Recovery from Gz-induced loss of consciousness: psychophysiologic considerations

Eight healthy male volunteer members of the USAFSAM acceleration panel were exposed to two consecutive acceleration runs of +1 Gz to +7 Gz at 6 G.s-1 onset rates. The subjects were instructed to relax during the acceleration exposure in order to voluntarily induce loss of consciousness (LOC). The subjects were asked to relate dreams, thoughts, or other mental illusions experienced during G-LOC episodes. Most subjects were amused and surprised, as well as interested in, relating their experience, although they were embarrassed about the G-LOC episode itself. Early post-G-LOC transient paralysis, as well as late LOC myoclonic (flailing) movements, were evident. Heart-rate response to the acceleratory stress was uneventful; maximum heart rate occurred 3.2 s after the onset of LOC. The study of dreams during normal sleep stages has been reviewed by many investigators, but this research has not extended to acceleration/hypoxic types of unconsciousness where dreams also seem to occur. G-LOC dream-state analysis, post-G-LOC paralysis, and their possible repercussions upon performance and incapacitation periods should be investigated, not only as curious events, but as operationally important and psychophysiologically significant.     

Performance recovery following +Gz-induced loss of consciousness

Seven male baboons (average weight, 20.6 kg) were trained in a simple shock-avoidance performance task on the USAFSAM centrifuge. A red light was presented to the baboon at approximate 2-s intervals. The animal was allowed 1 s to turn off the light or receive a 1-s shock. The shock could be abbreviated by a late trigger pull. Thus, the animal could avoid, escape, or accept the full shock. EEG was monitored from three transcranial stainless steel electrodes. Loss of consciousness (LOC) was induced by a rapid onset (4 or 6/s) exposure to 8 +Gz and sustained until LOC was identified by a near isoelectric EEG signal. Performance recovery time was measured from the return of EEG activity to the time when the animal resumed the performance task. These data were compared with previously obtained human data and found to be very similar. Also, it was found that time of performance recovery became significantly shorter after multiple LOC exposures and the performance recovery time significantly increased with increased time of unconsciousness. This study demonstrates the utility of the baboon as an animal model for G-induced LOC (G-LOC) research.     

Legal and ethical aspects of deliberate G-induced loss of consciousness experiments

Informed consent is both a legal and accepted ethical prerequisite to nontherapeutic human experimentation. The informed consent obtained from the subject in G-LOC experimentation is in the same form as the risk disclosures used in high-G acceleration experiments. However, in high acceleration protocols G-LOC is a potential risk while in G-LOC experiments it is the result. The case law embodies three modern evidentiary standards (the "professional," "material fact," and "possible risks" tests) employed by common law courts when deciding whether the risk disclosures are sufficient to elicit the informed consent of the subject. Each standard is applied against the disclosures in the G-LOC protocol to determine if the elements of the requirement are met. The risk disclosures are wanting in specific identification under the three tests. The deficiency is the failure to inform the subject that G-LOC may result in a pathologic state of unconsciousness about which little is known. Without complete disclosure of this lacking state of medical knowledge, it is questionable whether informed consent can be given. If subjected to judicial scrutiny, the disclosures stated in the G-LOC protocol used in government sponsored research will probably be found deficient.     

Medical considerations for human exposure to acceleration-induced loss of consciousness

Unconsciousness in humans has probably been occurring since before recorded history. Acceleration-induced loss of consciousness (G-LOC) in flight has been occurring since 1919. Loss of consciousness and syncope are common occurrences in clinical medicine with G-LOC, occurring in a large number of aircrew and research subjects during centrifuge exposures. Although the major risk to humans exposed to centrifuge-induced G-LOC is related directly to the central nervous, cardiac, and musculoskeletal (neck and back) systems, other risks are also present. Human exposure to G-LOC is required to help solve the G-LOC problem in aviators. To perform such human research, the benefits must clearly outweigh the risks to the human. Even if the risk-benefit ratio is considered favorably balanced, continued monitoring of individuals exposed to G-LOC is mandatory. To facilitate monitoring of humans exposed to G-LOC, a central nervous system (CNS) insult classification system would be of significant value. A suggested classification scheme which considers the type of CNS insult, the history of exposure to G-LOC, and the temporal evolution of potential CNS insult is developed. To date there is no indication that G-LOC episodes have any associated long term or persistent psychophysiological sequelae. Improved acute and long term evaluation of humans exposed to G-LOC are, however, important aspects of conducting G-LOC research with humans. Such research and careful monitoring are necessary to understand and eventually solve the G-LOC problem in aviators.     

Preventing G-induced loss of consciousness: 20 years of operational experience

INTRODUCTION: Although anecdotal reports of G-induced loss of consciousness (G-LOC) in military aviation date back to before 1920, regular reporting did not begin until 1982. The effectiveness in the operational setting of G-LOC preventive measures, such as positive pressure breathing for G protection (PBG), has not been studied. METHODS: We use the term "crash" to represent an event where the aircraft was destroyed and "incident" to define those events where the crew reported a G-LOC episode and the aircraft was not damaged. Data on G-LOC crashes, incidents, and aircraft sorties (number of take-offs) were obtained from the USAF Safety Center database for FY 82-01. RESULTS: During FY 82-01, there were 29 G-LOC crashes while those aircraft at risk of G-LOC crashes flew a total of 13,959,816 sorties. Poisson regression showed a non-significant decrease in crashes with an incidence rate ratio (IRR) of 0.096 (CI 0.89-1.03) (4% per yr). G-LOC crashes decreased from 4.4 per million flight sorties (PMFS) to 1.6 after the implementation of anti-G-LOC training programs beginning in 1985. However, G-LOC crashes remained unchanged after implementation of PBG in 1995. In contrast, incidents showed an IRR of 1.04 (CI 1.02-1.06) for G-LOC incidents, an estimated increase of 5% per yr. DISCUSSION: The physical/mechanical limitations of PBG, risk homeostasis, and the possibility that G-LOC rates have reached their asymptotic minimum are all discussed as possible explanations for the failure of PBG to decrease G-LOC crashes.     

+Gz-induced loss of consciousness: a case for training exposure to unconsciousness

+Gz-induced loss of consciousness (G-LOC) continues to be a threat to aircrew flying high-performance fighter aircraft. All avenues to prevent G-LOC, and to reduce the resulting incapacitation should G-LOC occur, must be explored. Research has begun to accurately quantify all aspects of the G-LOC phenomenon. The emerging pattern from this research indicates that, theoretically, G-LOC incapacitation could be significantly reduced. Comparison of G-LOC with LOC induced by acute arrest of cerebral circulation reveals that the G-LOC incapacitation could be reduced by as much as 17 s. Results also indicate that the relative incapacitation period (confusion and disorientation) following unconsciousness could be reduced by at least 9 s for an individual who has previously experienced G-LOC. This suggests that exposure to G-LOC during centrifuge training could provide this orientation to G-LOC and potentially reduce the incapacitation period should it occur inflight. This exposure may be likened to the current altitude-hypoxia training requirement for aircrew. Experience to date supports the contention that such training may be accomplished with an acceptable safety margin.     

A new look at the loss of consciousness experience within the U.S. Naval forces

Two surveys on the incidence of G-induced loss of consciousness (G-LOC) in U.S. Navy aircraft have been completed. Questionnaires returned (981) indicated an incidence rate of 12.2% in the first survey. A slightly higher incidence rate was found in the second survey based on the 2,459 questionnaires returned. Results indicated that G-LOC is a significant problem in naval aviation in older as well as newer generation aircraft. Age, height, and weight of respondents did not appear to be related to incidence of G-LOC. Results indicated a need for improvement in the anti-G protective system and its use. Different forms of physical fitness training may differentially influence G-tolerance.     

A review of central nervous system effects of G-induced loss of consciousness on volunteer subjects

A review of the literature on the central nervous system (CNS) effects of repeated centrifuge acceleration studies involving G-induced loss of consciousness (G-LOC) reveals that remarkably few adverse effects have been reported, aside from the G-LOC itself, even in subjects with numerous exposures. However, most of the followup studies were performed before the availability of sophisticated neuropsychological tests and non-invasive means of imaging the CNS, such as computerized tomography (CT), magnetic resonance imaging (MRI), brain electrical activity measurement (BEAM), and positron emission tomography (PET). Further, only a handful of long-term followup studies have been done. Thus, although repeated G-LOC may have induced some long-term adverse CNS effects, either organic or functional, little has been done to detect them. Even granted that some damage may be done, this risk must be weighed against the risk of aviators of similar damage from high +Gz exposures in flight, and even more against the risk of fatal G-LOC aircraft accidents. Volunteers for centrifuge acceleration studies should be fully informed about what is known and not known in this regard. As an ancillary measure, head restraints may be useful in avoiding postural trauma to the cervical spine, or impact injury to the head when G-LOC occurs and the head snaps forward and down.     

Analysis of mission and aircraft factors in G-induced loss of consciousness in the USAF: 1982-2002

INTRODUCTION: Previous studies have used questionnaires to evaluate G-LOC incident rates in different aircraft types, but no studies of G-LOC-related incident, crash, and fatality rates in different aircraft types were found in a search of the literature. METHODS: G-LOC events (including both incidents and crashes) for the fiscal years 1982 to 2002 were obtained from the USAF Safety Center. Aircraft sortie numbers were obtained for all aircraft that had a G-LOC event reported. Contingency table analysis and Chi-squared tests were used to evaluate differences in G-LOC rates. RESULTS: Overall 559 G-LOC events occurred for a rate of 25.9 per million sorties (PMS), but event rates differed by almost two orders of magnitude between aircraft categories, being highest in basic training aircraft, intermediate in single crewmember fighters, and lowest in other aircraft types (p < 0.001). The proportion of events resulting in crashes was 30% in single-crewmember aircraft compared with 0.6% in trainers and other two-crewmember aircraft (p < 0.001). All of the crashes and fatalities occurred in aircraft occupied at the time by only a single crewmember. The crash fatality rate was 100% in attack aircraft, 73% in single-crewmember fighters, and zero in basic trainers (p < 0.05). The F-15 and F-16 aircraft did not have higher G-LOC rates than other single-seat fighters. DISCUSSION: The data suggest that both crew complement and mission play a role in determining G-LOC rates. The data also suggest that G-LOC in an aircraft with a ground attack mission is more likely to result in a fatality.     

Experiment assessment of mass effects in the rat: implications for small animal PET imaging

In vivo imaging using positron emission tomography (PET) is important in the development of new radiopharmaceuticals in rodent animal models for use as biochemical probes, diagnostic agents, or in drug development. We have shown mathematically that, if small animal imaging studies in rodents are to have the same "quality" as human PET studies, the same number of coincidence events must be detected from a typical rodent imaging "voxel" as from the human imaging voxel. To achieve this using the same specific activity preparation, we show that roughly the same total amount of radiopharmaceutical must be given to a rodent as to a human subject. At high specific activities, the mass associated with human doses, when administered to a rodent, may not decrease the uptake of radioactivity at non saturable sites or sites where an enzyme has a high capacity for a substrate. However, in the case of binding sites of low density such as receptors, the increased mass injected could saturate the receptor and lead to physiologic effects and non-linear kinetics. Because of the importance of the mass injected for small animal PET imaging, we experimentally compared high and low mass preparations using ex vivo biodistribution and phosphorimaging of three compounds: 2-fluoro-2-deoxyglucose (FDG), 6-fluoro-L-metatyrosine (FMT) and one receptor-directed compound, the serotonin 5HT1A receptor ligand, trans-4-fluoro-N-[2-[4-(2-methoxylphenyl) piperazino]ethyl]-N-(2-pyridyl) cyclohexane- carboxamide (FCWAY). Changes in the mass injected per rat did not affect the distribution of FDG, FMT, and FCWAY in the range of 0.6-1.9 nmol per rat. Changes in the target to nontarget ratio were observed for injected masses of FCWAY in the range of approximately 5-50 nmol per rat. If the specific activity of such compounds and/or the sensitivity of small animal scanners are not increased relative to human studies, small animal PET imaging will not correctly portray the "true" tracer distribution. These difficulties will only be exacerbated in animals smaller than the rat, e.g., mice.     

Defining risk in aerospace medical unconsciousness research

The maneuverability envelopes of current and future fighter/attack aircraft exceed unprotected human tolerance to environmental stress. Human exposure to unconsciousness therefore can result not only inflight, but in research and training laboratories which endeavor to provide methods of enhanced protection for aircrew. Solving the problem of unconsciousness requires a thorough understanding of the phenomenon itself. This can only be accomplished by defining the psychophysiologic aspects of unconsciousness and techniques to prevent its occurrence or enhance recovery, should it occur. The safety of experimental human exposure to G-LOC however, remains of some concern. A framework for discussing the relative insult to the central nervous system may be constructed from what is currently known about G-LOC. The results of animal experimentation allow an estimation of the central nervous system tolerance to hypoxia without permanent alteration of tissue integrity. Clinical medicine documentation of syncope and fainting episodes, coupled with a long history of uncomplicated G-LOC episodes suggests that a certain window of safe exposure exists. Utilization of G-LOC as an endpoint included exposure of very large numbers of humans to unconsciousness without significant complication. Animal experimentation suggests that 180 s of central nervous system hypoxia is associated with uncomplicated recovery. Human exposure as long as 100 s has also been safely accomplished. Centrifuge G-LOC exposure typically results in only 15-20 s of central nervous system hypoxia. As long as G-LOC experimentation using humans is performed within well defined limits, it may be accomplished within an acceptable risk envelope.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiologic bases of G-induced loss of consciousness (G-LOC)

Exposure of pilots to high sustained +Gz (head to feet) or rapid onset of +Gz can produce a variety of pathophysiologic effects ranging from the loss of peripheral vision to total blackout and, finally, G-induced loss of consciousness (G-LOC). A G-LOC research program divided into four phases has been organized at USAFSAM/Crew Technology Division. In contrast to previous studies in acceleration, this program will focus exclusively on the ultimate problem in G-LOC; namely, inadequate cerebral perfusion leading to impaired brain energy metabolism, structure and function. The primary objective of this research program is to identify and arrange chronologically the numerous physiological and biochemical alterations in the brain that comprise the mechanism of G-LOC.     

The medical civic action program in Vietnam: success or failure?

Medical services have long been an integral part of the military and warfare. Civilians, however, are also caught up in wars. This article discusses the care of the indigenous civilians by U.S. military medical personnel during the Vietnam War. Civilian medical care is rendered both for altruistic purposes and to satisfy the policy aims of the U.S. government. Evaluation of these two aspects of the programs does not lead to the same conclusions. Doctors doubted the value of the programs, whereas the command structure was enthusiastic. For a program to be of sustained value to the people, it must persist over time and train those who will remain after U.S. forces are withdrawn. This did not occur in Vietnam. Furthermore, I doubt that medical care rendered by U.S. troops in uniform can serve to build up loyalty to another organization, such as the host government.     

G-induced loss of consciousness: definition, history, current status

G-induced loss of consciousness (G-LOC) is defined as "a state of altered perception wherein (one's) awareness of reality is absent as a result of sudden, critical reduction of cerebral blood circulation caused by increased G force." This phenomenon was first identified in Great Britain in World War I (circa 1918-1919) as "fainting in the air." In the United States G-LOC was first encountered in 1922 during the Pulitzer Trophy Air Race. Although recognized during World War II as an operational hazard for fighter aircraft, the invention of the pneumatic anti-G suit reduced concern about G-LOC at that time. A 1984 survey of pilots of high performance aircraft has shown G-LOC to be an operational problem--probably one that has caused aircraft mishaps for several years. The concern of this panel was to focus on various approaches in reducing the G-LOC hazard.     

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes,animal models and FDA-approved countermeasures

Purpose: The increasing global risk of nuclear and radiological accidents or attacks has driven renewed research interest in developing medical countermeasures to potentially injurious exposures to acute irradiation. Clinical symptoms and signs of a developing acute radiation injury, i.e. the acute radiation syndrome, are grouped into three sub-syndromes named after the dominant organ system affected, namely the hematopoietic, gastrointestinal, and neurovascular systems. The availability of safe and effective countermeasures against the above threats currently represents a significant unmet medical need. This is the first article within a three-part series covering the nature of the radiation sub-syndromes, various animal models for radiation countermeasure development, and the agents currently approved by the United States Food and Drug Administration for countering the medical consequences of several of these prominent radiation exposure-associated syndromes.

Conclusions: From the U.S. and global perspectives, biomedical research concerning medical countermeasure development is quite robust, largely due to increased government funding following the 9/11 incidence and subsequent rise of terrorist-associated threats. A wide spectrum of radiation countermeasures for specific types of radiation injuries is currently under investigation. However, only a few radiation countermeasures have been fully approved by regulatory agencies for human use during radiological/nuclear contingencies. Additional research effort, with additional funding, clearly will be needed in order to fill this significant, unmet medical health problem.     

Neutrophil infiltration in exercise-injured skeletal muscle: how do we resolve the controversy?

Neutrophils have not consistently been detected in exercise-injured skeletal muscle and, therefore, neutrophil infiltration in this muscle has become a controversial issue. Thirty-eight animal and human studies that assessed injured muscle for neutrophils and employed acute exercise (e.g. level, uphill or downhill running, eccentric contractions, or swimming) were analysed to help clarify the relationship between neutrophil infiltration and exercise-induced muscle injury. Findings from nearly three-quarters of the reviewed studies suggest that neutrophil accumulation follows exercise-induced muscle injury. Intramuscular neutrophil infiltration was present in 85% and 55% of the animal and human studies, respectively. However, no consistent relationship between the potential damaging effect of the exercise type and neutrophil infiltration can be conclusively established from these studies. Specific animal-related factors that could influence these results include age, animal strain, catecholamines, corticosterone, acute stressors and muscle type, whereas a specific human-related influencing factor is physical activity status. Factors affecting both animal and human studies could include sex hormones, muscle sampling techniques and neutrophil detection approaches. General categories of methods that have been used to detect neutrophil infiltration are microscopy, myeloperoxidase (MPO) biochemical assay, antibody staining and white blood cell radionuclide imaging. Only studies employing white blood cell radionuclide imaging have consistently detected neutrophil infiltration. However, antibody staining with a quantitative analysis is currently the most feasible, valid and sensitive method. Research recommendations, therefore, are warranted to resolve the neutrophil infiltration controversy. We propose two approaches for animal studies. The first approach encompasses (i) studying or measuring factors that could influence neutrophil infiltration; (ii) using quantitative antibody staining analysis (in all studies and employing a panel of anti-neutrophil antibodies); (iii) examining the relationship between fibre morphological changes and neutrophil antigen expression; and (iv) developing a neutrophil antibody-radionuclide imaging technique. The second approach will yield animal findings complementing or addressing the gaps from the human exercise studies. For human studies, we suggest that (i) physical activity status is investigated; (ii) quantitative antibody staining analysis is performed (including staining injured muscle with a panel of antibodies such as anti-elastase, anti-MPO, anti-CD11b and anti-CD15 or assessing injured muscle using both immunohistochemistry and the MPO biochemical assay); and (iii) the relationship between fibre morphological changes and neutrophil antigen expression is examined. Studies that incorporate these recommendations could lead to an increased understanding of whether neutrophils are essential for the recovery from an exercise-induced muscle injury.     

Recognizing +Gz-induced loss of consciousness and subject recovery from unconsciousness on a human centrifuge

Human exposure to +Gz-induced loss of consciousness (G-LOC) remains of some concern relative to the well-being of the individuals experiencing the unconscious episodes. Detailed kinetic analysis of over 500 G-LOC episodes on a human centrifuge allowed an evaluation of the time for subjective recognition by observers of the onset of G-LOC and subsequent recovery to normal baseline conditions. The characteristics of early, coincident, and late recognition of the onset of G-LOC were evaluated. Earlier recognition of G-LOC was observed to occur when the rate of onset of the +Gz-stress was gradual (less than 0.6 G/s). Rapid onset rate (greater than 0.6 G/s) exposures were more likely to result in late recognition of G-LOC. The duration of the resulting period of unconsciousness (absolute incapacitation) was very sensitive to the time for recognition of G-LOC and most rapid return to a normal (+1 Gz) environment. The absolute incapacitation increased significantly from early (10.7 s) to coincident (11.4 s) to late (13.2 s) recognition of G-LOC which differed by a total of only 4.6 s. The results allow development of an initial standard of care envelope for apparently safe exposure of human subjects to centrifuge G-LOC since no adverse effects were observed with any of the exposures. The results also demonstrate the extreme sensitivity of the central nervous system to small changes in exposure to +Gz-stress which can be accurately measured.     

Panel summary: from Zen riddle to the razor's edge

A summary of the Panel on Deliberate G-induced Loss of Consciousness reviews the global issue of rendering human subjects unconscious in the centrifuge as a research procedure. Major issues summarized are informed consent, a common taxonomy for G-LOC events, and medical surveillance of subjects made deliberately unconscious.     

加速度致意识丧失前驱反应特征及预警方法研究

目的 观察加速度致意识丧失(G-LOC)的前驱反应特征,寻找监测和预警G-LOC的指标和方法.方法 在人体离心机上对37名男性健康志愿者进行了+Gz耐力检查,实时监测了多种生理指标和行为参数的变化.结果 通过对比分析未发生G-LOC前驱反应组(n=21)和发生G-LOC前驱反应组(n=16)受试者在+Gz作用中各项生理指标和行为参数的差异,找到了额部血管搏动幅度、眼水平动脉收缩压、心水平动脉收缩压、心电图QT和RR间期的比值、最大心率、头部位置、边灯信号对答情况、眨眼间隔时间、对语音提示信号的反应等指标和参数可用来判断受试者是否出现G-LOC前驱反应,因而可作为G-LOC预警指标.初步建立了多指标综合判断G-LOC前驱反应是否出现的方法,该方法总的预测符合率达91.9%.结论 本研究观察到的G-LOC前驱反应特征和建立的G-LOC预警方法有望在G-LOC预警和恢复系统研制中应用.