Predicting the Need for Fluid Therapy-Does Fluid Responsiveness Work?

Fluid overdose can be harmful in critically ill patients. Since central venous pressure (CVP) is currently considered to be an inappropriate indicator of preload, much attention is being given to predicting fluid responsiveness, i.e., the response of stroke volume (SV) or cardiac output (CO) to fluid challenge. However, when fluid responsiveness was evaluated in critically ill patients, including sepsis, only 40-50% of the patients responded. Moreover, most fluid responders do not show significant hemodynamic improvement after fluid administration. In this review, we discuss why fluid responsiveness based on the Starling mechanism did not work well in the clinical setting. According to the Starling mechanism, a patient whose SV/CO significantly increases after a fluid challenge is considered to be a fluid responder and judged to need fluid therapy. However, the currently recommended fluid challenge dose of crystalloid 250-500 mL has little effect on increasing blood volume and is not sufficient to increase the preload of the Starling curve. Especially in septic patients, due to their vascular hyperpermeability, increase in blood volume is even smaller. Furthermore, Infusion induced hemodilution is known to reduce blood viscosity and hematocrit, as a result, decreasing afterload. This indicates that the increased SV/CO after fluid challenge is caused not only by increased preload but also by decreased afterload. For these reasons, fluid responsiveness with small crystalloid challenge is questionable as a clinical indicator of fluid therapy.

Geraniol, E-3,7-dimethyl-2,6-octadien-1-ol, as the alarm pheromone of the sycamore lace bug Corythucha ciliata (Say).

Although adult sycamore lace bugs Corythucha ciliata (Say) show no sign of aggregation, nymphs at all developing stages are gregarious. When an individual nymph in the center of a colony was squashed with a needlepoint, proximate nymphs showed evasive behavior. The same evasive reaction was produced by exposing aggregated nymphs to nymph hexane extract. The active component, E-3,7-dimethyl-2,6-octadien-1-ol, geraniol, was responsible for the evasive behavior, and identified as the alarm pheromone. One nanogram of the alarm pheromone elicited activity similar to that in a third instar nymph. Presence of 2-acylcyclohexane-1,3-diones and their 4-hydroxy analogues are reconfirmed as nymph-specific components, though their biological significance remains unknown.

[Experience of ultrasound-guided popliteal sciatic nerve block and femoral nerve perineural catheter placement in a morbidly obese patient undergoing total knee arthroplasty].

A 60-year-old morbidly obese woman (150 cm, 112 kg, BMI 49.8) underwent total knee replacement under general anesthesia combined with sciatic nerve block and continuous femoral nerve block. Following induction of general anesthesia and tracheal intubation, the sciatic nerve was blocked using the popliteal approach with the patient in the supine position. Then the femoral nerve block was performed, followed by perineural catheter placement for postoperative continuous local anesthetic infusion. For both procedures, real-time ultrasound imaging was used to facilitate needle placement and confirm the adequate local anesthetic deposition. Twenty-five and 30 ml of 0.375% ropivacaine was injected around the sciatic and femoral nerves, respectively. Postoperatively 0.15% ropivacaine was infused at the rate of 5 ml x hr(-1) for 60 hours through the femoral catheter, which provided satisfactory pain relief in combination with scheduled loxoprofen administration. No block-related complications were noted. Our experience suggests that the ultrasound-guided technique may prove useful to facilitate safe and accurate block when technical difficulties are anticipated with anatomic landmark-based approaches.

Pregnancy does not enhance volatile anesthetic sensitivity on the brain: an electroencephalographic analysis study.

BACKGROUNDS: Parturients are thought to be more sensitive to inhalational anesthetics because their minimum alveolar concentration is decreased. However, this conventional theory may be wrong, because, according to recent animal studies, minimum alveolar concentration indicates anesthetic effect on the spinal cord but not on the brain. The aim of this electroencephalographic study was to investigate the differences in the hypnotic effect of sevoflurane on parturients and nonpregnant patients. METHODS: Fifteen parturients undergoing cesarean section and 15 patients undergoing elective gynecologic surgery were enrolled. Anesthesia was induced with 4 mg/kg thiopental, 2 microg/kg fentanyl, and 2 mg/kg suxamethonium or 0.15 mg/kg vecuronium. Anesthesia was maintained with sevoflurane and fentanyl. The electroencephalographic signals, obtained from the bispectral index monitor, were recorded on a computer. We calculated 95% spectral edge frequency, amplitude, and bicoherence using custom software (Bispectrum Analyzer for bispectral index). After confirming that end-tidal sevoflurane had reached equilibrium, we measured electroencephalographic parameters of sevoflurane at 2.0 and 1.5% during surgery and at 1.0 and 0.5% after surgery. RESULTS: With the decrease of end-tidal sevoflurane concentration from 2.0 to 0.5%, 95% spectral edge frequency, amplitude, bispectral index, and bicoherence values changed dose-dependently in pregnant and nonpregnant women (P<0.0001). However, there were no significant differences in those electroencephalographic parameters in pregnant and nonpregnant women. CONCLUSIONS: This electroencephalographic study has shown that pregnancy does not enhance hypnotic effect of sevoflurane. These results suggested that the decrease in minimum alveolar concentration during pregnancy does not mean an enhanced volatile anesthetic effect on the brain.

[Controversial issues regarding general anesthesia for cesarean section].

Although, general anesthesia for cesarean section still seems to be the method of choice in extremely urgent settings, past anesthetic evidence has shown that general anesthesia is with increased risk of anesthesia-related maternal mortality. The major disadvantage with general anesthesia is the risk of aspiration of gastric contents and a "cannot ventilate, cannot intubate" situation. Awareness is another concern. There has been a decrease in the number of cesarean section performed under general anesthesia, and a progress in the management of aspiration of gastric contents and difficult airway. This review examines the recent knowledge of these topics. We also describe the benefits and risks of new drugs, such as propofol, remifentanil and rocuronium in general anesthesia for cesarean section.

Incidence of embolic events during acetabular prosthesis insertion in total hip arthroplasty, and effect of intramedullary decompression in preventing embolism: higher risk of embolism with one-piece type prosthesis.

PURPOSE: In total hip arthroplasty (THA), there is a high risk of bone marrow embolism during femoral prosthesis insertion. However, the incidence during acetabular prosthesis insertion has received less attention. The first goal of this study was to determine the incidence of bone marrow embolism associated with acetabular prosthesis insertion. The second goal was to evaluate the effects of intramedullary decompression of the acetabulum in suppressing bone marrow embolism. METHODS: To achieve the first goal, we evaluated the effects of prosthesis insertion on the incidence of bone marrow embolism, and on respiratory and cardiovascular dynamics. For the evaluation of bone marrow embolism, images obtained by transesophageal echocardiography were rated using Pitto's classification. To achieve the second goal, patients undergoing THA with a one-piece type acetabular prosthesis were divided into a control group and an acetabulum-decompression group, and the effects of insertion were analyzed in the same fashion. RESULTS: In the 150 patients in the study, bone marrow embolism was rated as grade 0 in 9, grade 1 in 46, grade 2 in 61, and grade 3 in 34 patients. Patients rated as grade 2 and 3 exhibited significant reductions in blood pressure and Pa(O) (2) 5 min after acetabular prosthesis insertion. The results of multivariate analysis suggested that the incidence of bone marrow embolism was higher for the one-piece type prosthesis than for the two-piece type. Among the 60 patients who underwent THA with a one-piece type prosthesis, the incidence of bone marrow embolism was significantly lower in the decompression group. CONCLUSION: As there are increasing indications for one-piece type acetabular prostheses in Japan, we must pay attention to the possibility of bone marrow embolism, not only during femoral prosthesis insertion but also during acetabular prosthesis insertion.

Involvement of endoplasmic reticulum (ER) stress in podocyte injury induced by excessive protein accumulation.

BACKGROUND: An imbalance between protein load and folding capacity is referred to as endoplasmic reticulum (ER) stress. As a defense mechanism, cells express ER stress inducible chaperons, such as oxygen-regulated proteins 150 (ORP150) and glucose-regulated proteins (GRPs). While ER stress is important in various diseases, a pathophysiologic role for ER stress in kidney disease remains elusive. Here we investigate expression of ER stress proteins in cultured rat podocytes as well as in our recently developed animal model of abnormal protein retention within the ER of podocytes (i.e., megsin transgenic rat). METHODS: The expression of ER stress inducible proteins (ORP150, GRP78, or GRP94) in cultured podocytes treated with tunicamycin, A23187, SNAP, hypoxia, or hyperglycemia, and the renal tissues or isolated glomeruli from megsin transgenic rats was analyzed by Western blotting analysis, immunohistochemistry, or confocal microscopy. RESULTS: Cultured podocytes demonstrated that treatment with tunicamycin, A23187, and SNAP, but not hypoxia or hyperglycemia, up-regulate expression of ER stress proteins. Extracts of isolated glomeruli from megsin transgenic rats reveal marked up-regulation of ER stress chaperones in podocytes, which was supported by immunohistochemical analysis. Confocal microscopy revealed that ER stress in podocytes was associated with cellular injury. Podocytes of transgenic rats overexpressing a mutant megsin, without the capacity for polymerization within the ER, do not exhibit ER stress or podocyte damage, suggesting a pathogenic role of ER retention of polymerized megsin. CONCLUSION: This paper implicates a crucial role for the accumulation of excessive proteins in the podocyte ER in the induction of ER stress and associated podocyte injury.

Circulating mature adrenomedullin is related to blood volume in full-term pregnancy.

Plasma adrenomedullin concentration increases during pregnancy. We measured blood volume and mature adrenomedullin concentration in plasma and cerebrospinal fluid and examined whether mature adrenomedullin in plasma and cerebrospinal fluid was associated with increasing blood volume during pregnancy. We enrolled 47 women undergoing surgery with spinal anesthesia in this study. We first measured mature adrenomedullin concentration in plasma and cerebrospinal fluid of nonpregnant women undergoing orthopedic surgery, pregnant women between 15 and 18 wk of gestation undergoing gynecological surgery, and pregnant women at full-term undergoing cesarean delivery. The second study included 20 healthy and full-term parturients scheduled for cesarean delivery. We measured arterial blood pressure and blood volume by noninvasive pulse spectrophotometry using indocyanine green. Plasma-mature adrenomedullin concentration was 1.24 +/- 0.98, 2.79 +/- 1.23, 4.79 +/- 2.61 fmol/mL (mean +/- sd) in the nonpregnant, the early gestation, and the full-term groups, respectively. But in cerebrospinal fluid, mature adrenomedullin did not significantly increase. Furthermore, mature adrenomedullin in plasma, but not cerebrospinal fluid, had a significant correlation with blood volume per unit body weight (r2= 0.46; P = 0.0009). These findings demonstrate that plasma-mature adrenomedullin concentration increased and that increased plasma-mature adrenomedullin is associated with increased blood volume during pregnancy.

Determination of the standard value of circulating blood volume during anesthesia using pulse dye-densitometry: a multicenter study in Japan.

PURPOSE: The standard value for circulating blood volume (BV) during anesthesia was determined by a multicenter study in Japan. The significance of BV on the reduction of blood pressure after the induction of anesthesia was also examined. METHODS: The study included 184 patients from eight university hospitals. After the induction of anesthesia, pulse dye-densitometry was performed according to a uniform protocol. Factors contributing to reduced blood pressure after induction of anesthesia were examined by multiple logistic regression analysis. RESULTS: The mean and standard deviation of BV was 80.0 +/- 13.9 ml x kg(-1); for females and 84.2 +/- 15.3 ml x kg(-1) for males (P > 0.05). There was no age difference in terms of BV. After adjusting for the effects of height, weight, and age, the factors predisposing to a reduction in blood pressure of >20 mmHg after induction of anesthesia were found to be age (P < 0.01) and BV (ml x kg(-1)) (P < 0.001). CONCLUSION: We determined the BV of anesthetized patients before surgery in Japan using pulse dye-densitometry. It is suggested that age is not a factor regarding BV, and that blood pressure tends to be reduced in hypovolemic patients after induction of anesthesia.

Electroencephalographic bicoherence is sensitive to noxious stimuli during isoflurane or sevoflurane anesthesia.

BACKGROUND: The authors previously reported changes in electroencephalographic bicoherence during isoflurane anesthesia combined with epidural anesthesia. Here, they examined the influence of noxious stimuli on electroencephalographic bicoherence as well as on the Bispectral Index (BIS) and the 95% spectral edge frequency (SEF95). METHODS: The authors enrolled 48 elective abdominal surgery patients (aged 22-77 years; American Society of Anesthesiologists physical status I or II). Raw electroencephalographic signals as well as BIS and SEF95 were recorded on a computer using a BIS monitor (A-1050) and Bispectrum Analyzer (BSA) for BIS (the authors' original software). Using BSA for BIS, the authors evaluated the two peak heights of electroencephalographic bicoherence. Anesthesia was induced with 3 mg/kg thiopental and was maintained with, in air-oxygen, 1.0% isoflurane or 1.5% sevoflurane. After confirming the steady state, the authors recorded baseline values. In experiment 1, they administered 3 microg/kg fentanyl 5 min after incision and investigated the changes in electroencephalographic derivatives at 5 and 10 min after incision. In experiment 2, they administered a similar dose of fentanyl 5 min before incision and investigated the changes in electroencephalographic derivatives immediately before and 5 min after incision. RESULTS: In experiment 1, after incision, both peak heights of electroencephalographic bicoherence significantly decreased but returned to control values after fentanyl administration. By contrast, after incision, BIS and SEF95 showed individual variability. In experiment 2, although fentanyl itself did not affect all electroencephalographic derivatives before incision, the variables remained unchanged after incision. CONCLUSION: Noxious stimuli decreased the peak heights of electroencephalographic bicoherence, an effect that was counteracted by fentanyl analgesia.

Transcriptional regulation of a mesangium-predominant gene, megsin.

The cDNA of a new human mesangium-predominant gene, megsin, a novel member of the serpin superfamily, has recently been cloned. This study investigates the regulatory mechanisms of megsin gene expression. A genomic clone of the human megsin gene was obtained by screening bacterial artificial chromosome (BAC) library with the megsin cDNA. The analysis for exon-intron junctions of megsin genomic DNA demonstrated that the gene contained 8 exons and 7 introns, spanned 20 kbp, and that the genomic structure of the serpin superfamily was highly conserved. Fluorescence in situ hybridization (FISH) revealed that the megsin gene is localized in chromosome 18q21.3, close to the other serpin genes. The transcriptional start site, located by primer extension analysis, was 391 bp upstream from the start codon. The sequence and reporter analyses on 4021-bp-long 5'-flanking region of megsin gene demonstrated a consensus promoter segment within this region and a relatively strong promoter activity in human mesangial cells and A431, a human tumor cell line recently reported to express a novel serpin identical with megsin. Moreover, this study utilized site-directed and deletion mutagenesis analyses, and electrophoretic mobility shift assay identified one positive regulatory motif, an incomplete activator protein-1 (AP-1) binding motif (CTGATTCAC) within the -120 to -112 region. This cis-acting element in the 5'-flanking region of megsin is involved in the activation of the megsin gene in mesangial cells.