World J. Surg. 16, 918-923, 1992
World Journal of Surgery O 1992 by the Soci~t6 intemational¢ de Chlrurgie
Irradiated Trauma Victims: The Impact of Ionizing Radiation on Surgical Considerations Following a Nuclear Mishap Erwin F. Hirsch, M.D. and G a r y J. Bowers, M.D. Departments of Surgery, Boston University School of Medicine, Boston, Massachusetts and Uniformed Services University of the Health Sciences, Bethesda, Maryland, U.S.A. The combination of conventional traumatic injuries and radiation exposure has synergistic consequences, the full extent of which may take days to weeks to become apparent. Our understanding of such is derived from a variety of laboratory and clinical scenarios involving both therapeutic and accidental exposures. When presented with such an individual one must discern whether the victim has been bodily contaminated versus exposed to a source or both. The former will necessitate decontamination procedures which may be as simple as declothing and showering the individual. Simply removing the victim from the source will suffice to halt further radiation induced injury. In the vast majority of cases basic life support and other emergency medical procedures should be expeditiously instituted as warranted and without fear of personal hazard for health care teams. Following stabilization, further medical/surgical support must be predicated upon the extent of the radiation injury with the circulating absolute lymphocyte count serving as both a reliable and readily accessible indicator of the degree of underlying radiation injury. As radiation has profound consequences on immune and wound healing systems, therapies must be tempered by an understanding of the impact of radiation upon these systems. Overall, the consequences of irradiation injury will be the potential for an exacerbation of the effects of conventional traumatic injuries with a higher than expected morbidity and mortality.
In 1980, Dr. Francis Moore, Harvard Medical School Emeritus Mosley Professor of Surgery, extended an intellectual and clinical challenge to the assembled audience attending the American College of Surgeons Meeting. Dr. Moore asked the group to speculate on what the average general surgeon might know about the the impact of ionizing radiation if called upon to care for an irradiated patient who additionally may have suffered other types of trauma. During the interim years, the authors and their collaborators at the Armed Forces Radiobiology Research Institute (AFRRI) have addressed these concerns in a variety of capacities, developing an investigationai, clinical, and educational program on which this paper is based. The combination of ionizing radiation injury with conventional blunt or penetrating trauma and/or burn injuries has been termed the Combined Injury Syndrome [1]. The potential impact that high energy ionizing radiation has on the manageReprint requests: Erwin F. Hirsch, M.D., Chief, Department of Surgery, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts 02118, U.S.A.
ment of conventional trauma victims does pose certain ramifications which warrant considering this entity as a separate and unique form of trauma. Extensive laboratory data suggest that this combination of injuries has synergistic implications which can be very deleterious to the victim [2, 3]. The association on a large scale of radiation injury, trauma, and burns has occurred only twice in this century, both following the detonation of nuclear devices over Hiroshima and Nagasaki. During the intervening years, the increased production and proliferation of nuclear weapons, the widespread development of energy generating reactors, and the expanding use of radioactive isotopes in industry, science, and the health fields has resulted in an ever increasing risk for accidental exposure and injury. Several incidents, resulting in either potential or real victims, military and civilian, have occurred both within the United States of America and abroad; witness the Three Mile Island accident in Pennsylvania and more recently the events at Chernobyl, Ukraine, and Goiania, Brazil. The magnitude of such accidents measured in the number of casualties has varied from one to thousands. In the majority of these cases injury has resulted when fissionable material was inadvertently allowed to assume a configuration in which excess neutrons were produced. In this critical state the unstable nuclear configuration generated the subsequent release of a large amount of very high energy. The accompanying explosions produced a varying number of victims with a variety of injuries, both pure radiation and combined injury. All too frequently these accidents were accompanied by a high mortality rate. In other scenarios, unsuspecting individuals have come into contact with highly radioactive devices and/or substances which, owing to prolonged body exposure, inflicted radiationinduced tissue necrosis with subsequent significant wound problems. These latter accidents, exemplified by that occurring recently in Goiania, Brazil, can generally be attributed to ignorance, lax or nonexisting safety procedures, or criminal activities. Our understanding of the Japanese experience with the Combined Injury Syndrome during World War II is limited io scope. This is in part due to the extent of the damage caused by the war as well as the impact of compromised resources on the
E.F. Hirsch and G.J. Bowers: Irradiated Trauma Victims
Japanese ability to deliver comprehensive medical care. Furthermore, the true biological consequences of ionizing radiation were largely unknown at the time. In survivors of these nuclear blasts, many with seemingly nonlethal injuries, an unexpected incidence of hemorrhagic complications, infectious problems, and poor to absent wound healing were frequently observed With a resulting higher than expected mortality. Isolated accidents in this country during the early years of atomic research Produced victims with extreme hemodynamic instability far out of proportion to the extent of their nonradiation injuries. These individuals invariably died despite massive fluid and other medical support. In the recent accidents at Chernobyl (1986) and Goiania (I987), comprehensive medical care was available to victims either close to the site (Goiania) or at a reasonable distance (Chernobyl). The management of these individuals as Well as the now large number of victims associated with the various reported accidents serves as the reference base for our clinical knowledge of the Combined Injury Syndrome. Biological Effects of Ionizing Radiation
The effects of acute radiation injury are mediated at the cellular level with various cell populations exhibiting a range of sensitivities to the effects of irradiation. In general, replicating pools of cells such as the stem cells associated with the bone marrow, gastro-intestinal tract, skin epithelium, and gonads are the most sensitive. Mature, stable, nonreplicating cell populations as contained in most solid organs, nerve, bone, and connective tissues tend to be relatively resistant to the primary effects of the radiation; nonetheless, these populations are susceptible to the secondary effects arising from hemodynamic and other inflammatory mediated disturbances occurring within the organism as a consequence of the radiation exposure. One exception to the latter group is the lymphocyte, which exhibits extreme sensitivity to the primary effects of radiation injury. The resultant cellular response in all cell populations range from Cell death to alterations in cellular function, either temporary or Permanent, which concomitant effects on organ system function. Even following recovery there may be long-term effects SUch as transformation, the mechanisms of which are poorly Understood. There is a spectrum of radiation energies including both Particles (alpha, beta, neutron and other high energy particles) and photons (gamma and x-rays) which have specific characteristic energies and depth of tissue penetration. The potential for biological injury correlates with the amount of energy given up by the particle and/or photon when it interacts with the target; this is referred to as the linear energy transfer. The exact mechanism of injury remains unclear. Early manifestations are generally a result of an acute inflammatory response which, depending on the magnitude of the radiation exposure, can be most profound. Late effects, i.e,, those appearing days to weeks following the exposure, tend to arise from disturbances in organ function due to either the loss of replicating cell pools critical for the maintenance of normal Organ function or progressive sclerosing of affected tissues. Considerable evidence documents the disruptive effects of radiation on cellular nucleic acids and membranes, much of Which appears to be mediated by the generation of charged OXygen radicals as a consequence of the interaction of the
919
radiation energy with the water content of the cell [4]. These nucleic acid disruptions are likely to be the basis for the failure of replicating pools to propagate themselves. How much of this may also be influenced by the affects of highly reactive inflammatory mediators on the stem cell environment is unclear. Numerous inflammatory mediators are released during the early inflammatory response to acute radiation exposure. As is well known, many of these substances have potent biological consequences on cell and organ function resulting in profound disturbances both locally and systemically with both acute and delayed effects. It is important to ascertain whether the victim has been exposed to a radioactive source, is actually contaminated with radioactive debris, or a combination of the two. In the former case, removing the victim from the field of radiation will suffice to stop further radiation exposure and injury. No specific decontamination procedures are warranted. In the latter two scenarios, the victim must be decontaminated erstwhile ongoing exposure and subsequent injury will persist. Decontamination protocols vary widely; however, approximately 90% to 95% of the radioactive source can be effectively eliminated simply by removing the victim's clothing and subsequently bathing the skin with mild soapy water. When bodily contaminated with radioactive debris (source contact) the victim may be conserved with debris emitting a variety of energized particles and/or photons. Such will depend on the exact composition of the source. If the emitter releases alpha particles the deposition of energy is over a short distance; hence, the depth of penetration is exceedingly small. Shielding can be effectively accomplished by clothing, thin layers of paper, and even the stratum corneum of the skin. Decontamination is a simple procedure requiring only the basics as outlined above. In general, these particles do not present any significant external hazard; however, if inhaled or ingested they can be readily incorporated into biological tissues with localized yet potentially significant consequences. Beta particles are identical to electrons; their depth of penetration in biological systems is measured in millimeters. While external contamination in most instances does not present an insurmountable problem with the beta emitters, if allowed to remain in place for a prolonged period of exposure partialthickness to full-thickness burns can occur. The resultant wounds fortunately, if thoroughly cleansed and debrided of the contaminating source or the source is simply removed from contact with the body, can generally be managed with traditional wound management principles with favorable outcomes. Protection from this type of energy can be accomplished by shielding with one inch of most materials. As with alpha particles, internal contamination with beta emitters either by ingestion or inhalation can present a serious problem which, because of the more penetrating capability of the beta particle, can be more deleterious than the former. Overall, the effects of alpha and beta irradiation are localized and would not be expected to create systemic problems. If internal contamination with any radioactive source is suspected aggressive measures should be employed to rid the body of these agents before tissue incorporation occurs. Such measures may include the use of expectorants coupled with bronchopulmonary lavage, emetics, cathartics, fluid infusions plus diuretics. Once these agents have become incorporated it
920 may be impossible to remove them even with more aggressive approaches including chelating agents. Time is important as incorporation occurs within a matter of a few hours, depending on dose and mode of entry. Neutrons and other high energy particles are very penetrating and like the equally penetrating photon energies (x-ray and gamma rays) can be very damaging with widespread consequences to the entire organism. Protection can only be achieved by distance from the source and/or a high degree of shielding, a sometimes very complex problem. Photon sources are commonly associated with devices of industrial and medical purposes. Accidental or unknowing prolonged exposure to these sources can have far more serious ramifications than those described above for alpha and beta emitters. The extent and magnitude of injury will be predicated upon the duration and the extent of the body surface area involved. Typically such injury produces serious, progressive, nonhealing wounds. Animal data suggests that high photon energies may also interfere with the healing of conventional injuries [2, 3]. Management of these wounds can be very tasking and quite complex. The zone of injury may take weeks to months to become apparent. The ongoing tissue necrosis is not accompanied by the normal wound healing mechanisms. These wounds persist, can be quite painful, continue to ooze fluids including blood. Because they are rapidly colonized with bacteria, they can continue to serve as a nidus for repetitive bacteremias. In general, aggressive debridement endeavors should be avoided. The recent t37cesium spill in Goiania, Brazil, resulted in a large number of patients with localized, repetitive exposures to high energy photons for a prolonged duration of time [5]. Painful lesions on the face, neck, upper extremities, occasionally the trunk, and legs were not uncommon. The initial appearance was characterized by erythema followed by blisters and pain. Thereafter, most of the areas converted to an ulcertype lesion which in most instances failed to heal for several months. In some instances, full-thickness scars developed. Early in the clinical course some of these wounds were treated by excision and closure. Not uncommonly these lesions recurred. Evaluation of some of these wounds by magnetic resonance imaging (MRI) showed that significant changes, identified as edema and vasculitis, often extended far from the wound. This experience seems to indicate that early surgical management of these wounds, unless they compromise life, is not indicated. Radiation-induced ulcers occasionally occur clinically following soft tissue therapeutic irradiation for the treatment of various malignancies. The extent of ulceration generally does not become apparent for several weeks to months. Once they have fully demarcated, we totally excise the ulcer including a healthy rim of normal tissue. The resultant wound is generally not amenable to traditional wound closure techniques. Utilizing various plastic surgery maneuvers, including a variety of myocutaneous flaps, we are able to successfully close these defects. Such an approach was tried in Goiania [5] and may well prove to be the treatment of choice for accident related radiation ulcers arising in other similar situations. High energy and very devastating neutrons and other highly energized heavy particles are only encountered in association with nuclear fission. In these scenarios, high energy photons
World J. Surg. Vol. 16, No. 5, Sept./Oct. 1992 will also be encountered. For effective decontamination, one only needs to remove the victim from the emitting source's radiation field. Unfortunately, in those scenarios involving an uncontrolled fission process with an associated explosion, as occurred in Chernobyl, one can expect the entire gamut of the radiation spectrum to be present. Besides the victim likely being contaminated with radioactive debris, the individual will also have experienced some degree of whole body irradiation; hence, in addition to any localized effects of the radiation the victim will also experience some degree of systemic toxicity.
The Acute Radiation Syndrome: Hemopoietic, GastroIntestinal, Cardiovascular, and Neurologic Responses Following any acute whole body irradiation injury, four stages are typically observed: a prodromal period lasting from hours to days, a latent period of days to weeks followed by a period of overt illness of variable duration, and finally a recovery period. The overall effect on the organism, the magnitude, and duration of each of these stages is very much dependent upon the extent of the body surface involved, the duration of the exposure, and the homogeneity of the radiation field. The end result, very much dependent on the severity of the radiation insult, is either death or recovery, the latter generally having permanent and sometimes progressive sequalae. The specific physiologic disturbances and subsequent clinical manifestations comprise the Acute Radiation Syndrome, a constellation of signs and symptoms classically grouped under the subtitles hematopoeitic, gastro-intestinal, cardiovascular, and central nervous system syndromes.
Hematologic Consequences The magnitude of the hematologic changes is both dose dependent and related to the extent of bone marrow involvement. Whole body exposures of 100 centigray or less are virtually asymptomatic. Above this threshold, significant alterations in the circulating white cell, red cell, and platelet pools develop which correlate with the dose absorbed by the marrow (biological dosimetry). The degree and rapidity of onset of the lymphopenia can serve as an index of the degree of radiation injury [2, 3]. During the prodromal stage, the patient will exhibit varying degrees of nausea, vomiting, anorexia and possibly even diarrhea, particularly with higher exposures. The clinical presentation as well as the rapidity of its onset will be directly proportional to the severity of the exposure. As these acute manifestations subside, the patient may be asymptomatic, the latent phase; however, progressive lymphopenia, granulocytopenia, anemia and thrombocytopenia will be evident because of the underlying injury to the marrow stem cells. As a result of this injury the patient can be expected to ultimately develop new clinical problems. As the patient begins to exhibit manifest illness (usual onset within 2-3 weeks) problems related to hemorrhage, poor oxygen carrying capacity, poor wound healing, and local and systemic sepsis ensue. With higher doses of whole body irradiation the effects on the marrow will be irreversible, a consequence of an obliteration of the marrowy regenerative capacity. The only hope for recovery in these patients is a bone marrow transplant; however, the Chernobyl
E.F. Hirsch and G.J. Bowers: Irradiated Trauma Victims
experience was associated with a less than ideal outcome due to both expected and unexpected inherent problems associated with this technology. With lesser degrees of marrow injury, recovery is possible provided that the patient can be supported during this phase of their illness. Transfusion of blood products may be required, if so these units should be irradiated to prevent complications of graft vs. host reactions which can occur. Antisepsis measures will be most important in these individuals due to profound alterations in their immune function. Prophylactic "sterilization" of the gut with oral antimicrobials should be considered as gut derived pathogens play a key role in the demise of these patients. Before embarking upon aggressive management of associated wounds one must be cognizant of the fact that the Usual granulation processes and other mechanisms of wound healing will be severely retarded. Clearly these wounds will need to be properly cleansed of foreign matter, debris, and severely devitalized tissue with appropriate antimicrobial agents applied but aggressive debridement should be tempered by the realizatiofi that despite thorough surgical care, these WOUnds will show little propensity for healing. Unfortunately, so long as they remain open, these wounds will continue to serve as a nidus for potential invasive infections. Given a state of near global immunologic dysfunction, invading organisms Will encounter ineffective inflammatory and antimicrobial meaSUres. Hence one must consider the liberal use of antibiotics With a very low threshold of initiating this therapy. One must also bear in mind that problems with atypical and opportunistic °rganisras will likely arise. Additionally, the constant loss of body fluids will task patient fluid, electrolyte, and protein reserves. Aggressive measures will need to be instituted to replenish these losses. Plastic surgery techniques may be employed to manage these wounds if needed; however, such must be postponed until the recovery phase of the radiation injury to avoid an unacceptably high mortality. As marrow function resumes, some degree of normal healing may itself occur thus Obviating any need for more complicated closure techniques. Only time will tell.
Gastro-Intestinat Consequences ~Vith increasing doses of whole body irradiation (> 400-500 centigray), in addition to the profound alterations in bone marrow function, significant gastro-intestinal disturbances beconic evident [2, 3]. The gastro-intestinal syndrome is characterized by injury to the villi due to an underlying failure of enterocyte replication. As cell losses are not matched by cell replacement the villi become foreshortened, the normal columnar epithelium assumes a squamous pattern. The glycocalyx is lost. Absorptive function ceases; fluids are lost to the lumen by a Very leaky gut with resultant watery diarrhea. Profound hyP°v°lemia results. Bowel perforator vessels become dilated, tortuous, and leak large amounts of fluids, electrolytes, and Proteins into the interstitium with resultant bowel edema. An ileus develops. If the magnitude of injury is severe enough naucosal ulcerations will ultimately develop progressing to a ffruartkhemorrhagic necrosis of the mucosa. Bleeding may occur, er depleting circulating formed blood elements. Normal gut aSSociated lymphoid tissue disappears. Enteric pathogens although initially affected by the radiation rebound quickly.
921
Portal and subsequent systemic bacteremias/endotoxemias arise. In general, this degree of injury coupled with the near total marrow obliteration associated with this magnitude of irradiation is lethal. The individual, if not dying from the consequences of volume and electrolyte depletions, will ultimately expire from septic causes. None of our current therapies are likely to reverse this scenario. During the prodromal period of gastro-intestinal toxicity, severe nausea, vomiting, and watery, sometimes explosive, diarrhea are common occurrences within a few hours from exposure. As these problems subside a latent period may ensue with the victim being relatively asymptomatic; however, this period will be of brief duration and soon followed by the overt clinical picture during which the previously described signs and symptoms will return, being far more severe than before.
Cardiovascular and Central Nervous System Consequences Whole body irradiation in excess of 1000 centigray is associated with a rapid onset of symptomatology [2, 3]. These patients experience a generalized burning skin sensation, nausea, vomiting, confusion, and hemodynamic instability, all within a matter of minutes to a few hours of the event. Soon respiratory distress ensues with further neurologic deterioration and coma. In the event that these signs and symptoms are present, it is a clear indication that the magnitude of exposure is incompatible with life. Despite aggressive medical management with massive amounts of fluid and pressor support, in all patients to date this magnitude of radiation injury has been associated with a fatal outcome within 24--36 hours, The presence or absence of traditional traumatic injuries is irrelevant in these individuals. Management of Nuclear Casualties
Medical personnel involved in the resuscitation and subsequent management of combined injury patients must recognize that there is no life threatening hazard to them from the irradiated casualties. It is only with the very extremes of radiation exposure that any of the tissues of irradiated individuals have become themselves radioactive sources. Invariably all of these victims have been found dead. Therefore, it is imperative that priorities should be directed to the recognition and treatment of conventional injuries. The basics of advanced trauma life support should be adhered to including maintenance and/or establishment of patient ability to adequately ventilate and oxygenate as well as to maintain normovolemia. Decontamination procedures other than merely removing the victim's clothing should occur after stabilization. While efforts to protect the combined injury patient's ability to ventilate and oxygenate do not require modification of the traditional trauma life support protocols, hemodynamic management may require modifications. The recent experiences in the Ukraine and Brazil confirmed that prior irradiation of transfused whole or packed blood cells with 1500 centigrade is necessary to eliminate viable leukocytes which depending on the magnitude of the exposure may set the stage for a graft vs. host condition. Otherwise, crystaUoid management should be as usual except that in the generalized inflammatory response
922
induced by whole body irradiation, fluid requirements may be greater than normally expected. The magnitude of the radiation exposure will be in most instances difficult to ascertain shortly after most accidents. Casualties will generally not have worn a dosimeter; personnel available to read such a device may be unavailable. Furthermore, areas of the body may have been shielded such that, even if present, the dosimeter may not reflect the total body exposure. Currently perhaps the most useful indicator of the magnitude of radiation injury is the degree of alteration occurring in the circulating lymphocyte count during the initial 24 hours following the event. The degree of lymphopenia and the rapidity of onset has been validated in numerous investigational and clinical situations as a reliable biological dosimeter. A decline of 50% or greater in the circulating absolute lymphocyte count developing within 24 hours is clear evidence for a clinically significant exposure to ionizing radiation [2, 3]. These individuals can be expected to manifest signs and symptoms of the Acute Radiation Syndrome in addition to any other problems associated with the conventional injuries. There are a number of clinical scenarios during which surgical intervention can or should be considered for the treatment of conventional trauma injuries following accidental exposure to ionizing radiation. A lifesaving procedure may be required within a matter of minutes or hours after the accident. Furthermore, either owing to the nature of the conventional injury or as a consequence of developments arising during the subsequent clinical management, emergent surgical procedures required to diminish morbidity, mortality as well as improve rehabilitation may be required in the days following the exposure. Current data does reinforce the concept that lifesaving procedures (i.e., control of hemorrhage, debridement of dead or severely devitalized tissues, repair of vital structures or certain neurological or orthopedic procedures) should be expeditiously performed following aggressive resuscitation [2, 3, 6]. In planning such procedures, consideration must be given to the likelihood that the effects of ionizing radiation may preclude further surgery for 3 or 4 months. The performance of any surgical procedures during the latent period or period of manifest illness of the Acute Radiation Syndrome needs to be considered in relation to the magnitude of the radiation exposure and the degree of underlying hematopoeitic dysfunction. If there is any evidence to suggest any significant alterations in marrow dysfunction (reflected in either the circulating cell pools or the marrow itself) all surgical intervention short of absolute lifesaving procedures must be avoided. Due to profound immunosuppression, the associated mortality will be prohibitive. Only after there is clear evidence for marrow improvement, which may take weeks to months, should surgical therapies be entertained. Bear in mind also that even during the recovery phase related complications to various surgical procedures may still be slightly higher than otherwise expected. While until recently support of the bone marrow was limited to component transfusions and antimicrobial prophylaxis was traditionally based on antibiotic therapy, the rapidly developing field of immunomodulators and differential growth factors has the potential to alter this. As such, in some of these high risk surgical candidates a more favorable status may be achieved. In conclusion, the combination of radiation injury and con-
World J. Surg. Vol. 16, No. 5, Sept./Oct. 1992
ventional trauma has synergistic effects. The full extent of the combined injury will be difficult to assess early in the course of management. Nonetheless, every attempt should be made to provide for early emergency medical support to the victims of combined injury. Subsequent management must be predicated upon the extent of the underlying bone marrow injury and with the principle that days may pass before the full extent of this specific injury is known. Our present technology is such that any combined injury victim sustaining a radiation insult, independent of any associated conventional injury, of a magnitude to produce profound marrow and gastro-intestinal disturbances will most likely not survive. Furthermore, the effects of the radiation injury will have a protean impact upon the victim's immunologic function and subsequent would healing. The consequences of such will be that otherwise nonlethal traumatic injuries will be associated with a higher than expected mortality. R6sumE
L'association des lesions traumatiques et de l'exposition aux irradiations a des cons6quences synergiques. Les effets complets peuvent prendre des jours ou des mois pour se manifester. Notre compr6hension de ces ph~Snom~nes est bas6e sur une variEt6 de situations de laboratoire et clinique et concerne aussi bien les effets secondaires ~ une exposition aux rayons, que celle-ci soit accidentale ou th6rapeutique. En presence d'une victime d'irradiation, il faut d'abord d6terminer si elle a Et6 contaminEe par son environement ou par une source ponctuelle ou par les deux. Dans le premier cas, la d6contamination peut 6tre aussi simple que de deshabiller et de faire laver la victime. Dans le second, extraire la victime de la source d'irradiation peut suffire ~t arr6ter l'irradiation et ses consequences. Dans la plupart des situations, la reanimation de base, et d'autres gestes d'urgence doivent 6tre mis en route immEdiatement et sans qu'il y ait un risque accru pour les membres de l'Equipe de soins. Une fois stabilis6, le patient doit continuer de bEnEficier des soins, bases sur la numeration des lymphocytes circulants qui est un indicateur fiable et facilement accessible du degr6 des lesions radiques. Comme l'irradiation a des consequences profondes sur la cicatrisation et le syst~me immunitaire, la thErapeutique doit 6tre adapt6e en connaissance de cause. Globalement, les consequences d'une irradiation sont une possible exacerbation des effets d'un traumatisme traditionnel avec une morbiditE et une mortalit6 plus Elev6es. Resumen
La combinaci6n de lesiones traum,'lticas convencionales con la exposici6n a irradiaci6n tiene consecuencias sin6rgicas, cuyO impacto total aparentemente s61o se puede establecer dias o semanas despuEs. Nuestra comprensi6n de tal fen6meno se deriva de una variedad de observaciones clinicas y de labora" torio referentes tanto alas exposiciones terapEuticas como alaS exposiciones accidentales. Ante un individuo que haya sufrido tal combinaci6n es necesario distinguir entre si la v/ctima ha sido gravemente contaminada versus su exposici6n a una fuente de irradiaci6n, o ambos. Lo primero requiere ejecutar proced" imientos de descontaminaci6n, los cuales pueden ser tan si~" pies como retirar las vestimentas o duchar a la persona. 1~1
E.F. Hirsch and G.J. Bowers: Irradiated Trauma Victims simple acto de alejar a la victima de la fuente puede ser suficiente para evitar que se produzcan lesiones adicionales por irradiaci6n. En la vasta mayorfa de los casos los procedimientos b~isicos de soporte vital y otros procedimientos m6dicos de ernergencia deben ser instituidos en forma expedita segtin necesidad, sin temor al riesgo p a r a los miembros del equipo hurnano encargado de su cuidado. Lograda la estabilizaci6n, se procede a instaurar soporte y tratamiento m6dico/quirtigico adicional segtin la gravedad de la lesi6n por irradiaci6n, con el recuento total de los linfocitos circulantes como un indicador, eonfiable y r~tpidamente asequible, de su gravedad. Puesto que la radiaci6n tiene consecuencias profundas sobre el sistema inrnune y sobre el proceso de cicatrizaci6n de las heridas, las naodalidades terap6uticas deben ser ajustadas segtln el impacto de la radiaci6n sobre estos sistemas. Globalmente, las consecuencias de la irradiaci6n son las de una potencial exacerbaci6n de los efectos de las lesiones traurn~iticas convencionales, lo cual se traduce en tasas de morbilidad y mortalidad m~ts altas de 1o usual.
Acknowledgment The opinions and assertions are those of the authors and are not necessarily those of the Department of Defense, the United
923 States Navy, the United States Air Force, nor the Defense Nuclear Agency.
References 1. Wintz, H.: Die vor und nachbehandlung bei der rotgenbestrahlung. Ther. Gegnew. 64:209, 1973 2. Bowers, G.J.: The Combined Injury Syndrome. In Military Radiobiology, J.J. Conklin, R.I. Walker, editors, Orlando, Academic Press, 1987, pp. 191-217 3. Conklin, J.J., Walker, R.I., Hirsch, E.F.: Current concepts in the management of radiation injuries and associated trauma. Surg. Gynecot. Obstet. 156:809, 1983 4. Little, J.B.: Development of radiation injury in cells. N. Engl. J. Med. 278:369, 1968 5. Oliveira, A.R., Valverde, N.J.L, Mello, C.E.B., Almeida, C.E.V., Farina, R., Amaral, C.M,R.: Skirt lesions associated with the Goiania accident. In The Medical Basis For Radiation Accident Preparedness. II. Clinical Experience Since 1979, R.C. Ricks, S.A. Fry, editors, New York, Elsevier North Holland, Inc., 1990, pp. 88-102. 6. Hirsch, E.F.: The status of combined injuries. In Treatment of Radiation Injuries, D. Browne, editor, New York, Plenum Press, 1990, pp. 141-144.
World Journal of Surgery O 1992 by the Soci~t6 intemational¢ de Chlrurgie
Irradiated Trauma Victims: The Impact of Ionizing Radiation on Surgical Considerations Following a Nuclear Mishap Erwin F. Hirsch, M.D. and G a r y J. Bowers, M.D. Departments of Surgery, Boston University School of Medicine, Boston, Massachusetts and Uniformed Services University of the Health Sciences, Bethesda, Maryland, U.S.A. The combination of conventional traumatic injuries and radiation exposure has synergistic consequences, the full extent of which may take days to weeks to become apparent. Our understanding of such is derived from a variety of laboratory and clinical scenarios involving both therapeutic and accidental exposures. When presented with such an individual one must discern whether the victim has been bodily contaminated versus exposed to a source or both. The former will necessitate decontamination procedures which may be as simple as declothing and showering the individual. Simply removing the victim from the source will suffice to halt further radiation induced injury. In the vast majority of cases basic life support and other emergency medical procedures should be expeditiously instituted as warranted and without fear of personal hazard for health care teams. Following stabilization, further medical/surgical support must be predicated upon the extent of the radiation injury with the circulating absolute lymphocyte count serving as both a reliable and readily accessible indicator of the degree of underlying radiation injury. As radiation has profound consequences on immune and wound healing systems, therapies must be tempered by an understanding of the impact of radiation upon these systems. Overall, the consequences of irradiation injury will be the potential for an exacerbation of the effects of conventional traumatic injuries with a higher than expected morbidity and mortality.
In 1980, Dr. Francis Moore, Harvard Medical School Emeritus Mosley Professor of Surgery, extended an intellectual and clinical challenge to the assembled audience attending the American College of Surgeons Meeting. Dr. Moore asked the group to speculate on what the average general surgeon might know about the the impact of ionizing radiation if called upon to care for an irradiated patient who additionally may have suffered other types of trauma. During the interim years, the authors and their collaborators at the Armed Forces Radiobiology Research Institute (AFRRI) have addressed these concerns in a variety of capacities, developing an investigationai, clinical, and educational program on which this paper is based. The combination of ionizing radiation injury with conventional blunt or penetrating trauma and/or burn injuries has been termed the Combined Injury Syndrome [1]. The potential impact that high energy ionizing radiation has on the manageReprint requests: Erwin F. Hirsch, M.D., Chief, Department of Surgery, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts 02118, U.S.A.
ment of conventional trauma victims does pose certain ramifications which warrant considering this entity as a separate and unique form of trauma. Extensive laboratory data suggest that this combination of injuries has synergistic implications which can be very deleterious to the victim [2, 3]. The association on a large scale of radiation injury, trauma, and burns has occurred only twice in this century, both following the detonation of nuclear devices over Hiroshima and Nagasaki. During the intervening years, the increased production and proliferation of nuclear weapons, the widespread development of energy generating reactors, and the expanding use of radioactive isotopes in industry, science, and the health fields has resulted in an ever increasing risk for accidental exposure and injury. Several incidents, resulting in either potential or real victims, military and civilian, have occurred both within the United States of America and abroad; witness the Three Mile Island accident in Pennsylvania and more recently the events at Chernobyl, Ukraine, and Goiania, Brazil. The magnitude of such accidents measured in the number of casualties has varied from one to thousands. In the majority of these cases injury has resulted when fissionable material was inadvertently allowed to assume a configuration in which excess neutrons were produced. In this critical state the unstable nuclear configuration generated the subsequent release of a large amount of very high energy. The accompanying explosions produced a varying number of victims with a variety of injuries, both pure radiation and combined injury. All too frequently these accidents were accompanied by a high mortality rate. In other scenarios, unsuspecting individuals have come into contact with highly radioactive devices and/or substances which, owing to prolonged body exposure, inflicted radiationinduced tissue necrosis with subsequent significant wound problems. These latter accidents, exemplified by that occurring recently in Goiania, Brazil, can generally be attributed to ignorance, lax or nonexisting safety procedures, or criminal activities. Our understanding of the Japanese experience with the Combined Injury Syndrome during World War II is limited io scope. This is in part due to the extent of the damage caused by the war as well as the impact of compromised resources on the
E.F. Hirsch and G.J. Bowers: Irradiated Trauma Victims
Japanese ability to deliver comprehensive medical care. Furthermore, the true biological consequences of ionizing radiation were largely unknown at the time. In survivors of these nuclear blasts, many with seemingly nonlethal injuries, an unexpected incidence of hemorrhagic complications, infectious problems, and poor to absent wound healing were frequently observed With a resulting higher than expected mortality. Isolated accidents in this country during the early years of atomic research Produced victims with extreme hemodynamic instability far out of proportion to the extent of their nonradiation injuries. These individuals invariably died despite massive fluid and other medical support. In the recent accidents at Chernobyl (1986) and Goiania (I987), comprehensive medical care was available to victims either close to the site (Goiania) or at a reasonable distance (Chernobyl). The management of these individuals as Well as the now large number of victims associated with the various reported accidents serves as the reference base for our clinical knowledge of the Combined Injury Syndrome. Biological Effects of Ionizing Radiation
The effects of acute radiation injury are mediated at the cellular level with various cell populations exhibiting a range of sensitivities to the effects of irradiation. In general, replicating pools of cells such as the stem cells associated with the bone marrow, gastro-intestinal tract, skin epithelium, and gonads are the most sensitive. Mature, stable, nonreplicating cell populations as contained in most solid organs, nerve, bone, and connective tissues tend to be relatively resistant to the primary effects of the radiation; nonetheless, these populations are susceptible to the secondary effects arising from hemodynamic and other inflammatory mediated disturbances occurring within the organism as a consequence of the radiation exposure. One exception to the latter group is the lymphocyte, which exhibits extreme sensitivity to the primary effects of radiation injury. The resultant cellular response in all cell populations range from Cell death to alterations in cellular function, either temporary or Permanent, which concomitant effects on organ system function. Even following recovery there may be long-term effects SUch as transformation, the mechanisms of which are poorly Understood. There is a spectrum of radiation energies including both Particles (alpha, beta, neutron and other high energy particles) and photons (gamma and x-rays) which have specific characteristic energies and depth of tissue penetration. The potential for biological injury correlates with the amount of energy given up by the particle and/or photon when it interacts with the target; this is referred to as the linear energy transfer. The exact mechanism of injury remains unclear. Early manifestations are generally a result of an acute inflammatory response which, depending on the magnitude of the radiation exposure, can be most profound. Late effects, i.e,, those appearing days to weeks following the exposure, tend to arise from disturbances in organ function due to either the loss of replicating cell pools critical for the maintenance of normal Organ function or progressive sclerosing of affected tissues. Considerable evidence documents the disruptive effects of radiation on cellular nucleic acids and membranes, much of Which appears to be mediated by the generation of charged OXygen radicals as a consequence of the interaction of the
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radiation energy with the water content of the cell [4]. These nucleic acid disruptions are likely to be the basis for the failure of replicating pools to propagate themselves. How much of this may also be influenced by the affects of highly reactive inflammatory mediators on the stem cell environment is unclear. Numerous inflammatory mediators are released during the early inflammatory response to acute radiation exposure. As is well known, many of these substances have potent biological consequences on cell and organ function resulting in profound disturbances both locally and systemically with both acute and delayed effects. It is important to ascertain whether the victim has been exposed to a radioactive source, is actually contaminated with radioactive debris, or a combination of the two. In the former case, removing the victim from the field of radiation will suffice to stop further radiation exposure and injury. No specific decontamination procedures are warranted. In the latter two scenarios, the victim must be decontaminated erstwhile ongoing exposure and subsequent injury will persist. Decontamination protocols vary widely; however, approximately 90% to 95% of the radioactive source can be effectively eliminated simply by removing the victim's clothing and subsequently bathing the skin with mild soapy water. When bodily contaminated with radioactive debris (source contact) the victim may be conserved with debris emitting a variety of energized particles and/or photons. Such will depend on the exact composition of the source. If the emitter releases alpha particles the deposition of energy is over a short distance; hence, the depth of penetration is exceedingly small. Shielding can be effectively accomplished by clothing, thin layers of paper, and even the stratum corneum of the skin. Decontamination is a simple procedure requiring only the basics as outlined above. In general, these particles do not present any significant external hazard; however, if inhaled or ingested they can be readily incorporated into biological tissues with localized yet potentially significant consequences. Beta particles are identical to electrons; their depth of penetration in biological systems is measured in millimeters. While external contamination in most instances does not present an insurmountable problem with the beta emitters, if allowed to remain in place for a prolonged period of exposure partialthickness to full-thickness burns can occur. The resultant wounds fortunately, if thoroughly cleansed and debrided of the contaminating source or the source is simply removed from contact with the body, can generally be managed with traditional wound management principles with favorable outcomes. Protection from this type of energy can be accomplished by shielding with one inch of most materials. As with alpha particles, internal contamination with beta emitters either by ingestion or inhalation can present a serious problem which, because of the more penetrating capability of the beta particle, can be more deleterious than the former. Overall, the effects of alpha and beta irradiation are localized and would not be expected to create systemic problems. If internal contamination with any radioactive source is suspected aggressive measures should be employed to rid the body of these agents before tissue incorporation occurs. Such measures may include the use of expectorants coupled with bronchopulmonary lavage, emetics, cathartics, fluid infusions plus diuretics. Once these agents have become incorporated it
920 may be impossible to remove them even with more aggressive approaches including chelating agents. Time is important as incorporation occurs within a matter of a few hours, depending on dose and mode of entry. Neutrons and other high energy particles are very penetrating and like the equally penetrating photon energies (x-ray and gamma rays) can be very damaging with widespread consequences to the entire organism. Protection can only be achieved by distance from the source and/or a high degree of shielding, a sometimes very complex problem. Photon sources are commonly associated with devices of industrial and medical purposes. Accidental or unknowing prolonged exposure to these sources can have far more serious ramifications than those described above for alpha and beta emitters. The extent and magnitude of injury will be predicated upon the duration and the extent of the body surface area involved. Typically such injury produces serious, progressive, nonhealing wounds. Animal data suggests that high photon energies may also interfere with the healing of conventional injuries [2, 3]. Management of these wounds can be very tasking and quite complex. The zone of injury may take weeks to months to become apparent. The ongoing tissue necrosis is not accompanied by the normal wound healing mechanisms. These wounds persist, can be quite painful, continue to ooze fluids including blood. Because they are rapidly colonized with bacteria, they can continue to serve as a nidus for repetitive bacteremias. In general, aggressive debridement endeavors should be avoided. The recent t37cesium spill in Goiania, Brazil, resulted in a large number of patients with localized, repetitive exposures to high energy photons for a prolonged duration of time [5]. Painful lesions on the face, neck, upper extremities, occasionally the trunk, and legs were not uncommon. The initial appearance was characterized by erythema followed by blisters and pain. Thereafter, most of the areas converted to an ulcertype lesion which in most instances failed to heal for several months. In some instances, full-thickness scars developed. Early in the clinical course some of these wounds were treated by excision and closure. Not uncommonly these lesions recurred. Evaluation of some of these wounds by magnetic resonance imaging (MRI) showed that significant changes, identified as edema and vasculitis, often extended far from the wound. This experience seems to indicate that early surgical management of these wounds, unless they compromise life, is not indicated. Radiation-induced ulcers occasionally occur clinically following soft tissue therapeutic irradiation for the treatment of various malignancies. The extent of ulceration generally does not become apparent for several weeks to months. Once they have fully demarcated, we totally excise the ulcer including a healthy rim of normal tissue. The resultant wound is generally not amenable to traditional wound closure techniques. Utilizing various plastic surgery maneuvers, including a variety of myocutaneous flaps, we are able to successfully close these defects. Such an approach was tried in Goiania [5] and may well prove to be the treatment of choice for accident related radiation ulcers arising in other similar situations. High energy and very devastating neutrons and other highly energized heavy particles are only encountered in association with nuclear fission. In these scenarios, high energy photons
World J. Surg. Vol. 16, No. 5, Sept./Oct. 1992 will also be encountered. For effective decontamination, one only needs to remove the victim from the emitting source's radiation field. Unfortunately, in those scenarios involving an uncontrolled fission process with an associated explosion, as occurred in Chernobyl, one can expect the entire gamut of the radiation spectrum to be present. Besides the victim likely being contaminated with radioactive debris, the individual will also have experienced some degree of whole body irradiation; hence, in addition to any localized effects of the radiation the victim will also experience some degree of systemic toxicity.
The Acute Radiation Syndrome: Hemopoietic, GastroIntestinal, Cardiovascular, and Neurologic Responses Following any acute whole body irradiation injury, four stages are typically observed: a prodromal period lasting from hours to days, a latent period of days to weeks followed by a period of overt illness of variable duration, and finally a recovery period. The overall effect on the organism, the magnitude, and duration of each of these stages is very much dependent upon the extent of the body surface involved, the duration of the exposure, and the homogeneity of the radiation field. The end result, very much dependent on the severity of the radiation insult, is either death or recovery, the latter generally having permanent and sometimes progressive sequalae. The specific physiologic disturbances and subsequent clinical manifestations comprise the Acute Radiation Syndrome, a constellation of signs and symptoms classically grouped under the subtitles hematopoeitic, gastro-intestinal, cardiovascular, and central nervous system syndromes.
Hematologic Consequences The magnitude of the hematologic changes is both dose dependent and related to the extent of bone marrow involvement. Whole body exposures of 100 centigray or less are virtually asymptomatic. Above this threshold, significant alterations in the circulating white cell, red cell, and platelet pools develop which correlate with the dose absorbed by the marrow (biological dosimetry). The degree and rapidity of onset of the lymphopenia can serve as an index of the degree of radiation injury [2, 3]. During the prodromal stage, the patient will exhibit varying degrees of nausea, vomiting, anorexia and possibly even diarrhea, particularly with higher exposures. The clinical presentation as well as the rapidity of its onset will be directly proportional to the severity of the exposure. As these acute manifestations subside, the patient may be asymptomatic, the latent phase; however, progressive lymphopenia, granulocytopenia, anemia and thrombocytopenia will be evident because of the underlying injury to the marrow stem cells. As a result of this injury the patient can be expected to ultimately develop new clinical problems. As the patient begins to exhibit manifest illness (usual onset within 2-3 weeks) problems related to hemorrhage, poor oxygen carrying capacity, poor wound healing, and local and systemic sepsis ensue. With higher doses of whole body irradiation the effects on the marrow will be irreversible, a consequence of an obliteration of the marrowy regenerative capacity. The only hope for recovery in these patients is a bone marrow transplant; however, the Chernobyl
E.F. Hirsch and G.J. Bowers: Irradiated Trauma Victims
experience was associated with a less than ideal outcome due to both expected and unexpected inherent problems associated with this technology. With lesser degrees of marrow injury, recovery is possible provided that the patient can be supported during this phase of their illness. Transfusion of blood products may be required, if so these units should be irradiated to prevent complications of graft vs. host reactions which can occur. Antisepsis measures will be most important in these individuals due to profound alterations in their immune function. Prophylactic "sterilization" of the gut with oral antimicrobials should be considered as gut derived pathogens play a key role in the demise of these patients. Before embarking upon aggressive management of associated wounds one must be cognizant of the fact that the Usual granulation processes and other mechanisms of wound healing will be severely retarded. Clearly these wounds will need to be properly cleansed of foreign matter, debris, and severely devitalized tissue with appropriate antimicrobial agents applied but aggressive debridement should be tempered by the realizatiofi that despite thorough surgical care, these WOUnds will show little propensity for healing. Unfortunately, so long as they remain open, these wounds will continue to serve as a nidus for potential invasive infections. Given a state of near global immunologic dysfunction, invading organisms Will encounter ineffective inflammatory and antimicrobial meaSUres. Hence one must consider the liberal use of antibiotics With a very low threshold of initiating this therapy. One must also bear in mind that problems with atypical and opportunistic °rganisras will likely arise. Additionally, the constant loss of body fluids will task patient fluid, electrolyte, and protein reserves. Aggressive measures will need to be instituted to replenish these losses. Plastic surgery techniques may be employed to manage these wounds if needed; however, such must be postponed until the recovery phase of the radiation injury to avoid an unacceptably high mortality. As marrow function resumes, some degree of normal healing may itself occur thus Obviating any need for more complicated closure techniques. Only time will tell.
Gastro-Intestinat Consequences ~Vith increasing doses of whole body irradiation (> 400-500 centigray), in addition to the profound alterations in bone marrow function, significant gastro-intestinal disturbances beconic evident [2, 3]. The gastro-intestinal syndrome is characterized by injury to the villi due to an underlying failure of enterocyte replication. As cell losses are not matched by cell replacement the villi become foreshortened, the normal columnar epithelium assumes a squamous pattern. The glycocalyx is lost. Absorptive function ceases; fluids are lost to the lumen by a Very leaky gut with resultant watery diarrhea. Profound hyP°v°lemia results. Bowel perforator vessels become dilated, tortuous, and leak large amounts of fluids, electrolytes, and Proteins into the interstitium with resultant bowel edema. An ileus develops. If the magnitude of injury is severe enough naucosal ulcerations will ultimately develop progressing to a ffruartkhemorrhagic necrosis of the mucosa. Bleeding may occur, er depleting circulating formed blood elements. Normal gut aSSociated lymphoid tissue disappears. Enteric pathogens although initially affected by the radiation rebound quickly.
921
Portal and subsequent systemic bacteremias/endotoxemias arise. In general, this degree of injury coupled with the near total marrow obliteration associated with this magnitude of irradiation is lethal. The individual, if not dying from the consequences of volume and electrolyte depletions, will ultimately expire from septic causes. None of our current therapies are likely to reverse this scenario. During the prodromal period of gastro-intestinal toxicity, severe nausea, vomiting, and watery, sometimes explosive, diarrhea are common occurrences within a few hours from exposure. As these problems subside a latent period may ensue with the victim being relatively asymptomatic; however, this period will be of brief duration and soon followed by the overt clinical picture during which the previously described signs and symptoms will return, being far more severe than before.
Cardiovascular and Central Nervous System Consequences Whole body irradiation in excess of 1000 centigray is associated with a rapid onset of symptomatology [2, 3]. These patients experience a generalized burning skin sensation, nausea, vomiting, confusion, and hemodynamic instability, all within a matter of minutes to a few hours of the event. Soon respiratory distress ensues with further neurologic deterioration and coma. In the event that these signs and symptoms are present, it is a clear indication that the magnitude of exposure is incompatible with life. Despite aggressive medical management with massive amounts of fluid and pressor support, in all patients to date this magnitude of radiation injury has been associated with a fatal outcome within 24--36 hours, The presence or absence of traditional traumatic injuries is irrelevant in these individuals. Management of Nuclear Casualties
Medical personnel involved in the resuscitation and subsequent management of combined injury patients must recognize that there is no life threatening hazard to them from the irradiated casualties. It is only with the very extremes of radiation exposure that any of the tissues of irradiated individuals have become themselves radioactive sources. Invariably all of these victims have been found dead. Therefore, it is imperative that priorities should be directed to the recognition and treatment of conventional injuries. The basics of advanced trauma life support should be adhered to including maintenance and/or establishment of patient ability to adequately ventilate and oxygenate as well as to maintain normovolemia. Decontamination procedures other than merely removing the victim's clothing should occur after stabilization. While efforts to protect the combined injury patient's ability to ventilate and oxygenate do not require modification of the traditional trauma life support protocols, hemodynamic management may require modifications. The recent experiences in the Ukraine and Brazil confirmed that prior irradiation of transfused whole or packed blood cells with 1500 centigrade is necessary to eliminate viable leukocytes which depending on the magnitude of the exposure may set the stage for a graft vs. host condition. Otherwise, crystaUoid management should be as usual except that in the generalized inflammatory response
922
induced by whole body irradiation, fluid requirements may be greater than normally expected. The magnitude of the radiation exposure will be in most instances difficult to ascertain shortly after most accidents. Casualties will generally not have worn a dosimeter; personnel available to read such a device may be unavailable. Furthermore, areas of the body may have been shielded such that, even if present, the dosimeter may not reflect the total body exposure. Currently perhaps the most useful indicator of the magnitude of radiation injury is the degree of alteration occurring in the circulating lymphocyte count during the initial 24 hours following the event. The degree of lymphopenia and the rapidity of onset has been validated in numerous investigational and clinical situations as a reliable biological dosimeter. A decline of 50% or greater in the circulating absolute lymphocyte count developing within 24 hours is clear evidence for a clinically significant exposure to ionizing radiation [2, 3]. These individuals can be expected to manifest signs and symptoms of the Acute Radiation Syndrome in addition to any other problems associated with the conventional injuries. There are a number of clinical scenarios during which surgical intervention can or should be considered for the treatment of conventional trauma injuries following accidental exposure to ionizing radiation. A lifesaving procedure may be required within a matter of minutes or hours after the accident. Furthermore, either owing to the nature of the conventional injury or as a consequence of developments arising during the subsequent clinical management, emergent surgical procedures required to diminish morbidity, mortality as well as improve rehabilitation may be required in the days following the exposure. Current data does reinforce the concept that lifesaving procedures (i.e., control of hemorrhage, debridement of dead or severely devitalized tissues, repair of vital structures or certain neurological or orthopedic procedures) should be expeditiously performed following aggressive resuscitation [2, 3, 6]. In planning such procedures, consideration must be given to the likelihood that the effects of ionizing radiation may preclude further surgery for 3 or 4 months. The performance of any surgical procedures during the latent period or period of manifest illness of the Acute Radiation Syndrome needs to be considered in relation to the magnitude of the radiation exposure and the degree of underlying hematopoeitic dysfunction. If there is any evidence to suggest any significant alterations in marrow dysfunction (reflected in either the circulating cell pools or the marrow itself) all surgical intervention short of absolute lifesaving procedures must be avoided. Due to profound immunosuppression, the associated mortality will be prohibitive. Only after there is clear evidence for marrow improvement, which may take weeks to months, should surgical therapies be entertained. Bear in mind also that even during the recovery phase related complications to various surgical procedures may still be slightly higher than otherwise expected. While until recently support of the bone marrow was limited to component transfusions and antimicrobial prophylaxis was traditionally based on antibiotic therapy, the rapidly developing field of immunomodulators and differential growth factors has the potential to alter this. As such, in some of these high risk surgical candidates a more favorable status may be achieved. In conclusion, the combination of radiation injury and con-
World J. Surg. Vol. 16, No. 5, Sept./Oct. 1992
ventional trauma has synergistic effects. The full extent of the combined injury will be difficult to assess early in the course of management. Nonetheless, every attempt should be made to provide for early emergency medical support to the victims of combined injury. Subsequent management must be predicated upon the extent of the underlying bone marrow injury and with the principle that days may pass before the full extent of this specific injury is known. Our present technology is such that any combined injury victim sustaining a radiation insult, independent of any associated conventional injury, of a magnitude to produce profound marrow and gastro-intestinal disturbances will most likely not survive. Furthermore, the effects of the radiation injury will have a protean impact upon the victim's immunologic function and subsequent would healing. The consequences of such will be that otherwise nonlethal traumatic injuries will be associated with a higher than expected mortality. R6sumE
L'association des lesions traumatiques et de l'exposition aux irradiations a des cons6quences synergiques. Les effets complets peuvent prendre des jours ou des mois pour se manifester. Notre compr6hension de ces ph~Snom~nes est bas6e sur une variEt6 de situations de laboratoire et clinique et concerne aussi bien les effets secondaires ~ une exposition aux rayons, que celle-ci soit accidentale ou th6rapeutique. En presence d'une victime d'irradiation, il faut d'abord d6terminer si elle a Et6 contaminEe par son environement ou par une source ponctuelle ou par les deux. Dans le premier cas, la d6contamination peut 6tre aussi simple que de deshabiller et de faire laver la victime. Dans le second, extraire la victime de la source d'irradiation peut suffire ~t arr6ter l'irradiation et ses consequences. Dans la plupart des situations, la reanimation de base, et d'autres gestes d'urgence doivent 6tre mis en route immEdiatement et sans qu'il y ait un risque accru pour les membres de l'Equipe de soins. Une fois stabilis6, le patient doit continuer de bEnEficier des soins, bases sur la numeration des lymphocytes circulants qui est un indicateur fiable et facilement accessible du degr6 des lesions radiques. Comme l'irradiation a des consequences profondes sur la cicatrisation et le syst~me immunitaire, la thErapeutique doit 6tre adapt6e en connaissance de cause. Globalement, les consequences d'une irradiation sont une possible exacerbation des effets d'un traumatisme traditionnel avec une morbiditE et une mortalit6 plus Elev6es. Resumen
La combinaci6n de lesiones traum,'lticas convencionales con la exposici6n a irradiaci6n tiene consecuencias sin6rgicas, cuyO impacto total aparentemente s61o se puede establecer dias o semanas despuEs. Nuestra comprensi6n de tal fen6meno se deriva de una variedad de observaciones clinicas y de labora" torio referentes tanto alas exposiciones terapEuticas como alaS exposiciones accidentales. Ante un individuo que haya sufrido tal combinaci6n es necesario distinguir entre si la v/ctima ha sido gravemente contaminada versus su exposici6n a una fuente de irradiaci6n, o ambos. Lo primero requiere ejecutar proced" imientos de descontaminaci6n, los cuales pueden ser tan si~" pies como retirar las vestimentas o duchar a la persona. 1~1
E.F. Hirsch and G.J. Bowers: Irradiated Trauma Victims simple acto de alejar a la victima de la fuente puede ser suficiente para evitar que se produzcan lesiones adicionales por irradiaci6n. En la vasta mayorfa de los casos los procedimientos b~isicos de soporte vital y otros procedimientos m6dicos de ernergencia deben ser instituidos en forma expedita segtin necesidad, sin temor al riesgo p a r a los miembros del equipo hurnano encargado de su cuidado. Lograda la estabilizaci6n, se procede a instaurar soporte y tratamiento m6dico/quirtigico adicional segtin la gravedad de la lesi6n por irradiaci6n, con el recuento total de los linfocitos circulantes como un indicador, eonfiable y r~tpidamente asequible, de su gravedad. Puesto que la radiaci6n tiene consecuencias profundas sobre el sistema inrnune y sobre el proceso de cicatrizaci6n de las heridas, las naodalidades terap6uticas deben ser ajustadas segtln el impacto de la radiaci6n sobre estos sistemas. Globalmente, las consecuencias de la irradiaci6n son las de una potencial exacerbaci6n de los efectos de las lesiones traurn~iticas convencionales, lo cual se traduce en tasas de morbilidad y mortalidad m~ts altas de 1o usual.
Acknowledgment The opinions and assertions are those of the authors and are not necessarily those of the Department of Defense, the United
923 States Navy, the United States Air Force, nor the Defense Nuclear Agency.
References 1. Wintz, H.: Die vor und nachbehandlung bei der rotgenbestrahlung. Ther. Gegnew. 64:209, 1973 2. Bowers, G.J.: The Combined Injury Syndrome. In Military Radiobiology, J.J. Conklin, R.I. Walker, editors, Orlando, Academic Press, 1987, pp. 191-217 3. Conklin, J.J., Walker, R.I., Hirsch, E.F.: Current concepts in the management of radiation injuries and associated trauma. Surg. Gynecot. Obstet. 156:809, 1983 4. Little, J.B.: Development of radiation injury in cells. N. Engl. J. Med. 278:369, 1968 5. Oliveira, A.R., Valverde, N.J.L, Mello, C.E.B., Almeida, C.E.V., Farina, R., Amaral, C.M,R.: Skirt lesions associated with the Goiania accident. In The Medical Basis For Radiation Accident Preparedness. II. Clinical Experience Since 1979, R.C. Ricks, S.A. Fry, editors, New York, Elsevier North Holland, Inc., 1990, pp. 88-102. 6. Hirsch, E.F.: The status of combined injuries. In Treatment of Radiation Injuries, D. Browne, editor, New York, Plenum Press, 1990, pp. 141-144.
