meta-analysis

IntroductionNosocomial pneumonia is a significant cause of in-hospital morbidity and mortality. Oral care interventions have great potential to reduce the occurrence of nosocomial pneumonia. Studies using topical antiseptic agents yielded mixed results. We hypothesized that the use of chlorhexidine for oral decontamination would reduce the incidence of nosocomial pneumonia in patients requiring mechanical ventilation.MethodsThis study is a meta-analysis of randomized controlled trials assessing the effect of chlorhexidine on the incidence of nosocomial pneumonia. Data sources were Medline, EMBASE, Cochrane library, citation review of relevant primary and review articles, and contact with expert informants. Out of 1,251 articles screened, 4 randomized, controlled trials were identified that included a total of 1,202 patients. Descriptive and outcome data were extracted by two reviewers independently. Main outcome measures were the incidence of nosocomial pneumonia, and mortality. A random effects model was used.ResultsThe incidence of nosocomial pneumonia in the control group was 7% (41 out of 615) compared to 4% (24 out of 587) in the treatment group. Gram-negative bacteria accounted for 78% of the total isolates, with Pseudomonas aeruginosa being the most frequently isolated pathogen irrespective of the intervention provided. Duration of mechanical ventilation and intensive care unit length of stay were comparable between the two groups. Overall, the use of oral decontamination with chlorhexidine did not affect the incidence of nosocomial pneumonia (odds ratio of 0.42; 95% confidence interval 0.16–1.06) or the mortality rate (odds ratio 0.77, 95% confidence interval 0.28–2.11).ConclusionThe use of oral decontamination with chlorhexidine did not result in significant reduction in the incidence of nosocomial pneumonia in patients who received mechanical ventilation, nor altered the mortality rate. The lack of benefit may reflect the few studies conducted in this area. Future trials should focus on a combination strategy of mechanical and pharmacological interventions.

Noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index ≥35 kg·m-2) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9–29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia.

RATIONALE Pseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates. OBJECTIVES To determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response. METHODS Thirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay. MEASUREMENTS AND MAIN RESULTS Twenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins. CONCLUSIONS The increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.

Outcome of Septic Shock in Older Adults After Implementation of the Sepsis “Bundle”

OBJECTIVES: To evaluate the effect on 28‐day mortality of implementation of a sepsis “bundle” protocol for the treatment of older adults with septic shock.

Determinants of short and long term functional recovery after hospitalization for community-acquired pneumonia in the elderly: role of inflammatory markers

BackgroundHospitalization for older patients with community-acquired pneumonia (CAP) is associated with functional decline. Little is know about the relationship between inflammatory markers and determinants of functional status in this population. The aim of the study is to investigate the association between tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and Activities of Daily Living, and to identify risk factors associated with one year mortality or hospital readmission.Methods301 consecutive patients hospitalized for CAP (mean age 73.9 ± 5.3 years) in a University affiliated hospital over 18 month period were included. All patients were evaluated on admission to identify baseline demographic, microbiological, cognitive and functional characteristics. Serum levels for TNF-α and CRP were collected at the same time. Reassessment of functional status at discharge, and monthly thereafter till 3 months post discharge was obtained and compared with preadmission level to document loss or recovery of functionality. Outcome was assessed by the composite endpoint of hospital readmission or death from any cause up to one year post hospital discharge.Results36% of patients developed functional decline at discharge and 11% had persistent functional impairment at 3 months. Serum TNF-α (odds ratio [OR] 1.12, 95% CI 1.08–1.15; p < 0.001) and the Charlson Index (OR = 1.39, 95% CI 1.14 to 1.71; p = 0.001) but not age, CRP, or cognitive status were independently associated with loss of functionality at the time of hospital discharge. Lack of recovery in functional status at 3 months was associated with impaired cognitive ability and preadmission comorbidities. In Cox regression analysis, persistent functional impairment at 3 months, impaired cognitive function, and the Charlson Index were highly predictive of one year hospital readmission or death.ConclusionSerum TNF-α levels can be useful in determining patients at risk for functional impairment following hospitalization from CAP. Old patients with impaired cognitive function and preexisting comorbidities who exhibit delay in functional recovery at 3 months post discharge may be at high risk for hospital readmission and death. With the scarcity of resources, a future risk stratification system based on these findings might be proven helpful to target older patients who are likely to benefit from interventional strategies.

Diagnostic yield of quantitative endotracheal aspirates in patients with severe nursing home-acquired pneumonia

IntroductionDiagnostic strategies based on tracheal aspirates in patients with severe nursing home-acquired pneumonia have not previously been evaluated. The objectives of the study were to investigate, in patients with severe nursing home-acquired pneumonia, the diagnostic value of quantitative endotracheal aspirate (QEA) cultures using increasing interpretative cutoff points, as compared with bronchoalveolar lavage (BAL) and protected specimen brush (PSB) quantitative cultures.MethodsSeventy-five nursing home patients requiring mechanical ventilation for suspected pneumonia were studied. Endotracheal aspirate, PSB, and BAL samples were obtained consecutively. The diagnostic yield of QEA at thresholds raging from 103 to 107 colony-forming units (cfu)/ml was assessed by calculating sensitivities, specificities, and accuracy rates. A receiver operator characteristic curve for the series of cutoff points was constructed.ResultsForty-nine patients were diagnosed with pneumonia either by BAL (≤ 104 cfu/ml) or PSB (≤ 103 cfu/ml). Diagnostic accuracy of QEA was most favorable at 104 cfu/ml. At this threshold, endotracheal aspirates coincided with both BAL and PSB in 30 cases, whereas partial agreement was observed in 14 cases. This resulted in sensitivity and specificity of 90% (95% confidence interval 78% to 97%) and 77% (95% confidence interval 56% to 91%), respectively. QEA findings correlated significantly with both PSB and BAL quantitative cultures (r = 0.71 [P < 0.001] and r = 0.77 [P < 0.001], respectively).ConclusionQEA may be used as a diagnostic tool to determine the presence of pneumonia in ventilated patients admitted from nursing homes when bronchoscopic procedures are not feasible or available.

Clinical and hemostatic responses to treatment in ventilator-associated pneumonia: role of bacterial pathogens.

Objective:To determine pathogen-specific kinetic changes in the alveolar procoagulant (PC) activity, tissue factor (TF), and tissue factor pathway inhibitor (TFPI) expression during the course of ventilator-associated pneumonia (VAP) and to assess the relationship between clinical resolution, intra-alveolar bacterial eradication, and restoration of hemostatic balance. Design:Prospective, multiple-center study in a cohort of VAP patients. Setting:Two university-affiliated intensive care units. Patients:Thirty-five patients with microbiologically documented VAP who received adequate antimicrobial coverage and 13 controls. Interventions:Nonbronchoscopic bronchoalveolar lavage was performed at the onset of VAP and on days 4 and 8 after initiation of antibiotic therapy. Samples were assayed for PC, TF, TFPI, and thrombin-antithrombin complex (TATc). The corresponding Clinical Pulmonary Infection Score (CPIS) was collected simultaneously. Measurements and Main Results:Isolated pathogens included Pseudomonas aeruginosa (n = 13), methicillin-resistant Staphylococcus aureus (MRSA) (n = 8), methicillin-sensitive S. aureus (MSSA) (n = 7), and Escherichia coli (n = 7). Although PC activity and TF were increased among the various pathogens at the onset of VAP, the levels of those with P. aeruginosa remained elevated at the end of treatment compared with controls and other etiological agents. TFPI levels were elevated for the duration of the study for all pathogens. A universal increase in TATc was noted at the onset of VAP, but the difference among the group of pathogens was significant at days 4 and 8 posttherapy. Despite the persisting hemostatic imbalance and incomplete intra-alveolar eradication of P. aeruginosa at end of therapy, the CPIS fell comparably at each time point irrespective of the etiological agents. Conclusions:Alveolar activation of the TF-dependent pathway may be species-specific in VAP and may not be adequately balanced by TFPI. The disparity between clinical response and eradication of P. aeruginosa from the intra-alveolar space suggests the need for biological markers to guide response to therapy.

Diaphragmatic function after intense exercise in congestive heart failure patients

Respiratory muscle strength and endurance is reduced in patients with congestive heart failure, making these patients susceptible to diaphragmatic fatigue during exercise. In order to determine whether or not contractile fatigue of the diaphragm occurs in patients with congestive heart failure following intense exercise, twitch transdiaphragmatic pressures (twitch Ptdi) were measured during unpotentiated and potentiated cervical magnetic stimulation (CMS) of the phrenic nerves before and at intervals after cycle endurance exercise. Ten patients aged 65.7±6.0 yrs (mean±sd) with an ejection fraction of 31.2±9.8% performed a constant-load symptom-limited exercise test at 60% of their peak work capacity. Twitch Ptdi at baseline were 15.9±6.3 cmH2O (unpotentiated CMS) and 28.8±10.7 cmH2O (potentiated CMS) and at 10 min postexercise were 16.4±4.7 cmH2O (unpotentiated CMS) and 27.6±10.1 cmH2O (potentiated CMS). One patient demonstrated a sustained fall in twitch Ptdi of ≥15%, considered potentially indicative of diaphragmatic fatigue. Contractile diaphragmatic fatigue is uncommon in untrained patients with congestive heart failure following high-intensity constant-workload cycle exercise. Therefore, diaphragmatic fatigue is an unlikely cause of exercise-limitation during activities of daily living in heart failure patients.