Randomized controlled trial of the effect of depth of anaesthesia on postoperative pain.

BACKGROUND: Our hypothesis was that deep anaesthesia, as estimated by a low target bispectral index (BIS) of 30-40, would result in less postoperative pain than that achieved at a conventional depth of anaesthesia. METHODS: We undertook a randomized double-blind controlled study at two tertiary teaching hospitals in New Zealand (2010-1) recruiting 135 adult patients ASA I-II presenting for non-emergent surgery under general anaesthesia requiring tracheal intubation. Anaesthesia was maintained with desflurane and a multimodal analgesia regimen comprising fentanyl infusion, i.v. paracetamol, and parecoxib. Patients were randomly assigned to either a low BIS (30-40) group or a high BIS (45-60) group. Desflurane concentrations were titrated to achieve these targets. Postoperative pain was assessed by: the pain on awakening (0-10, verbal rating scale, VRS(awake)) in the post-anaesthetic care unit; pain on activity at 20-24 h after operation (VRS(d1A)); and the rate of morphine patient-controlled analgesia (PCA) usage over the first 24 h. RESULTS: There was no statistically significant difference between the two groups for any of the pain scores. The median [inter-quartile range (IQR)] VRS(awake) was 4.0 (0-8) for the low and 4.0 (0-8) for the high BIS groups (P=0.56). The median (IQR) VRS(d1A) was 3.0 (1-5) for the low and 3.0 (1.5-4.5) for the high BIS groups (P=0.83). The median PCA morphine consumption in the low BIS group was 0.61 mg h(-1) (0.04-1.5) vs 0.43 mg h(-1) (0-1.59) in the high BIS group (P=0.98). CONCLUSIONS: We conclude that there is no clinically useful analgesic effect of a deep anaesthesia regimen.

The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice.

Gap junction blockade is a possible mechanism by which general anaesthetic drugs cause unconsciousness. We measured the sensitivity of connexin36 knockout mice to the hypnotic effects of isoflurane and propofol. The experimental endpoint was recovery of the righting reflex of the anaesthetised animals during 0.2% step-reductions in isoflurane concentration, or following intraperitoneal injection of propofol (100 mg.kg(-1) ). Connexin36 knockout animals were more sensitive to the hypnotic effects of isoflurane than 'normal' wild-type animals. The half maximal effective concentration (EC50) for recovery of righting reflex was 0.37% for connexin36 knockout vs 0.49% for wild-type animals (p < 0.001). For propofol, connnexin36 knockout animals showed more rapid loss of righting reflex than wild-type animals (mean (SD) 2.8 (0.13) vs 3.8 (0.27) min); and young (< 60 days) connexin36 knockout animals remained anaesthetised for longer than young wild-type mice (47.2 (2.9) vs 30.5 (1.7) min; p < 0.00001). These findings suggest that the hypnotic effects of anaesthetic drugs may be moderately enhanced by gap junction blockade.

The use of real time rtPCR to quantify inflammatory mediator expression in leukocytes from patients with severe sepsis.

Real-time reverse transcriptase polymerase chain reaction (RT rtPCR) was used to quantify the pattern of inflammatory mediator mRNA expression in circulating leukocytes from adult patients diagnosed with severe sepsis. We analysed 29 blood samples from 26 severely septic patients with different septic sources and eight samples from eight healthy adult volunteers. RT rtPCR was used to quantify mRNA expression of 21 different inflammatory mediators in peripheral leukocytes. The median variability in gene expression in the sepsis patients was 10.5 times greater than the variability of the healthy comparison group. We found a significant change in the regulation for the following genes: C5aR (20-fold, P < 0.001), IL-8 (29-fold, P < 0.001), MMP9 (72-fold, P < 0.001), HSP70 (2.4-fold, P = 0.02), and RIP2 (1.8-fold, P < 0.04) were up-regulated. Conversely the median expression of IFNgamma, and IL-6 were zero (P < 0.001), and mtHSP (0.4-fold, P = 0.02) was significantly down-regulated. Using linear discriminant analysis, IFNgamma, IL-12, and TLR4 were correlated to a negative outcome. Different septic sources (peritonitis, burn, pneumonia and musculo-skeletal infections) resulted in significantly different mRNA patterns. The RT rtPCR is a useful tool to monitor the immune response in septic patients. We found a very high variability in inflammatory mediator expression among septic patients compared to healthy volunteers. This suggests that any future immune-modulatory therapy may need to be individualized to the patient's requirements as monitored by RT rtPCR. Different sources of sepsis may result in markedly different activation patterns.

A survey of genetic counselors' use of informed consent documents for prenatal genetic counseling sessions.

Thirty six members of the Prenatal Diagnosis Special Interest Group of the National Society of Genetic Counselors were interviewed about their use of informed consent documents for the genetic counseling component of their prenatal genetic counseling sessions and their perceptions of the utility and feasibility of such documents. Major findings include (1) None of the genetic counselors currently used a consent document describing the genetic counseling component of the session itself; (2) Only three participants stated that they had ever used an informed consent document for this component of the session; (3) They disagreed about the importance and usefulness of such a document; (4) There was variability in their reported likelihood of using a document if one were available; (5) There was a fair amount of agreement about the types of information to include on an informed consent document for genetic counseling; over half of the sample endorsed 8 of 10 topics; and (6) Participants identified 10 obstacles to using such a document. Recommendations for genetic counseling practice, policy, and research are given.

Electron arc therapy: chest wall irradiation of breast cancer patients.

From 1980 to October 1985 we treated 45 breast cancer patients with electron arc therapy. This technique was used in situations where optimal treatment with fixed photon or electron beams was technically difficult: long scars, recurrent tumor extending across midline or to the posterior thorax, or marked variation in depth of target tissue. Forty-four patients were treated following mastectomy: 35 electively because of high risk of local failure, and 9 following local recurrence. One patient with advanced local regional disease was treated primarily. The target volume boundaries on the chest wall were defined by a foam lined cerrobend cast which rested on the patient during treatment, functioning as a tertiary collimator. A variable width secondary collimator was used to account for changes in the radius of the thorax from superior to inferior border. All patients had computerized tomography performed to determine Internal Mammary Chain depth and chest wall thickness. Electron energies were selected based on these thicknesses and often variable energies over different segments of the arc were used. The chest wall and regional node areas were irradiated to 45 Gy-50 Gy in 5-6 weeks by this technique. The supraclavicular and upper axillary nodes were treated by a direct anterior photon field abutted to the superior edge of the electron arc field. Follow-up is from 10-73 months with a median of 50 months. No major complications were observed. Acute and late effects and local control are comparable to standard chest wall irradiation. The disadvantages of this technique are that the preparation of the tertiary field defining cast and CT treatment planning are labor intensive and expensive. The advantage is that for specific clinical situations large areas of chest wall with marked topographical variation can be optimally, homogeneously irradiated while sparing normal uninvolved tissues.

Postoperative radiation therapy for pathologic stage C prostate cancer.

From 1971 to 1981, 26 patients with pathologic Stage C prostate cancer were referred to this department for postoperative radiation therapy. During the same period 24 patients, undergoing radical prostatectomy at this institution, were found to have pathologic Stage C disease but did not receive adjuvant irradiation. Both groups of patients are compared at 5 years post surgery for disease-free survival, local control, and distant failure in an attempt to determine whether there is a demonstrable benefit of adjuvant irradiation in this setting. All irradiated patients started therapy 1 to 4 months post surgery. All were treated with megavoltage irradiation. The majority were treated to the pelvis by a 4-field technique to an absorbed dose of 46-50 Gy followed by a prostate boost via multiple fields to a total dose of 54-70 Gy. Three patients received 50-52 Gy to the pelvis only and 5 patients received 56-65 Gy to localized prostate fields only. Moderate complications in the irradiated group were 23% with no severe complications observed. This rate may be reduced with treatment of local prostate fields only. There was no significant difference in 5-year survival, 5-year disease-free survival, or distant metastases in patients treated with surgery only or surgery plus radiation. However, local recurrence at 5 years was significantly different (p = 0.046), 16.6% in the surgery only group and 0 in the irradiated group. This difference was more pronounced in the subset of patients with seminal vesicle invasion: 30% local recurrence in the surgery only group versus 0 in the irradiated group. These data suggest that the addition of postoperative irradiation in pathologic Stage C prostate cancer yields an improvement in local control, and that for the subset of patients at significant risk of local relapse, those with seminal vesicle invasion, adjuvant prostate bed irradiation should be recommended.

Breast irradiation following silicone gel implants.

Little information is found in the literature regarding breast irradiation in patients with reconstructed or augmented breasts. From November 1970 to October 1984, we treated ten patients with silicone gel prostheses with external radiation for recurrent disease, or as primary therapy. All patients were treated with megavoltage equipment. Technique and doses varied with the clinical situation, but generally, patients received 5000 rad in five weeks to the breast or mound with opposed tangential fields. The majority of patients had excellent cosmetic results with minimal late skin changes and no fibrosis or contracture. We conclude that, with proper surgical and radiotherapeutic techniques, good cosmetic results can be obtained in these patients, without compromising their therapy.

Dose response analysis of pediatric neuroblastoma to megavoltage radiation.

Children with neuroblastoma treated in Salt Lake City from 1966 through 1982 were analyzed in an attempt to develop guidelines for external beam radiation. Particular attention was addressed to time-dose relationships in those patients with residual disease post-resection (Stages II and III). Altogether, 76 patients were analyzed and survival rates were: Stage I--100%; Stage II--84%; Stage III--69.2%; Stage IV--14.3%; Stage IV-S--71.4%. Survival rates were correspondingly better in younger children and in infants. Indications for postoperative radiation therapy in this population were: unresectable or gross remaining tumor; residual tumor in neural foramina; tumor spill during surgery; positive regional lymph nodes or positive surgical margins. Local control was achieved in a majority of patients undergoing surgery and radiation for limited disease. In children younger than 1 year of age, no local failures were observed at doses above 1200 rad. In children between 1-2 years of age, no local failures were observed with doses as low as 1440 rad. In children older than 3 years, local failures were observed up to 4500 rad.