Taking the lead - how keratinocytes orchestrate skin T cell immunity.

The skin comprises a complex coordinated system of epithelial tissue cells and immune cells that ensure adequate immune reactions against trauma, toxins and pathogens, while maintaining tissue homeostasis. Keratinocytes form the outermost barrier of the skin, and sense changes in barrier integrity, intrusion of microbial components and stress molecules. Thus, they act as sentinels that continuously communicate the status of the organ to the cutaneous immune system. Upon damage the keratinocytes initiate a pro-inflammatory signaling cascade that leads to the activation of resident immune cells. Simultaneously, the tissue mediates and supports immune-suppressive functions to contain inflammation locally. After resolution of inflammation, the skin provides a niche for regulatory and effector memory T cells that can quickly respond to reoccurring antigens. In this review we discuss the central role of keratinocyte-derived signals in controlling cutaneous T cell immunity.

Image-based monitoring of one-lung ventilation.

BACKGROUND AND OBJECTIVES: With the increasing demand for one-lung ventilation in both thoracic surgery and other procedures, identifying the correct placement becomes increasingly important. Currently, endobronchial intubation is suspected based on a combination of auscultation and physiological findings. We investigated the ability of the visual display of airflow-induced vibrations to detect single-lung ventilation with a double-lumen endotracheal tube. METHODS: Double-lumen tubes were placed prior to surgery. Tracheal and endobronchial lumens were alternately clamped to produce unilateral lung ventilation of right and left lung. Vibration response imaging, which detects vibrations transmitted to the surface of the thorax, was performed during both right- and left-lung ventilation. Geographical area of vibration response image as well as amount and distribution of lung sounds were assessed. RESULTS: During single-lung ventilation, the image and video obtained from the vibration response imaging identifies the ventilated lung with a larger and darker image on the ventilated side. During single-lung ventilation, 87.2 +/- 5.7% of the measured vibrations was detected over the ventilated lung and 12.8 +/- 5.7% over the non-ventilated lung (P < 0.0001). It was also noted that during single-lung ventilation, the vibration distribution in the non-ventilated lung had a majority of vibration detected by the medial sensors closest to the midline (P < 0.05) as opposed to the midclavicular sensors when the lung is ventilated. CONCLUSIONS: During single-lung ventilation, vibration response imaging clearly showed increased vibration in the lung that is being ventilated. Distribution of residual vibration differed in the non-ventilated lung in a manner that suggests transmission of vibrations across the mediastinum from the ventilated lung. The lung image and video obtained from vibration response imaging may provide useful and immediate information to help one-lung ventilation assessment.

The effects of chronic exercise on anesthesia induced hepatotoxicity.

UNLABELLED: A hypoxic rat model of halothane-induced hepatotoxicity, which is known to produce liver damage, was used to determine the effects of chronic exercise on halothane-induced hepatotoxicity and on reduced hepatic glutathione (GSH) levels. Metabolism of volatile anesthetics may generate metabolites that can cause mild and transient hepatotoxicity. METHODS: Six male Sprague-Dawley rats completed a 10-wk (5 d x wk(-1)) treadmill running protocol. Twelve age-matched animals were used as sedentary controls. After the completion of exercise training, rats were exposed for 2 h to 1% halothane in 14% O2. Twenty-four hours later, animals were anesthetized with sodium pentobarbital and sacrificed. Livers were excised, stained, and evaluated for hepatotoxicity using a histopathological 0 (normal) to 5 (severe damage) point categorical scale and for the determination of GSH levels. RESULTS: Median histopathologic scores revealed significantly lower indications of hepatotoxicity in exercise animals as compared with control animals (score = 0.25 vs 1.50; P < 0.05). Liver damages scores between 1 and 5 were observed in 75% (9 of 12) of the control animals, whereas only 1 of 6 exercise animals had a score greater than 1 (P < 0.05). No significant difference was observed in reduced GSH levels. CONCLUSIONS: Chronic exercise improves the detoxicant ability of the liver for halothane anesthesia as noted by the ameliorated liver damage and reduced incidence of halothane-induced hepatotoxicity in the exercise animals.

The efficacy and safety of EMLA cream for awake fiberoptic endotracheal intubation.

EMLA Cream (EC; Astra, Westborough, MA) has been widely used as a local anesthetic. Limited safety information is available with respect to the application of EC to the oral mucous membranes. The purpose of this pilot study was to evaluate the efficacy and safety of EC when applied to oral mucosa for fiberoptic intubation. Twenty ASA physical status I-IV patients (11 women and 9 men), 28-57 yr old, who were scheduled for awake, fiberoptic, intubation participated in this open-label study. A total of 4 g of EC was used for 5 min until the patient showed no evidence of a gag reflex (this was evaluated clinically by the patient's acceptance of the William's airway and considered the endpoint for assessing adequate topicalization of the oropharynx). The measured peak plasma concentration of lidocaine or prilocaine did not reach toxic levels in any patient. Methemoglobin levels did not exceed normal values (1.5%) in any patient, and there was no relationship between methemoglobin levels and patient weight, amount of EC used, measured peak plasma concentration, or times to measured peak concentrations of prilocaine or lidocaine. We conclude that EC provided satisfactory topical anesthesia allowing for successful oral fiberoptic intubation in all patients and should be considered a safe alternative for anesthetizing the airway of patients requiring awake oral fiberoptic intubation.

Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.

UNLABELLED: Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. IMPLICATIONS: We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).

High-quality filtration allows reuse of anesthesia breathing circuits resulting in cost savings and reduced medical waste.

STUDY OBJECTIVES: To determine if the new Filta-Therm filter prevents contamination and allows the reuse of breathing circuit with considerable cost and environmental savings. DESIGN: Prospective study. PATIENTS: 52 ASA physical status I, II, III, and IV patients, aged 18 to 75 years. INTERVENTIONS: Each morning a new breathing circuit was assembled. The Filta-Therm filter (Intersurgical, Inc., Liverpool, NY) elbow, and mask, but not the circuit, were changed between patients. The filter was placed between the Y-piece and the elbow of the breathing circuit. Prior to anesthesia, samples were obtained at the Y-piece, and the inspiratory and expiratory ports of breathing circuit. Following anesthesia, samples were obtained at the Murphy eye of endotrachael tube, and at the Y-piece. The samples were incubated, and the results examined at 24 and 48 hours. MEASUREMENTS AND MAIN RESULTS: Prior to anesthesia, cultures of the Y-piece and the inspired and expired ports samples showed no growth. Following anesthesia, all 52 samples obtained at the endotracheal tube were contaminated with various organisms, while all 52 Y-piece samples showed negative growth. CONCLUSIONS: The single use of Filta-Therm filter prevents bacterial contamination and allows reuse of breathing circuit at least twice, resulting in significant cost savings ($50,778 per year). Further studies are needed to establish the safety of reusing breathing circuits when appropriate bacterial filters are used.

Entrapment of an exchange wire by an inferior vena caval filter: a technique for removal.

The anesthesiology literature does not describe entrapment of a guidewire by an inferior vena caval filter. Because anesthesiologists are involved in central access in various perioperative and intraoperative settings, consideration of this complication is important. A case of guidewire entrapment by an inferior vena caval filter and a unique technique for removal of the entrapped wire is presented.

The effects of general anesthesia and surgery on basal and interferon stimulated natural killer cell activity of humans.

UNLABELLED: Natural killer (NK) cells can lyse certain tumor cells as well as virally infected cells without prior sensitization. Animal studies have shown that general anesthesia (GA) alone or GA followed by surgery decreases both basal NK cytotoxicity and enhancement of NK activity by interferon (IFN). The purpose of this study was to determine whether similar inhibition of NK activity by anesthesia and surgery occurs in humans. Venous blood was drawn 1 h before and 20-24 h after surgery under isoflurane/N2O anesthesia. Peripheral blood mononuclear cells (PBMC) were assayed for basal and IFN-alpha-stimulated NK cytotoxicity using a chromium release assay with K562 cells as targets. Flow cytometry was used to enumerate NK, T-helper, and T-cytotoxic/suppressor cell populations in each sample. Basal NK activity was significantly depressed after GA and GA and surgery. Although the postoperative IFN treatment increased NK activity to the preoperative basal level, the level achieved was significantly lower than the level observed after IFN stimulation of PBMC as evaluated preoperatively. This decreased activity does not seem to be the result of a decrease in the percentage of circulating NK cells. The decrease in NK activity after anesthesia and surgery may lead to increased susceptibility to infection and/or tumor dissemination and thus needs to be explored. IMPLICATIONS: Natural killer cells can kill cancer cells and virally infected cells. This study shows that surgery with general anesthesia leads to decreased natural killer cell activity as assessed int he laboratory. This decreased natural killer cell activity may lead to infection or tumor dissemination. NK activity can be restored to presurgery levels by treating isolated NK cells with interferon-alpha.

Double-blind comparison of two doses of rocuronium and succinylcholine for rapid-sequence intubation.

STUDY OBJECTIVE: To compare the pharmacodynamics of two commonly recommended doses of rocuronium bromide (0.7 mg/kg and 0.9 mg/kg) and succinylcholine (1.5 mg/kg) when used for rapid-sequence intubation. DESIGN: Prospective, double-blind, randomized study. SETTING: Operating rooms at a university hospital. PATIENTS: 45 ASA physical status I and II adult patients scheduled for elective surgeries under general anesthesia. INTERVENTIONS: Nonpremedicated patients were anesthetized with fentanyl 2 mcg/kg followed by thiopental sodium 4 to 5 mg/kg and muscle relaxant using rapid-sequence technique. Group 1 (n = 15) received rocuronium bromide 0.7 mg/kg. Group 2 (n = 16) received rocuronium bromide 0.9 mg/kg, and Group 3 (n = 14) received succinylcholine 1.5 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant. MEASUREMENTS AND MAIN RESULTS: The case of intubation was scored using a scale of 1 to 4. Blood pressure and heart rate were measured beginning one minute before induction of anesthesia up to 5 minutes after intubation. Intubation scores were similar in groups 2 and 3 and were noted as good or excellent in all patients. Group 1 displayed a significantly lower intubation score than the other two groups; 60% were rated as poor. No significant differences in hemodynamic data were seen among the three groups. CONCLUSIONS: Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following a 0.7 mg/kg dose of rocuronium are not as good as those following a 0.9 mg/kg dose of rocuronium or a 1.5 mg/kg dose of succinylcholine.

The effects of the menstrual cycle on the incidence of emesis and efficacy of ondansetron.

Postoperative nausea and vomiting after general anesthesia remains a complex and perturbing phenomenon associated with several factors. In women, the phase of the menstrual cycle as a factor in postoperative nausea and emesis is controversial. This retrospective study was performed to assess the effects of the menstrual cycle and efficacy of the antiemetic ondansetron on postoperative emesis. A total of 1169 ASA grade I-II patients from two double-blind, placebo-controlled studies were enrolled in 18 centers. Patients with irregular cycles or taking estrogens or progesterones were excluded from the analysis, leaving 873 patients eligible for this study. The patients were stratified on the basis of their last menses into four groups: 1) 1-8, 2) 9-16, 3) 17-28, and 4) 29-35 days. All patients received a general anesthetic with endotracheal intubation. Patients received either 1, 4, or 8 mg ondansetron or placebo given intravenously before induction of anesthesia. All patients were studied for a 24-h period. Emesis rates were compared with respect to the phase of the menstrual cycle and between menstruating and nonmenstruating patients. There was no relationship (P = 0.100) between the incidence of emesis and the phase of the menstrual cycle in the group receiving the placebo. There was, however, a significant reduction (P < 0.001) in emesis for the ondansetron-treated patients regardless of the phase of the menstrual cycle. In addition, ondansetron had a similar dose-response curve in both menstruating and nonmenstruating women.

The effect of isoflurane versus balanced anesthesia on rocuronium's pharmacokinetics and infusion requirement.

STUDY OBJECTIVE: To compare the effects of two anesthetic techniques, balanced and isoflurane anesthesia, on the response to an intubating dose and an infusion of rocuronium, and on rocuronium's pharmacokinetics. DESIGN: Randomized, open-label study. SETTING: A university-affiliated hospital. PATIENTS: Twenty-two healthy adults undergoing elective surgery. INTERVENTIONS: The patients were anesthetized with a balanced technique (nitrous oxide, fentanyl, midazolam) or isoflurane (nitrous oxide, isoflurane 0.5-1.0%). Rocuronium was administered initially as a 500-micrograms/kg bolus, then by infusion to maintain approximately 86-94% depression of twitch tension. Plasma samples to determine rocuronium concentrations were obtained before, during, and after the infusion. Pharmacokinetics were determined using a population-based approach. MEASUREMENTS AND MAIN RESULTS: Onset time and initial recovery after the bolus dose were similar for the two groups. Infusion requirements also were similar. Plasma clearance was greater during isoflurane than during balanced anesthesia (4.48 vs 3.49 ml/kg/min). Distribution clearances and volumes of distribution were similar for the two groups. CONCLUSIONS: The similarity of response to an intubating dose and an infusion of rocuronium suggests that clinicians need not alter the dose or rate of rocuronium administration during isoflurane anesthesia with a of duration less than 1 hour. However, the greater clearance of rocuronium, in light of the similarity of infusion requirements, suggests that isoflurane potentiates rocuronium compared with balanced anesthesia.

Efficacy of electroconvulsive therapy after propofol and methohexital anesthesia.

Fifty-eight patients with major depression were randomly assigned to receive a hypnotic dose of either propofol or methohexital for their complete treatment series of electroconvulsive therapy (ECT). As expected, seizure duration was significantly shorter with propofol than with methohexital anesthesia. Both groups recovered from their depression at the same rate. There was a significant improvement in the Hamilton Rating Scale for Depression scores between the first and last ECT session. However, this was independent of the choice of propofol or methohexital as the anesthetic. This study supports previous reports that seizure duration does not influence recovery from depression.

Doppler-guided cannulation of the internal jugular vein: a prospective, randomized trial.

OBJECTIVES: The internal jugular vein (IJ) is commonly used as an access to the central venous system. Despite the high success rate for cannulation of the IJ, the incidence of complications (1% to 16%) has remained essentially the same, with most complications resulting from unintentional punctures of surrounding structures. In an attempt to reduce the complication rate of this technique, we evaluated the use of a Doppler-guided needle device to cannulate the IJ. METHODS: The study was performed on 41 patients scheduled for cardiothoracic or major vascular surgery requiring central vein cannulation as part of their anesthetic management. RESULTS: The number of needle advances in the Doppler group was 1.35 (SD 0.88) compared with 2.8 (SD 2.78) in the control group (p = 0.037). A significantly greater percentage of cannulations were successful on the first attempt in the Doppler group (85%), compared with the control group (55%) (95% CI for proportion = 0.3 to 0.57). CONCLUSION: The Doppler-guided cannulation technique can reduce the number of attempts required for successful IJ cannulation.

Postoperative nystagmus and nausea.

OBJECTIVE: To evaluate the presence and the relationship between postoperative nystagmus and nausea. DESIGN: Open-label study. SETTING: University hospital. PATIENTS: Sixty-six patients recovering from general anesthesia following elective ambulatory surgeries. INTERVENTIONS: Patients were tested postoperatively for nystagmus using an electronystagmography, and were monitored for nausea and vomiting for the first postoperative day. MAIN OUTCOME MEASURES: A comparison of the incidence of nausea was made among patients with and without postoperative nystagmus. RESULTS: Twenty-four patients (36 percent) experienced postoperative nausea and 28 patients (42 percent) had nystagmus. There were no significant differences in age, weight, height, dosage of fentanyl, or postoperative use of narcotics between those who experienced postoperative nausea or had nystagmus than those who did not. A significantly greater percentage of female patients compared with male patients had nausea during the first postoperative day. Sixty percent of patients with nystagmus experienced nausea in the hospital compared with 18 percent of the patients without nystagmus (p < 0.01, 95 percent confidence interval [CI] of the difference = 11.3 to 61.3 percent). Twenty-two patients (78 percent) with nystagmus experienced nausea during the first postoperative day compared with 14 patients (36 percent) with no nystagmus (p < 0.01, 95 percent CI of the difference = 20.1 to 63.3 percent). Eighty-three percent of the nauseated patients experienced vomiting during the first postoperative day. CONCLUSIONS: The presence of nystagmus in the early part of recovery from general anesthesia is associated with a higher incidence of nausea and vomiting during the first postoperative day.

Comparison of ondansetron versus placebo to prevent postoperative nausea and vomiting in women undergoing ambulatory gynecologic surgery.

BACKGROUND: Postoperative nausea and emesis, especially in ambulatory surgical patients, remains a troublesome problem. This study was performed to compare the incidence of nausea and emesis during the 24-h postoperative period in ondansetron-treated patients versus placebo-treated patients. METHODS: Using a randomized prospective double-blind study design, women between the ages of 18 and 70 yr undergoing gynecologic surgical procedures with general opioid anesthesia on an outpatient basis were enrolled. Ondansetron or placebo was administered prior to induction of anesthesia. Patients were stratified according to history of nausea and emesis during previous exposure to general anesthesia and randomized to dose received. RESULTS: Data from the 544 women showed that all doses of intravenous ondansetron tested (1, 4, and 8 mg) were significantly more effective (62%, 76%, and 77%, respectively) than placebo (46%) in reducing the incidence of emesis following surgery until 24 h after recovery room entry. All these doses were more effective than placebo in patients with no prior history of emesis following surgery and the 4- and 8-mg doses were more effective than placebo in patients with a prior history of emesis following surgery. All doses of ondansetron tested were generally well tolerated with adverse events, clinical laboratory tests, and recovery room vital signs similar to those of placebo. Serum aspartate transaminase (AST) was increased in five patients (1 mg, 2 patients; 4 mg, 1 patient; 8 mg, 2 patients). In the three patients in whom subsequent analysis were performed, the serum AST had decreased to preoperative levels. CONCLUSIONS: Ondansetron given intravenously to prevent postoperative nausea and emesis was highly effective in the 4- and 8-mg doses in women having ambulatory gynecologic surgery.

The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations.

It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage.

Prophylactic intravenous ondansetron in female outpatients undergoing gynaecological surgery: a multicentre dose-comparison study.

The efficacy and safety of prophylactic intravenous ondansetron in preventing postoperative nausea and vomiting was investigated in a randomized, stratified, double-blind, placebo-controlled, dose-comparison study of 580 ASA physical class I and II female outpatients undergoing gynaecological surgery and receiving general anaesthesia. Patients received either ondansetron 1, 4 or 8 mg, or placebo i.v. immediately prior to a standardized technique for induction and maintenance of anaesthesia. All patients were intubated and received nitrous oxide and a narcotic. All doses of ondansetron were significantly more effective than placebo in preventing emesis over the 24 h postoperative period. Ondansetron significantly decreased nausea and emesis scores over 24 h postoperatively without causing sedation. No changes in laboratory parameters (haematology, blood chemistry, and liver enzymes) or vital signs (heart rate, blood pressure, and respiratory rate) were observed. Headache and dizziness were the most common side-effects; however, their incidence was the same as with placebo. Ondansetron was generally well tolerated, as evidenced by an adverse event, laboratory safety, and vital sign profile similar to placebo. Ondansetron 4 mg was found to be the optimal prophylactic i.v. dose for female outpatients over the entire 24 h postoperative period. Higher doses may offer an added benefit in some patients, such as those with a history of nausea and vomiting following general anaesthesia.