Seminar_Prof. Lukšić.pptx

Seminar – Acute poisoning and first aid Venomous snakebites in children in southern Croatia Prof. Boris Lukšić, MD., PhD. Clinical Department of Infectious Diseases University Hospital of Split Split, Croatia Introduction  There are 3 million people all over the world that suffer from snake ven...

Seminar – Acute poisoning and first aid Venomous snakebites in children in southern Croatia Prof. Boris Lukšić, MD., PhD. Clinical Department of Infectious Diseases University Hospital of Split Split, Croatia Introduction  There are 3 million people all over the world that suffer from snake venom poisoning per year and 125 000 of them die.  In the whole Europe, including European Russia and Turkey, the annual number of snakebite cases is estimated to be approximately 7 500, and 1 000 of which are severe envenomation.  It is considerated to be in average 4 of deaths annually in Europe. Introduction  Venom poisoning mortality percentage amounts 0.41.8% in Croatia.  Generally, snakebites are most common in tropical and subtropical areas, but they are also found in regions with temperate clime.  Only family of vipers (Viperidae) habitat in Europe, mainly subfamily of real vipers (Viperinae). Introduction  On European continent, Croatia is one of the area where vipers are most wide spread.  In Croatia three venomous snakes habitat: ◦ the nose-horned viper (Vipera ammodytes) ◦ the common adder (Vipera berus) ◦ the meadow viper (Vipera ursinii). Vipera ammodytes Introduction  The severest clinical manifestations appear after the nose-horned viper (V. ammodytes) bites, which is the largest and the most poisonous European viper.  It is also the one which causes the most snake envenomations in southern Croatia.  Poisonous glands of adult specimen carrie 10 to 45 mg of venom. Introduction  Amount of 20 mg excreted by one bite can be lethal for humans.  Different toxic polypeptides are responsible for most of the toxic effects of snake envenomation, and two main clinical results of snake venom are haematotoxic and neurotoxic. Introduction  In this research we have showed: ◦ the epidemiological characteristics ◦ clinical presentation ◦ local and general complications ◦ and received treatment in children after experiencing snake envenomation. Materials and Methods  In this retrospective, clinical-epidemiological research, data were collected from the archives and medical history of patients treated from snake venom poisoning in the University Hospital Centre Split during the 35-year period (from 1 st January 1979 to 31st December 2013).  The study has been done on the area of the southern Croatia; specifically in the Split-Dalmatia County in southern Croatia where 455 242 inhabitants live. Materials and Methods  Every venom poisoned victim has been treated in the Clinical Department of Infectious Diseases in the University Hospital Centre Split in Croatia.  We assume that during this period in this area, the real number of affected children was higher than we noticed, but because of the very mild clinical manifestation of snake envenomation, after the judgement of general practitioner or paediatrician, victims were not sent in the Clinical Department of Infectious Diseases so they were not enrolled in this retrospective study. Materials and Methods  The case of a snakebite was recorded if the subjects and/or thier familly or witness have recognized the viper or in the appearance of the puncture sites that were convincingly from a snakebite.  The registrated patients were further confirmed based on clinical presention of envenomation.  The subjects who had suspected snakebites, but did not develop symptoms and sings of poisoning, were excluded from the study. Materials and Methods  All subjects in our study were children and adolescents; from zero to eighteen years of age.  The largest number of bites were caused by the nosehorned viper, and only a few of them by the common adder and the meadow viper.  The total number of respondents was 160 (N = 160). Materials and Methods  All data in this research were divided into several parts: epidemiological data, clinical data with laboratory parameters, and treatment data.  General and epidemiological data about patients were recorded as following: ◦ ◦ ◦ ◦ gender patients age (days, months or years) date when bite occurred (month) localization of bite (upper limbs – fist, arm; lower limbs – foot, leg; and other localizations). Materials and Methods  In the clinical part, following data were recorded: ◦ symptoms and signs of envenomation     oedema and/or redness haematoma enlarged regional lymph nodes vomiting and diarrhoea. ◦ and development of local complications at the place of snake bite      haemorrhagic blister compartment syndrome necrosis of the skin and/or muscle thrombosis and/or thrombophlebitis infections. Materials and Methods  Recorded parameters were also: ◦ blood pressure and heart rate as a clinical evaluation of cardiovascular system during hospitalization ◦ assessment of consciousness (somnolence, sopor, coma) ◦ and the existence of paresis or paralysis of the cranial nerves, as well as any other neurological impairment. Materials and Methods  Laboratory parameters were also recorded: ◦ white cell count, platelet and erythrocyte count, hematocrit, hemoglobin ◦ glucose, blood urea nitrogen, serum creatinine, electrolytes ◦ aspartate aminotransferase, alanine aminotransferase, γglutamyl transferase, bilirubin ◦ lactate dehydrogenase, creatine kinase ◦ plasma fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimers ◦ and the changes in urine. Materials and Methods  Cardiovascular parameters, neurological status, and laboratory parameters were registrated to evaluate the frequency of general complications.  The treatment data included following informations: ◦ Data about first aid and/or other help provided by layman (placing a tourniquet, incision, suction and/or displacement of toxins from the wound, limb immobilization). ◦ Furthermore, data if patient received antivenom therapy as well as the number of doses of antivenom, and complications after receiving antivenom (anaphylactic reaction, serum disease) were also recorded. Materials and Methods  This part included also data about administrating antibiotics, antihistamines, corticosteroids, tetanus protection and surgical intervention (incision of haemorrhagic blister, fasciotomy, necretomy, limb amputation).  Finally, length of hospital accomodation (days) was also noted.  All patients received the antivenom produced by the Institute of Immunology in Zagreb, Croatia. Materials and Methods  Classification of envenomation was made according to Reid and modified by Persson, so clinical condition of subjects were indicated in following order: ◦ minor reaction - local oedema, without general signs and symptoms, except patient's fear ◦ mild reaction - local or more expanded oedema, with or without gastrointestinal sings and symptoms, but without any other systemic effect ◦ moderate reaction - extensive oedema, shock lasting less than two hours, other signs and symptoms of moderate poisoning ◦ severe reaction - shock lasting for more than two hours or recurrent episodes of shock, other signs and symptoms of severe systemic envenomation ◦ fatal reaction (death) - obvious systemic poisoning ending lethal. Materials and Methods  Categorical variables (gender, month when bite occurred, localization of snake bite, signs and symptoms of envenomation, local and general complications, information about provided help, applied treatment, complications after giving antivenom) are presented as number and percentage (N, %).  Quantitative data (number of doses of antivenom, length of hospital accomodation) are expressed as average value. Materials and Methods  Age of children (years) are shown as median (min-max).  With attention to represent the severity of envenomation all children were divided into three groups according to age: ◦ a group of children from 0-7 years ◦ from 8-14 years ◦ and 15-18 years.  Results are presented in tables and graphs. Results  During this retrospective study 160 children (aged zero to eighteen) were treated because of snakebite envenomation in the Clinical Department of Infectious Diseases in the University Hospital Centre Split.  Among observed children, 114 (71%) were boys and 46 (29%) were girls.  The median age of all children was 10.5 years (min-max: 1-18 years).  The median age of boys was 11 years (min-max: 1-18 years), and 10 years in girls (min-max: 2-18 years). Results  Most bites occurred during warm months ◦ especially during spring and summer ◦ mostly in May and June.  From early May to late August, 128 (80%) children were victims of snake bite poisoning (Fig. 1.). Results  According to localization of bite ◦ 94 (59%) children experienced upper limb bites, ◦ 64 (40%) lower limb bites, ◦ and 2 (1%) patients received those on other localizations;  one child was biten directly on the neck  and one received bite on the thorax. Results  All of the observed children have developed oedema (100%), and almost all haematoma (97.5%; Table 1.).  The oedema and haematoma were variously expressed (Fig. 2.), sometimes they were all over the entire limb and even on the thorax in cases of upper limb bites.  Enlarged regional lymph nodes were found in almost half of patients (48%; Table 1.). Results  The most common local complication was haemorrhagic blister (20%), followed by compartment syndrome (7.5%), necrosis of the skin or/and muscle (4.4%), thrombosis and/or thrombophlebitis (0.6%), and infections (0.6%; Table 1.).  Haemorrhagic blisters were presented in various sizes, from size of a pea and much bigger.  In most cases incision of haemorhagic blister was done. Results     Compartment syndrome, which is the most serious local complication, developed more often after bites in the upper limbs, and fasciotomy was made in all those subjects. Necrectomy was made only in cases of extensive necrosis of the skin and muscle. Gastrointestinal symptoms (vomiting and diarrhoea) were rarely identified in this study. Vomiting was present in 21%, and diarrhoea in 2.5% registrated children (Table 1.). Results  Paresis or paralysis of the cranial nerves, which is caused by the neurotoxic component of venom, was the most frequent general complication (11.2%; Table 1.).  The most common paresis was the paresis of the nerve occulomotorius which is clinically manifested as eyelid ptosis (Fig. 3.).  Other general complications were less often registrated (Table 1.). Results  Shock symptoms were manifested in 7.0%, somnolence in 5.0%, and blood clotting disorders in 3.1% children.  The most rare general complications were kidney disorders (2.5%), liver damage (2.0%), and sopor or coma (0.6%; Table 1.). Results  According to severity of envenomation, 15 (9.4%) children had minor manifestations, 56 (35.0%) mild, 49 (30.6%) moderate, and 39 (24.4%) children had severe clinical manifestations of envenomation.  Only one (0.6%) child at the age of one and a half month (45-day-old), who was bitten directly on the neck ended fatally. Results  Children in the age group from 0-7 years usually had severe and moderate clinical presentation of envenomation, meanwhile the children in the age group from 8-14 years and 15-18 years had mostly mild clinical manifestation of envenomation (Table 2.).  Average duration of hospitalization was 13 days in cases of severe clinical manifestation of envenomation, and 9 days in children with moderate reaction to snake bite (Table 2.). Results  Totally 41 (26%) children received first medical care in the outpatient medical care centre, while 119 (74%) subjects received primary medical assistance in the University Hospital Centre Split.  Before receiving expert medical care in the outpatient medical care centre or in the hospital, several number of our patients was provided with the non-expert help immediately after experiencing the snakebite. Results  The distribution of lay assistance and/or self-help was as following: ◦ 119 (74.4%) children did not receive any lay first aid, ◦ 26 (16.2%) placed a tourniquet, ◦ 5 (3.2%) sucked the wound and/or drained the poison, ◦ 10 (6.2%) placed a tourniquet and sucked and/or drained the poison.  None of the registrated children received a limb immobilization by a layman. Results  In hospital, all respondents received antivenom and tetanus prophylaxis.  The majority had also received antibiotics (96%), corticosteroids (84%), and antihistamines (71%; Table 3.). Results  Distribution of children according to dose of applied antivenom was as following: ◦ 125 (78.1%) children received one dose of antivenom, ◦ 33 (20.6%) patients received two, ◦ and 2 (1.3%) subjects were treated with three doses of antivenom therapy.  Neighter anaphylactic reaction nor serum disease were noticed in our patients after administrating antivenom. Results      A total of 41 (26%) children underwent surgical interventions. Usually, incision of haemorrhagic blister was applied as surgical treatment. It was preformed in 25 (15.6%) patients, while fasciotomy was done in 12 (7.5%), and necrectomy in 4 (2.5%) children. No limb amputation was preformed in our subjects. All of our surgically treated patients recovered successfully. Discussion  In southern Croatia vipers are active from the begining of the spring to late autumn, and most snakebites are noticed during warm months when humans are occupated in performing rural activities, and children are playing outdoors .  Besides the agricultural working, the appearance of increased recreational and tourism activities in rural areas nowdays couse higher bite incidence in humans, particulary among children, and especially during recreation and sport activities. Discussion  Europen countries in general have very similar seasonal trend in the frequency of viper bites.  In our research the most frequent number of bites was registrated within children in May and June.  The peak incidence of vipers bite in southern Croatia was previously noticed in May, whereas in Turkey was noticed in June, and in Italy in August. Discussion  In the whole Europe male adults were described to be more likely to suffer snakebites than women.  This fact has been observed worldwide, but has not yet been explained.  According to gender, boys in pediatric population have also been described to be more usually victims of envenomation, which is accordable with results in our study where boys were more frequently bitten by V. ammodytes. Discussion  The bites on the upper limbs were described more often, especially when agricultural procedures and rural activities are performed, which is compatible with studies in Croatia, Italy, Switzerland, and Sweden.  In opposite, some other researches noticed that snakebites were more frequently localized on the lower limbs.  In our pediatrics population snakebites occourred more usually in the upper extremity (59%). Discussion  The bites directly into a blood vessel, and elsewhere near the heart are especially severe.  The inoculation of the venom into the bloodstream usually leads to toxic shock which may rapidly end lethal, as happened in 45-day-old male infant registrated in this research, who was bitten directly on the neck and who passed away six hours after the V. ammodytes bite inspite receiving all the necessary and supportive treatment. Discussion      Authors from Israel described two cases in children of V. palestinae bite on the head and neck, with no reported death outcomes. In the study of Seifert et al. in USA mortality in children was noticed to be 0.06% after native viperid and elapid species bites. Our research revealed one lethal case (0.6%) in children. In general population, it is approximated to be in average 4 of deaths annullay in Europe. Mentioned studies provide an insight to bites of Viperinae in general, but do not underline venomous snakebites in children. Discussion  Clinical presentation that appears after venomous snakebite is mainly a consequence of the haematotoxic and neurotoxic effect of the venom.  Local swelling, discoloration of skin, and ecchymosis in the place of bite, usually occour soon after the venom is inoculated or within two to four hours, and those sings we use in every-day-practice to clinically differentiate a venomous from a non-venomous bite. Discussion  In research of Lukšić et al. conducted in Croatia among adults and children, oedema, skin redness, and ecchymosis were presented in mainly all victims of envenomation.  Tekin et al. in Turkey described also the appearance of same local clinical presentation of poisoning in adult and pediatric patients.  Oedema and redeness were presented mainly in all the children involved in this research, which is accordable with described studies. Discussion  Other researchers in Europe also revealed identical local sings and symptoms of envenomation, but these were all registered in adult and mostly after Viperinae bites in general.  Extensive sweeling at the bite site increases tissue pressure within the close-tighed bonefascial space which may lead in compartment syndrome. Discussion  Compartment syndrome in adults and children appears more often after the snakebites in the upper extremity.  In our research fasciotomy was the second commonest provided surgical treatment in children, and was preformed in 7.5% subjects, all because developed compartment syndrome. Discussion  Malina et al. in Hungary registrated that fasciotomy was done in 8.3% patients after envenomating with exotic snakes, but compartment syndrome was not reported after V. berus and V. ursinii envenomation in general population.  Ozay et al. in Turkey described also a relatively high incidence of compartment syndrome (9.1%) after viper bites in children. Discussion  Tekin et al. in Turkey reported that compartment syndrome was the most common complication in adult victims after V. lebetina bites, presented in 3% adults, and Paret et al. in Israel reported 5.4% cases of compartment syndrome in children after bites of V. palestinae.  In opposite, Campbell et al. from USA noticed a very low incidence of performed fasciotomy (1.8%) in children after snake envenomation. Discussion  Lukšić et al. in Croatia also reported the appearance of compartment syndrome and consecutively performed fasciotomy in 1.8% adult victims of envenomation.  Surgical interventions in general can provide complication and/or permanent disability, and therefore should be wisely applied, and carried out only in subjects with objective indications. Discussion  Fasciotomy sholud be done in patients with clinical presentation of compartment syndrome verified according to neurovascular examination, and confirmed with measured compartment pressure over 30 mmHg.  In our participants compartment syndrome was verified according to clinical examination, and comparment pressure was not measured because the instrument was not available. Discussion  Haemorrhagic blister was the most common local complication in our subjects with frequency in 20% children, and the incision of it was done in 15.6% subjects.  Lukšić et al. who conducted their research in Croatia registrated the appearance of haemorrhagic blister in 13% cases.  Tekin et al. in Turkey reported the formation of haemorrhagic vesicle in 18.6% adults and in 24.4% children after experiencing V. lebetina bites. Discussion  The rarest local complications in our study were secondary skin infections, described in 0.6% children, and that is accordable with previously conducted researches where cellulitis and apscess were noticed in 0.9% subjects.  Such an outcome can be a result of high percentage of prophylactically prescribed antibiotics. Discussion  Ozay et al. in Turkey reported a high incidence of tissue necrosis (13%) after suffering snakebites in children.  Other studies registrated necrosis of tendons and extremity contractures.  The necrosis of surrounding tissue after the nose-horned viper in our study was reported in 4.4% children and the necrectomy was performed only in cases of extensive necrosis. Discussion  In research of Tekin et al. statistical comparison between clinical presentation of envenomation in adults and children was made, and it has been concluded that children had a significantly higher percentage of tissue necrosis after snakebite (29.3% vs. 9.6%), and significantly more complications of envenomation compared to adults (33.3% vs. 7.8%). Discussion  Cranial nerve paresis or paralysis, which is a result of the neurotoxic effect of snake venom, was the most common general complication in our research, manifested in 11.2% children.  Previously reported studies in Croatia revealed 16.0% adult subjects with cranial nerve paresis, and 5.9% patients with central nervous system depression only, without shock state or any other haemodynamic instability. Discussion  In this research conscious disturbances were presented in total of 5.6% children, somnolence being the most frequent (5.0%).  In opposite, other studies that describe snakebite envenomation do not report any kind of neurological impairment or central nervous system depression without shock in children and adults after viper bites. Discussion  Since in our study predominate V. ammodytes bites, this can be due to direct outcome of the neurotoxic component of the crude venom on central nervous system.  Shock symptoms or state of threatening shock accompained with tachycardia, hypotension, tachydyspnoea, and severe disfunction of general clinical status were registrated in 7.0% children. Discussion  Ozay et al. in Turkey also noticed shock state in 5.2% children, which was very similar (5.1%) with provided information in Croatian population.  Malina et al. in Hungary reported one case of shock after V. ammodytes bite, without specifying the age of patient.  Other authors in Europe do not underline shock state in subjects after suffering snakebites. Discussion  The dose of venom delivered to human body is a function of the size of the snake, the location of the bite, and the feature of the patient.  Because of children's smaller relative size, they receive a higher dose of venom per unit of body weight.  Although, snakebites have similar clinical presentation in adults and children, the clinical course is more severe and complications develop more prevalent in children. Discussion  In this study severe clinical envenomation was described in 24.4% children in general, and in the age group 0-7 years we registrated the highest number of severe and moderate cases of poisoning.  Paret et. al. who conducted their study in Israel documented 19% cases of severe envenomation, and noticed equal percentage of cases (40.5%) with moderate and mild envenomation in children after V. palestinae bites. Discussion  Tekin et al. in Turkey registrated 56.9% cases of moderate envenomation after V. lebetina bites, and 8.1% children developed a mild clinical presentation of poisoning.  Our research revealed 30.6% children with moderate, and 9.4% cases with mild envenomation.  The average duration of hospital accomodation in our research was longer than averages reported in other studies, which correlates with the severity of envenomation and the age of children. Discussion     The snake envenomation is a medical emergency that requires urgent treatment. At the time of bite, victims sholud be rested, the bite site cleaned, and in case of extremity bite, limb should be immobilized. No alternative or other lay assistance is recommended. It is interesting to point out that in this research no limb immobilization was made by a layman, while other options of lay assistance in the field that are not recommended were preformed in various percentage. Discussion  Malina et al. in Hungary also reported a different frequency of non-expert care assistance after snakebites.  Once the victim received first aid on the place of the incident, the person must be immediately transported to the nearest medical center to receive expert medical treatment.  In the hospital the patient should be closely monitored, seeking for sings and symptoms of systemic poisoning that would reveal the development of severe or moderate clinical presentation of envenomation. Discussion  All our subjects received antivenom therapy, which is a more frequent treatment applied, than it is reported in other studies and recommendations in other countries.  In our area we recommend administrating antivenom to patients with severe and moderate clinical outcome of envenomation, especially in children.  Therefore, in our subjects the antivenom was used more often than it was suggested by the severity of envenomation. Discussion  In the research of Lukšić et al. all adult subjects and children enrolled in Croatian study received antivenom, and complications of its administrating were rare.  Various other studies reported different data about applying antivenom, and complications after administrating it.  Tekin et al. in Turkey provided antivenom therapy to all their victims of V. lebetina bites, and reported two patients with developed allergic reaction on the antivenom treatment. Discussion  In contrast, other studies registrated lower percentage of applying antivenom therapy.  Paret et al. administrated antivenom to 43% subjects suffering V. palestinae bites.  Malina et. al in Hungary treated 31.1% cases of envenomation with antivenom, and two patients (3.3%) experienced anaphylaxis or anaphylactoid reaction.  In our study we used antivenom produced by the Institute of Immunology in Zagreb, and found no complication after providing it. Conclusions  Snakebites are medical emergency cases and require prompt medical intervention, especially in cases of severe envenomation and life-threatening conditions.  All patients, particularly children sholud be closely monitored and treated in the hospital that provides 24-hours medical care and Intensive Care Unit.  Administrating antivenom, and other conservative and supportive therapy, as well as surgical interventions, intent to prevent permanent disability and lethal outcomes after experiencing snakebite envenomations. Literature  Chippaux JP. 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