Patterns of complementary and alternative medicine use in ED patients and its association with health care utilization.

This study characterizes the use of complementary and alternative medicines (CAM) among ED patients and demonstrates patterns of healthcare utilization among users and nonusers of CAM therapies. A cross-sectional observational study was performed by administering questionnaires to ED patients at a university teaching hospital. Of the 356 patients surveyed, more than half (55%) had tried at least one complementary and alternative therapy within the past 12 months and 17% had tried CAM for their presenting medical problem. The use of CAM interventions varied significantly among different demographic groups. The number of ED visits over the past year did not differ between the users and nonusers of CAM, but those using alternative therapies did have more visits to outpatient physicians over the past 12 months (7.8 vs. 5.2; 95% confidence interval [CI], 7-4.6; P <.01). After controlling for age, ethnicity, education level, religion, income, and self-report of overall health status, users of CAM had more frequent visits to outpatient physicians (odds ratio [OR], 1.06; 95% CI, 1.02-1.1; P <.01), had no difference in their rates of hospitalization, but trended toward spending fewer days in the hospital when they were admitted (OR,.96; 95% CI,.92-1.0; P =.06). Complementary and alternative medicines are being used by a majority of ED patients with a significant number having used CAM for their presenting complaint before visiting the ED. CAM users do not differ in their utilization of the ED when compared with nonusers, but do have a significantly increased frequency of outpatient physician visits.

Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock.

OBJECTIVE: This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock. DESIGN: Experimental. SETTING: Laboratory. SUBJECTS: Twenty-three anesthetized adult swine. INTERVENSIONS: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg-1.hr-1 and increased to 4.0 mL.kg-1.hr-1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion. MEASUREMENTS AND MAIN RESULTS: Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased Pao2, as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p <.05). Thromboxane B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p <.05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups. CONCLUSIONS: Prostacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.

The cardiovascular hemodynamics and leukotriene kinetics during prostacyclin and anti-prostacyclin antibody infusions in septic shock.

This study evaluated whether or not prostacyclin (PGI2) was necessary or sufficient by itself in a pathophysiologic concentration to mediate the cardiovascular dysfunction of septic shock. Anesthetized adult swine received anesthesia only (ANESTHESIA CONTROL, n = 6); graded Aeromonas hydrophila, 10(10)/mL, infusion at 0.2 mL/kg/h that increased to 4.0 mL/kg/h over 3 h (SEPTIC SHOCK CONTROL, n = 6); pathophysiologic prostacyclin infusion to match septic shock control plasma levels without bacteremia (PGI2 INFUSION, n = 6), or graded Aeromonas hydrophila plus anti-prostacyclin antibody infusion (ANTI-PGI2-Ab INFUSION, n = 5). This graded porcine bacteremia model was 100% lethal after 4 h. Cardiovascular hemodynamics, arterial blood gases, and plasma levels of arachidonate metabolites were measured at baseline and hourly over a 4-h period. The results showed that PGI2 was not a necessary mediator of impaired cardiovascular hemodynamics in graded bacteremia, as anti-PGI2 antibody infusion did not improve the cardiac index, systemic vascular resistance, or peripheral oxygen balance in septic animals. Also, PGI2 was not sufficient alone to cause the cardiovascular dysfunction of sepsis, as pathophysiologic infusion of PGI2 did not reproduce such changes in normal animals. PGI2 blockade during bacteremia significantly increased LTC4D4E4, and LTB4 whereas PGI2 infusion suppressed LTC4D4E4 concentration, suggesting that endogenous PGI2 may blunt leukotriene release during septic shock. These results indicate a complex dynamic equilibrium among prostacyclin and leukotrienes in septic shock.

Platelet-activating factor and arachidonic acid metabolites mediate tumor necrosis factor and eicosanoid kinetics and cardiopulmonary dysfunction during bacteremic shock.

OBJECTIVE: Platelet-activating factor (PAF) and eicosanoids are putative mediators of septic shock that are associated with release of tumor necrosis factor (TNF). The purpose of this investigation was to a) examine temporal patterns of TNF and arachidonic acid metabolite release in a porcine model of bacteremic shock and b) selectively block PAF, thromboxane A2, prostacyclin, and leukotrienes to determine the relationships among these inflammatory response mediators and the alterations in cardiorespiratory dysfunction for which they are required. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-four female Yorkshire swine. INTERVENTIONS: Animals were divided into six experimental groups: five septic groups receiving an infusion of Aeromonas hydrophila at 0.2 mL/kg/hr, gradually increasing to 0.4 mL/kg/hr over 4 hrs. Each of four septic groups was pretreated with a specific mediator inhibitor (PAF receptor antagonist, n = 6; prostacyclin antibody, n = 5; leukotriene synthesis inhibitor, n = 5; and thromboxane receptor antagonist, n = 6). One septic group (n = 6) received no mediator inhibitor and served as a septic control, and one anesthesia control group (n = 6) received no intervention. MEASUREMENTS AND MAIN RESULTS: PAF receptor blockade significantly increased systemic hypotension and mixed venous oxygen saturation and decreased pulmonary artery pressure, oxygen extraction and consumption, hemoconcentration, and levels of TNF and eicosanoids. Leukotriene inhibition increased mean arterial pressure, pulmonary and systemic vascular resistance indices, and arterial and mixed venous oxygen saturation and reduced pulmonary hypertension, oxygen delivery, oxygen extraction, oxygen consumption, and all measured mediators. Thromboxane receptor blockade lowered TNF and leukotriene levels, ameliorated systemic and pulmonary vasoconstriction, and significantly increased arterial and tissue oxygenation compared with septic controls. Prostacyclin antagonism reduced prostacyclin plasma concentrations, arterial hypoxemia, and oxygen consumption during sepsis and increased circulating leukotriene B4. CONCLUSIONS: Elevations in plasma TNF predictably precede peak levels of eicosanoids in this model. PAF, leukotrienes, and thromboxane A2 are necessary for pulmonary hypertension during bacteremia. Systemic hypotension and increased vascular permeability are mediated by both leukotrienes and PAF. There are complex interactions among mediators during sepsis and further studies are required to define these relationships.

Interleukin-1 mediates hemodynamic dysfunction and release of eicosanoids and tumor necrosis factor during graded bacteremia.

The pathophysiologic events of sepsis mediated by interleukin-1 (IL-1) remain ill-defined. The purpose of this study was to identify the circulatory derangements of which IL-1 was a necessary mediator and evaluate its interactions with tumor necrosis factor (TNF) and the eicosanoids during graded bacteremia. Eleven adult female swine were anesthetized, mechanically ventilated, and monitored with pulmonary artery catheters and arterial lines; they received intravenously either saline vehicle (septic control, n = 6) or human recombinant IL-1 receptor antagonist (IL-1ra, n = 5). The animals were then infused with Aeromonas hydrophila (10(9)/mL) for 4 h at rates gradually increased from .2 mL/kg/h to 4 mL/kg/h over 3 h, then sacrificed after 4 h. Mean arterial pressure (MAP), left ventricular stroke work index (LVSWI), and systemic vascular resistance index (SVRI) were recorded at baseline and hourly thereafter, and plasma 6-keto-PGF1alpha (6-KETO), tumor necrosis factor-alpha (TNF) and leukotrienes B4(LTB4) and C4D4E4 (LTCDE), pg/mL, were measured by ELISA. MAP, LVSWI, arterial P(O2) all decreased in the septic control group to levels significantly below those of the IL-1 antagonist animals. Circulating 6-KETO, LTCDE, and TNF increased significantly in all septic animals. Plasma LTB, and TNF were reduced by IL-1 blockade, compared with septic controls. TxB2 was not affected by IL-1 inhibition. There were no intergroup differences in platelet aggregation, but the in vitro aggregation response decreased from baseline in septic controls to 54+/-27% (p < .05). IL-1 is necessary to the development of systemic hypotension impaired LVSWI, and increased intravascular platelet aggregation during graded bacteremia. Conversely, IL-1 helps to maintain stroke volume and low SVRI in graded bacteremia, possibly through increased prostacyclin release. It may contribute to impaired pulmonary gas exchange and increased tissue oxygen demands. TNF release is stimulated in the presence of unopposed IL-1 and may be synergistic with it in the adverse hemodynamic effects of endogenous IL-1. IL-1 is required for increased leukotriene and prostacyclin levels in this model, but it is not involved in thromboxane release. Whether the lack of survival benefit from IL-1ra in human sepsis is due to these mixed cardiopulmonary and mediator effects, to species differences, or to timing of IL-1ra administration is not clear from the data.

A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate in the management of selected pediatric facial lacerations.

OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children. METHODS: This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months. RESULTS: Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores. CONCLUSIONS: In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.

An assessment of clinical wound evaluation scales.

OBJECTIVE: To compare 2 clinical wound scales and to determine a minimal clinically important difference (MCID) on the visual analog cosmesis scale. METHODS: Using data from 2 previously published clinical trials, 91 lacerations and 43 surgical incisions were assessed on the 2 scales; a 100-mm visual analog scale (VAS) (0 = worst possible scar, 100 = best possible scar) and a wound evaluation scale (WES) assessing 6 clinical variables (a score of 6 is considered optimal, while a score of < or =5 suboptimal). All wound assessments on the VAS were done by 2 cosmetic surgeons who rated photographs on 2 occasions. A cohort of wounds on the WES were assessed by a second observer. The difference of the mean optimal and suboptimal VAS scores for each study was used to determine a MCID on the VAS scale. RESULTS: The VAS scale yielded intraobserver agreements of 0.93 and 0.87 (95% CI: 0.89-0.96 and 0.78-0.93) and interobserver agreements of 0.50 and 0.71 (95% CI: 0.32-0.65 and 0.52-0.84) for lacerations and incisions, respectively. Kappa coefficient measuring agreement on the WES was 0.79 (95% CI: 0.57-1.0). The mean (+/-SD) VAS scores of optimal wounds were 72 +/- 12 mm and 65 +/- 20 mm, while the mean scores of suboptimal wounds were 57 +/- 17 mm and 50 +/- 23 mm for lacerations and incisions, respectively. CONCLUSIONS: An MCID on the VAS cosmesis scale is 15 mm. Studies should be designed to have a sample size and power to detect this difference.

A new tissue adhesive for laceration repair in children.

To determine the effectiveness of a new tissue adhesive, 2-Octylcyanoacrylate (2-OCA), for laceration repair, 83 children presenting to T.C. Thompson Children's Hospital Emergency Department with lacerations meeting eligibility requirements between February and June 1996 were randomized to receive 2-OCA or nonabsorbable sutures/staples. The length of time for repair was recorded. The length of time for laceration repair was decreased (2.9 minutes 2-OCA vs 5.8 minutes suture/staple; p < 0.001), the parents' assessment of the pain felt by their children in the 2-OCA group was less, and the wounds closed with tissue adhesive had slightly lower cosmesis scores. 2-OCA is an acceptable alternative to conventional methods of wound repair with comparable cosmetic outcome.

Prospective, randomized, controlled trial of tissue adhesive (2-octylcyanoacrylate) vs standard wound closure techniques for laceration repair. Stony Brook Octylcyanoacrylate Study Group.

OBJECTIVE: To compare a new tissue adhesive, 2-octylcyanoacrylate, with standard wound closure techniques for the repair of traumatic lacerations. METHODS: A prospective, randomized, controlled clinical trial enrolled consecutive patients > 1 year of age with non-bite, non-crush-induced lacerations who presented < 6 hours after injury. Structured closed-question data sheets were completed at the time of laceration repair and suture removal. Patients were randomly assigned to treatment with either 2-octylcyanoacrylate or standard wound closure. Infection was determined at the time of suture removal. Long-term cosmetic appearance (> 3 months) was assessed by physicians using a previously validated categorical cosmetic scale and by patients using a 100-mm visual analog scale. RESULTS: There were 63 patients randomized to the octylcyanoacrylate group and 61 patients treated with standard wound closure techniques. The 2 treatment groups were similar with respect to age, gender, race, medical history, and wound characteristics. At the 5-to-10-day follow-up, only 1 wound was infected and only 2 wounds required reclosure due to dehiscence. These 3 patients received treatment with octylcyanoacrylate. At long-term follow-up, the cosmetic appearances were similar according to the patients (octylcyanoacrylate, 83.8 +/- 19.4 mm vs standard techniques, 82.5 +/- 17.6 mm; p = 0.72) and the physicians (optimal cosmetic appearance, 77% vs 80%; p = 0.67). CONCLUSIONS: Wounds treated with octylcyanoacrylate and standard wound closure techniques have similar cosmetic appearances 3 months later.

Differences in eicosanoid and cytokine production between injury/hemorrhage and bacteremic shock in the pig.

Plasma concentrations of the eicosanoids leukotriene (LT)B4, LTC4D4E4, thromboxane (TX)A2 and prostaglandin (PG)I2, and tumor necrosis factor (TNF) were measured during acute bacteremic shock and injury/hemorrhage in two porcine models. As TXA2 and PGI2 are rapidly metabolized, we measured their stable metabolites TXB2 and 6-keto-PGF1 alpha. Bacteremic shock was induced by a graded infusion of Aeromonas hydrophila over 4 h. Injury/hemorrhage was produced by a 30 min, 30% total blood volume hemorrhage followed by a 30 min shock period and then reinfusion of shed blood. Nociceptive afferent nerve stimulation was applied to the brachial plexi to mimic the cardiovascular responses to tissue injury. There was no increase in eicosanoid or TNF levels in the injury/hemorrhage model. In sepsis there was an early peak in TNF (at 60 min) followed by peaks in LTB4 and LTC4D4E4 at 180 min. Both TXB2 and 6-keto-PGF1 alpha showed large increases at the end of the study but there was no evidence that they had reached a peak. These results suggest that the very early inflammatory response in bacteremic shock and injury/hemorrhagic shock may be quite different. This may have implications for any therapies aimed at reducing the incidence of multiple organ failure after either of these physiological insults.

Multivariate regression modeling for the prediction of inflammation, systemic pressure, and end-organ function in severe sepsis.

The purpose of this study was to evaluate the feasibility of developing multivariate equations that predicted blood pressure and measured levels of end-organ function indicators quantitatively up to 72 h in advance in critically ill patients with severe sepsis. Data collected prospectively from 59 patients entered into two sequential placebo-controlled clinical trials of recombinant interleukin-1 receptor antagonist in severe sepsis and septic shock was analyzed retrospectively. A series of multivariate equations were developed to predict systemic pressure, coagulation, and vital organ function indicators quantitatively at 24, 48, and 72 h after the onset of severe sepsis. These equations used physiologic and clinical laboratory measurements, plus circulating levels of eicosanoids and cytokines obtained when severe sepsis criteria first were met, and end-organ function indicators measured 24, 48, and 72 h later. Multivariate predictive equations were developed for temperature, white blood cell count, mean arterial pressure (MAP), Pao2/FiO2 ratio, the Murray acute lung injury score, alanine and aspartate aminotransferases, prothrombin time, partial thromboplastin time, platelet count, serum creatinine, and Glasgow Coma Scale. The percentage of data variation explained by the equations ranged from 11.4% (MAP at 48 h) to 85.1% (platelet count at 24 h). Linear regression analysis of predicted values, obtained by entering baseline data from individual patients into the multivariate equations, versus observed results at 24, 48, and 72 h yielded regression coefficients ranging from .371 (MAP at 48 h) to .924 (platelet count at 24 h). Among patients without end-organ dysfunction at baseline, sensitivities for predicting values consistent with the onset of organ failure were > or = 88% in 21/27 (78%) of the predictive equations. Resolution of organ failure indicators present at baseline was predicted successfully in individual patients, with 20/27 (74%) specificities > or = 76%. In critically ill patients with severe sepsis, multivariate analysis of interactions among clinical observations, standard laboratory tests, and inflammatory response mediators produced equations that predicted systemic blood pressure and inflammatory and end-organ function indicators quantitatively up to 72 h in advance. Whether or not this methodology might be developed further to predict subclinically the onset and resolution of acute organ failure and shock in critically ill patients, and if it can be validated in a prospective trial will require further studies.

Unopposed interleukin-1 is necessary for increased plasma cytokine and eicosanoid levels to develop in severe sepsis.

OBJECTIVE: The purpose of the study was to identify the changes in plasma prostaglandin, leukotriene, and cytokine levels during clinical severe sepsis for which interleukin-1 was necessary. SUMMARY BACKGROUND DATA: Circulating prostaglandins, leukotrienes, and cytokines have been implicated as causative agents of systemic inflammation due to sepsis. However, interactions between interleukin-1 and the other cytokine and eicosanoid mediators of severe sepsis are not well-defined. METHODS: As part of two sequential multisite, prospective, randomized, double-blind, placebo-controlled clinical trials, 37 patients with severe sepsis received interleukin-1 receptor antagonist (IL-1ra) 100-mg bolus followed by 2 mg/kg per hour intravenously for 72 hours (n = 20) or placebo (n = 17). Plasma thromboxane B2 (TxB2), prostaglandin 6-keto-F1alpha (PGI), leukotriene B4 (LTB4), leukotriene C4D4E4 (LTC4D4E4), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay before study drug infusion (baseline) and at 24, 48, and 72 hours after the beginning of the study drug infusion. RESULTS: Differences between placebo and IL-1ra for plasma LTB4 were not significant, but only IL-1ra LTB4 increased from baseline. Plasma TxB2, PGI, LTC4D4E4, TNF, and IL-6, expressed as % baseline, decreased significantly in patients receiving IL-1ra compared with the placebo group (p < 0.05), whereas plasma IL-1 increased significantly. CONCLUSIONS: Interleukin-1 may be a necessary mediator of increased circulating PGI, TxB2, LTC4D4E4, TNF, and IL-6 levels in patients with severe sepsis. Plasma IL-1 and LTB4 are increased with infusion of IL-1 receptor antagonist. The clinical significance of IL-1 in modifying circulating eicosanoid and cytokine concentrations in clinical sepsis is not clear from the data.

Pilot study of cytokines in emergency department patients with systemic inflammatory response syndrome.

OBJECTIVE: To determine the potential utility of cytokine and arachidonic acid metabolite levels in ED patients with systemic inflammatory response syndrome (SIRS) as a predictor of progression to severe sepsis. METHODS: A prospective, observational study of test performance was performed using convenience samples of adult control subjects and admitted patients. The latter patients were identified in the ED as having signs of SIRS. Level of cytokines and arachidonic acid metabolites measured from specimens obtained in the ED were compared between groups and associated with the progression of sepsis within 24 hours in the SIRS patients. RESULTS: There were 30 control patients and 29 SIRS patients. There were 8 SIRS subjects who progressed to severe sepsis within 24 hours using the following criteria (hypotension, n = 1; and organ dysfunction, n = 2). Of the 21 SIRS subjects who did not progress to severe sepsis, 11 had resolution of SIRS criteria at 24 hours. There were no significant differences in mean mediator levels between the SIRS patients who progressed to severe sepsis and those who did not. Of the 11 patients with resolution of SIRS criteria at 24 hours, the mean interleukin-6 (IL-6) level was significantly lower than that for the patients who did not recover or who progressed at 24 hours (n = 18); 65.4 +/- 49.1 vs 230 +/- 112 pg/mL, p = 0.001). Six of 15 subjects with IL-6 > 150 pg/mL progressed to severe sepsis (p = NS). Using threshold values based on the range of levels for normals, the sensitivity of an abnormal marker for the development of severe sepsis within 24 hours varied from 50% to 87%, while the specificity varied from 11% to 84%. CONCLUSION: While mean levels were significantly elevated when compared with those of normal control subjects, they had limited ability to predict the subset of patients likely to progress to severe sepsis. However, initial low levels of cytokines may have exclusionary prognostic value. Prospective validation of the latter finding is warranted.

Pathophysiologic plasma levels of leukotriene C4 in relation to the hemodynamic dysfunction and mediator release of graded bacteremia.

This study was undertaken to identify those events of bacteremic shock that pathophysiologic levels of leukotriene C4 (LTC4) alone were sufficient to cause. Sixteen adult swine were studied for 4 h in three groups: ANES (n = 6) received anesthesia only; Septic (n = 6) received Aeromonas hydrophila, 10(9)/mL, intravenously, increased incrementally from .2 to 4.0 mL/kg/h; LTC4 (n = 4) received LTC4 infused intravenously, at rates that approximated LTC4 levels of Septic animals. Measurements included mean arterial pressure and arterial PO2, mmHg, pulmonary and systemic (SVRI) vascular resistance indexes, cardiac index (CI), oxygen extraction ratio, hematocrit; thromboxane B2 (TxB2), prostaglandin 6 keto F1 alpha (6 keto), leukotrienes B4 and C4D4E4, and tumor necrosis factor were measured in pg/mL by ELISA. Statistical analysis was performed by ANOVA and general linear model). Mean arterial pressure increased from 100 +/- 5 to 141 +/- 9 in the LTC4 group, but decreased in the Septic group from 90 +/- 7 at baseline to 62 +/- 6 at 3 h. In the LTC4 group, SVRI did not differ from ANES, and pulmonary vascular resistance, PO2, and CI did not change from baseline. In the LTC4 group, TxB2 and 6 keto levels decreased from 149 +/- 26 to 87 +/- 18 and 58 +/- 10 to 44 +/- 12, respectively; in the Septic group, TxB2 increased 140-fold and 6 keto increased 60-fold. Pathophysiologic LTC4 is not sufficient alone to cause the derangements in CI and SVRI, and tissue metabolism induced by graded bacteremia. Significantly increased systemic blood pressure suggests that endogenous pathophysiologic LTC4 may be involved. LTC4 does not increase plasma eicosanoids and tumor necrosis factor, but may down-regulate prostaglandin and leukotriene release.

A prospective comparison of octylcyanoacrylate tissue adhesive and suture for the closure of head and neck incisions.

OBJECTIVE: To compare the tissue adhesive octylcyanoacrylate with subcuticular suture for the closure of head and neck incisions. DESIGN: A prospective comparison with a blinded assessment of cosmetic outcome. SUBJECTS: Fifty consecutive patients undergoing head and neck procedures at two University of Ottawa teaching hospitals. METHODS: Twenty-six patients underwent skin closure with monofilament suture and 24 were closed with tissue adhesive. At 4 to 6 weeks the incisions were evaluated with a validated wound scale. Photographs of the incisions were rated using a visual analogue scale by two facial-plastic otolaryngologists who were blinded to the method of skin closure. RESULTS: The adhesive provided faster skin closure (29.7 seconds vs 289.0 seconds, p < .0001), and there were no differences in complications between the two groups. The primary outcome measure was the cosmetic appearance of the incision at 4 to 6 weeks. Although the adhesive group scored higher on both cosmesis scales, the visual analogue scale (octylcyanoacrylate 58.7 mm vs suture 53.2 mm) and the wound evaluation scale (57% vs 50% optimal wound scores), there were no statistical or clinically significant differences on either scale. The two facial-plastic otolaryngologists had good intraobserver and interobserver agreement when rating the cosmetic outcomes (0.87 and 0.71 respectively). CONCLUSIONS: Octylcyanoacrylate was found to be an effective method of skin closure in clean head and neck incisions. The practical advantages of tissue adhesives are reviewed.

Evaluation of enzyme-linked immunosorbent assays for quantitation of eicosanoid mediators of sepsis syndrome.

Thromboxane, prostacyclin, and the leukotrienes are eicosanoids that have been implicated as mediators of the host inflammatory response to infection and injury. Commercial enzyme-linked immunosorbent assays (ELISA) are being increasingly utilized to quantitate plasma eicosanoid concentrations in both clinical and experimental systemic inflammatory conditions. The objectives of this study were to 1) critically examine the performance characteristics of commercial ELISA kits for thromboxane B2, 6 keto-prostaglandin F1 alpha, leukotriene B4, and leukotrienes C4, D4, and E4; 2) apply the four ELISA kits in obtaining actual eicosanoid plasma values under both baseline and septic conditions; and 3) recommend quality control measures for general use. Although averages of multiple standard curves from individual assays were variable, there was a strong linear regression relationship between the backfit dose and nominal dose for each level of standard. Precision profiles constructed for each assay type defined a working range where the intra-assay coefficient of variation is less than 10%. Backfit doses deviated most from nominal doses at both extremes of the standard curves and this variation is reflected in the higher percentage errors in these regions. Recovery of each eicosanoid analyte was 96-103%. Calculated sensitivities were somewhat higher than the manufacturer's specifications. When applied to actual measurements in human and porcine plasma, the assays yielded values that fell within the working ranges of the standard curves with the exception of leukotriene B4. Thus, the ELISAs examined were reproducible, precise, and accurate within a specific working range for each assay type. However, internal controls were lacking in the commercial kits examined, which made assessment of intra- and inter-assay variation difficult.

Platelet activating factor mediates cardiopulmonary dysfunction during graded bacteremic shock.

OBJECTIVE: To determine whether or not platelet activating factor (PAF) is a necessary mediator of cardiovascular dysfunction during graded bacteremia, and to identify PAF interactions with eicosanoids and tumor necrosis factor-alpha (TNF-alpha). METHODS: Seventeen anesthetized, hemodynamically monitored adult swine were studied for 4 hours in three groups. Group 1 (ANES, n = 5) were anesthesia controls; group 2 (septic control, SC, n = 6) received intravenous Aeromonas hydrophila (109/mL) at rates incrementally increased from 0.2 to 4.0 mL/ kg/h; group 3 (WEB, n = 6) received the PAF receptor antagonist WEB 2086, 3.0 mg/kg intravenously, then A. hydrophila. Cardiopulmonary parameters and plasma thromboxane B2 (TXB2), prostaglandin 6-keto F1 alpha (PGI2), leukotriene B4 (LTB4), leukotrienes C4D4E4 (LTC4D4E4), and TNF-alpha were measured hourly. Statistical analysis was carried out using two-way analysis of variance (ANOVA) for repeated measurements, Dunnett's t test, and Student's t test, where appropriate. Statistical significance was determined at the 95% confidence interval. Values are presented as the mean +/- SEM. RESULTS: Pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure heart rate, VO2 and O2ER decreased significantly after WEB 2086 infusion, compared with SC, and mean arterial pressure, systemic vascular resistance index, stroke volume index, and left ventricular stroke work index increased. Arterial pH decreased significantly in SC animals, but was maintained at normal levels during bacteremia in the WEB group. Differences between WEB and SC for cardiac index, pulmonary vascular resistance index, right ventricular stroke work index, PaO2, SaO2, and PcO2, were not significant. The addition of WEB 2086 significantly decreased plasma levels of TXB2, PGI2, LTB4, and TNF-alpha compared with the SC group. LTC4D4E4 was decreased in WEB compared with SC animals, in which LTC4D4E4 increased during graded bacteremia. CONCLUSIONS: PAF is necessary to the development of systemic vasodilation and hypotension, pulmonary hypertension, decreased stroke volume, metabolic acidosis, and increased oxygen uptake during graded bacteremia. PAF-induced eicosanoid and cytokine release may be involved.

Randomized double-blind controlled trial comparing room-temperature and heated lidocaine for digital nerve block.

STUDY OBJECTIVE: To determine whether warming of lidocaine decreases the pain of its injection during digital nerve block. DESIGN: Prospective, randomized, double-blind, controlled trial. INTERVENTIONS: Twenty healthy volunteers received bilateral digital nerve blocks of their middle finger. They were first randomly assigned to receive either room-temperature (21 degrees C) or heated (42 degrees C) 2% lidocaine in their first block. They were then randomly assigned to receive the first block in either the right or left hand. The blocks were performed in a standardized fashion by a single physician, who was blinded to which solution was being used. The volunteers rated the pain of each digital block on a 100-mm visual analog scale (VAS). Efficacy of each digital block was tested at 5 minutes. RESULTS: Heating of the lidocaine was associated with a significantly lower median VAS pain score (31.5 versus 25.0; P < .05). There was no difference in pain score between the two solutions in relation to which hand was used (P = .29) or whether the injection was the first or the second (P = .37). When all factors (temperature, order, and hand) were considered in the ANOVA with respect to VAS pain score, the only significant relation found was that between the temperature of the solution and the VAS pain score (P = .028). CONCLUSION: Heating of lidocaine decreases the pain of injection during digital nerve block.