Elaine K. Daily

Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery

Background: Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid orreduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion. Methods: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post–cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post–cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population. Results: During the period from the end of cardiopulmonary bypass surgery through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused. Conclusions: Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.

A safety assessment of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of hemorrhagic, hypovolemic shock.

OBJECTIVE To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of patients in Class II-IV hemorrhagic, hypovolemic shock. DESIGN Multicenter, randomized, normal saline-controlled, dose-escalation study. SETTING Eleven hospitals in the U.S. and Belgium. SUBJECTS One hundred and thirty-nine (139) hospitalized patients with Class II-IV hemorrhagic, hypovolemic shock within the previous 4 hours who still were requiring therapy for shock. INTERVENTIONS Beginning with the lowest dose, patients were randomized to receive 50, 100, or 200 mL of either 10% DCLHb or normal saline infused intravenously over 15 minutes. Following infusion of either treatment, further fluid resuscitation could be given, as necessary, to maintain perfusion. Vital signs, laboratory assessments, blood and fluid administration, complications, and adverse events were recorded at various times from the end of infusion through 72 hours after infusion. RESULTS A total of 29 (13 DCLHb- and 16 saline-treated) patients died during the study period. Adverse events were experienced by 61% of patients in the DCLHb group and 53% of patients in the saline group; serious adverse events occurred in 28% of DCLHb-treated patients and 30% of saline-treated patients. The incidence of prospectively defined, clinical complications, including renal insufficiency and renal failure, was similar between the treatment groups except for the occurrence of dysrhythmias/conduction disorders, which occurred significantly more frequently in the saline-treated patients than the DCLHb-treated patients (p = 0.041). At the highest dose level (200 mL), statistically significant between-group differences were observed with greater increases in serum amylase, LDH, the isoenzymes LD1,2,4 and 5, and CK-MB in the DCLHb group compared to the control group; none were of clinical significance. The volume of blood administered did not differ between the groups. Overall 24- and 72-hour survival rates were similar between treatment groups, although the hospital discharge rate was slightly higher in the DCLHb-treated patients (80%) compared with the saline-treated patients (74%). CONCLUSION Administration of 50 to 200 mL of DCLHb to patients in hemorrhagic, hypovolemic shock was not associated with evidence of end organ toxicity or significant adverse events. Further studies involving larger doses and, perhaps, earlier administration of DCLHb are warranted.

Research and Evaluations of the Health Aspects of Disasters, Part II: The Disaster Health Conceptual Framework Revisited.

A Conceptual Framework upon which the study of disasters can be organized is essential for understanding the epidemiology of disasters, as well as the interventions/responses undertaken. Application of the structure provided by the Conceptual Framework should facilitate the development of the science of Disaster Health. This Framework is based on deconstructions of the commonly used Disaster Management Cycle. The Conceptual Framework incorporates the steps that occur as a hazard progresses to a disaster. It describes an event that results from the changes in the release of energy from a hazard that may cause Structural Damages that in turn, may result in Functional Damages (decreases in levels of function) that produce needs (goods and services required). These needs can be met by the goods and services that are available during normal, day-to-day operations of the community, or the resources that are contained within the communitys Response Capacity (ie, an Emergency), or by goods and services provided from outside of the affected area (outside response capacities). Whenever the Local Response Capacity is unable to meet the needs, and the Response Capacities from areas outside of the affected community are required, a disaster occurs. All responses, whether in the Relief or Recovery phases of a disaster, are interventions that use the goods, services, and resources contained in the Response Capacity (local or outside). Responses may be directed at preventing/mitigating further deterioration in levels of functions (damage control, deaths, injuries, diseases, morbidity, and secondary events) in the affected population and filling the gaps in available services created by Structural Damages (compromise in available goods, services, and/or resources; ie, Relief Responses), or may be directed toward returning the affected community and its components to the pre-event functional state (ie, Recovery Responses). Hazard Mitigation includes interventions designed to decrease the likelihood that a hazard will cause an event, and should an event occur, that the amount of energy released will be reduced. Capacity Building consists of all interventions undertaken before an event occurs in order to increase the resilience of the community to an event related to a hazard that exists in an area-at-risk. Resilience is the combination of the Absorbing, Buffering, and Response Capacities of a community-at-risk, and is enhanced through Capacity-Building efforts. A disaster constitutes a failure of resilience.

Research and Evaluations of the Health Aspects of Disasters, Part VI: Interventional Research and the Disaster Logic Model

Disaster-related interventions are actions or responses undertaken during any phase of a disaster to change the current status of an affected community or a Societal System. Interventional disaster research aims to evaluate the results of such interventions in order to develop standards and best practices in Disaster Health that can be applied to disaster risk reduction. Considering interventions as production functions (transformation processes) structures the analyses and cataloguing of interventions/responses that are implemented prior to, during, or following a disaster or other emergency. Since currently it is not possible to do randomized, controlled studies of disasters, in order to validate the derived standards and best practices, the results of the studies must be compared and synthesized with results from other studies (ie, systematic reviews). Such reviews will be facilitated by the selected studies being structured using accepted frameworks. A logic model is a graphic representation of the transformation processes of a program [project] that shows the intended relationships between investments and results. Logic models are used to describe a program and its theory of change, and they provide a method for the analyzing and evaluating interventions. The Disaster Logic Model (DLM) is an adaptation of a logic model used for the evaluation of educational programs and provides the structure required for the analysis of disaster-related interventions. It incorporates a(n): definition of the current functional status of a community or Societal System, identification of needs, definition of goals, selection of objectives, implementation of the intervention(s), and evaluation of the effects, outcomes, costs, and impacts of the interventions. It is useful for determining the value of an intervention and it also provides the structure for analyzing the processes used in providing the intervention according to the Relief/Recovery and Risk-Reduction Frameworks.

Research and evaluations of the health aspects of disasters, part I: an overview

The ultimate goals of conducting disaster research are to obtain information to: (1) decrease risks that a hazard will produce a disaster; (2) decrease the mortality associated with disasters; (3) decrease the morbidity associated with disasters; and (4) enhance recovery of the affected community. And decrease the risks that a hazard will produce a disaster. Two principal, but inter-related, branches of disaster research are: (1) Epidemiological; and (2) Interventional. Epidemiological research explores the relationships and occurrences that comprise a disaster from a particular event. Interventional research involves evaluations of interventions, whether they are directed at relief, recovery, hazard mitigation, capacity building, or performance. In response to the need for the discipline of Disaster Health to build its science on data that are generalizeable and comparable, a Disaster Logic Model (DLM) and a set of five Frameworks have been developed to structure the information and research of the health aspects of disasters. These Frameworks consist of the: (1) Conceptual; (2) Temporal; (3) Societal; (4) Relief/Recovery; and (5) Risk-Reduction Frameworks. The Frameworks provide a standardized format for studying and comparing the epidemiology of disasters, and with the addition of the DLM, for evaluating the interventions (responses) provided prior to, during, and following a disaster, especially as they relate to the health status of the people affected by, or at-risk for, a disaster. Critical to all five Frameworks is the inclusion of standardized definitions of the terms. The Conceptual Framework describes the progression of a hazard that becomes an event, which causes structural damage, which, in turn, results in compromised, decreased, or losses of function(s) (functional damage) that, in turn, produce needs that lead to an emergency or a disaster. The Framework incorporates a cascade of risks that lead from the presence of a hazard to the development of a disaster. Risk is the likelihood that each of the steps leading from a hazard to a disaster will take place, as well as the probabilities of consequences of each of the elements in the Conceptual Framework. The Temporal Framework describes this chronological progression as phases in order of their appearance in time; some may occur concurrently. In order to study and compare the effects of an event on the complex amalgam that constitutes a community, the essential functions of a community have been deconstructed into 13 Societal Systems that comprise the Societal Framework. These diverse, but inter-related, Societal Systems interface with each other through a 14th System, Coordination and Control. The DLM can be used to identify the effects, costs, outcomes, and impacts of any intervention. Both the Relief/Recovery and Risk-Reduction Frameworks are based on the DLM. The Relief/Recovery Framework provides the structure necessary to systematically evaluate the processes involved in interventions provided during the Relief or Recovery phases of a disaster. The Risk-Reduction Framework details the processes involved in interventions aimed at mitigating the risk that a hazard will produce a destructive event, and/or in capacity building to augment the resilience of a community to the consequences of such an event.

Research and evaluations of the health aspects of disasters, Part V: epidemiological disaster research

Studies of the health aspect of disasters focus either on the epidemiology of disasters to define the causes and the progression from a hazard to a disaster, or the evaluations of interventions provided during any phase of a disaster. Epidemiological disaster research studies are undertaken for the purposes of: (1) understanding the mechanisms by which hazards evolve into a disaster; (2) determining ways to mitigate the risk(s) that a specific hazard will progress into a disaster; (3) predicting the likely damages and needs of the population-at-risk for an event; and (4) identifying potential measures to increase the resilience of a community to future events. Epidemiological disaster research utilizes the Conceptual, Temporal, and Societal Frameworks to define what occurs when a hazard manifests as an event that causes a disaster. The findings from such studies should suggest interventions that could augment the absorbing, buffering, or/and response capacities to lessen the probability of similar damages occurring from the next event. Ultimately, the use of these Frameworks in studying the health aspects of a disaster will help define what to expect in a specific setting and the standards and best practices upon which education, training, competencies, performance, and professionalization will be built.

Research and evaluations of the health aspects of disasters, Part IV: framework for societal structures: the societal systems

For the purposes of research and/or evaluation, a community/society is organized into 13 Societal Systems under the umbrella of an overall Coordination and Control System. This organization facilitates descriptions of a community/society or a component of a community for assessment at any designated time across the Temporal Phases of a disaster. Such assessments provide a picture of the functional status of one or more Systems that comprise a community. Since no system operates in isolation from the other systems, information of the concomitant status of several Societal Systems is crucial to gaining a complete understanding of compromised functions, as well as the effects and side effects of any intervention directed at restoring the functional state of the affected community or risk-reduction interventions of a community-at-risk. The 13 Societal Systems include: (1) Public Health; (2) Medical Care; (3) Water and Sanitation; (4) Shelter and Clothing; (5) Food and Nutrition; (6) Energy Supply; (7) Public Works and Engineering; (8) Social Structures; (9) Logistics and Transportation; (10) Security; (11) Communications; (12) Economy; and (13) Education. Many functions and sub-functions of the Systems overlap, or share some common sub-functions with other systems. For the purposes of research/evaluation, it is necessary to assign functions and sub-functions to only one of the Societal Systems.

Research and evaluations of the health aspects of disasters, Part III: framework for the temporal phases of disasters

Each of the elements described in the Conceptual Framework for disasters has a temporal designation; each has a beginning and end time. The Temporal Framework defines these elements as phases that are based on characteristics rather than on absolute times. The six temporal phases include the: (1) Pre-event; (2) Event; (3) Structural Damage; (4) Functional Damage (changes in levels of functions of the Societal Systems); (5) Relief; and (6) Recovery phases. Development is not a phase of a disaster. The use of the Temporal Framework in studying and reporting disasters allows comparisons to be made between similar phases of different disasters, regardless of the hazard involved and/or the community impacted. For research and evaluation purposes, assessments, plans, and interventions must be described in relation to the appropriate temporal phase.

Research and Evaluations of the Health Aspects of Disasters, Part VII: The Relief/Recovery Framework.

The principal goal of research relative to disasters is to decrease the risk that a hazard will result in a disaster. Disaster studies pursue two distinct directions: (1) epidemiological (non-interventional); and (2) interventional. Both interventional and non-interventional studies require data/information obtained from assessments of function. Non-interventional studies examine the epidemiology of disasters. Interventional studies evaluate specific interventions/responses in terms of their effectiveness in meeting their respective objectives, their contribution to the overarching goal, other effects created, their respective costs, and the efficiency with which they achieved their objectives. The results of interventional studies should contribute to evidence that will be used to inform the decisions used to define standards of care and best practices for a given setting based on these standards. Interventional studies are based on the Disaster Logic Model (DLM) and are used to change or maintain levels of function (LOFs). Relief and Recovery interventional studies seek to determine the effects, outcomes, impacts, costs, and value of the intervention provided after the onset of a damaging event. The Relief/Recovery Framework provides the structure needed to systematically study the processes involved in providing relief or recovery interventions that result in a new LOF for a given Societal System and/or its component functions. It consists of the following transformational processes (steps): (1) identification of the functional state prior to the onset of the event (pre-event); (2) assessments of the current functional state; (3) comparison of the current functional state with the pre-event state and with the results of the last assessment; (4) needs identification; (5) strategic planning, including establishing the overall strategic goal(s), objectives, and priorities for interventions; (6) identification of options for interventions; (7) selection of the most appropriate intervention(s); (8) operational planning; (9) implementation of the intervention(s); (10) assessments of the effects and changes in LOFs resulting from the intervention(s); (11) determination of the costs of providing the intervention; (12) determination of the current functional status; (13) synthesis of the findings with current evidence to define the benefits and value of the intervention to the affected population; and (14) codification of the findings into new evidence. Each of these steps in the Framework is a production function that facilitates evaluation, and the outputs of the transformation process establish the current state for the next step in the process. The evidence obtained is integrated into augmenting the respective Response Capacities of a community-at-risk. The ultimate impact of enhanced Response Capacity is determined by studying the epidemiology of the next event.

Defining the Skills of Disaster Responders

Daily E . Defining the skills of disaster responders. Prehosp Disaster Med. 2017;32(2):231-232.