OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in... more OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28–29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up surve...
The journal of pain : official journal of the American Pain Society, Jan 13, 2018
Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric ... more Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), fac...
We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and α‐tocopherol (200 m... more We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and α‐tocopherol (200 mg, P.O.) on the depressant effect of subanaesthetic doses of halothane (0.11 % end‐tidal concentration) on the acute isocapnic hypoxic ventilatory response (AHR), i.e. the ventilatory response upon inhalation of a hypoxic gas mixture for 3 min (leading to a haemoglobin saturation of 82 ± 1.8 %) in healthy male volunteers. In the first set of protocols, two groups of eight subjects each underwent a control hypoxic study, a halothane hypoxic study and finally a halothane hypoxic study after pretreatment with AOX (study 1) or placebo (study 2). Halothane reduced the AHR by more than 50 %, from 0.79 ± 0.31 to 0.36 ± 0.14 l min−1 %−1 in study 1 and from 0.79 ± 0.40 to 0.36 ± 0.19 l min−1 %−1 in study 2, P < 0.01 for both. Pretreatment with AOX prevented this depressant effect of halothane in the subjects of study 1 (AHR returning to 0.77 ± 0.32 l min−1 %−1, n.s. from control), whereas plac...
Background A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near i... more Background A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (P[ET]O2) and carbon dioxide (P[ET]CO2) tensions to alter global cerebral oxygen saturation. Methods In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in P[ET]O2 resulting in arterial saturation ranging from approximately 70% to 100% under conditions of controlled normocapnia (each person's resting P[ET]CO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO2) and jugular bulb venous (S[jv]O2) saturations during each P(ET)O2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO2) and an estimated jugular venous saturation (S[jv]O2), derived from a combination of SaO2 and rSO2, were compared with the measured S(jv)O2. Results The S(jv)O2 was significantly higher with hyperca...
Background Since propofol and remifentanil are frequently combined for monitored anesthesia care,... more Background Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. Methods The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard erro...
Background Effective communication in the preanesthesia clinic is important in patient-centered c... more Background Effective communication in the preanesthesia clinic is important in patient-centered care. Although patient-physician communication has been studied by recordings in other contexts, there have been no observational studies of the communication patterns of anesthesiologists and patients during the preanesthesia interview. Methods Two experienced standardized patients were trained to portray the same clinical situation by using different coping styles (maximizing information or "monitoring" vs. minimizing information or "blunting"). Interviews of standardized patients by anesthesiologists took place in the preanesthesia clinic and recorded with the knowledge of the subjects. Audio recordings were analyzed, and the visit was separated into nine components. Discussion of the risks/informed consent process was examined, looking for discussion of common morbidities. The standardized patients completed a survey on the patient-centeredness of the interview. Re...
Background The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase ... more Background The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase followed by a slower decline. In humans, there is evidence that the magnitude of the decline in ventilation is proportional to the size of the initial increase. This study was done to define the role of exogenous opioids in the ventilatory decline seen with prolonged hypoxia. Methods Ten healthy persons were exposed to isocapnic hypoxia for 25 min, followed by 5 min of isocapnic normoxia and 5 min of isocapnic hypoxia. These conditions were repeated during a computer-controlled alfentanil infusion. Results Serum alfentanil levels were constant among the volunteers (38+/-12 ng/ml). Alfentanil decreased both the initial and second acute hypoxic responses (from 1.27+/-0.73 to 0.99+/-0.39 l x min(-1) x %(-1), P < 0.05; and from 0.99+/-0.70 to 0.41+/-0.29 l x min(-1) x %(-1), P < 0.05, respectively). The magnitude of the decrease in ventilation during the 25 min of hypoxia was not chang...
Background Normoxic and hypoxic ventilation are influenced by chemoreceptor and nonchemoreceptor ... more Background Normoxic and hypoxic ventilation are influenced by chemoreceptor and nonchemoreceptor drives. Although inhalational anesthetics blunt hypoxic ventilation, this effect is reversed by audiovisual stimulation but not by pain. Opioids reduce both normoxic and hypoxic ventilation, but their interaction with pain and audiovisual stimulation has not been fully reported. Methods Isocapnic, acute hypoxic ventilatory responses (AHRs) were measured in 11 volunteers. AHR and normoxic ventilation were measured under the following conditions: (1) eyes closed, no audio stimulation (low wakefulness); (2) low wakefulness conditions plus painful thermal stimulation; and (3) playing a computer game (high wakefulness), each with and without remifentanil infusion. Results The average (+/- sd) remifentanil dose was 0.035 +/- 0.012 microg x kg x min(-1). Both normoxic and hypoxic ventilation were significantly reduced by the remifentanil infusion under all three conditions. The AHR values under...
The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, estab... more The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and...
The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, estab... more The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and...
In this report, we describe a six-year experience (2007-2012) in a single CTSA awardee institutio... more In this report, we describe a six-year experience (2007-2012) in a single CTSA awardee institution on the development, implementation and evaluation of a hybrid online mentoring curriculum that is applicable to CTSA trainees at various levels (graduate, medical students, and junior faculty) of career training. The curriculum offers convenience, engagement, and financial sustainability. Overall, we found high levels of satisfaction with the curriculum and mentoring experience among both protégés and mentors. Qualitative data showed remarkable consensus of 14 of the 15 domains of mentoring that form the framework of the mentoring curriculum: (1) accessibility, (2) selectivity, (3) engagement/support, (4) teaching/training, (5) clarity of performance/expectations, (6) sponsorship/sharing power judiciously, (7) demystifying the system (academia), (8) challenging/encouraging risk taking, (9) affirming, (10) providing exposure/visibility, (11) being an intentional role model, (12) protect...
OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in... more OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28–29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up surve...
The journal of pain : official journal of the American Pain Society, Jan 13, 2018
Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric ... more Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), fac...
We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and α‐tocopherol (200 m... more We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and α‐tocopherol (200 mg, P.O.) on the depressant effect of subanaesthetic doses of halothane (0.11 % end‐tidal concentration) on the acute isocapnic hypoxic ventilatory response (AHR), i.e. the ventilatory response upon inhalation of a hypoxic gas mixture for 3 min (leading to a haemoglobin saturation of 82 ± 1.8 %) in healthy male volunteers. In the first set of protocols, two groups of eight subjects each underwent a control hypoxic study, a halothane hypoxic study and finally a halothane hypoxic study after pretreatment with AOX (study 1) or placebo (study 2). Halothane reduced the AHR by more than 50 %, from 0.79 ± 0.31 to 0.36 ± 0.14 l min−1 %−1 in study 1 and from 0.79 ± 0.40 to 0.36 ± 0.19 l min−1 %−1 in study 2, P < 0.01 for both. Pretreatment with AOX prevented this depressant effect of halothane in the subjects of study 1 (AHR returning to 0.77 ± 0.32 l min−1 %−1, n.s. from control), whereas plac...
Background A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near i... more Background A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (P[ET]O2) and carbon dioxide (P[ET]CO2) tensions to alter global cerebral oxygen saturation. Methods In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in P[ET]O2 resulting in arterial saturation ranging from approximately 70% to 100% under conditions of controlled normocapnia (each person's resting P[ET]CO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO2) and jugular bulb venous (S[jv]O2) saturations during each P(ET)O2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO2) and an estimated jugular venous saturation (S[jv]O2), derived from a combination of SaO2 and rSO2, were compared with the measured S(jv)O2. Results The S(jv)O2 was significantly higher with hyperca...
Background Since propofol and remifentanil are frequently combined for monitored anesthesia care,... more Background Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. Methods The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard erro...
Background Effective communication in the preanesthesia clinic is important in patient-centered c... more Background Effective communication in the preanesthesia clinic is important in patient-centered care. Although patient-physician communication has been studied by recordings in other contexts, there have been no observational studies of the communication patterns of anesthesiologists and patients during the preanesthesia interview. Methods Two experienced standardized patients were trained to portray the same clinical situation by using different coping styles (maximizing information or "monitoring" vs. minimizing information or "blunting"). Interviews of standardized patients by anesthesiologists took place in the preanesthesia clinic and recorded with the knowledge of the subjects. Audio recordings were analyzed, and the visit was separated into nine components. Discussion of the risks/informed consent process was examined, looking for discussion of common morbidities. The standardized patients completed a survey on the patient-centeredness of the interview. Re...
Background The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase ... more Background The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase followed by a slower decline. In humans, there is evidence that the magnitude of the decline in ventilation is proportional to the size of the initial increase. This study was done to define the role of exogenous opioids in the ventilatory decline seen with prolonged hypoxia. Methods Ten healthy persons were exposed to isocapnic hypoxia for 25 min, followed by 5 min of isocapnic normoxia and 5 min of isocapnic hypoxia. These conditions were repeated during a computer-controlled alfentanil infusion. Results Serum alfentanil levels were constant among the volunteers (38+/-12 ng/ml). Alfentanil decreased both the initial and second acute hypoxic responses (from 1.27+/-0.73 to 0.99+/-0.39 l x min(-1) x %(-1), P < 0.05; and from 0.99+/-0.70 to 0.41+/-0.29 l x min(-1) x %(-1), P < 0.05, respectively). The magnitude of the decrease in ventilation during the 25 min of hypoxia was not chang...
Background Normoxic and hypoxic ventilation are influenced by chemoreceptor and nonchemoreceptor ... more Background Normoxic and hypoxic ventilation are influenced by chemoreceptor and nonchemoreceptor drives. Although inhalational anesthetics blunt hypoxic ventilation, this effect is reversed by audiovisual stimulation but not by pain. Opioids reduce both normoxic and hypoxic ventilation, but their interaction with pain and audiovisual stimulation has not been fully reported. Methods Isocapnic, acute hypoxic ventilatory responses (AHRs) were measured in 11 volunteers. AHR and normoxic ventilation were measured under the following conditions: (1) eyes closed, no audio stimulation (low wakefulness); (2) low wakefulness conditions plus painful thermal stimulation; and (3) playing a computer game (high wakefulness), each with and without remifentanil infusion. Results The average (+/- sd) remifentanil dose was 0.035 +/- 0.012 microg x kg x min(-1). Both normoxic and hypoxic ventilation were significantly reduced by the remifentanil infusion under all three conditions. The AHR values under...
The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, estab... more The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and...
The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, estab... more The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and...
In this report, we describe a six-year experience (2007-2012) in a single CTSA awardee institutio... more In this report, we describe a six-year experience (2007-2012) in a single CTSA awardee institution on the development, implementation and evaluation of a hybrid online mentoring curriculum that is applicable to CTSA trainees at various levels (graduate, medical students, and junior faculty) of career training. The curriculum offers convenience, engagement, and financial sustainability. Overall, we found high levels of satisfaction with the curriculum and mentoring experience among both protégés and mentors. Qualitative data showed remarkable consensus of 14 of the 15 domains of mentoring that form the framework of the mentoring curriculum: (1) accessibility, (2) selectivity, (3) engagement/support, (4) teaching/training, (5) clarity of performance/expectations, (6) sponsorship/sharing power judiciously, (7) demystifying the system (academia), (8) challenging/encouraging risk taking, (9) affirming, (10) providing exposure/visibility, (11) being an intentional role model, (12) protect...
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