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.

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-kappaB 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-kappaB activation.

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 (FEV(1)) 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 FEV(1) drop -10.75% SD +/- 1.89, p < 0.001) and UNDW induced (maximum FEV(1) drop -12% SD +/- 0.15, p < 0.001), while pretreatment with placebo did not protect patients against FEV(1) drop following MC (maximum FEV(1) drop -33.22% SD +/- 1.42, p < 0.001) and UNDW challenge (maximum FEV(1) 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.

[Duration of the diagnostic process for lung cancer versus other solid tumors at the National Oncology Institute of Ecuador]. / Duración de la valoración diagnóstica del cáncer de pulmón frente a otros tumores sólidos en el Instituto Oncológico Nacional de Ecuador.

OBJECTIVE: To determine the duration of the outpatient diagnostic process for lung cancer in comparison to that of other solid organ tumors/all tumors at the National Oncology Institute-Society to Fight Cancer (ION-SOLCA) of Ecuador. PATIENTS AND METHODS: All patients with non-small cell lung cancer (NSCLC) seen between January 1 and December 31, 1995 at the ION-SOLCA, a specialized tertiary care hospital in Guayaquil, Ecuador, were studied. The duration of the patients' diagnostic process was compared to that of other patients with solid organ tumors (1 control per NSCLC patient). DESIGN: Retrospective study of health care services to measure the duration of each stage of the diagnostic process for cancer patients at the ION-SOLCA. MEASURES: The main variable was the duration of the diagnostic process. The duration of each phase of the process was also recorded. RESULTS: Results are given as means ( standard deviations, with standard errors between parentheses). The overall duration of the diagnostic process for all solid organ tumors (lung and others) at the ION-SOLCA was 54.5 days 62.3 (7.6). No differences were detected between the duration of diagnosis for lung and other tumors. The durations of the different phases of diagnosis were as follows: from the first pre-admission contact with the hospital until a visit with a specialist, 12.5 days 11.4 (1.4); from the visit with a specialist until a diagnostic procedure, 33.3 days 57 (7); and from the diagnostic procedure until the pathological diagnosis, 8.7 days 6.9 (0.8). CONCLUSIONS: Outpatient evaluation is an inefficient, slow and potentially dangerous process in cases in which the probability of a cancer diagnosis is high. A more interventionist process involving hospital admission may accelerate diagnosis in such cases.

Duración de la valoración diagnóstica del cáncerde pulmón frente a otros tumores sólidosen el Instituto Oncológico Nacional de Ecuador / Duration of the diagnostic process for lung cancer versus other solid tumors at the National Oncology Institute of Ecuador

OBJETIVO: Determinar la duración del proceso diagnóstico del cáncer (pulmón frente a tumores de órganos sólidos/todos) en el ION-SOLCA utilizando la modalidad de evaluación ambulatoria. POBLACIÓN Y MÉTODOS: La totalidad de los pacientes con cáncer de pulmón de células no pequeñas (CPCNP) evaluados durante el período comprendido entre el 1 de enero y el 31 de diciembre de 1995 en el ION-SOLCA de Guayaquil, Ecuador (hospital de referencia terciario), comparando con la duración de la evaluación diagnóstica de otras neoplasias de órganos sólidos en la institución. DISEÑO: Estudio retrospectivo de servicios de salud que cuantifica la duración de cada etapa del proceso diagnóstico de los pacientes con cáncer en el ION-SOLCA. Se consideró como variable índice del estudio la duración de la evaluación diagnóstica de los casos estudiados en el ION-SOLCA. Simultáneamente se obtuvo la duración de cada componente de la variable índice. RESULTADOS: La duración media de la evaluación diagnóstica global en el ION-SOLCA para los tumores de órganos sólidos (pulmón y otros) es de 54,5 ñ 62,3 días (error estándar [EE], 7,6). No se encontró diferencia entre los dos grupos. Los componentes de esta estimación se fraccionan del siguiente modo: primer contacto con el instituto (preadmisión)-visita con el especialista, 12,5 ñ 11,4 días (EE, 1,4); visita con el especialista-procedimiento diagnóstico, 33,3 ñ 57 días (EE, 7), y procedimiento diagnóstico-resultado de anatomía patológica, 8,7 ñ 6,9 días (EE, 0,8).CONCLUSIONES: La valoración ambulatoria de los pacientes con alta probabilidad de cáncer es un proceso ineficiente, lento y posiblemente peligroso. Una modalidad de ingreso intervencionista podría acelerar el proceso diagnóstico en estos pacientes (AU)

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.

Neurocysticercosis among patients with cerebral gliomas.

BACKGROUND: Parasites have been implicated in the pathogenesis of human cancer. Anecdotal reports have suggested an association between neurocysticercosis and brain tumors. OBJECTIVE: To determine whether neurocysticercosis is a risk factor for cerebral glioma. DESIGN: Case-control study. SETTING: A university general hospital and a cancer referral center. PATIENTS: Forty-three consecutive patients with a cerebral glioma and 172 controls matched for age, sex, and socioeconomic status. METHODS: We determined the ratio between the frequency of neurocysticercosis in patients with a cerebral glioma and in matched controls. We also evaluated differences in the characteristics of the patients and in the histological type of the neoplasm among case patients with and without neurocysticercosis. In addition, we noted relationships between the location of the cerebral glioma and that of parasitic lesions. RESULTS: Eight (16.8%) of 43 patients with a glioma and 5 (2.9%) of 172 controls had neurocysticercosis (P < .001). The odds ratio for this association was 7.63 (95% confidence interval, 2.03-31.09). Patients with glioma and neurocysticercosis were older than those without neurocysticercosis (mean [+/-SD] age, 62.75 +/- 18.34 years vs 44.69 +/- 14.04 years; P = .02). Glioblastoma multiforme was more frequent among case patients with neurocysticercosis than among those without neurocysticercosis (87.5% vs 48.6%); however, this difference was not statistically significant (P = .24). Six of the 8 patients with neurocysticercosis and a cerebral glioma had calcified parasitic lesions within and around the tumor. CONCLUSIONS: Results from this study suggest that neurocysticercosis is a risk factor for cerebral glioma. The intense astrocytic gliosis that surrounds calcified cysticerci, together with the suppression of the cellular immune response induced by cysticerci, may contribute to the development of malignant glial cells in patients with neurocysticercosis.