Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Reframing climate change as a public health issue: an exploratory study of public reactions

Background  

Climate change is taking a toll on human health, and some leaders in the public health community have urged their colleagues to give voice to its health implications. Previous research has shown that Americans are only dimly aware of the health implications of climate change, yet the literature on issue framing suggests that providing a novel frame - such as human health - may be potentially useful in enhancing public engagement. We conducted an exploratory study in the United States of people's reactions to a public health-framed short essay on climate change.     

Chronic lower extremity ischemia: a human model of ischemic tolerance.

BACKGROUND: Ischemic preconditioning (IPC) has been found in animals to have a protective effect against future ischemic injury to muscle tissue. Such injury is unavoidable during some surgical procedures. To determine whether chronic ischemia in the lower extremities would imitate IPC and reduce ischemic injury during vascular surgery, we designed a controlled clinical study. PATIENTS AND METHODS: Two groups of patients at a university-affiliated medical centre with chronic lower-extremity ischemia served as models of IPC: 6 patients awaiting femoral distal bypass (FDB) and 4 scheduled for aortobifemoral (ABF) bypass grafting for aortoiliac occlusive disease. Seven patients undergoing elective open repair of an infrarenal abdominal aortic aneurysm (AAA) were chosen as non-IPC controls. Three hematologic indicators of skeletal-muscle injury, lactate dehydrogenase (LDH), creatine kinase (CK) and myoglobin, were measured before placement of the proximal clamp, during surgical ischemia, immediately upon reperfusion, 15 minutes after and 1 hour after reperfusion, and during the first, second and third postoperative days. RESULTS: Baseline markers of skeletal-muscle injury were similar in all groups. In postreperfusion samples, concentrations of muscle-injury markers were significantly lower in the 2 PC groups than in the control group. For example, at day 2, LDH levels were increased by about 30% over baseline measures in the elective AAA (control) group, whereas levels in the FDB and ABF groups remained statistically unchanged from baseline. Myoglobin in controls had increased by 977%, but only by 160% in the FDB and 528% in the ABF groups. CK levels, in a similar trend, were 1432% higher in the control group and only 111% (FDB) and 1029% (ABF) in the study groups. Taken together, these data represent a significant level of protection. CONCLUSIONS: Patients with chronic lower-extremity ischemia suffered less severe ischemic injury after a period of acute ischemia than those with acute ischemia alone. Ischemic preconditioning is one proposed mechanism to help explain this protective effect.     

Effectiveness of needle and syringe programmes for preventing HIV transmission

Objective: To examine the effectiveness of needle and syringe programmes (NSPs) in preventing HIV transmission among injecting drug users (IDUs).Methods: An ecological study design was used to determine change in HIV prevalence among injecting drug users between cities with and without NSPs. Several data sources, such as electronic journal databases, surveillance reports, websites, and index review of relevant journals, were used to identify studies of HIV seroprevalence among IDUs, and presence of NSPs. The rate of change in HIV prevalence was estimated by regression analysis.Results: There were 778 years of data from 99 cities globally included in the analysis. HIV prevalence decreased by 18.6% per annum in cities that introduce NSPs, and increased by 8.1% in cities that had never introduced NSPs (mean difference −24.7% [95% CI: −43.8, 0.5%], P=0.06). The mean difference was –33% when comparison was weighted to one over the variance of the regression estimator (29% decrease in cities with NSPs and 5% increase in cities without NSPs, P<0.001). When analysis was restricted to cities with first HIV seroprevalence less than 10%, the average annual change in seroprevalence was 18% lower in cities with NSPs (P=0.03).Conclusions: Despite the inherent limitations within an ecological study design, the study provides additional evidence that NSPs reduce transmission of HIV infection. The rapid spread of HIV among IDU populations and increasing rates of injecting in many countries calls for scaling up of NSPs as well as other harm reduction strategies.     

Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled leukotriene b4 antagonist.

Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. METHODS: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. RESULTS: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate.