Amado X. Freire

Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients.

Objective:To evaluate the literature and identify important aspects of insulin therapy that facilitate safe and effective infusion therapy for a defined glycemic end point. Methods:Where available, the literature was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to assess the impact of insulin infusions on outcome for general intensive care unit patients and those in specific subsets of neurologic injury, traumatic injury, and cardiovascular surgery. Elements that contribute to safe and effective insulin infusion therapy were determined through literature review and expert opinion. The majority of the literature supporting the use of insulin infusion therapy for critically ill patients lacks adequate strength to support more than weak recommendations, termed suggestions, such that the difference between desirable and undesirable effect of a given intervention is not always clear. Recommendations:The article is focused on a suggested glycemic control end point such that a blood glucose ≥150 mg/dL triggers interventions to maintain blood glucose below that level and absolutely <180 mg/dL. There is a slight reduction in mortality with this treatment end point for general intensive care unit patients and reductions in morbidity for perioperative patients, postoperative cardiac surgery patients, post-traumatic injury patients, and neurologic injury patients. We suggest that the insulin regimen and monitoring system be designed to avoid and detect hypoglycemia (blood glucose ⩽70 mg/dL) and to minimize glycemic variability.Important processes of care for insulin therapy include use of a reliable insulin infusion protocol, frequent blood glucose monitoring, and avoidance of finger-stick glucose testing through the use of arterial or venous glucose samples. The essential components of an insulin infusion system include use of a validated insulin titration program, availability of appropriate staffing resources, accurate monitoring technology, and standardized approaches to infusion preparation, provision of consistent carbohydrate calories and nutritional support, and dextrose replacement for hypoglycemia prevention and treatment. Quality improvement of glycemic management programs should include analysis of hypoglycemia rates, run charts of glucose values <150 and 180 mg/dL. The literature is inadequate to support recommendations regarding glycemic control in pediatric patients. Conclusions:While the benefits of tight glycemic control have not been definitive, there are patients who will receive insulin infusion therapy, and the suggestions in this article provide the structure for safe and effective use of this therapy.

Characteristics associated with analgesia ordering in the intensive care unit and relationships with outcome

Objective To describe clinical characteristics associated with analgesia utilization in the intensive care unit. Design A prospective cohort study of adult patients admitted to a medical intensive care unit. Subjects Four hundred adult patients. Setting Twelve-bed medical intensive care unit of an inner-city, university-affiliated hospital. Measurements and Main Results Collected data included demographics, sedation and neuromuscular blocking agents used, mechanical ventilation, hemodynamic monitoring, Therapeutic Intervention Scoring System score, Logistic Organ Dysfunction System (LODS) score, and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Hospital outcome was noted. The odds ratio and 95% confidence intervals were determined by using multiple logistic regression analyses. Patients’ mean age (±sd) was 47.8 ± 17.1 yrs; 58% were male, 84% African-American. Their APACHE II-predicted hospital mortality rate was 33%. Analgesics were used in 36% of patients. There were no differences in demographics, initial LODS score, APACHE II score, and mechanical ventilation use between patients who did and did not receive analgesics. Multiple logistic regression analysis showed that analgesic use was independently associated with sedation (odds ratio, 2.47; 95% confidence interval, 1.47–4.14), neuromuscular blockade (odds ratio, 4.98; 95% confidence interval, 1.85–13.41), and pulmonary artery flotation catheter utilization (odds ratio, 2.31; 95% confidence interval, 1.27–4.20). The median duration of mechanical ventilation was 5 days for those who received analgesia compared with 2 for those who did not (p = .0001). The median length of stay in the intensive care unit (4 vs. 2, p < .0001) and hospital (11 vs. 7, p < .0001) was higher in patients who received analgesics. There were no significant differences in intensive care unit and hospital mortality rates between patients who did and did not receive analgesics. Conclusions Intensive care unit patients for whom analgesics were prescribed have a higher frequency of hemodynamic monitoring and use of sedative and neuromuscular blocking agents, more mechanical ventilation days, and longer intensive care unit and hospital lengths of stay.

A Comparison Study of Continuous Insulin Infusion Protocols in the Medical Intensive Care Unit: Computer-Guided Vs. Standard Column-Based Algorithms

PURPOSE To compare the safety and efficacy of continuous insulin infusion (CII) via a computer-guided and a standard paper form protocol in a medical intensive care unit (ICU). METHODS Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL. RESULTS The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within-patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561). CONCLUSION Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer-based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol.

Association of pulmonary artery catheter use with in-hospital mortality

Objective To determine the association of pulmonary artery catheter (PAC) use with in-hospital mortality. Design Prospective, observational study. Setting The medical intensive care units (MICU) of two teaching hospitals. Methods The study included 751 adults who were admitted to the MICU, excluding those who stayed for <24 hrs. Demographics and the worst Acute Physiology and Chronic Health Evaluation (APACHE) II score within the first 24 hrs of MICU admission were obtained. Daily logistic organ dysfunction system (LODS) scores were calculated. The associations of in-hospital mortality with the admission source, admission disease category, APACHE II scores, the worst LODS scores, mechanical ventilation, and PAC use were determined using chi-square, Mann-Whitney U, and multiple logistic regression analysis tests. p Values < 0.05 were considered significant. Results Mean patient age was 52.6 ± 17.1 yrs; 425 (57%) were male; 464 (62%) were African-American, 275 (37%) Caucasian, 6 (1%) Asian, and 6 (1%) Hispanic. PAC was used in 119/751 (16%). The median APACHE II and worst LODS scores were 19 and 4, respectively. The in-hospital mortality rate was 159/751 (21%). The median APACHE II score for survivors was 17.5, compared with 28.0 for nonsurvivors (p < .0001). The worst median LODS score was 4 for survivors, compared with 11 for nonsurvivors (p < .0001). Sixty-four (54%) of the 119 patients with PAC died, compared with 95 (15%) of the 632 without PAC (p < .0001). Multiple logistic regression analysis showed that higher APACHE II-predicted mortality rate (p = .0088) and worst daily LODS score (p < .0001) were associated with increased mortality. The admission source, admission disease category, PAC use, and mechanical ventilation were not associated with in-hospital mortality. Conclusions This study could not detect an association between PAC use and mortality. The APACHE II-predicted mortality rate and the development of multiple organ dysfunction were the main determinants of poor outcome in critically ill patients admitted to MICU.

Predictors of Mortality in Elderly Subjects with Obstructive Airway Disease: The PILE Score

PURPOSE To identify significant covariates in addition to spirometry that predict mortality in elderly subjects with obstructive airway disease (OAD). METHODS Two hundred sixty-eight (268) participants with OAD from the Health, Aging and Body Composition study, a community-based observational cohort of well-functioning elderly aged 70-79 years, were followed on average for 6.1 years. Covariates related to pulmonary and physical function, comorbidity, demographics, and three inflammatory markers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein) were evaluated for their association with all-cause mortality (31%) by means of Kaplan Meier analysis and Cox proportional hazards modeling. RESULTS Percent predicted forced expiratory volume in one second (PPFEV1; hazard ratio [HR] = 2.03, p < 0.0001), knee extensor strength (HR = 1.36, p = 0.0002), interleukin-6 (HR = 1.37, p = 0.0002) and 400 m corridor walk time (HR = 1.24, p = 0.008) significantly predicted mortality. A multidimensional index, the PILE score, was constructed from PPFEV(1), interleukin-6, and knee extensor strength. Each one-point increase in PILE score (range: 1-10) was associated with a 30% increase in mortality (95% confidence interval: 0.16-0.47) after adjusting for age, race, gender, smoking, and comorbidity, resulting in a 10.4-fold higher risk of death between the highest and lowest risk category. CONCLUSIONS Subjects with OAD have a wide gradient of risk for mortality that can potentially be incorporated in clinical decision making.

Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS

Acute respiratory distress syndrome (ARDS) is a disease of multifactorial etiology characterised by rapid development of severe diffuse and nonhomogenous inflammation of the pulmonary lobules causing life-threatening hypoxaemic respiratory failure. The current authors tested a therapeutic intervention on a previously defined pathophysiological model of ARDS. The model was defined by investigating, during the natural history of ARDS, the relationship among the three fundamental elements of a disease process pathogenesis, structural alterations, and functional consequences. In these studies, the present authors provided biological and morphological evidence indicating that ARDS patients failing to improve after 1 week of mechanical ventilation (unresolving ARDS) have intense and protracted (dysregulated) pulmonary and systemic inflammatory and neo-fibrogenetic activity. Nuclear factor-κB and the glucocorticoid receptor have diametrically opposed functions in regulating inflammation. This chapter will review recent data indicating that poor outcome in acute respiratory distress syndrome might be related in part to failure of the activated glucocorticoid receptors to downregulate the transcription of inflammatory cytokines despite elevated levels of circulating cortisol. In a small randomised study of patients with unresolving acute respiratory distress syndrome, the current authors have shown that prolonged glucocorticoid supplementation improved all aspects of glucocorticoid receptors function and enhanced glucocorticoid-mediated anti-inflammatory action by interfering with nuclear factor-κB activation.

Dual Time Point Positron Emission Tomography/Computed Tomography Scan in Evaluation of Intrathoracic Lesions in an Area Endemic for Histoplasmosis and With High Prevalence of Sarcoidosis

Background:We explored the role of dual time point fluorodeoxyglucose positron emission tomography/computed tomography (DTP PET/CT) scan in the differentiation of benign and malignant lung and mediastinal lesions. Methods:We studied a sample of 72 consecutive patients who underwent DTP PET/CT scan for intrathoracic lesions. Information on demographics, initial and delayed maximum standardized uptake values (SUVmax) of lesions and final diagnosis were collected. Clinical criteria to diagnose benign lesions were defined as stability or regression of the lesion on follow-up after 2 years of initial detection. Sensitivity, specificity, predictive values and likelihood ratio and retention index were calculated using standard methods. Results:Sixty-three (87%) patients had increased SUVmax in delayed scan (1 hour after initial scan). Among the patients with increased delayed uptake, 51 (80%) had malignant lesion and 12 (20%) had nonmalignant lesions. All 9 patients whose SUVmax decreased on delayed scan had nonmalignant lesions. The increased SUV on delayed scan was 100% sensitive in diagnosis of cancer but was only 42% specific. The positive predictive value was 80%, whereas the negative predictive value was 100%. Likelihood ratio for positive test was 1.75. Conclusions:All the lesions with decreased SUVmax in delayed PET scan were nonmalignant. This was true for both lung and mediastinal lesions. This could be a very helpful diagnostic finding in areas with high prevalence of benign conditions such as histoplasmosis and sarcoidosis. Multiple invasive diagnostic modalities could be prevented in a significant percentage of patients, with attendant decrease in morbidity and health care costs.

Lung scedosporiosis in human immunodeficiency virus/acquired immunodeficiency syndrome.

A 31-year-old African American woman with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (recent CD4 count of 66/mm3) presented to the emergency room with a tension pneumothorax that required an emergent chest tube placement. Computed tomography scan showed fungus balls in multiple lung cavities and surrounding infiltrates. The patient showed remarkable improvement with voriconazole suggesting aspergillosis. However, the patient was serologically negative for Aspergillus and other common fungal infections. Because of a persistent air leak, surgical intervention was needed. The histological finding was consistent with invasive mycosis, and cultures were positive for Scedosporium apiospermum. Literature review showed that, among patients with HIV/AIDS, Scedosporium can present from focal localized to systemic disease, is resistant to traditional antifungal agents, and may respond to prompt management with voriconazole.

Effect of Zafirlukast on Methacholine and Ultrasonically Nebulized Distilled Water Challenge in Patients with Mild Asthma

Background: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hyperresponsiveness due to the release of multiple mediators, such as cysteinyl-leukotrienes (cys-LTs). Objective: Our study was designed to investigate whether oral pretreatment with zafirlukast (a cys-LTs receptor antagonist) reduces bronchoconstriction against methacholine (MC) and ultrasonically nebulized distilled water (UNDW) challenge in patients with mild asthma. Methods: Fourteen non-atopic patients (8 males, 20–42 years, forced expiratory volume in 1 s (FEV1) 97% SD ± 0.4) with mild, intermittent bronchial asthma performed a sequential weekly pulmonary function test following challenge with MC or UNDW 2 h after zafirlukast or placebo administration, according to a single-blind method. Results: We found that pretreatment with zafirlukast significantly decreased bronchoconstriction MC (maximum FEV1 drop –10.75% SD ± 1.89, p < 0.001) and UNDW induced (maximum FEV1 drop –12% SD ± 0.15, p < 0.001), while pretreatment with placebo did not protect patients against FEV1 drop following MC (maximum FEV1 drop –33.22% SD ± 1.42, p < 0.001) and UNDW challenge (maximum FEV1 drop –30.02% SD ± 0.4, p < 0.001). Conclusions: Pretreatment with zafirlukast significantly reduced bronchoconstriction against MC and UNDW challenge in individuals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as preventive therapy in these patients population.

Bone Mineral Density Patterns in Vitamin D Deficient African American Men With Sickle Cell Disease

Objective:To describe bone mineral density (BMD) patterns by densitometry in adult African American (AA) men with sickle cell disease (SCD) who are vitamin D deficient (Vit DD). Inclusion/Exclusion Criteria:All SCD phenotypes were eligible. Those with chronic renal failure or hyperparathyroidism were excluded. Data Collection:Demographics, body mass index and SCD genotype. Laboratory:Albumin, ferritin, calcium, phosphorus, 25-hydroxy vitamin D and intact–parathyroid hormone were obtained. BMD, T and Z scores: T scores at the lumbar spine were used to categorize normal, osteopenia and osteoporosis based on World Health Organization criteria. Statistical Analyses:Mean ± standard deviation was used to describe continuous data, whereas categorical data were described by counts and percentages. The &khgr;2 test was used to analyze categorical variables; Students t test or one-way analysis of variance, when appropriate, was used to compare continuous variables. Rates of osteopenia-osteoporosis were determined, and the parameter with 95% confidence interval (CI) of a proportion was constructed. All tests were 2-sided, and a P ⩽ 0.05 was considered statistically significant. We used StatView Version 5.01 (SAS institute Inc, Cary, NC) for the statistical analysis. Results:Seventy-eight AA men with SCD disease and Vit DD were enrolled in this study. We found that 42% of the men studied had low-BMD (osteopenia or osteoporosis) using T scores at the lumbar spine to establish densitometry strata. The prevalence of osteoporosis was 14%. Conclusions:A large proportion of adult AA men with SCD and Vit DD showed low BMD.