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Biomedical subjects

Alejandro C Arroliga

Publications and source records attributed to Alejandro C Arroliga.

At least 37 records · Page 2Linked to original sources
PubMed2004

Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH), a fatal disease of unknown etiology characterized by impaired regulation of pulmonary hemodynamics and vascular growth, is associated with low levels of pulmonary nitric oxide (NO). Based upon its critical role in mediating vasodilation and cell growth, decrease of NO has been implicated in the pathogenesis of PAH. We evaluated mechanisms for low NO and pulmonary hypertension, including NO synthases (NOS) and factors regulating NOS activity, i.e. the substrate arginine, arginase expression and activity, and endogenous inhibitors of NOS in patients with PAH and healthy controls. PAH lungs had normal NOS I-III expression, but substrate arginine levels were inversely related to pulmonary artery pressures. Activity of arginase, an enzyme that regulates NO biosynthesis through effects on arginine, was higher in PAH serum than in controls, with high-level arginase expression localized by immunostaining to pulmonary endothelial cells. Further, pulmonary artery endothelial cells derived from PAH lung had higher arginase II expression and produced lower NO than control cells in vitro. Thus, substrate availability affects NOS activity and vasodilation, implicating arginase II and alterations in arginine metabolic pathways in the pathophysiology of PAH.

Arginase↗
PubMed2004

Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes.

OBJECTIVE: To determine the frequency, characteristics and outcomes of severe agitation among ventilated medical intensive care unit (MICU) patients. DESIGN: Prospective cohort study. SETTING: Eighteen-bed MICU in 964-bed tertiary care center. PATIENTS: All ventilated patients, aged 18 years or older and admitted for more than 24 h between January 1, 2001 and May 8, 2001. INTERVENTIONS: None. MEASUREMENTS: Data were collected daily by concurrent chart abstractions. Variables included sociodemographic, clinical, laboratory, pharmacologic and non-pharmacologic interventions, ventilator settings and adverse events. Severe agitation, the main outcome variable, was defined as two or more Motor Activity Assessment Scale (MAAS) scores above 4 in a 24-h period and sedative and/or narcotic doses above the established sedation and analgesia protocol or a combination of two or more sedatives. RESULTS: Twenty-three (16.1%) of 143 enrolled patients exhibited severe agitation. Agitated patients were younger (hazard ratio [HR] 1.32), more likely to be admitted from an outside hospital ICU (HR 2.48), had lower pH (HR 1.55) and PaO(2)/FIO(2) less than 200 mmHg (HR 2.59). Agitated patients had longer MICU stays (median 12 versus 5 days, p<0.0001) and more ventilator days (median 14 versus 6, p<0.0001). Agitated patients were more likely to self-extubate (26% versus 6%, p=0.002). Benzodiazepines, narcotics and neuromuscular blocking agents were administered more frequently and at higher doses, but haloperidol was not. CONCLUSION: Severe agitation occurs commonly in critically ill patients and is associated with adverse events including longer ICU stays, duration of mechanical ventilation and self-extubation.

Adult↗
PubMed2004

Ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication that is associated with modern techniques for in vitro fertilization. Extensive efforts have been made to understand the pathophysiology and to improve the management of this entity. The severe and life-threatening forms of the ovarian hyperstimulation syndrome are still challenging for critical care physicians. This article reviews the pathogenesis, epidemiology, classification, clinical manifestations, and complications of these forms of OHSS. The different therapeutic options currently available are reviewed, and a stepwise approach for the management of these patients is provided.

Female↗
PubMed2004

Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults.

OBJECTIVES: The primary objective was to evaluate the relationship between high-dose lorazepam and serum propylene glycol concentrations. Secondary objectives were a) to document the occurrence of propylene glycol accumulation associated with continuous high-dose lorazepam infusion; b) to assess the relationship between lorazepam dose, serum propylene glycol concentrations, and propylene glycol accumulation; and c) to assess the relationship between the osmol gap and serum propylene glycol concentrations. DESIGN: Prospective, observational study. SETTING: Tertiary care, medical intensive care unit. PATIENTS: Nine critically ill adults receiving high-dose lorazepam (> or =10 mg/hr) infusion. INTERVENTIONS: Cumulative lorazepam dose (mg/kg) and the rate of infusion (mg.kg(-1).hr(-1)) were monitored from initiation of lorazepam infusion until 24 hrs after discontinuation of the high-dose lorazepam infusion. Serum osmolarity was collected at 48 hrs into the high-dose lorazepam infusion and daily thereafter. Serum propylene glycol concentrations were drawn at 48 hrs into the high-dose lorazepam infusion, and the presence of propylene glycol accumulation, as evidenced by a high anion gap (> or =15 mmol/L) metabolic acidosis with elevated osmol gap (> or =10 mOsm/L), was assessed at that time. MEASUREMENTS AND MAIN RESULTS: The mean cumulative high-dose lorazepam received and mean high-dose lorazepam infusion rate were 8.1 mg/kg (range, 5.1-11.7) and 0.16 mg.kg(-1).hr (-1)(range, 0.11-0.22), respectively. A significant correlation between high-dose lorazepam infusion rate and serum propylene glycol concentrations was observed (r =.557, p =.021). Osmol gap was the strongest predictor of serum propylene glycol concentrations (r =.804, p =.001). Propylene glycol accumulation was observed in six of nine patients at 48 hrs. No significant correlation between duration of lorazepam infusion and serum propylene glycol concentrations was observed (p =.637). CONCLUSION: Propylene glycol accumulation, as reflected by a hyperosmolar anion gap metabolic acidosis, was observed in critically ill adults receiving continuous high-dose lorazepam infusion for > or =48 hrs. Study findings suggest that in critically ill adults with normal renal function, serum propylene glycol concentrations may be predicted by the high-dose lorazepam infusion rate and osmol gap.

Acid-Base Equilibrium↗
PubMed2004

Overview of treprostinil sodium for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a life-threatening disorder that refers to a group of diseases characterized by an abnormal elevation of the blood pressure within the pulmonary circulation due to a vasculopathy of the pulmonary microcirculation (1). If left untreated, the overall prognosis of pulmonary arterial hypertension is poor, with a 5-year survival rate of 34%. The most common cause of death is progressive right-sided heart failure (2). There is no pharmacologic cure for pulmonary arterial hypertension, and a team approach is required for the proper care of these patients (3). Treatment is directed at improving clinical symptoms, increasing exercise tolerance and extending survival. Until just a few years ago, standard treatment options for the treatment of pulmonary arterial hypertension were limited and included coumarin derivatives, calcium channel blockers, diuretics, digoxin and oxygen supplementation (4). In the last decade, the therapeutic options for pulmonary arterial hypertension have made considerable advances. In at least three major randomized controlled trials, the continuous intravenous infusion of epoprostenol, a synthetic salt of prostacyclin with potent vasodilatory ability, has been shown to improve exercise tolerance, hemodynamics, survival and quality of life in patients with New York Heart Association (NYHA) functional classes III and IV with either primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma (5-9). Epoprostenol has now become a mainstay therapy in the long-term treatment of primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma. Nevertheless, epoprostenol is far from an ideal form of therapy. Issues such as the short half-life of the drug, need for continuous central intravenous access and significant side effects have led to the development of more stable prostacyclin analogues as alternative therapies for primary pulmonary hypertension. These alternative therapies include iloprost (inhaled delivery) and treprostinil (subcutaneous delivery). As a result, the Food and Drug Administration (FDA) recently approved treprostinil for the treatment of pulmonary arterial hypertension in patients with NYHA classes II-IV. This review will offer a discussion of the basic pharmacology of treprostinil, its similarities to and differences from epoprostenol, the animal studies as well as the initial investigational studies leading to its FDA approval, and clinical uses of the drug alone or in combination with newer therapies directed at pulmonary arterial hypertension developed over the last decade.

Antihypertensive Agents↗
PubMed2004

Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates.

STUDY OBJECTIVE: To study the diagnostic role of flexible bronchoscopy (FB) in immunocompromised patients with pulmonary infiltrates. DESIGN: Prospective, observational study. SETTING: Tertiary care hospital. PATIENTS: A total of 104 consecutive non-HIV-infected immunocompromised patients with lung infiltrates in whom FB was performed. METHODS: The primary outcome measure was the diagnostic yield of FB, which was derived as the number of the diagnoses made using FB results divided by all final diagnoses. Final diagnoses were established using data from FB, surgical lung biopsy (SLB), and microbiology and serology testing, and by the clinical response to empiric therapy. We also studied the diagnostic yields of individual sampling procedures such as BAL, transbronchial biopsy (TBB), and protected-specimen brush (PSB) sampling. RESULTS: Overall, 128 diagnoses were made in 104 patients. The overall diagnostic yield of FB was 56.2% (95% confidence interval [CI], 47 to 64%). FB provided at least one diagnosis in 53 of 104 patients (51%; 95% CI, 40 to 62%). FB was more likely to establish the diagnosis when the lung infiltrate was due to an infectious agent (81%; 95% CI, 67 to 90%) than to a noninfectious process (56%; 95% CI, 43 to 67%; p = 0.011). The diagnostic yields of BAL (38%; 95% CI, 30 to 47%) and TBB (38%; 95% CI, 27 to 51%) were similar (p = 0.94). The diagnostic yield of PSB sampling was lower (13%; 95% CI 6 to 24%; p = 0.001) than that of BAL. The combined diagnostic yield of BAL and TBB (70%; 95% CI, 57 to 80%) was higher than that of BAL alone (p < 0.001). Finally, the diagnostic yield of FB with PSB sampling, BAL, and TBB was similar to that of FB with BAL and TBB. The complication rate from FB was 21% (95% CI, 15 to 31%). Minor bleeding (13%) and pneumothorax (4%) were the most common complications. CONCLUSIONS: FB has a high diagnostic yield in immunocompromised patients with pulmonary infiltrates. Based on our results, we recommend performing TBB in these patients, whenever possible.

Adult↗
PubMed2004

On the dilemma of enigmatic refusal of life-saving therapy.

When patients give no reason for refusing therapy (an enigmatic refusal), this creates the dilemma of whether or not to administer the therapy by force, especially when the therapy poses low risk and offers significant benefit. We argue that there is a duty to assess the patient's decision-making capacity, as well as attempt to understand a patient's reason(s) for refusing treatment. While some patients may not readily offer reasons for refusing treatment, this does not preclude an obligation for clinicians to inquire about such. The reasons for treatment refusal can be related to the patient's goals, values, fears, and mental state.

Aged↗
PubMed2004

Predictors of long-term mortality in patients with cirrhosis of the liver admitted to a medical ICU.

CONTEXT: The long-term survival of patients with cirrhosis of the liver admitted to the ICU has not been described. OBJECTIVE: The main objectives were to determine the 1-year and 5-year mortality rates of a cohort of patients admitted to a medical ICU (MICU), and to identify the risk factors that may predict long-term outcomes. DESIGN: This is a cohort study. We used a model-building (MB) and model validation (MV) procedure that has previously been described to determine the risk factors for overall mortality. SETTINGS: An MICU in a major referral medical center. PATIENTS: Four hundred twenty consecutive patients admitted to the ICU from January 1, 1993, through October 31, 1998, met the inclusion criteria of diagnosis of liver failure, cirrhosis, chronic liver disease, variceal bleeding, hepatic encephalopathy, or hepatorenal syndrome. Patients with acute liver failure who had undergone liver transplantation, or candidates for orthotopic liver transplantation were excluded. INTERVENTION: None. RESULTS: The 1-year mortality rate was 69%, and the 5-year mortality rate was 77%. The median survival time was 1 month. The independent predictors of mortality in patients in the MB group who retained their significance in the MV group were as follows: an acute physiology, age, and chronic health evaluation (APACHE) III score of >/= 90 (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.6 to 2.8; p < 0.0001), the use of pressors (HR, 2.5; 95% CI, 1.9 to 3.2; p < 0.0001), and jaundice (HR, 1.7; 95% CI, 1.4 to 2.2; p < 0.0001). Patients with all three risk factors (ie, APACHE III score >/= 90, use of pressors, and jaundice) had a 92% 1-month mortality rate compared to 11.2% for patients with no risk factors. CONCLUSIONS: Patients admitted to an MICU with underlying cirrhosis who are not eligible for liver transplantation have a poor long-term prognosis, even if they survive the ICU admission, particularly as the number of risk factors increases.

APACHE↗
PubMed2003

Prevalence of antineutrophil cytoplasmic antibodies in patients with various pulmonary diseases or multiorgan dysfunction.

OBJECTIVE: To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with diseases that may mimic systemic vasculitides, such as severe multiorgan dysfunction (MOD) and parenchymal pulmonary disorders. METHODS: We conducted a prospective study of patients with MOD admitted to the medical intensive care unit and patients with various lung diseases seen at the outpatient pulmonary clinic of a tertiary care hospital. Patients with a documented diagnosis of Wegener's granulomatosis (WG) served as positive controls. ANCA were determined in serum samples from each patient by a combination of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) for antibodies to proteinase-3 and myeloperoxidase (anti-MPO). RESULTS: Ninety-nine patients with MOD, 29 outpatients with various lung disorders, and 18 patients with WG were included in the study. ANCA were detected by IIF alone in 16% (15/96) of patients with nonvasculitic MOD and 17% (5/29) of outpatients with various pulmonary disorders. The majority of the positive IIF specimens from each group displayed an atypical IIF pattern (73% and 80%, respectively). Only 1 specimen from patients with nonvasculitic disorders was positive for anti-MPO. ANCA by both IIF and ELISA were detected in 78% (12/14) of control patients with WG. CONCLUSION: Detection of ANCA by the combination of IIF and antigen-specific assays for proteinase 3 and myeloperoxidase in diseases that mimic systemic vasculitides is highly specific for WG, microscopic polyangiitis, and Churg-Strauss syndrome.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2003

Correlation between ammonia levels and the severity of hepatic encephalopathy.

PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r(s)) were calculated. RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r(s) = 0.61, P < or = 0.001), venous total ammonia (r(s) = 0.56, P < or = 0.001), arterial partial pressure of ammonia (r(s) = 0.55, P < or = 0.001), and venous partial pressure of ammonia (r(s) = 0.52, P < or = 0.001). CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.

Adult↗
PubMed2003

A rational approach to the evaluation and treatment of the infected patient in the intensive care unit.

Critically ill patients are at increased risk of acquiring nosocomial infections. A thorough clinical evaluation and the selection of appropriate diagnostic techniques are important elements in the evaluation of these patients. Nonetheless, this selection process can be difficult because of the wide spectrum of disease that is seen in the ICU and the lack of standardized studies that have evaluated the different diagnostic methods that are available. Many different antimicrobials are available for the treatment of ICU-acquired infections. Most antimicrobial regimens have not been evaluated in large-scale, prospective, randomized trials. Until this information is available, the clinician must make an effort to be familiar with the different clinical and epidemiologic variables that can be used to stratify patients at the moment of selecting antimicrobial therapy. The information provided in this article, used in association with good clinical judgment, will help the critical care physician provide optimal initial management of the infected patient in the ICU.

Algorithms↗
PubMed2003

Association between hyperhomocysteinemia and primary pulmonary hypertension.

STUDY OBJECTIVE: This case-control study was conducted to test the hypothesis that fasting homocysteine levels are higher in PPH patients than in healthy controls. DESIGN: Levels of plasma total homocysteine, serum folate, vitamin B-12, and serum creatinine in 18 consecutive patients with PPH were compared with data from 36 age- and sex-matched controls. RESULTS: Eight of the 18 patients (44.4%) and three of the 36 controls (8.3%) had elevated plasma total homocysteine (tHcy) levels (> or = 15 mol/l, odds ratio 8.8; 95% CI: 2.0-39.6; P = 0.005). There was an inverse correlation between tHcy levels and creatinine clearance in patients with PPH (P = 0.036). CONCLUSION: PPH patients are significantly more likely to have hyperhomocysteinemia, and higher mean plasma total homocysteine levels than in controls. Plasma total homocysteine may be an important factor in the pathogenesis of PPH.

Adolescent↗
PubMed2003

Emerging systemic pharmacologic approaches in acute respiratory distress syndrome.

The increased understanding of the pathophysiology of ALI that has been achieved over the last decade has led to several new pharmacologic approaches for the prevention and management of ALI and ARDS. Based on in vitro information and animal model data, many of these strategies seem quite compelling. Nevertheless, to date, no specific pharmacologic approach for the prevention or treatment of ARDS has been conclusively validated in clinical trials. Active basic and clinical research continues, and it is hoped that these investigations will lead to new therapies that can be applied by the clinician to improve clinical outcomes for patients who have ALI and ARDS.

Adrenal Cortex Hormones↗
PubMed2003

Cor pulmonale: an overview.

Chronic cor pulmonale involves the enlargement of the right ventricle as a result of pulmonary hypertension due to pulmonary disorders involving the lung parenchyma, bellows function, or ventilatory drive. The right ventricular hypertrophy that occurs in chronic cor pulmonale is a direct result of chronic hypoxic pulmonary vasoconstriction and subsequent pulmonary artery hypertension, leading to increased right ventricular work and stress. We discuss methods by which hypoxic vasoconstriction and reduction in the pulmonary vascular bed lead to the development of pulmonary artery hypertension. This article reviews the interaction of the pulmonary vasculature and right ventricle in the non-diseased state as well as during disease exacerbations. Ventricular dependence and its contribution to the pathophysiology of right ventricular failure are also reviewed. In addition, we provide an overview of specific disease states that can result in the development of chronic cor pulmonale including chronic obstructive pulmonary disease (COPD), interstitial lung disease, sleep apnea, alveolar hypoventilation disorders, and primary pulmonary hypertension. We also review the current diagnostic studies used to evaluate and study cor pulmonale.

Journal Article↗