Henry Silverman

Weaning from mechanical ventilation

Weaning covers the entire process of liberating the patient from mechanical support and from the endotracheal tube. Many controversial questions remain concerning the best methods for conducting this process. An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process. An 11-member international jury answered five pre-defined questions. 1) What is known about the epidemiology of weaning problems? 2) What is the pathophysiology of weaning failure? 3) What is the usual process of initial weaning from the ventilator? 4) Is there a role for different ventilator modes in more difficult weaning? 5) How should patients with prolonged weaning failure be managed? The main recommendations were as follows. 1) Patients should be categorised into three groups based on the difficulty and duration of the weaning process. 2) Weaning should be considered as early as possible. 3) A spontaneous breathing trial is the major diagnostic test to determine whether patients can be successfully extubated. 4) The initial trial should last 30 min and consist of either T-tube breathing or low levels of pressure support. 5) Pressure support or assist–control ventilation modes should be favoured in patients failing an initial trial/trials. 6) Noninvasive ventilation techniques should be considered in selected patients to shorten the duration of intubation but should not be routinely used as a tool for extubation failure.

Impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock : association with myocardial hyporesponsiveness to catecholamines

ObjectivesTo determine whether myocardial hyporesponsiveness to administered catecholamines occurs in human sepsis and whether this phenomenon is associated with impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate. DesignProspective study. SettingMedical ICU in a university hospital. PatientsNormal human volunteers (n = 7), critically ill patients who were not septic (n = 9), septic patients not in shock (n = 16), and septic patients in shock (n = 17). Measurements and Main ResultsPulmonary artery catheter-derived hemodynamic data were obtained in patients with sepsis and septic shock. Isoproterenol and sodium fluoride-stimulated cyclic adenosine monophosphate accumulations were measured in circulating lymphocytes. The hemodynamic response to sequential infusions of dobutamine, 5 and 10 μg/ kg/min, was obtained in septic and septic shock patients. Baseline hemodynamic values for mean arterial pressure, cardiac index, left ventricular stroke work index, and oxygen delivery index at approximately 2 days after the onset of sepsis were significantly lower in septic shock patients compared with septic (nonshock) patients (p < .01, p < .05, p < .001, p < .01, respectively). Isoproterenol-and sodium fluoride-stimulated cyclic adenosine monophosphate accumulations were significantly reduced in septic shock patients compared with those accumulations observed in septic patients (p < .01 and p < .001, respectively). The heart rate response to 10 μg/ kg/min of dobutamine was significantly (p < .01) lower in septic shock patients compared with septic patients. ConclusionsIn patients with septic shock, impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate is associated with myocardial hyporesponsiveness to catecholamines, suggesting that β-adrenergic receptor dysfunction may contribute to the reduced myocardial performance observed in this shock state. (Crit Care Med 1993; 21:31–39)

Variability among institutional review boards' decisions within the context of a multicenter trial

BackgroundInstitutional review boards (IRBs) are given discretion to interpret and apply the federal regulations governing the protection of human subjects in research. ObjectiveTo determine the extent of the variability among different IRBs on their approved research practices and informed consent forms within the context of a multicenter trial that used a common protocol. DesignDescriptive analysis of survey information and informed consent forms. Setting and Participants Sixteen IRBs from the institutions participating in a multicenter trial comparing lower vs. traditional tidal volume ventilation in patients with acute lung injury. MeasurementsAnalysis of survey information on IRBs’ approved research practices. Analysis of informed consent forms for the presence and the adequacy of description of each basic element of informed consent specified in the federal regulations. Reading levels of informed consent forms. Main ResultsSurveys and IRB-approved consent forms were obtained from all of the contacted IRBs (n = 16). Variability was observed among several of the research practices; one IRB waived the requirement for informed consent, five IRBs permitted telephone consent, and three IRBs allowed prisoners to be enrolled. Three consent forms contained all of the basic elements of informed consent outlined in the federal regulations, and 13 forms had varying numbers of these elements absent (six forms without one element, four without two, one without three, and two without four). Reading levels of the consent forms ranged from grades 8.2 to 13.4 (mean ± sd was 11.6 ± 1.2 grade level). ConclusionsWithin a multicenter trial, IRBs reviewing a common protocol varied in several of their approved research practices and in the extent to which the basic elements of informed consent were included in their consent forms.

Adult Respiratory Distress Syndrome: Sequence and Importance of Development of Multiple Organ Failure

The adult respiratory distress syndrome (ARDS) represents a common denominator of acute lung injury leading to alveolar flooding, decreased lung compliance, and altered gas transport. In the absence of specific etiology and therapy, the management of ARDS remains largely supportive. Ubiquitous use of intermittent positive-pressure ventilation with positive end-expiratory pressure (PEEP) improves arterial oxygenation but with some risk of pulmonary barotrauma and decreased cardiac output. The recent understanding of lung inflation as a modulator of right heart afterload and the effect of the right ventricle on global cardiac performance continues to redefine optimal patterns of ventilatory and hemodynamic intervention in ARDS. ImagesFIG. 1

Clinical InvestigationsAdult Respiratory Distress Syndrome: Sequence and Importance of Development of Multiple Organ Failure

The adult respiratory distress syndrome (ARDS) represents a common denominator of acute lung injury leading to alveolar flooding, decreased lung compliance, and altered gas transport. In the absence of specific etiology and therapy, the management of ARDS remains largely supportive. Ubiquitous use of intermittent positive-pressure ventilation with positive end-expiratory pressure (PEEP) improves arterial oxygenation but with some risk of pulmonary barotrauma and decreased cardiac output. The recent understanding of lung inflation as a modulator of right heart afterload and the effect of the right ventricle on global cardiac performance continues to redefine optimal patterns of ventilatory and hemodynamic intervention in ARDS. ImagesFIG. 1

The European Union Directive and the protection of incapacitated subjects in research: an ethical analysis

ObjectiveWe perform an ethical analysis of European Union Directive 2001/20/EC on the simplification and harmonization of guidelines regarding good clinical practice in the conduct of clinical trials involving drugs.BackgroundThe Directive provides guidance on protecting incapacitated subjects who participate in drug clinical trials. Such guidance promotes society’s obligations of beneficence because the participation of incapacitated subjects in research is crucial in advancing the understanding and treatment of serious diseases. The Directive requires proxy consent for incapacitated subjects which adheres to the principle of respect for persons. The Directive also recommends additional safeguards to further protect subjects against exploitation and harm. These include respect for the assent and dissent of incapacitated subjects and the “necessity” and “subject-condition” requirements.ResultsWhile these essential protection mechanisms are commendable, the Directive fails to endorse other safeguards that have been recommended by other research ethics guidelines, especially for riskier research. The Directive’s silence regarding research in the emergency setting frustrates the principle of beneficence because the lack of guidance might prove to be a barrier for the conduct of such potentially beneficial research.ConclusionsWe conclude that the European Directive fails in many respects to promote several important ethical principles in research involving incapacitated subjects.

Identifying structures, processes, resources and needs of research ethics committees in Egypt

BackgroundConcerns have been expressed regarding the adequacy of ethics review systems in developing countries. Limited data are available regarding the structural and functional status of Research Ethics Committees (RECs) in the Middle East. The purpose of this study was to survey the existing RECs in Egypt to better understand their functioning status, perceived resource needs, and challenges.MethodsWe distributed a self-administered survey tool to Egyptian RECs to collect information on the following domains: general characteristics of the REC, membership composition, ethics training, workload, process of ethics review, perceived challenges to effective functioning, and financial and material resources. We used basic descriptive statistics to evaluate the quantitative data.ResultsWe obtained responses from 67% (12/18) of the identified RECs. Most RECs (10/12) have standard operating procedures and many (7/12) have established policies to manage conflicts of interests. The average membership was 10.3 with a range from 7-19. The predominant member type was physicians (69.5% of all of the REC members) with little lay representation (13.7%). Most RECs met at least once/month and the average number of protocols reviewed per meeting was 3.8 with a range from 1-10. Almost three-quarters of the members from all of the 12 RECs indicated they received some formal training in ethics. Regarding resources, roughly half of the RECs have dedicated capital equipment (e.g., meeting room, computers, office furniture, etc); none of the RECs have a formal operating budget. Perceived challenges included the absence of national research ethics guidelines and national standards for RECs and lack of ongoing training of its members in research ethics.ConclusionOur study documents several areas of strengths and areas for improvements in the operations of Egyptian RECs. Regarding strengths, many of the existing RECs meet frequently, have a majority of members with prior training in research ethics, and have written policies. Regarding areas for improvements, many RECs should strive for a more diverse membership and should receive more financial resources and administrative support personnel. We recommend that RECs include more individuals from the community and develop a continuing educational program for its members. Institutional officials should be aware of the resource capacity needs of their RECs.

Knowledge, Awareness, and Attitudes about Research Ethics among Dental Faculty in the Middle East: A Pilot Study

Objective. To assess the knowledge, awareness, and attitudes of dental faculty regarding research ethics and research ethics committees (RECs). Design. Through convenience sampling, we distributed a survey to academics at dental faculties at two universities in the Middle East. We used descriptive, chi-square, and logistic regression statistics to analyze the data. Results. Our response rate was 62.5%. A large majority (>90%) held positive attitudes towards RECs; however, almost half (44.0%) thought that RECs would delay research. Less than half (36.8%) had received prior training in research ethics, and the average score they achieved on the questions on research ethics was only 40.2%. Most (>90%), however, were favorable towards research ethics education. Finally, some faculty held attitudes regarding certain research ethics practices that were not optimal. Conclusions. We conclude that among the dental faculties participating in our study, there is broad-based acceptance of RECs and training in research ethics, while there are knowledge gaps in research ethics. We recommend further studies to determine the generalizability of our findings to other institutions.

Protecting Vulnerable Research Subjects in Critical Care Trials: Enhancing the Informed Consent Process and Recommendations for Safeguards

Although critically ill patients represent a vulnerable group of individuals, guidelines in research ethics assert that ethically acceptable research may proceed with such vulnerable subjects if additional safeguards are in place to minimize the risk of harm and exploitation. Such safeguards include the proper obtainment of informed consent that avoids the presence of the therapeutic misconception and the assessment of decisional capacity in critically ill patients recruited for research. Also discussed in this review are additional safeguards for such vulnerable subjects, as well as the issues involved with proxy consent. Heightened awareness to principles of ethics and provision of additional safeguards to enhance protections of vulnerable subjects would help to maintain the public trust in the research endeavor.

Collection, storage and use of blood samples for future research: views of Egyptian patients expressed in a cross-sectional survey

Objective To determine the attitudes of Egyptian patients regarding their participation in research and with the collection, storage and future use of blood samples for research purposes. Design Cross-sectional survey. Study population Adult Egyptian patients (n=600) at rural and urban hospitals and clinics. Results Less than half of the study population (44.3%) felt that informed consent forms should provide research participants the option to have their blood samples stored for future research. Of these participants, 39.9% thought that consent forms should include the option that future research be restricted to the illness being studied. A slight majority (66.2%) would donate their samples for future genetic research. Respondents were more favourable towards having their blood samples exported to other Arab countries (62.0%) compared with countries in Europe (41.8%, p<0.001) and to the USA (37.2%, p<0.001). Conclusions This study shows that many individuals do not favour the donation of a blood sample for future research. Of those who do approve of such future research, many favour a consent model that includes an option restricting the future research to the illness being studied. Also, many Egyptians were hesitant to have their blood samples donated for genetic research or exported out of the Arab region to the USA and European countries. Further qualitative research should be performed to determine the underlying reasons for many of our results.