John K. Hayes

Protective Effects of Isoflurane Pretreatment in Endotoxin- induced Lung Injury

Background: The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury. Methods: Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure. Results: Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection. Conclusion: Isoflurane pretreatment reduces acute lung injury when given 1 or 12 h before an endotoxin challenge or within the first hour of an already established inflammation.

High Dose Brachytherapy as Monotherapy for Intermediate Risk Prostate Cancer

PURPOSE We evaluated our retrospective, single institution experience with high dose rate brachytherapy as monotherapy for intermediate risk prostate cancer. MATERIALS AND METHODS Our cohort included 284 patients with intermediate risk prostate cancer, defined as clinical stage T2b/T2c, Gleason score 7 and/or prostate specific antigen 10 to 20 ng/ml, and 1-year minimum followup. Treatment was 2 high dose rate brachytherapy sessions at 3 fractions of 6.5 Gy each for a mean of 19 days. Prostate specific antigen failure was defined as nadir +2 ng/ml. RESULTS Mean followup was 35.1 months (median 31.9). Actuarial 5-year cause specific survival and clinical local control were 100%, distant-metastasis-free survival 98.8% and biochemical disease-free survival 94.4%. Clinical stage predicted biochemical disease-free survival. For stage T2a or less 5-year biochemical disease-free survival was 95.1% vs 100% for stage T2b and 77.4% for T2c (p = 0.012). Percent positive biopsy cores and prostate specific antigen nadir were also predictive. International Prostate Symptom Score results remained stable and potency was maintained in 82.6% of patients at 2 years. Pads were used for the first time after brachytherapy in 22 patients (7.7%), mostly for grade 1 incontinence (occasionally or less per week). Excluding patients with prior transurethral prostatectomy, stroke or tremor 2.5% used pads for the first time after treatment. No patient had urethral stricture. Radiation Therapy Oncology Group grade 1 rectal toxicity developed in 12 patients (4.2%) but not beyond grade 1. CONCLUSIONS High dose rate brachytherapy as monotherapy is safe and effective for patients with intermediate risk prostate cancer. We recommend caution for percent positive biopsy cores exceeding 75% or clinical stage T2c. Excluding such patients the 5-year biochemical disease-free survival rate was 97.5%.

Isoflurane Pretreatment Inhibits Lipopolysaccharide-induced Inflammation in Rats

Background Previous studies have indicated that volatile anesthetic pretreatment protects cells from inflammation in vitro; therefore, the authors hypothesized that pretreatment with isoflurane may attenuate the hemodynamic and pathologic changes to the vasculature that are associated with inflammation in vivo. Methods Rats received intravenous lipopolysaccharide or saline placebo with and without pretreatment with isoflurane (1.4% for 30 min immediately before lipopolysaccharide). Mean arterial pressure (MAP) and response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators were assessed hourly for 6 h. Tumor necrosis factor-&agr; concentrations, arterial blood gases, and vascular histology were also determined. Results Lipopolysaccharide decreased MAP and vasodilation to acetylcholine and sodium nitroprusside. Lipopolysaccharide also caused acidosis, endothelial swelling, and endothelial detachment from the smooth muscle. Isoflurane pretreatment prevented the decrease in MAP for 5 h and attenuated the decrease at 6 h. Pretreatment increased the vasodilation to acetylcholine in lipopolysaccharide rats to control concentrations but had no effect on sodium nitroprusside. In control rats, isoflurane pretreatment increased the response to acetylcholine and sodium nitroprusside but had no effect on MAP. Isoflurane pretreatment prevented the acidosis and endothelial damage to mesenteric and aortic vessels, and attenuated the increase in tumor necrosis factor-&agr; associated with lipopolysaccharide-induced inflammation. Conclusion Pretreatment with 30 min of isoflurane attenuated the decrease in MAP and endothelium-dependent vasodilation, the acidosis, the increase in tumor necrosis factor-&agr;, and the damage to the vascular endothelium associated with lipopolysaccharide-induced inflammation in rats. This study suggests that isoflurane pretreatment may protect the vasculature during inflammation.

Definitive radiation therapy in bile duct carcinoma

Between 1980 and 1985, 24 patients with primary adenocarcinoma of the bile duct were treated with various combinations of surgery, biliary intubation, external irradiation, and transcatheter brachytherapy. Seventy-five percent of tumors were in the proximal bile ducts. Ten patients received no or only palliative radiation, Group 1, whereas 14 patients received definitive courses of radiation (4 by external beam irradiation, 2 by transcatheter irradiation, and 8 by both modalities), Group 2. Survival in Group 1 and Group 2 was significantly different (p less than 0.005) with median survivals of 2.0 and 12.8 months, respectively. This result may be in part due to differences in treatment and in part due to selection bias because the series is small, uncontrolled, and retrospective. Median survival of the 8 patients treated with combined modalities was 13.2 months (range 7.4-30.3) with 4 patients alive 8.7 to 16.2 months, 3 without cholangiographic evidence of disease. Complications of therapy were common, including bacterial sepsis (58%), cholangitis (38%), gastrointestinal bleeding (46%), intra or extrahepatic abscesses (33%), and recurrent biliary obstruction (25%). Cholangitis, hemorrhage, abscesses, and ulcers appeared more frequently in definitively treated patients, whereas recurrent biliary obstruction was absent in this group and frequent in Group 1. Differences in complication rates between groups were not statistically significant. Early diagnosis and management usually reversed a downhill clinical course in patients with abscess and hemorrhage. Both surgical and percutaneous techniques of biliary decompression, the usual initial form of therapy in bile duct cancer, are associated with frequent and serious complications. Although many of our complications may have derived from biliary decompression, it is possible that definitive treatment may have increased the frequency of serious complications.

Endoscopic CO2 laser excisional biopsy of early supraglottic cancer

Endoscopic CO2 laser excisional biopsy of selected early supraglottic cancer patients has been described. None of these patients experienced the perioperative morbidities of bleeding, airway obstruction, or aspiration beyond 3 or 4 days. All patients were treated with full-course standard irradiation therapy after their laser procedures. Our very preliminary data suggest that stage I and stage II patients are effectively treated with endoscopic CO2 laser excisional biopsy, whereas stage III patients should undergo open surgeries where medically possible.

American society for radiation oncology (ASTRO) and american college of radiology (ACR) practice guideline for the performance of high-dose-rate brachytherapy

High-Dose-Rate (HDR) brachytherapy is a safe and efficacious treatment option for patients with a variety of different malignancies. Careful adherence to established standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for HDR brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrists. Review of the leading indications for HDR brachytherapy in the management of gynecologic, thoracic, gastrointestinal, breast, urologic, head and neck, and soft tissue tumors is presented. Logistics with respect to the brachytherapy implant procedures and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful HDR brachytherapy program.

Carotid thrombosis following neck irradiation

Therapeutic irradiation may accelerate atherosclerosis, increasing the risk of vascular stenosis or occlusion several to many years following radiation. However, intimal damage following irradiation may result earlier in thrombosis without stenosis. This report discusses three cases of carotid occlusion that occurred within 3 years of moderate dose irradiation. Angiographic studies showed that occlusion occurred in the absence of atherosclerotic stenosis. A review of the literature supports the conclusion that people who receive neck irradiation are at risk not only for the delayed development of diffuse atherosclerosis but also for thrombotic occlusion within months to several years. We suggest that patients who develop neurological symptoms or signs following neck irradiation, regardless of age, dose of radiation, or interval since radiation, should be evaluated for carotid or vertebral artery disease.

Monitoring anesthetic vapor concentrations using a piezoelectric detector: evaluation of the Engstrom EMMA.

The Engstrom anesthetic gas analyzer (EMMA) was evaluated to determine the reproducibility, response time, gas interference, water vapor dependence, and sensitivity. The analyzer also was evaluated clinically in 20 children undergoing orthopedic surgery. Difference between the analyzer output and anesthetic gas standard (reproducibility) ranged from 0.013 +/- 0.008 vol % to 0.018 +/- 0.018 vol %. Response times decreased from 710 ms at 5 l X min-1 to 149 ms at 30 l X min-1. Nitrous oxide caused an offset of +0.11 +/- 0.007 vol %. Water vapor caused positive offsets of 0.25 +/- 0.044 vol %, 0.51 +/- 0.027 vol %, and 0.80 +/- 0.037 vol % at 25 degrees C, 30 degrees C, and 34 degrees C, respectively. The analyzer reproducibly measured dry gas concentrations, but compensation had to be made for water vapor when measuring wet gases. The analyzers usefulness for end-tidal monitoring was questioned because of its slow response time and its sensitivity to water vapor.

Monitoring body-core temperature from the trachea : Comparison between pulmonary artery, tympanic, esophageal, and rectal temperatures

Introduction. We designed an endotracheal tube (ETT) for acquiring body-tore temperature from the trachea. This ETT had two temperature sensors, one attached to the inside surface of the cuff, the other mounted on the ETT shaft underneath the cuff. The ETT was evaluatedin vitro and in dogs to determine: 1) optimal position of temperature sensors and 2) the responsiveness, accuracy, and resistance to ventilatory artifacts.Methods.In vitro. An artificial trachea assessed the response-time and accuracy of ETT temperature sensors to abrupt temperature changes and ventilatory flow-rates.In vivo. Body temperature in 5 dogs was lowered to approximately 26°C then elevated toward 39°C using a heat exchanger during carotid jugular bypass. ETT temperature measurements were compared simultaneously with those from the artificial trachea (in vitro) or from the pulmonary artery, tympanic cavity, esophagus, and rectum of dogs using dry and humidified gas.Results. Cuff temperature sensor responded quickly and accurately to temperature changes and was less prone than the tube sensor to ventilatory and humidity artifacts. During carotid-jugular bypass,in vivo tube and cuff mean temperatures averaged 1.4°C and 0.36°C lower, respectively, than pulmonary artery temperatures. There were no statistical differentes (P > 0.05) between cuff temperatures and those measured from the pulmonary artery, tympanic cavity, esophagus, and rectum. Heating and humidifying the inspiratory gas of dogs with a water-bath humidifer or heat moisture exchanger (HME) had minimal effects on the cuff temperature sensor. An in-line HME increasedin vivo tube temperature from baseline values by 1.13 ± 0.80 °C, while cuff temperature increased by 0.21 ±0.24°C.Conclusion. The cuff of the ETT is a reliable site for measuring body-tore temperature in intubated patients.

Microcirculatory response to halothane and isoflurane anesthesia

Microcirculatory hemodynamics are often used to monitor tissue and organ survival. This study investigated the effect of halothane and isoflurane anesthesia on peripheral microcirculation using the cremaster muscle during intravital microscopy. Twenty-three Sprague-Dawley rats were studied in four groups. Two groups served as controls and did not undergo flap isolation but did receive halothane (N = 6) or isoflurane (N = 5). After induction with a single dose of intraperitoneal pentobarbital (40 mg per kilogram), rats were ventilated with either 2 minimum alveolar concentration (MAC) halothane or 2 MAC isoflurane. Esophageal temperature, electrocardiography, central venous pressure, mean arterial pressure, and blood gases were measured over 4 hours. In groups receiving surgery with either halothane (N = 6) or isoflurane (N = 6), the cremaster muscle was isolated on the neurovascular pedicle. Microcirculatory responses to both halothane and isoflurane anesthesia were evaluated by measuring red blood cell (RBC) velocity, vascular diameters in arterioles (A1, A2-1, A2-2, and A3) and the main venule (V1), functional capillary perfusion, and leukocytic endothelial interactions in postcapillary venules (rolling, adherent, and transmigrating leukocytes). Hemodynamic variables were compared among all four groups, and microcirculatory variables were compared between the two surgical groups. During isoflurane anesthesia in animals with flaps, significantly higher (p < 0.05) RBC velocities were recorded in arterioles A1 (24.4%), A2-2 (28.2%), and A3 (17.4%). Capillary perfusion was significantly higher in animals with flaps and halothane anesthesia (17.8%; p < 0.05). The number of rolling leukocytes (39.4%) was significantly higher during isoflurane anesthesia in animals with flaps (p < 0.05). Better flow hemodynamics in the peripheral microcirculation were seen during halothane anesthesia, and were confirmed by greater functional capillary perfusion and fewer activated leukocytes. In the isoflurane group, RBC velocity alone cannot serve as an indicator of microcirculatory function.