Effect of patient position on the incidence of vasovagal response to venous cannulation.

BACKGROUND: This study was undertaken to determine the effect of patient position on the incidence of vasovagal responses to venous cannulation in ambulatory surgery patients. METHODS: Three hundred surgical outpatients, aged 18 to 40 years, were randomly assigned by week to the sitting or recumbent position. Blood pressure and heart rate were recorded during and for 6 minutes following venous cannulation. An observer recorded signs and symptoms suggestive of a vasovagal response. RESULTS: A vasovagal reaction occurred in 12.6% of sitting patients and 2.1% of recumbent patients. Two sitting patients, 1.3%, experienced frank syncope. Symptomatic patients were more likely (39.1%) than asymptomatic patients (8.3%) to have a history of fainting. In symptomatic patients who were sitting, mean arterial pressure fell from 90.4 mm Hg (SD, 10.6) at baseline to 64.4 mm Hg (SD, 14.3) during cannulation. Similarly, heart rate fell from 76.6 beats per minute (SD, 15.6) at baseline to 59.0 beats per minute (SD, 11.7) after cannulation. CONCLUSIONS: The vasovagal response during venous cannulation occurs more frequently in the sitting patient who has a history of fainting and is associated with a significant decline in blood pressure and heart rate.

Preoperative aspirin therapy and reoperation for bleeding after coronary artery bypass surgery.

We performed a case-control study to estimate the relative risk of reoperation for bleeding in coronary artery bypass graft patients who had taken aspirin within the 7 days preceding surgery. Comparison of 90 cases of reoperation with 180 matched control subjects gave an estimated odds ratio for reoperation of 1.82 (95% confidence interval, 1.23 to 3.32). Although their preoperative coagulation values were similar, cases used significantly more whole blood (cases, 9.5 +/- 5.2 units; control subjects, 3.0 +/- 2.0 units; median +/- interquartile range), packed red blood cells (cases, 2.1 +/- 4.0 units; control subjects, 0.9 +/- 2.0 units), and platelets (cases, 12.2 +/- 12.0 units; control subjects, 2.9 +/- 4.0 units) than control subjects. Cases had intensive care unit stays of 4.7 +/- 5.7 days (mean +/- SD) vs 2.1 +/- 1.9 days for control subjects and postoperative hospitalizations of 10.9 +/- 8.2 days vs 7.0 +/- 3.2 days for control subjects. We conclude that aspirin exposure within 7 days before coronary bypass surgery is associated with an increased rate of reoperation for bleeding and that reoperation is associated with large increases in transfusion requirements and intensive care unit and hospital stays.

Indinavir did not increase the short-term risk of adverse cardiovascular events relative to nucleoside reverse transcriptase inhibitor therapy in four phase III clinical trials.

A retrospective person-time analysis of the randomized and non-randomized extension phases of four phase III trials was performed to assess the incidence of adverse cardiovascular events in 2680 HIV-infected patients receiving indinavir or nucleoside reverse transcriptase inhibitor therapy, or both. The observed rate of cardiovascular events was not increased in patients receiving indinavir-based regimens compared with therapy without a protease inhibitor. Extrapolation of these findings is limited by the brief length of therapy and the small number of cases.

Neurobehavioral outcomes in cardiac operations. A prospective controlled study.

To assess the severity and duration of new organic brain dysfunction after cardiac operations, we used an extensive battery of neuropsychologic tests to evaluate 65 patients undergoing coronary artery bypass grafting and 25 patients undergoing intracardiac operations with cardiopulmonary bypass. Patients were tested the day before the operation, before discharge from the hospital, and approximately 7 months later. Compared to 47 nonsurgical control subjects tested at comparable time intervals, surgical subjects showed generalized impairment of neuropsychologic abilities near the time of discharge from the hospital. At follow-up testing, there was no evidence of residual impairment among the surgically treated patients as a whole. In fact, they showed greater improvement compared to initial test scores than did control subjects. However, performance of 10 patients (11%) declined on half of the neuropsychologic variables between preoperative and follow-up testing. Neurobehavioral outcome was not related to the type of operation (coronary bypass versus intracardiac), to factors of cardiopulmonary bypass (duration, aortic occlusion time, hypotension, arterial carbon dioxide tension, minimum hematocrit value, minimum temperature). The only predictor of negative outcome was advanced age. We conclude that, although neurobehavioral impairment is common during hospitalization after cardiac operations, the prognosis for eventual full recovery is favorable, although less so among the elderly.

Hemodynamic effects of rapidly evacuating prolonged pneumothorax in rabbits.

Clinical observations suggest that systemic hypotension may be caused by rapid evacuation of persistent pneumothorax. This observation has not been substantiated experimentally and the mechanism(s) are unknown. In this study, we measured systemic hemodynamic parameters in rabbits before and for 2 h during negative pressure evacuation of a right-sided pneumothorax of 7-9 days duration. Three groups of animals were studied: 10 rabbits breathed room air and were hypoxemic during pneumothorax (hypoxemic pneumothorax = HP); 10 rabbits breathed 40% O2-60% N2, which prevented arterial hypoxemia during pneumothorax (supraoxemic pneumothorax = SP); seven normal control animals were untreated during this time period (NC). Pneumothoraces in HP and SP were evacuated by negative pressure applied to the right pleural space for 2 h while animals were anesthetized and mechanically ventilated. The NC group was anesthetized and ventilated without prior pneumothorax. Serial hemodynamic measurements were made before and during pleural suction.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous plasma proteins in edematous lungs and alveolar fluid in rabbits.

In this study, we compared two methods of differentiating hydrostatic and permeability types of pulmonary edema. The first method entailed measurement of protein concentrations directly in samples of alveolar fluid (AF); the second method was an indirect technique in which protein concentration in extravascular extracellular water (EVECW) was calculated on the basis of separate measurements of the quantity of protein in the lung and the volume of EVECW. The concentration of albumin (Alb) and gamma-G-globulin was measured in EVECW and alveolar fluid in excised edematous rabbit lungs. Edema was caused by elevation of left ventricular end-diastolic pressure to 25 Torr (hydrostatic edema, HE) or by intravenous oleic acid, 0.09 ml/kg (permeability edema, PE). The volume of distribution of Na+ was utilized as a measure of EVECW in the lung. Protein concentration in EVECW and AF relative to plasma (EV/PL and AF/PL, respectively) was compared in the two types of edema. The EV/PL was 0.61 +/- 0.12 (SD) for Alb in He compared with 1.18 +/- 0.47 in PE (P less than 0.02). The AF/PL was 0.54 +/- 0.12 and 1.25 +/- 0.33 in HE and PE, respectively (P less than 0.001). There was good correlation between EV/PL and AF/PL for Alb (r = 0.74, P less than 0.001) but not for gamma-G-globulin. Thus EV/PL for Alb, AF/PL for Alb, and gamma-G-globulin all differentiated hydrostatic from permeability edema.

Extracellular fluid volume during pneumothorax and hypoxemia in rabbits.

This study was designed to test the hypothesis that persistent pneumothorax of greater than or equal to 6 days duration causes a decrease of extracellular fluid volume (ECF). Such changes are of interest as they may be causally related to persistent hypotension that has occurred in humans following pneumothorax evacuation. Experiments were done in rabbits to determine the effect on ECF of persistent pneumothorax with or without systemic hypoxemia. Animals were divided into four treatment groups: 1) pneumothorax with hypoxemia [fractional concentration of O2 in inspired gas (FIO2) = 0.21, n = 30], 2) pneumothorax without hypoxemia (FIO2 = 0.40, n = 25), 3) hypoxemia alone (FIO2 = 0.14, n = 11), and 4) normal controls (FIO2 = 0.21, n = 15). Measurements of ECF were made in the base-line control state and after 6 days of treatment using the dilution volume of thiocyanate sodium as an estimate of ECF volume. We found a reduction of ECF in 53% of animals with pneumothorax plus hypoxemia (range -47% to +13%) and in 54% of animals with hypoxemia alone (range -26% to +25%). ECF declined in only 7% of normal controls and 20% of animals with pneumothorax without hypoxemia. Arterial O2 tensions after 6 days of treatment were 58 +/- 12.6, 141 +/- 28, 60 +/- 5.1, and 97 +/- 9.3 Torr (mean +/- SD) in groups 1-4, respectively. The results suggest that pneumothorax with hypoxemia or hypoxemia alone may contribute to depletion of ECF, but this response is variable and unpredictable in individual animals.

Methodology for three-dimensional reconstruction of the left ventricle from transesophageal echocardiograms.

A technique is presented for three-dimensional (3-D) reconstruction of the left-ventricular endocardial surface from multiplanar transesophageal echocardiograms, using both commercial software and investigator written Fortran programs for Intel 80286 and 80386 microcomputers. The approach provides quantitative global and regional cardiac performance measures and allows viewing the endocardial surface, at end-diastole and end-systole, from chosen perspectives. Anatomical landmarks are incorporated to aid in orientation. For regional calculation, the surface is divided into equal angular elements with each conceptually connected to the left-ventricular end-diastole centroid, forming a pyramidal volume element. This angular division automatically normalizes for heart size. The fractional change of these elements over the cardiac cycle provides a regional ejection fraction measure which is color-coded on the reconstructed endocardial surface. Composite perspective views, regional ejection fraction histograms and calculations of global end-diastolic, end-systolic, and stroke volumes, are all performed by the method.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive HIV-infected individuals with CD4 cell counts between 50 and 250/mm3.

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.

BACKGROUND: In animals, insulin-like growth factor-1 (IGF-1) increases clearance of beta-amyloid, a pathologic hallmark of Alzheimer disease (AD), from the CNS. Serum IGF-1 level decreases with age, and shows a further decrease in AD. We examined whether the growth hormone secretagogue MK-677 (ibutamoren mesylate), a potent inducer of IGF-1 secretion, slows the rate of progression of symptoms in patients with AD. METHODS: A double-blind, multicenter study was conducted in which 563 patients with mild to moderate AD were randomized to receive MK-677 25 mg or placebo daily for 12 months. Efficacy measures were mean change from baseline at month 12 on the Clinician's Interview Based Impression of Change with caregiver input (CIBIC-plus), the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating-sum of boxes (CDR-sob). RESULTS: A total of 416 patients completed treatment and assessments at 12 months. Administration of MK-677 25 mg resulted in a 60.1% increase in serum IGF-1 levels at 6 weeks and a 72.9% increase at 12 months. In mixed-effects models that included treatment, time (month), randomization strata (baseline MMSE score < or =20 vs >20), and interaction of treatment-by-time, there were no significant differences between the treatment groups on the CIBIC-plus or the mean change from baseline scores on the ADAS-Cog, ADCS-ADL, or CDR-sob scores over 12 months. CONCLUSION: Despite evidence of target engagement as indicated by an increase in serum insulin-like growth factor-1, the human growth hormone secretagogue MK-677 25 mg was ineffective at slowing the rate of progression of Alzheimer disease.

Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits.

In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a 24Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion.

Vaso-vagal reactions in an ambulatory surgery center.

This prospective study was undertaken to determine the incidence and factors predisposing to vaso-vagal reactions during venous cannulation in an ambulatory surgery population. In 141 ambulatory surgery patients, signs and symptoms of a reaction together with mean arterial pressure and heart rate were recorded at 1-min intervals during and for 6 min after venous cannulation. Overall, 10.6% of patients were symptomatic (95% confidence interval [CI] 6%-17%). The incidence was 16.6% (95% CI 8.4%-24.9%) in patients < or = 40 yr and 33.3% (95% CI 6.7%-60.0%) with a prior fainting history. Young age, duration or number of attempts at venous cannulation, and fainting history were independently associated with increased risk of a reaction (P < 0.03-0.004 by multiple repression analysis). Minimum mean arterial pressure was less in symptomatic patients than in those who were asymptomatic (58 mm Hg +/- 11.3 SD versus 82 mm Hg +/- 14.3 SD, P < 0.0001). We conclude that reactions occur commonly, particularly in the young or in patients with a history of fainting. Reactions are typically associated with significant hypotension that may require treatment.

Effects of breathing 80% oxygen on water and albumin accumulation in oleic acid-injured rabbit lungs.

This study was done to determine whether breathing 80% oxygen would enhance edema formation in oleic acid (OA) lung injury. Rabbits breathed air (n = 51) or 80% oxygen (n = 51) for 1 to 7 days after OA lung injury (0.09 ml/kg iv). Control groups breathed 80% oxygen (n = 37) or room air (n = 8) without OA injury. Pulmonary vascular permeability was assessed by measuring 131I-albumin (RISA) concentration in extravascular, extracellular lung water (EVECW) relative to plasma (RISAL/RISAPL). EVECW (ml/g dry lung) was measured by 24Na, and total lung water (TLW) by wet/dry weight (g/g dry lung). Air-breathing control values were 4.53 +/- 0.25 (SD) for TLW and 0.40 +/- 0.09 for RISAL/RISAPL. In the air-breathing OA group, TLW and RISAL/RISAPL increased to 8.32 +/- 0.85 and 0.93 +/- 0.16, respectively, 2 h after OA (p less than .001) but by 24 h, were equal to air-breathing controls. TLW and RISAL/RISAPL in the oxygen treated OA group did not differ from the air breathing OA group on days 2 through 7 inclusive, suggesting that 80% oxygen had no effect on edema formation in the OA-injured lung. Breathing 80% oxygen alone, without OA injury, significantly (p less than .005) increased TLW and RISAL/RISAPL on days 5 and 6. Thus, preexisting lung injury had a protective effect against edema formation from a high fraction of inspired oxygen.

Three-dimensional transesophageal echocardiography for depiction of regional left-ventricular performance: initial results and future directions.

To assess the potential of a prototype transesophageal echocardiography probe for evaluating left-ventricular wall motion in three dimensions, we acquired images under anesthesia in 15 patients who had akinesia or dyskinesia and 8 patients who had normal function demonstrated on preoperative ventriculography. Short-axis, oblique transgastric scans were obtained in 16 of the patients and four-chamber, long-axis oblique scans were obtained in 12 patients, with five patients (22%) yielding good-quality scans of both types. Off-line, we outlined the endocardial borders manually and used the outlines to make computer-generated three-dimensional models of the endocardial surfaces, color-tiled according to regional ejection fraction. Compared with contrast ventriculograms, the regional ejection fraction histograms derived from these models showed 86% concordance for detecting dyssynergy. However, the concordance between the ventriculograms and the color-tiled models in localizing the dyssynergy was only 67% overall. Uncertainty in rotational alignment between the reconstructions and the ventriculograms appeared to contribute to misreading the location of dyssynergy. In addition, the apical region appeared to have been missed in 8 (50%) of the short-axis scans, whereas it was visualized in all long-axis scans. We conclude that three-dimensional analysis of the location, extent, and degree of left-ventricular dyssynergy is feasible from transesophageal echocardiograms and could have wide application in the study of regional ventricular function. However, improvements are necessary to enable the transducer to scan the cardiac apex more reliably from the short-axis viewpoint and to have a means for spatially orienting the images with respect to an external frame of reference.

Extravascular, extracellular water in rabbit lung using Na and sucrose indicators.

We compared the volume of the pulmonary extravascular, extracellular water space using sodium and sucrose indicators in 8 normal and 11 edematous rabbit lungs by steady-state techniques. The volume of the extravascular, extracellular space (EVECW), expressed in milliliters per gram dry lung, was determined from the volume of distribution of 24Na, [3H]sucrose, or total sodium in 1) supernatant solutions obtained by centrifugation of homogenized lung or 2) intact lung fragments. There was no significant difference in EVECW measured in normal lungs [24Na 1.88 +/- (SD) 0.31; [3H]sucrose 1.84 +/- (SD) 0.27] or edematous lungs [24Na 4.78 +/- (SD) 1.44; [3H]sucrose 4.41 +/- (SD) 1.33] when comparing supernate solutions of homogenized lungs. Similarly, there was no significant difference between the volumes of distribution (EVECW) of these two isotopes when measured in intact fragments of normal lung [24Na 2.08 +/- (SD) 0.28; [3H]sucrose 1.68 +/- (SD) 0.37]. The volume of EVECW measured in supernates was less than in fragments with both isotopes. Washing the centrifuged tissue pellet and adding the wash activity to the initial supernate activity yielded results that were equal to the fragment technique. The failure to detect significant differences between 24Na and [3H]sucrose spaces in the lung suggests that the contribution on intracellular sodium to the measurement of lung water is small and relatively insignificant, at least within the confines of this experiment.

Left ventricular ejection fraction: single-plane and multiplanar transesophageal echocardiography versus equilibrium gated-pool scintigraphy.

The relative accuracy and precision of estimating left ventricular ejection fraction (EF) in dogs were assessed by two-dimensional transesophageal echocardiography (2D-TEE) and by three-dimensional transesophageal echocardiographic (3D-TEE) imaging and reconstruction. This assessment was accomplished by comparing each echocardiographic method to a gated equilibrium blood pool radionuclide (RN) standard. By using both correlation and regression analysis, 2D-TEE performed reasonably well in estimating RNEF (correlation coefficient [r] = 0.80, slope = 1.01, intercept = 6.37, standard error of the estimate [SEE], 8.98), but not as well as 3D-TEE (r = 0.86, slope = 0.83, intercept = 3.38, SEE, 5.74). Using Altman and Bland's methods of comparison analysis, it was found that 2D-TEE overestimated RNEF by 7% (standard deviation [SD], 8.8). This degree of overestimation was not consistent across the range of measurement. In contrast, 3D-TEE slightly underestimated RNEF by less than 3% and showed less variability (SD, 6.0). The accuracy of the 3D-TEE determinations was not dependent on the magnitude of EF. Additionally, a significantly higher proportion of the 2D-TEE measurements (0.30) compared with the 3D-TEE measurements (0.10) differed from RN values by more than 10% (P = 0.009, McNemar's test). At the clinically important low end of the EF range (RNEF less than or equal to 35%), 2D-TEE may be expected (with 95% confidence) to be within -15% to +28% EF of reference values, whereas 3D-TEE can be expected to be within -8% to +5% EF relative to RN.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic profile and tolerability of indinavir-ritonavir combinations in healthy volunteers.

This was a randomized, double-blind, placebo-controlled parallel study in human immunodeficiency virus type 1 (HIV-1)-uninfected healthy subjects to investigate the pharmacokinetic interaction between indinavir (IDV) and ritonavir (RTV). Subjects were allocated to treatment groups of IDV given with RTV in the following milligram doses twice daily: 800 mg of IDV-100 mg of RTV (800-100 mg), 800-200, 800-400, and 400-400 mg, placebo of IDV with RTV doses of 100, 200, and 400 mg, and placebo of both IDV and RTV. Doses of both drugs were administered for 14 days with a low-fat meal and one dose on day 15 with a high-fat meal. Blood was obtained for drug concentration measurements on days 14 and 15. Seventy-three volunteers enrolled in the study: 29 men and 44 women. Fifty-three volunteers completed the study. When compared to standard historical data for 800 mg of IDV every 8 h (q8h), the IDV area under the concentration-time curve for 24 h (AUC(24)) of IDV-RTV regimens 400-400, 800-100, and 800-200 mg were at least 1.4, 2.3, and 3.3 times higher, respectively, regardless of meal. The concentrations at the end of the dosing interval were 10 to 25 times higher than that observed in the standard regimen of 800 mg of IDV q8h for IDV-RTV 800-100 and 800-200 mg regimens, respectively. RTV at 200 mg maximally enhanced the IDV profile. Improved tolerability was associated with IDV-RTV 800-100 mg versus IDV-RTV 800-200, 800-400, and 400-400 mg q12h. The advantages of IDV-RTV twice daily over 800 mg of IDV q8h include no food restrictions and twice-daily dosing. Also, the regimens achieve levels of IDV that may be helpful in suppressing strains of HIV-1 that have reduced susceptibility to IDV or other protease inhibitors.

Transdermal fentanyl for postoperative pain management. A double-blind placebo study.

A double-blind, placebo-controlled, randomized design was used to evaluate the safety and efficacy of transdermal fentanyl citrate for postoperative pain management in 42 healthy adult patients undergoing major shoulder surgery. Transdermal systems rated to deliver fentanyl citrate at a rate of 75 micrograms/h were applied to the skin immediately prior to surgery and worn for 24 hours. Patients in the active group required significantly less morphine than the placebo group during the 24-hour period that systems were in place (0.8 +/- 0.61 vs 1.3 +/- 0.64 mg/h) and for the first 12 hours after removal (0.3 +/- 0.36 vs 0.5 +/- 0.32 mg/h). The incidence of vomiting was more frequent in the active group than in the placebo group (73% vs 30%), and respiratory rate in the active group was lower than in the placebo group during the 13- to 24-hour interval of system application (14 +/- 3 vs 16 +/- 2 breaths per minute). Nevertheless, transdermal fentanyl appears to be safe and effective after orthopedic surgery in healthy adult patients.

Clinical assessment of a flow-through fluorometric blood gas monitor.

We performed an observational study to evaluate a flow-through fluorometric instrument (Gas-STAT) that continuously measures the carbon dioxide tension (PCO2), oxygen tension (PO2), and pH of blood in the cardiopulmonary bypass circuit. Setup and calibration of the instrument typically required 20 minutes. During bypass, 129 blood samples were drawn from 16 patients for comparison with conventional measurements obtained with a blood gas machine. Data for each variable, within each sensor, were analyzed by linear regression. The ranges of the standard errors of the estimate were 0.7 to 4.2 mm Hg for PCO2, 18.3 to 78.7 mm Hg for the high PO2 range, 1.4 to 7.1 mm Hg for the low PO2 range, and 0.008 to 0.049 for pH. The regression lines differed from the identity line (P less than 0.05) in at least one variable in most patients, and large deviations from the line of identity in both slope and intercept were common. Among 58 sensors evaluated, failures occurred in 5 (2.9%) of the 174 optodes, and minor leakage occurred in 2 (3.4%) of the flow-through cells. We conclude that although this flow-through fluorometric instrument is an adequate monitor of trends in blood gases during cardiopulmonary bypass, it is not accurate enough to supplant conventional laboratory measurements.