OBJECTIVES:Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and ...beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance.
DESIGN:Double-blind, randomized clinical trial (ClinicalTrials.govNCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome.
SETTING:Five academic centers in the United States.
PATIENTS:Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome.
INTERVENTIONS:Aerosolized budesonide/formoterol versus placebo bid for up to 5 days.
MEASUREMENTS AND MAIN RESULTS:Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%).
CONCLUSIONS:Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.
OBJECTIVE:To determine if a video depicting cardiopulmonary resuscitation and resuscitation preference options would improve knowledge and decision making among patients and surrogates in the ICU.
...DESIGN:Randomized, unblinded trial.
SETTING:Single medical ICU.
PATIENTS:Patients and surrogate decision makers in the ICU.
INTERVENTIONS:The usual care group received a standard pamphlet about cardiopulmonary resuscitation and cardiopulmonary resuscitation preference options plus routine code status discussions with clinicians. The video group received usual care plus an 8-minute video that depicted cardiopulmonary resuscitation, showed a simulated hospital code, and explained resuscitation preference options.
MEASUREMENTS AND MAIN RESULTS:One hundred three patients and surrogates were randomized to usual care. One hundred five patients and surrogates were randomized to video plus usual care. Median total knowledge scores (0–15 points possible for correct answers) in the video group were 13 compared with 10 in the usual care group, p value of less than 0.0001. Video group participants had higher rates of understanding the purpose of cardiopulmonary resuscitation and resuscitation options and terminology and could correctly name components of cardiopulmonary resuscitation. No statistically significant differences in documented resuscitation preferences following the interventions were found between the two groups, although the trial was underpowered to detect such differences. A majority of participants felt that the video was helpful in cardiopulmonary resuscitation decision making (98%) and would recommend the video to others (99%).
CONCLUSIONS:A video depicting cardiopulmonary resuscitation and explaining resuscitation preference options was associated with improved knowledge of in-hospital cardiopulmonary resuscitation options and cardiopulmonary resuscitation terminology among patients and surrogate decision makers in the ICU, compared with receiving a pamphlet on cardiopulmonary resuscitation. Patients and surrogates found the video helpful in decision making and would recommend the video to others.
ICU patients/surrogates may experience adverse outcomes related to perceived inappropriate treatment. The objective was to determine the prevalence of patient/surrogate-reported perceived ...inappropriate treatment, its impact on adverse outcomes, and discordance with clinicians.
We conducted a multicenter, prospective, observational study of adult ICU patients.
For 151 patients, 1,332 patient, surrogate, nurse, and physician surveys were collected. Disagreement between patients/surrogates and clinicians regarding “too much” treatment being administered occurred in 26% of patients. Disagreement regarding “too little” treatment occurred in 10% of patients. Disagreement about perceived inappropriate treatment was associated with prognostic discordance (P = .02) and lower patient/surrogate satisfaction (Likert scale 1-5 of 4 vs 5; P = .02). Patient/surrogate respondents reported “too much” treatment in 8% of patients and “too little” treatment in 6% of patients. Perceived inappropriate treatment was associated with moderate or high respondent distress for 55% of patient/surrogate respondents and 35% of physician/nurse respondents (P = .30). Patient/surrogate perception of inappropriate treatment was associated with lower satisfaction (Family Satisfaction in the ICU Questionnaire-24, 69.9 vs 86.6; P = .002) and lower trust in the clinical team (Likert scale 1-5 of 4 vs 5; P = .007), but no statistically significant differences in depression (Patient Health Questionnaire-2 of 2 vs 1; P = .06) or anxiety (Generalized Anxiety Disorder-7 Scale of 7 vs 4; P = .18).
For approximately one-third of ICU patients, there is disagreement between clinicians and patients/surrogates about the appropriateness of treatment. Disagreement about appropriateness of treatment was associated with prognostic discordance and lower patient/surrogate satisfaction. Patients/surrogates who reported inappropriate treatment also reported lower satisfaction and trust in the ICU team.
Emergent use research-research involving human subjects that have a life-threatening medical condition and who are unlikely to provide informed consent-in critical illness is fraught with challenges ...related to obtaining informed consent. Per federal regulations, to meet criteria to conduct such trials, the investigators have to seek community consultations. Effective ways of obtaining this consultation remains ill-defined.
We sought to describe methods, interpretations, and our experiences of conducting community consultation in a planned emergent use randomized controlled trial.
As part of a planned emergent use clinical trial in our study, community consultation consisted of four focus groups sessions with members from the community in which the clinical trial was conducted. Three focus group sessions were conducted with members who had an affiliation to Mayo Clinic, and the other focus group session was conducted with non-Mayo affiliation members. The feedback from the focus group sessions led to the creation of the public notification plan. The public was notified of the trial through community meetings as well as social media.
As compared to community meetings, focus group sessions resulted in greater attendance with more interactive discussions. Moreover, focus group sessions resulted in greater in-depth conversations leading to institutional acceptance of the clinical trial under study.
Exception from informed consent can be acceptable to the community. Focus groups provided better participation and valuable interactive insight as compared to community meetings in our study. This could serve as a valuable guide for investigators pursuing exception from informed consent in their research studies.
Shared-decision-making about resuscitation goals of care for intensive care unit (ICU) patients depends on a basic understanding of cardiopulmonary resuscitation (CPR). Our objective was to develop ...and validate a survey to assess comprehension of CPR among ICU patients and surrogate decision-makers.
We developed a 12-item verbally-administered survey incorporating input from patients, clinicians, and expert focus groups.
We administered the survey to 32 ICU patients and 37 surrogates, as well as to 20 resident physicians to test discriminative validity. Median (interquartile range) total knowledge scores were 7 (5-10) for patients, 9 (7-12) for surrogates, and 14.5 (14-15) for physicians (p <.001). Forty-four percent of patients and 24% of surrogates could not explain the purpose of CPR. Eighty-eight percent of patients and 73% of surrogates could not name chest compressions and breathing assistance as two components of CPR in the hospital. Forty-one percent of patients and 24% of surrogates could not name a single possible complication of CPR. Forty-three percent of participants could not specify that CPR would be performed with a full code order and 25% of participants could not specify that CPR would not be performed with a do-not-resuscitate order. Internal consistency (Cronbach's alpha = 0.97) and test-retest reliability (Pearson correlation = 0.96, p < .001) were high.
This easily administered survey, developed to measure knowledge of CPR and resuscitation preference options among ICU patients and surrogates, showed strong face validity, content validity, internal consistency, test-retest reliability, and discriminative validity. A substantial proportion of ICU patients and surrogates decision-makers have poor knowledge of CPR and basic resuscitation options.
Endotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can severely ...impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability.
A randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients.
The overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population.
Clinicaltrials.gov: NCT02105415. 31 March 2014.
U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ ...substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention.
Our goal is to elaborate on the updated 2013 U.S. Food and Drug Administration (FDA) guidance document regarding an exemption from the requirement of obtaining informed consent from patients or their surrogates and to address certain elements within that document, thereby assisting clinicians in developing a framework for emergency research in accordance with the regulatory bodies at their own institutions and in the United States.
Review of the 2011 and updated FDA guidance document on exemption from informed consent.
The current process of obtaining informed consent within ICUs needs to be revisited, especially for research in which timely informed consent is not likely. In particular, the process of obtaining informed consent may not be appropriate or even ethical for critically ill patients in extremis who require an intervention for which there is no current acceptable standard of care and clinical equipoise exists. We provide clinicians with a viewpoint that further elaborates on the FDA guidance document.
The viewpoints provided herein are those of the authors and are therefore inherently limited by the personal views of a selected few. Other clinicians or researchers may not interpret the FDA guidelines in a similar manner. Moreover, the discussion of a guideline document is a limitation in and of itself. The guidelines set forth by the FDA are precisely that-guidelines. Therefore, they may not be followed as outlined in the guidance document within one's own institution. Our goal is that, by elaborating on the guidelines for planned research involving human subjects in the ICU, institutional regulatory bodies may gain a better understanding in drafting their own document when faced with a clinician or a researcher who wishes to conduct planned research in an ICU.
We believe that the interpretations provided will allow clinicians to safely undertake planned research in ICUs without endangering the main tenets of ethical research involving human participants. This research is needed for the advancement of care in the critically ill.
Objective: To determine the attitudes and beliefs of both parents and surgical clinicians regarding interventions to reduce secondhand smoke (SHS) exposure in children undergoing surgery. Methods: ...Structured interviews were conducted with 25 parents of children scheduled
for elective procedures and 10 surgical clinicians. Results: Major themes identified in parent interviews included: (1) parents are receptive to learning about the surgical risks posed by SHS exposure; (2) many are already attempting to reduce SHS exposure, and; (3) parents are more
accepting of SHS mitigation procedure than a recommendation to quit smoking. Clinicians were receptive to addressing perioperative SHS exposure. Conclusions: Both parents and clinicians are receptive to clinician-delivered interventions to reduce the SHS exposure of children scheduled
for elective surgery.
Background Endotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can ...severely impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability. Methods/design A randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients. Discussion The overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population. Trial registration Clinicaltrials.gov: NCT02105415. 31 March 2014. Keywords: Ketamine, propofol, drug combinations, etomidate, intubation, endotracheal, hemodynamics, adrenal insufficiency, randomized controlled trial, clinical research protocol, intensive care
Purpose An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to ...evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative’s goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER. Methods We performed a literature review to find existing guidelines for the selection of PRO measures. We also conducted an online survey of the International Society for Quality of Life Research (ISOQOL) membership to solicit input on PRO standards. A standard was designated as “recommended” when >50 % respondents endorsed it as “required as a minimum standard.” Results The literature review identified 387 articles. Survey response rate was 120 of 506 ISOQOL members. The respondents had an average of 15 years experience in PRO research, and 89 % felt competent or very competent providing feedback. Final recommendations for PRO measure standards included: documentation of the conceptual and measurement model; evidence for reliability, validity (content validity, construct validity, responsiveness); interpretability of scores; quality translation, and acceptable patient and investigator burden. Conclusion The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery. A next step is to expand these minimum standards to identify best practices for selecting decision-relevant PRO measures.
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