Michelle H. Biros

Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center

Our objective was to analyze the presentation, time to antibiotics, treatment, and mortality of patients with bacterial meningitis at a large urban county hospital over a 10-year period. A retrospective chart review of all patients with the diagnosis of bacterial meningitis was done. Information concerning presentation, etiologic organisms, treatment (including time to antibiotics), and outcomes were collected and analyzed. There were 165 charts reviewed with 171 total cases of bacterial meningitis. For adults with community-acquired meningitis, the mortality rate was 14%, for children it was 1.6%. Seventy-six percent of patients received antibiotics in the Emergency Department (ED) with a mean time to antibiotics of 1:08 h +/- 13 min. The rest received them as inpatients with a mean time to antibiotics of 6 +/- 9 h. The mortality rate for patients with community-acquired disease who received an Emergency Department antibiotic was 7.9%; for patients who received their antibiotics as inpatients the mortality rate was 29%. Our results indicate that the mortality rates from bacterial meningitis at our institution are lower than previously published results. Furthermore, our study supports the concept that the early administration of antibiotics in the ED may reduce mortality and may be an explanation of the lower mortality rates seen here.

Attitudes of emergency department patients and visitors regarding emergency exception from informed consent in resuscitation research, community consultation, and public notification

OBJECTIVE To assess public views on emergency exception to informed consent in resuscitation research, public awareness of such studies, and effective methods of community consultation and public notification. METHODS A face-to-face survey was conducted in two academic Level I trauma center emergency departments (EDs) in Oregon and Minnesota from June through August 2001. RESULTS Five hundred thirty people completed the survey, with an 82% response rate. The mean age of the respondents was 41 years (range 18-95) with a standard deviation of 14.5; 46% were female and 64% white. Most (88%) believed that research subjects should be informed prior to being enrolled, while 49% believed enrolling patients without prior consent in an emergency situation would be acceptable and 70% (369) would not object to be entered into such a study without providing prospective informed consent. Informing and consulting the community as a substitute for patient consent in emergency research was thought to be reasonable by 45% of the respondents. Most respondents would prefer to be informed about a study using emergency exception from informed consent by radio and television media (42%). Two hundred fifty-eight respondents (49%) stated they would attend a community meeting; the less educated were more likely to attend than those with college degrees (OR = 0.53; 95% CI = 0.33 to 0.85, p = 0.008). However, only 5% knew of ongoing studies in their community using emergency exception from informed consent. CONCLUSIONS Most respondents disagreed with foregoing prospective informed consent for research participation even in emergency situations; however, many would be willing to participate in studies using emergency exception from informed consent. Most respondents would not attend community meetings, and would prefer to rely upon the media for information. Very few were aware of emergency exception from informed consent studies in their community. This suggests that current methods of community notification may not be effective.

Research without consent: Current status, 2003

In November 1996, regulations developed by the US Food and Drug Administration (FDA) and the Department of Health and Human Services (HHS) went into effect to allow certain emergency and resuscitation human subjects research to proceed without prospective informed consent. These new regulations brought harmonization to the requirements of the 2 federal agencies charged with research oversight and ended a moratorium that had essentially shut down resuscitation research for almost 4 years. However, the FDAs emergency exception from informed consent and the HHSs waiver of informed consent have been used infrequently. Many perceived obstacles to implementation of the regulations have been described, including the additional regulatory burden for investigators and institutional review boards, the extra expense and time required to adequately fulfill the regulatory requirements, and the reluctance of institutional review boards to allow these studies to move forward because of concerns about potential legal ramifications. Regardless of the arguments advanced, these regulations are essentially the only current regulatory options that have been provided for research without consent. This article presents a brief history of the development of the FDAs Final Rule, a summary of its requirements and its use so far, and suggestions for its implementation. Some strategies to allow the resuscitation research community to suggest fine tuning of the regulations are suggested in hopes that research requiring an exception from informed consent is allowed to proceed in a manner acceptable to regulators, is stringent in patient protection, and yet is sensitive to the practical aspects of performing resuscitation research.

Randomized Clinical Trial of Propofol With and Without Alfentanil for Deep Procedural Sedation in the Emergency Department

OBJECTIVES The objectives were to compare the efficacy, occurrence of adverse events, and recovery duration of propofol with and without alfentanil for use in procedural sedation in the emergency department (ED). METHODS This was a randomized nonblinded prospective trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients with pain before the procedure were given intravenous (IV) morphine sulfate until their pain was adequately treated at least 20 minutes before starting the procedure. Patients received 1 mg/kg propofol either with or without a supplemental dose of 10 mug/kg alfentanil for deep procedural sedation. Doses, vital signs, nasal end-tidal CO(2) (ETCO(2)), pulse oximetry, and bispectral electroencephalographic (EEG) analysis scores were recorded. Subclinical respiratory depression was defined as a change in ETCO(2) of >10 mmHg, an oxygen saturation of <92% at any time, or an absent ETCO(2) waveform at any time. Clinical events related to respiratory depression were noted during the procedure, including the addition of or increase in the flow rate of supplemental oxygen, the use of a bag-valve mask apparatus, airway repositioning, or stimulation to induce breathing. After the procedure, patients were asked if they experienced pain during the procedure or had recall of the procedure. RESULTS A total of 150 patients were enrolled; 146 underwent sedation and were included in the analysis. Seventy-four patients received propofol, and 71 received propofol with alfentanil. No clinically significant complications were noted. Subclinical respiratory depression was seen in 24/74 patients in the propofol group and 30/71 patients in the propofol/alfentanil group (effect size = 9.8%, 95% CI = -5.8% to 25.5%). Clinical signs of respiratory depression included an increase in supplemental oxygen use in 25 of the 74 propofol patients and 31 of the 71 propofol/alfentanil patients (effect size 9.9%, 95% CI = -5.9% to 25.7%), the use of bag-valve mask apparatus in seven patients in the propofol group and 12 in the propofol/alfentanil group (effect size = 5.6%, 95% CI = -3.5% to 18.4%), airway repositioning in 13 propofol patients and 20 propofol/alfentanil patients (effect size = 10.6%, 95% CI = -3.0% to 24.2%), and stimulation to induce breathing in 11 propofol patients and 20 propofol/alfentanil patients (effect size = 13.3%, 95% CI = 0.1% to 26.5%). The total time of the procedure was longer for the alfentanil/propofol group (median = 11 minutes, range = 5-22 minutes) than for the propofol group (median = 9 minutes, range = 1 to 43 minutes; effect size = 1.93 minutes, 95% CI = 0.73 to 2.58, p = 0.02). Pain during the procedure was reported by 10 of the 74 patients in the propofol group and 7 of the 71 patients in the propofol/alfentanil group (effect size = 4.5%, 95% CI = -6.8% to 14.1%). Recall of some part of the procedure was reported by 12 patients in the propofol group and 9 in the propofol/alfentanil group (effect size = 3.5%, 95% CI = -7.9% to 15.0%). All procedures were successfully completed. CONCLUSIONS The use of supplemental alfentanil with propofol for procedural sedation did not result in a difference in reported pain or recall immediately after the procedure. There was an increase in the proportion of patients who required stimulation to induce respiration during the procedure in patients who received propofol with supplemental alfentanil. The addition of supplemental opioid to procedural sedation with propofol does not appear beneficial.

Community attitudes towards emergency research and exception from informed consent

OBJECTIVE To determine public attitudes towards emergency research, exception from informed consent (EFIC) and a specific proposed clinical trial using EFIC. METHODS As part of a planned community consultation activity, a survey was conducted at a popular public venue. Participants answered demographic questions and then were asked their opinions on specifically described consent circumstances in emergency research, including the proposed EFIC trial. Multiple logistic and linear regression were used to determine respondent characteristics associated with specific attitudes. RESULTS 1901 surveys were completed. The majority of respondents supported emergency research (88%) and the concept of surrogate consent by a legally authorized representative (78%). The concept of EFIC was less well supported (35%) but the application of EFIC was more accepted, especially when EFIC was applied to the respondent themselves (51%). The community believed the proposed EFIC study was acceptable (82%); a minority had concerns but most were related to patient safety and not to EFIC. Respondents with less education and lower incomes were less likely to express opinions about the consent and research concepts described. CONCLUSIONS Emergency research and the proposed EFIC trial is supported in this community. The concept of EFIC is less well supported but is more acceptable when a specific trial is described or when respondents consider EFIC for themselves. Specific respondent characteristics are associated with attitudes about research; this can assist in development of meaningful community consultation activities.

Implementation of the Exception From Informed Consent Regulations in a Large Multicenter Emergency Clinical Trials Network: The RAMPART Experience

Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks.

Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients.

Objective. To identify the effects of the removal of droperidol as a treatment option for sedation of agitated out-of-hospital patients. Methods. This was a retrospective review conducted January 1, 2001, through December 5, 2002, of patients with an out-of-hospital diagnosis of agitation who received either droperidol or midazolam prior to arrival in the emergency department (ED). The need for continuous cardiac or pulse oximetry monitoring, intubation, critical care ED management, intensive care unit admission, andmortality was reviewed. Results. Seventy-one patients received droperidol or midazolam for acute agitation in the out-of-hospital setting. Forty-one patients received droperidol in 2001 (D2001); three patients received midazolam in 2001 (M2001). No patients received droperidol in 2002, and27 patients received midazolam (M2002). Comparing the D2001 andM2002 groups, the need for continuous pulse oximetry monitoring in the ED [14/41 (34.1%) versus 18/27 (66.7%)], intubations [4/41 (9.8%) versus 10/27 (37.0%)], critical emergency medical services transports [5/41 (12.2%) versus 11/27 (40.7%)], critical ED care cases [6/41 (14.6%) versus 11/27 (40.7%)], andintensive care unit admissions [6/13 (46.2%) versus 14/15 (93.3%)] were increased in the M2002 group. No difference was found in the frequencies of ED cardiac monitoring, hospital admission, complications, or death. Conclusions. Since the removal of droperidol as a treatment option for out-of-hospital agitated patients, the authors have observed an increased frequency of continuous pulse oximetry monitoring, intubation, ED critical care management, andintensive care unit admission in patients requiring chemical sedation for control of agitation in the out-of-hospital setting.

Supporting emergency medicine research: developing the infrastructure.

The long-term goals of developing research within the specialty of emergency medicine (EM) include the following: 1) to continue to improve the quality and quantity of EM research in order to ultimately improve emergency patient care; 2) to maximize the research potential of emergency health care professionals in order to develop new emergency research talent and enthusiasm; and 3) to establish the academic research credentials of the specialty of EM in order to become competitive for federal research funding, and further improve emergency patient care. This article addresses the process by which the infrastructure for EM research can be developed at academic medical centers and provides recommendations. The roles of the academic chair, research director, senior researcher, and departmental faculty are discussed.

Doubling time α-aminoisobutyrate transport and calcium exchange in cultured fibroblasts from cystic fibrosis and control subjects

Abstract Population doubling time, kinetics of transport of α-aminoisobutyrate (AIB) and calcium (Ca) exchange were studied in skin fibroblast monolayers obtained from 5 subjects with cystic fibrosis (CF) and 5 age- and sex-matched controls. Population doubling time as estimated from cell count, protein and DNA was no different in the two groups. KM, Vmax, maximal uptake and time of half maximal uptake of AIB were no different in the two groups. Intracellular Ca pool size based on exchange of 45Ca with unlabelled Ca was significantly greater in monolayers from CF subjects.

Occult depressive symptoms in adolescent emergency department patients.

OBJECTIVES To estimate the frequency of occult depressive symptoms in adolescent emergency department (ED) patients (aged 13-17 years) and to determine patient characteristics associated with depressive symptoms. DESIGN A cross-sectional study of adolescent ED patients. SETTING The pediatric ED of Hennepin County Medical Center in Minneapolis, Minnesota, and the EDs of the Childrens Hospitals and Clinics of Minnesota. PATIENTS Medically stable adolescent ED patients with nonpsychiatric concerns. INTERVENTIONS Patients completed the Beck Depression Inventory II and answered questions about their attitudes, activities, and lifestyle choices. Guardians were asked about family demographics, living situations, and other patient characteristics. MAIN OUTCOME MEASURES The frequency of moderate and severe depressive symptoms as measured by the Beck Depression Inventory II. Group results were analyzed with descriptive statistics; patient characteristics associated with depressive symptoms were determined by multivariate analysis. RESULTS A total of 967 patients were enrolled. According to the Beck Depression Inventory II, 20% (197 patients) had moderate to severe depressive symptoms. Of these, 58% recognized their depressive symptoms and 50% were recognized by their guardians as having depressive symptoms. When compared with nondepressed patients, adolescents with depressive symptoms more often were female, were not involved in organized social activities, knew someone who intentionally hurt himself or herself or died a violent death, were currently involved in a sexual relationship, or used street drugs. Race, family income, family stability, and witnessing violence were not associated with a positive depression screen result. CONCLUSIONS Depressive symptoms occur frequently among adolescents and are often unrecognized. Efforts to increase awareness of depression among ED physicians, adolescents, and parents of adolescents may be beneficial.