Presence Of Peripheral Edema Research Articles

Pharmacokinetics and Pharmacodynamics of Enoxaparin in Multiple Trauma Patients

Enoxaparin is the only low molecular-weight heparin (LMWH) with documented efficacy for the prevention of venous thromboemobolism (VTE) following trauma, and it is currently considered the treatment of choice. Recent reports have suggested that the pharmacokinetics (PK) and pharmacodynamics of LMWH products may be altered in critically ill patients. Two cohorts of critically ill multiple trauma patients were enrolled in this study: A (nonedematous) and B (edematous, defined as the presence of peripheral edema and an increase in body weight of > or =10 kg). All patients received at least four doses of enoxaparin 30 mg subcutaneously every 12 hours before the study dose. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours following a morning dose. Plasma anti-Xa and antithrombin (AT) activities were determined using chromogenic assays. A compartmental PK analysis model was defined for the data. PK parameters for the two cohorts were compared using a Mann-Whitney Rank Sum test. The area under the curve (AUC)0-12 hour, maximal plasma anti-activated Factor Xa (anti-Xa) activity (Amax), and AT activity were significantly lower in the edematous trauma patients (p < 0.05). The AUC0-12 hour for plasma anti-Xa activity was highly variable in both study cohorts. Seven of the 10 edematous patients had barely quantifiable anti-Xa results. Activity levels were too low to reliably estimate the PK parameters for most patients in cohort B. The standard dose of enoxaparin recommended for the prevention of VTE following multiple trauma provides unreliable and highly variable anti-Xa activity in critically ill trauma patients, and is strongly affected by the presence of significant peripheral edema.

Activation of the NF‐κB system in peripheral blood leukocytes from patients with chronic heart failure

To evaluate the activation of transcriptional nuclear factor kappa-B (NF-kappaB) in peripheral blood leukocytes (PBL) from patients with chronic heart failure (CHF). In vitro experiments were used to elucidate the role of lipopolysaccharide (LPS) as a stimulus for the NF-kappaB system in PBL. We examined 46 CHF patients (age: 62+/-1 years, LVEF: 31+/-1%, NYHA class: 2.7+/-0.1), 11 coronary artery disease (CAD) patients without CHF, and 13 healthy young subjects. The immunocytochemical localisation of NF-kappaB in PBL was assessed using a polyclonal rabbit IgG anti-c-Rel-subunit antibody. NF-kappaB activation was expressed as the percentage of PBL nuclei stained positively for c-Rel (NF-kappaB+cell). PBL from healthy controls were exposed in vitro to the following concentrations of LPS from Escherichia coli (strain O111:B4): 0.1, 10 and 5000 ng/mL. CHF patients demonstrated the highest NF-kappaB activation in PBL (NF-kappaB+cells [%]: 37.1+/-1.5) as compared to CAD patients (29.1+/-3.0%) and controls (12.6+/-1.5%) (all p<0.05). There were three main clinical determinants of NF-kappaB activation in PBL from CHF patients: peak oxygen consumption (r=0.53, p=0.025), presence of peripheral oedema (r=0.37, p<0.05) and serum C-reactive protein (r=0.40, p=0.02). In PBL from healthy subjects, LPS at all concentrations increased NF-kappaB activity towards the pattern detected in CHF. The NF-kappaB system is highly overactive in PBL from CHF patients. LPS at low concentrations in peripheral blood may be involved in NF-kappaB activation in PBL, and is a potential target for future therapeutic applications.

Neutrophils, Nitric Oxide, and Microvascular Permeability in Severe Sepsis

Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients with severe sepsis had increased Kf, and whether the magnitude of Kf correlated with indexes of nitric oxide activity and neutrophil activation. Single-center, prospective study. Twenty-five-bed ICU of a medical college-affiliated teaching hospital. Fifteen ICU patients with severe sepsis based on the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria of 1992, and 10 nonseptic ICU patients as control subjects. Kf was measured by venous congestion plethysmography, plasma nitrate/nitrite (NOx) by chemiluminescence, and neutrophil expression of alpha4-integrin (an index of neutrophil activation) by flow cytometry. Septic patients had higher Kf than nonseptic control subjects. Kf of septic patients was 5.6 +/- 0.6 x 10(-3) mL.min(-1).100 mL tissue(-1).mm Hg(-1) (mean +/- SEM, mL.min(-1).100 mL tissue(-1).mm Hg(-1) = Kf units [KfU]) as compared to 3.9 +/- 0.5 x 10(-3) KfU in nonseptic ICU patients (p < 0.05). There was no correlation between plasma NOx and Kf, or between neutrophil alpha4-integrin expression and Kf in patients with sepsis. Septic patients with clinical evidence of edema had significantly higher Kf (p < 0.05) than nonedematous septic patients. ICU patients with severe sepsis have increased Kf, a noninvasive index of microvascular water permeability. The magnitude of hyperpermeability did not correlate with NOx levels or one index of neutrophil activation (alpha4-integrin expression). Presence of peripheral edema in these patients was associated with increased Kf, and may represent a simple, clinical indicator of altered microvascular permeability in sepsis.

Transcutaneous bilirubinometry with the Bilicheck® in very premature newborns

Objectives: To investigate the potential advantages of use of the Bilicheck® in the very preterm population, with special emphasis on the effect of possible adverse skin conditions on the accuracy of the measurements. In addition we estimated the potential for safe reduction of the number of blood samples taken for serum bilirubin determinations by introduction of the Bilicheck® into the neonatal intensive-care unit (NICU). Methods: Total serum bilirubin (TSB) and transcutaneous bilirubin (TcB) were determined in very preterm newborns (gestational age < 30 weeks). To assess the agreement between TSB and TcB values, Bland-Altman plots were analyzed. Accuracy and (intra-device) imprecision were determined by statistical analysis. A screening model was developed to estimate the potential for safe reduction of the number of blood samples taken for TSB determination. Results: Correlations between TcB and TSB values varied between 0.86 and 0.88 and all were statistically significant. Bland-Altman plots and statistical analysis showed that the agreement between TcB and TSB measurements was largest for the group with good skin conditions, as expected. The Bilicheck® device had an acceptable level of intra-device imprecision (2.29 ± 13.51 μmol/l). Applying the screening model to our entire study population, 35 of the 93 TSB measurements (38%) could have been saved. Conclusions: The Bilicheck® is a screening device with the potential to reliably indicate hyperbilirubinemia in very preterm infants. Caution is required when skin measurements are performed in the presence of peripheral edema and/or a poor peripheral circulation. Its application in the NICU environment has the potential to reduce the number of blood samples by 40%.

Transcutaneous bilirubinometry with the Bilicheck® in very premature newborns

To investigate the potential advantages of use of the Bilicheck in the very preterm population, with special emphasis on the effect of possible adverse skin conditions on the accuracy of the measurements. In addition we estimated the potential for safe reduction of the number of blood samples taken for serum bilirubin determinations by introduction of the Bilicheck into the neonatal intensive-care unit (NICU). Total serum bilirubin (TSB) and transcutaneous bilirubin (TcB) were determined in very preterm newborns (gestational age < 30 weeks). To assess the agreement between TSB and TcB values, Bland-Altman plots were analyzed. Accuracy and (intra-device) imprecision were determined by statistical analysis. A screening model was developed to estimate the potential for safe reduction of the number of blood samples taken for TSB determination. Correlations between TcB and TSB values varied between 0.86 and 0.88 and all were statistically significant. Bland-Altman plots and statistical analysis showed that the agreement between TcB and TSB measurements was largest for the group with good skin conditions, as expected. The Bilicheck device had an acceptable level of intra-device imprecision (2.29 +/- 13.51 micromol/l). Applying the screening model to our entire study population, 35 of the 93 TSB measurements (38%) could have been saved. The Bilicheck is a screening device with the potential to reliably indicate hyperbilirubinemia in very preterm infants. Caution is required when skin measurements are performed in the presence of peripheral edema and/or a poor peripheral circulation. Its application in the NICU environment has the potential to reduce the number of blood samples by 40%.

Emergency department prediction of heart failure by bedside physical examination

Study objectives: A variety of presenting symptoms and features of the bedside examination are all commonly used in the diagnosis and assessment of heart failure patients. We seek to determine the relative performance of presenting symptoms and features of the physical examination, including jugular venous distention (JVD), orthopnea, and computerized detection of abnormal heart sounds, in the emergency department (ED) for the diagnosis of heart failure. Methods: On presentation to the ED, and before treatment, patients with signs of heart failure had standardized reporting of symptoms and bedside examination (JVD, dyspnea, peripheral edema, paroxysmal nocturnal dyspnea, orthopnea), including a standard 12-lead ECG with acoustic signal recording for computerized detection of S3 using the validated AUDICOR algorithm (Inovise Medical, Inc.). Primary diagnosis of heart failure was based on hospital discharge diagnosis or ED diagnosis (if the patient was not admitted). Data were analyzed using logistic regression analysis. Wald values and P values are reported. Results: Of the 138 patients enrolled, 113 received full bedside examination and definitive diagnosis, 46 had a primary diagnosis of heart failure, and 67 had a non–heart failure diagnosis. Within the study population, there were 58.7% male patients in the heart failure group versus 44.8% male patients in the non–heart failure group, 67.4% black patients in the heart failure group versus 49.3% in the non–heart failure group, and the median age category was 66 to 70 years in the heart failure group versus 56 to 60 years in the non–heart failure group. Using a binary logistic regression model, features of bedside evaluation that were significant predictors of a primary diagnosis of heart failure (R2=0.396) were the AUDICOR S3 heart sound (11.599, P=.001) and peripheral edema (9.784, P=.002). JVD (0.981, P=.322), dyspnea (3.001, P=.083), orthopnea (2.857, P=.091), and paroxysmal nocturnal dyspnea (0.208, P=.648) were not significant determinants of primary diagnosis of heart failure. Conclusion: For bedside diagnosis of heart failure, the third heart sound detected by the computerized AUDICOR algorithm and the presence of peripheral edema were the best predictors for a primary diagnosis of heart failure.

Clinical estimation of survival and impact of other prognostic factors on terminally ill cancer patients in Oman.

A prospective study was carried out in the only tertiary oncology department in Oman to analyse the pattern of various prognostic factors in terminally ill cancer patients and their impact on these patients. Between September 1999 and February 2001, terminally ill cancer patients with solid tumours who fulfilled the eligibility criteria were included. All of them were coded Do Not Resuscitate (DNR). Clinical estimation of survival as well as recording of different symptoms and signs was carried out for each patient. Survival was calculated from the date of the DNR coding to the date of death. A total of 162 patients were included. Mean survival time was 41.5 days (median 10 days). The gastrointestinal tract (GIT) was the most common site of malignant disease, followed by the breast. Univariate analysis of evaluable patients showed that performance status (PS), dry mouth, presence of delirium, anorexia, peripheral oedema, absence of bone metastasis, low lymphocyte count and low albumin level had significant effects on survival. Multiple regression analysis showed that PS and oedema were the only independent predictors of survival. Clinical prediction of survival was correlated with observed survival. Patient's PS, presence of peripheral oedema and clinical estimate of survival are good predictors of survival in terminally ill cancer patients.

Neuromuscular monitoring in intensive care patients: milliamperage requirements for supramaximal stimulation

We investigated the effects of peripheral oedema on the supramaximal current required for neuromuscular monitoring of critically ill patients. We studied 32 sedated patients who had not needed a neuromuscular blocking drug. The presence of oedema over the volar aspect of both wrists was assessed by a blinded observer and graded (grade 0, no oedema; grade 1, mild oedema; grade 2, gross oedema). The supramaximal current was derived by applying an incrementally increasing current over the ulnar nerve and measuring the amplitude of the electromyographic (EMG) response of the first dorsal interosseous muscle. The supramaximal current was that current above which there was no significant increase in EMG amplitude. It was 40 mA in the absence of oedema. This current was significantly increased in the presence of grade 1 oedema (60 mA, Mann-Whitney test, P<0.01) and grade 2 oedema (82.5 mA, Mann-Whitney test, P<0.01). In the presence of oedema, the required supramaximal current decreased significantly after the application of pressure over the stimulating electrodes (Wilcoxon signed rank test, P<0.05). Supramaximal current in critically ill patients is increased in the presence of peripheral oedema. We recommend that nerve stimulators used for neuromuscular monitoring in the ICU are capable of delivering a stimulus current of at least 100 mA.

Predictive Factors Influencing the Therapeutic Response to Diuretic Treatment of Ascites in Nonazotemic Cirrhotic Patients

Background: A low-sodium diet and diuretics, although widely used, are not always the most satisfactory therapy for treatment of ascites in nonazotemic patients with liver cirrhosis. The objective of this investigation was to analyze various predictive factors influencing the therapeutic response to diuretic treatment of ascites in these patients. Methods: Twenty-seven patients with nonazotemic liver cirrhosis and ascites were initially treated with spironolactone, 200 mg/day. If no response was observed, furosemide was added at 40-120 mg/day. Before and during the diuretic therapy 30 clinical and laboratory variables were investigated as possible predictive factors influencing the therapeutic response to diuretics. The renal arterial resistive index (RI) (reflecting renal vascular resistance) was estimated with duplex Doppler ultrasonography. Results: Sixteen of the 27 patients (59%) responded to spironolactone alone, whereas 6 patients (22%) responded to combined diuretic therapy with spironolactone and furosemide. Five patients (19%) did not respond to diuretic treatment. Eight of the 30 variables analyzed were statistically significant as possible predictive factors influencing the diuretic response: previous episodes of ascites and gastrointestinal hemorrhage, the presence of peripheral edema, the amount of ascites, plasma renin activity, plasma aldosterone concentrations, urinary sodium excretion, and renal interlobar arterial RI. In all patients who had diuretic-resistant ascites, renal interlobar arterial RI was greater than 0.70. Only 9% of patients who responded satisfactorily to diuretic therapy had interlobar arterial RI greater than 0.70. Conclusions: According to our results, consideration for combining the clinical findings with noninvasively measured renal arterial RI using duplex Doppler ultrasonography would be mandatory in identifying a subgroup of cirrhotic patients with ascites who are at high risk for diuretic unresponsiveness.

Changes in atrial natriuretic peptide concentrations during intravenous saline infusion in hypoxic cor pulmonale.

The pathogenesis of oedema in hypoxic cor pulmonale is poorly understood. One possibility is a failure of atrial natriuretic peptide release, leading to salt and water retention. This hypothesis was tested by observing the response to an intravenous saline challenge in patients with and without cor pulmonale. Plasma atrial natriuretic peptide concentrations were measured before and for three hours after an intravenous saline load (0.1 ml 2.7% saline/kg/min for 60 minutes) in 20 patients with chronic obstructive airways disease. Ten patients with cor pulmonale, as judged clinically by the presence of peripheral oedema with a previously documented increase in the jugular venous pressure or pleural effusions during an acute exacerbation of airway obstruction (mean (SE) age 67 (3) years, FEV1 0.73 (0.08) 1, arterial oxygen tension (PaO2) 6.4 (0.4) kPa, and arterial carbon dioxide tension (PaCO2) 6.7 (0.3) kPa), were compared with 10 patients with hypoxic chronic obstructive airways disease who had never had oedema (mean age 63 (1) years, FEV1 1.07 (0.09) 1, PaO2 8.6 (0.4) kPa, and PaCO2 5.3 (0.2) kPa). All patients were studied fasting and after diuretics had been stopped for three days. No supplemental oxygen was given. The mean four hourly urine sodium excretion was less in the patients who had oedema (27 (4.6) mmol, 13% of the intravenous load) than in those without oedema (82 (15.5) mmol, 43% of the load). Initial mean plasma atrial natriuretic peptide values were significantly higher in the patients with cor pulmonale (19.1 (1.6) compared with 10.2 (0.7) pmol/l) and the mean peak rise in atrial natriuretic peptide after the intravenous saline load had been given was 13 (8.0) pmol/l in the patients with cor pulmonale and 5.5 (2.3) pmol/l in the controls. There were no significant differences in plasma and urinary osmolality, blood pressure, or creatinine clearance between the groups. Patients with chronic obstructive airways disease and cor pulmonale have an impaired ability to excrete a hypertonic intravenous saline load despite a normal physiological release of plasma atrial natriuretic peptide.

Muscle cramps in liver cirrhosis

A high incidence (64%) of muscle cramps was found in 112 cirrhotic patients, as compared with 17% in 169 hepatitis B surface antigen (HBsAg) negative healthy persons, 8% in 13 asymptomatic HBsAg carriers, 8% in 12 patients with acute hepatitis, and 28% in 25 patients with chronic hepatitis. The cramps were characterized by severe pain with more than one episode per week which occurred mainly during sleep in the lower extremities and lasted for few minutes. Besides the use of diuretics and the presence of peripheral edema, no definite etiologic factors could be found. The underlying pathophysiology of muscle cramps in patients with chronic liver disease remains obscure. However, the strikingly high incidence of muscle cramps could be recognized as a symptom of cirrhosis.

Diagnosis of acoustic neuroma with computed tomography.

Sixty-one acoustic neuromas were examined with computed tomography (CT). For differential diagnosis the tumors were thoroughly analyzed for manner of growth, shape, volume, calcification, attenuation pattern, constrast enhancement, presence of peripheral edema, and cisternal deformation.