Modifiable Risk Factors for Delirium in Critically Ill Trauma Patients: A Multicenter Prospective Study.

OBJECTIVE:: Intensive care unit (ICU)-acquired delirium has been associated with increased morbidity and mortality. Prevention strategies including modification of delirium risk factors are emphasized by practice guidelines. No study has specifically evaluated modifiable delirium risk factors in trauma ICU patients. Our goal was to evaluate modifiable risk factors for delirium among trauma patients admitted to the ICU. DESIGN:: Prospective observational study. SETTING:: Two level 1 trauma ICU centers. PATIENTS:: Patients 18 years of age or older admitted for trauma including mild to moderate traumatic brain injury were eligible for the study. INTERVENTIONS AND MEASUREMENTS:: Delirium was assessed daily using the confusion assessment method for the ICU (CAM-ICU). The effect of modifiable risk factors was assessed using multivariate Cox regression analysis adjusting for severity of illness and significant nonmodifiable risk factors. MAIN RESULTS:: A total of 58 of 150 recruited patients (38.7%; 95% confidence interval [CI] 30.9-46.5) screened positive for delirium during ICU stay. When adjusting for significant nonmodifiable risk factors, physical restraints (hazard ratio [HR]: 2.13; 95% CI: 1.07-4.24) and active infection or sepsis (HR: 2.12; 95% CI: 1.18-3.81) significantly increased the risk of delirium, whereas opioids (HR: 0.35; 95% CI: 0.13-0.98), episodes of hypoxia (HR: 0.55; 95% CI: 0.31-0.95), access to a television/radio in the room (HR: 0.26; 95% CI: 0.11-0.62), and number of hours mobilized per day (HR: 0.77; 95% CI: 0.68-0.88) were associated with significantly less risk of delirium. CONCLUSION:: We have identified modifiable risk factors for delirium. Future studies should aim at implementing strategies to modify these risk factors and evaluate their impact on the risk of delirium.

The relationship between Candida species cultured from the respiratory tract and systemic inflammation in critically ill patients with ventilator-associated pneumonia.

PURPOSE: In patients with ventilator-associated pneumonia (VAP), the isolation of Candida species (spp.) in respiratory secretions has been associated with worse outcomes. It is unclear whether Candida colonization is causally related or is a marker of disease severity. The objective of this study was to compare systemic inflammatory markers in patients with a clinical suspicion of VAP with Candida in respiratory tract (RT) cultures vs patients who have bacteria and those with no pathogens. METHODS: This was a prospective observational study in adults with a clinical suspicion of VAP who were enrolled within 24 hr of intensive care unit (ICU) admission. Patients were divided into four groups according to RT cultures, i.e., bacterial pathogens only, Candida spp. only, culture negative, and a control group with no clinical suspicion of VAP. Clinical outcomes were collected and compared as were systemic inflammatory and coagulation markers, including procalcitonin (PCT), C-reactive protein (CRP) and interleukin (IL)-6. RESULTS: The PCT, CRP, and IL-6 levels were similar in the Candida, bacterial pathogen, and culture negative groups but were significantly increased between the Candida group and the control group (P < 0.05). In the first 28 days, the number of ICU free days was significantly lower in the Candida group compared with the other groups, and mortality at 28 days was greater (Candida 42.9%, bacterial pathogen 25.0%, culture negative 19.8%, control 0.0%; P < 0.05). CONCLUSIONS: In patients with a clinical suspicion of VAP, the presence of Candida spp. only in the RT is associated with similar levels of inflammation and worse clinical outcomes compared with patients without Candida in RT secretions.

The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients.

PURPOSE: Clinical uncertainty exists regarding the significance of colonization confined to respiratory tract secretions with Candida sp in critically ill patients. Our objectives were to describe such colonization, its associated risk factors, and to examine the clinical outcomes in patients with a clinical suspicion of ventilator-associated pneumonia with isolated Candida colonization compared to those without. MATERIALS AND METHODS: In a retrospective analysis of the Canadian ventilator-associated pneumonia study, patients were divided into 2 groups according to the isolated presence or absence of Candida in the respiratory tract enrollment culture. We compared length of mechanical ventilation, intensive care unit and hospital stay, and mortality outcomes between groups. We used multiple logistic regression analysis to determine factors independently associated with Candida colonization and hospital mortality. RESULTS: Of the 639 eligible patients, 114 (17.8%) were colonized with Candida in the enrollment culture. A multivariate analysis identified female sex (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.02-2.65), number of comorbidities (OR, 1.35; 95% CI, 1.08-1.71), worsening or persistent infiltrate at randomization (OR, 1.92; 95% CI, 1.09-1.38), antibiotics started within 3 days of randomization (OR, 3.16; 95% CI, 1.71-5.83), and on antibiotics at randomization but all started more than 3 days before randomization (OR, 3.04; 95% CI, 1.68-5.50) as variables associated with Candida respiratory tract colonization. A significant increase in median hospital stay (59.9 vs 38.6 days, P = .006) and hospital mortality (34.2% vs 21.0%, P = .003) was observed in patients with Candida colonization. In a multivariate model, Candida colonization of the respiratory tract was independently associated with hospital mortality (OR, 2.47; 95% CI, 1.39-4.37). CONCLUSION: Respiratory tract Candida colonization is associated with worse clinical outcomes and is independently associated with increased hospital mortality. However, it is unclear whether Candida colonization is causally related to poor outcomes or whether it is a marker for increased morbidity and mortality.

Impact of Candida species on clinical outcomes in patients with suspected ventilator-associated pneumonia.

BACKGROUND: The significance of Candida species in respiratory tract (RT) secretions in critically ill patients is unclear. METHODS: A retrospective analysis of the Canadian ventilator-associated pneumonia (VAP) trial was conducted. Only patients with suspected VAP whose initial cultures failed to grow any known pathogens were included. Using two fundamentally different statistical techniques that adjusted for important confounding variables, the clinical outcomes of patients with Candida species recovered from RT cultures were compared with patients whose RT cultures were not positive for Candida species. RESULTS: RT cultures yielded no identifiable bacterial pathogens in 274 patients; 68 patients had Candida species in the RT alone, while 206 patients did not have Candida species recovered from any site. The unadjusted OR of hospital mortality for patients with Candida species was 2.9 (95% CI 1.6 to 5.2; P<0.001). The hazard ratio of time to hospital discharge was 0.54 (95% CI 0.38 to 0.77; P=0.001). Logistic regression analysis demonstrated that age, Acute Physiology score and Chronic Health Evaluation (APACHE) II score, primary diagnosis of respiratory failure, two or more comorbidities and Candida species were independently associated with increased hospital mortality. Similar trends were observed with time to hospital discharge. The association between Candida species and increased mortality remained after controlling for potential confounders using both propensity score stratification and multivariable modelling approaches. CONCLUSIONS: Patients with suspected VAP, in whom no bacterial pathogen was identified and in whom Candida species were isolated from RT cultures, exhibited a greater burden of illness compared with similar patients without Candida. Whether Candida species colonization of RT secretions is a marker of disease severity or actually contributes to poorer clinical outcomes remains unclear.

Possible interaction between lopinavir/ritonavir and valproic Acid exacerbates bipolar disorder.

OBJECTIVE: To describe a case of exacerbated mania potentially related to an interaction between lopinavir/ritonavir and valproic acid (VPA) and propose a mechanism of action for this interaction. CASE SUMMARY: A 30-year-old man with bipolar disorder and HIV initiated treatment with lopinavir/ritonavir, zidovudine, and lamivudine. Prior to beginning therapy with these antiretrovirals, he was receiving VPA 250 mg 3 times daily, with his most recent VPA concentration measured at 495 micromol/L. Twenty-one days after starting antiretroviral treatment, he became increasingly manic. His VPA concentration at admission was 238 micromol/L, a 48% decrease. The daily VPA dose was increased to 1500 mg, and olanzapine was introduced. The VPA concentration following this dose escalation was 392 micromol/L, and the patient improved clinically. DISCUSSION: Fifty percent of VPA is metabolized by glucuronidation, 40% undergoes mitochondrial beta-oxidation, and less than 10% is eliminated by the cytochrome P450 isoenzymes. Ritonavir can induce glucuronidation of several medications including ethinyl estradiol, levothyroxine, and lamotrigine. We believe that ritonavir-mediated induction of VPA glucuronidation resulted in a decrease in VPA concentrations and efficacy. An objective causality assessment suggested that the increased mania was probably related to the decrease in VPA concentration and that a possible interaction exists between lopinavir/ritonavir and VPA. CONCLUSIONS: A potential interaction exists between VPA and all ritonavir-boosted antiretroviral regimens. Clinicians should monitor patients closely for a decreased VPA effect when these medications are given concomitantly.