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| Year : 2003 | Volume
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| Issue : 2 | Page : 165-176 |
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| Snake Bites and Acute Renal Failure |
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HS Kohli1, V Sakhuja2
1 Associate Professor of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Professor and Head of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Click here for correspondence address and email
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How to cite this article:
Kohli H S, Sakhuja V. Snake Bites and Acute Renal Failure. Saudi J Kidney Dis Transpl 2003;14:165-76 |
 Introduction | |  |
While precise figures for global snake bite epidemiology are not available, best estimates suggest that there are more than 2.5 million venomous snake bites annually, with greater than 125,000 deaths. The risk is highest in the tropics and West Africa, predominantly amongst the rural population. In India, a large proportion of snake bites occur when people are working barefoot in the fields, or while walking at night or early morning through fields or along roads. [1] In Sweden, most snake bites occur in summer among holiday makers in the coastal regions. In Australia, the majority of bites occur in the warmer months in rural areas, but unlike Sweden, farmers and other locals are more frequently the victims. With some of the most dangerous species, such as the carpet viper, now invading cities and towns, urban dwellers are at increasing risk of fatal bites. There are more than 3000 species of snakes in the world but only about 350 are venomous. All the venomous species belong to one of four families:
Colubridae
These are back-fanged and generally harmless; however a few can be dangerous to humans. They include the boomslang (Dispholidus typus) and the bird snake (Thelotornis kirtlandi).
Elapidae
These are front fanged snakes and this family includes the cobras, kraits, mambas and coral snakes. Renal involvement is uncommon and their venom has a high concentration of neurotoxin.
Viperidae
These are folding fang snakes and include Russell's viper, Echis carinatus (saw scaled viper), European adders, African puff adders, Gaboon vipers and the pit vipers such as rattlesnakes, jararacusus, bushmasters, green pit vipers, Malayan pit vipers, habu snake, mamushi, and their kin. The pit vipers have been grouped under the subfamily Crotalidae as they differ from vipers in the presence of a pit on either side of the head between eye and nostril. The vipers are the most widely distributed species. Russell's viper is found in India, Burma, Pakistan, Thailand, and other areas of Asia; E. carinatus in Africa, India, Pakistan, Sri Lanka and the Middle East; and the puff adder (Bitis arietans) in Africa. Bites by the pit viper of the agkistrodon species are common in Japan, Korea, Hong Kong, Taiwan, Malaysia, and Indonesia, and those of the rattlesnake (crotalus species) and various species of bothrops (which also are pit vipers), are seen in Central and South America. [2],[3]
Hydrophidae or sea snakes
Bites are reported mainly among fishing folk of Malaysia, Thailand and Western Pacific coastal areas. [4] Sea snake venom is primarily myotoxic. Important species prevalent along the Malaysian coast are Enhydrina schistosa, Hydrophis cyanocinctus, and Lapemis hardwickii. Some species of hydrophis are also found along the coast of India. Pelamis platurus is a poisonous sea snake found along the Pacific coast of Mexico and the east coast of Africa. Australian land snakes, formerly classified as elapids, are now included in the hydrophidae family because of the myotoxic nature of their venom. [5]
Snake venoms are a mixture of complex toxins that may be independent, synergistic or antagonistic. The major groups of toxins are:
a) neurotoxins: there are many types with differing actions, but the most common cause flaccid paralysis of skeletal muscle by blocking transmission at the neuromuscular junction, either presynaptically or post-synaptically;
b) myotoxins: they are either local or systemic, the latter resulting in massive skeletal muscle breakdown, with resultant muscle weakness, pain, tenderness, high creatine kinase, myoglobinuria and potential for secondary renal failure and hyperkalemia;
c) coagulotoxins(hemotoxins): many venoms attack hemostasis and vascular integrity, through a wide variety of mechanisms, resulting in coagulopathy, hemorrhage, and sometimes, shock;
d) nephrotoxins: they cause primary and secondary damage to the kidneys, which varies from mild renal impairment to bilateral renal cortical necrosis and;
e) necrotoxins: they cause local tissue injury, varying from mild effects to major limb necrosis.
It is important to understand that the actual mix of toxins in the venom will vary by individual species and also by age and season. Equally, the quantity of venom injected in a bite is highly variable. Ineffective or "dry bites" account for more than 50% of all bites. [1]
Although nearly all snakes with medical relevance can induce acute renal failure (ARF), it is unusual except with bites by Russell's viper, E. Carinatus and members of the genera Crotalus and Bothrops. The most prevalent areas for these snakes are Asia and South America. The area of distribution of the five currently recognized subspecies (ssp) [6] of Russell's viper spans from Sri Lanka (ssp. pulchella) through the Indian subcontinent (ssp. russelli) to the east including Burma and Thailand (ssp. siamensis), and includes Taiwan (ssp. formosensis) and some Indonesian islands (ssp. limitis). Upto 90% of the approximately 1000 deadly snake bites occurring per annum in Burma are attributed to Russell's viper which is also the fifth most common cause of death [7] and the most common cause of ARF in Burma. In Thailand, 70% of ARF cases have been ascribed to Russell's viper envenomation. [8] In India, ARF is mostly associated with Russell's viper and E. carinatus bites. The snakes of the genus Bothrops are the leading cause of venomous snake bite in South America.
In India, the incidence of ARF following E. carinatus or Russell's viper bite is 13 to 32%. [2],[9],[10],[11],[12] Among patients hospitalized with snake bite in Nigeria, the incidence of ARF was approximately 1% after E. carinatus poisoning, [2],[3] and 10% following puff adder bites. [13] In other countries, the reported incidence rates of ARF are 6.2% following Palestinian viper bite in Israel, [14] 5% following Russell's viper and sea snake bite in Thailand, [15] and 27% following unidentified viper bites in Ceylon (Sri Lanka). [16]
| Pathogenesis of Acute Renal Failure | | |
The exact pathogenesis of ARF following snake bite in not well established. This is due to the lack of a reproducible animal model. However, a number of factors may contribute viz. bleeding, hypotension, circulatory collapse, intravascular hemolysis, disseminated intravascular coagulation, microangiopathic hemolytic anemia and also direct nephrotoxicity of the venom.
Hypotension
Bleeding either into tissues or externally, and loss of plasma into the bitten extremity can produce hypotension and circulatory collapse. This is caused by venom metalloproteinases that degrade basement membrane proteins surrounding the vessel wall, leading to loss of integrity. Hemorrhagic toxins have been isolated from venom of many snakes of Viperidae and Crotalidae families. [5] Additionally, vasodilatation and increased capillary permeability, both as a result of direct and indirect effects of venom, can aggravate the circulatory disturbances of shock. [17] Vipera palestinae venom is thought to cause shock by depression of the medullary vasomotor center. [18] Bitis arietans causes hypotension by a combination of myocardial depression, arteriolar vasodilation and increased vascular permeability. Irrespective of the cause, hypotension and circulatory collapse set in motion a chain of hemodynamic disturbances, which are known to culminate in ischemic ARF.
Intravascular hemolysis
Another factor thought to have pathogenetic significance in snake-bite-induced ARF is intravascular hemolysis. [9],[19] Hemolysis results from the action of phospholipase A 2 which is present in almost all snake venoms, and a basic protein called "direct lytic factor", found only in elapid venoms. [2] Phospholipase A 2 causes hemolysis by direct hydrolysis of red cell membrane phospholipids or indirectly via the production of the strongly hemolytic lysolecithin from plasma lecithin. Evidence of intravascular hemolysis in the form of anemia, jaundice, reticulocytosis, raised plasma free hemoglobin, abnormal peripheral blood smear, and hemoglobinuria is present in about 50% of patients following bites by the Russell's viper and E. carinatus. [2],[20] In an experimental model using male Wistar rats, severe hemolysis was shown by increased plasma LDH levels, free hemoglobin and late presence of hemolysed red blood cell casts in renal tubules after infusion of venom of Bothrops jararaca. [21]
Some have even suggested that renal failure following snake bite should be considered an example of the hemolytic uremic syndrome. [22] However, while intravascular hemolysis is frequently observed, microangiopathic hemolysis as seen in hemolytic uremic syndrome is encountered only rarely. More over, more than 70-80% of patients with snake bite induced renal failure have only acute tubular necrosis and do not exhibit the glomerular and arteriolar changes characteristically associated with the hemolytic uremic syndrome. [23]
Disseminated intravascular coagulation
The human hemostatic system is regulated via a number of critical interactions involving blood proteins, platelets, endothelial cells, and sub-endothelial structures. Snake venom proteins and peptides are known to activate or inactivate many of these interactions. Snake venoms, particularly those from the viper and pit viper families, contain many proteins that interact with members of the coagulation cascade and the fibrinolytic pathway.
Russell's viper venom (RVV) contains a factor V-activating serine proteinase, [24] which has been separated from a factor X-activating protein, also present in this venom. The enzyme (RVV-V) is a single chain glycoprotein with a molecular weight of 26,100 possessing one glycosylation site near the carboxy terminus. RVV-V cleaves a single peptide bond to convert factor V to factor V a (the activated clotting protein). Russell's viper venom also contains a potent activator of human coagulation factor X; this enzyme has been well characterized and is designated as RVV-X. [25] Factor X activators have also been isolated from Bothrops atrox and several other snake species. Russell's viper venom also activates factor IX by cleavage of a single peptide bond resulting in the formation of factor IX a.
There are several different types of prothrombin activators in snake venom. The activity of members of group I is not influenced by components of the prothrombin activator complex (factor V a , CaCl2 and phospholipid). Ecarin, from E. carinatus venom, is the most well studied member of this group. Group II activators resemble factor X a and can cleave both peptide bonds in prothrombin, leading to active 2-chain thrombin. Their activity is strongly stimulated by phospholipids and factor V a in the presence of CaCl 2 . These enzymes are found exclusively in the venoms of Australian elapid snakes, and the best studied one is from the tiger snake (Notechis scutatus). By contrast, activators in group III require only phospholipid and CaCl 2 for the activation of prothrombin. They do not require factor V a , but appear to possess a co-factor that is tightly bound to the catalytic subunit that plays a similar role to factor V a in prothrombin activation. This class of activator is also found in Australian elapids and is represented by the high molecular weight activator from Taipan venom (Oxyuranus scutellatus). [26]
Although thrombin has many activities, the ability of some snake venom enzymes to clot fibrinogen has resulted in these enzymes being called "thrombin-like". [27] These are widely distributed primarily in the venom of snakes from true vipers (Bitis gabonica, Cerastes vipera) and pit vipers (Agkistrodon contortrix, Crotalus adamanteus, Bothrops atrox). Snake venom fibrinogenclotting enzymes have been classified into several groups based on the rates of release of fibrinopeptides A and B from fibrinogen.
One mechanism of the anticoagulant action of snake venom proteins is attributed to the activation of protein C. Activated protein C degrades factors V a and VIII a and therefore, has anticoagulant activity. Another mechanism of anticoagulation involves inhibition of blood coagulation factors IX and X by a venom protein(s) that binds to either or both. Finally, anticoagulation is also achieved through the action of snake venom phospholipases that degrade phospholipids involved in the formation of complexes critical to the activation of the coagulation pathway. [28]
Direct-acting fibrinolytic enzymes have also been isolated from the venom of a number of north and south American snakes, including rattlesnakes and copperheads, and from elapids, including cobras and European vipers. [29] The venom fibrinolytic enzymes that have been characterized in detail are zinc metalloproteinases and may be classified as either α or β chain fibrin(ogen)ases. Snake venoms also contain a number of platelet active components, including those that cause platelet aggregation and those that inhibit platelet aggregation. [30]
The final coagulation disturbance depends upon the balance among the activity of procoagulant, anticoagulant, fibrinolytic and fibrinogenolytic components of injected venom. Disseminated intravascular coagulation (DIC) is a consistent feature in patients bitten by Russell's viper, E. carinatus, boomslang, and pit vipers. [31] The occurrence of DIC as a major hemostatic abnormality is well documented experimentally. Infusion of Russell's viper or E. carinatus venom into rhesus monkeys resulted in abnormal coagulation parameters suggestive of DIC within two hours of injection of a lethal dose of the venom, but these changes first occurred from a few hours to three weeks after sub-lethal envenomation. [32]
The presence of fibrin thrombi in the renal microvasculature and in the glomerular capillaries, and the findings of microangiopathic hemolytic anemia and thrombocytopenia in patients with cortical necrosis strongly suggest that DIC plays a major pathogenetic role in snake-bite induced cortical necrosis. [9] Snake venom initiates a chain reaction involving the coagulation, fibrinolytic, kinin and complement systems. Venom-induced alterations lead to vascular coagulation and to deposition of fibrin thrombi in blood vessels. These changes occur in patients as well as in experimental models. [9],[33] Intraglomerular fibrin deposition of lesser degree has been suspected as causing acute tubular necrosis via a temporary hemodynamic alteration.
The role of the above factors in causing ARF was shown in an experimental model by Burdmann et al. [21] They intravenously injected male Wistar rats with 0.4 mg/kg of Bothrops jararaca venom and produced functional and morphological changes similar to those observed in human snake-biteinduced ARF. There was an acute and significant decrease in the glomerular filtration rate, urine output, renal plasma flow and serum fibrinogen levels. There was intravascular hemolysis, as shown by a significant decrease in hematocrit, an increase in plasma lactate dehydrogenase levels and free hemoglobin. Light and electron microscopy showed massive fibrin deposition in glomerular capillaries apart from proximal and distal tubular necrosis and red blood cell casts in renal tubules. In this model, ischemia related to glomerular coagulation and intravascular hemolysis were the most important pathogenetic factors causing a decrease in the glomerular filtration rate, although direct venom nephrotoxicity could not be excluded.
Direct nephrotoxicity
The earlier experimental studies performed on rabbits with habu venom did provide important clues to the evolution of glomerular lesions occasionally seen in human snake bite victims, but these do not seem to be relevant to patients developing renal failure, as most of them show histological changes of acute tubular or cortical necrosis. Schmidt et al [34] examined the ultrastructural alterations caused by rattlesnake (Crotalus atrox) and sea snake (Laticauda semifasciata) venoms in Swiss white mice. Sea snake venom caused only focal organellar swelling and intracellular edema of the visceral epithelium, but the proximal tubular epithelium was unaffected. In contrast, rattlesnake envenomation caused marked changes in the glomeruli and proximal tubules. Experimental studies with 1 125 -labeled E. carinatus venom [35] and the demonstration of venom antigen in human victims of snake bite using enzyme-linked immunosorbent assay technique have shown that the venom is excreted in the urine, without necessarily causing any damage to the kidney. [36] Urinary beta-N acetylglucosaminidase showed considerable change in patients bitten by Russell's viper, without DIC, indicating a direct toxic effect of venom on the kidney. [37]
In a study, the administration of a lethal dose of Russell's viper or E. carinatus venom to rhesus monkeys, resulted in hemorrhages in the kidneys and other organs in all animals, and mild acute tubular necrosis in 20% of animals, within 24 hrs of envenomation. After a sublethal venom dose, however, more than 50% of animals developed acute tubular necrosis, and fibrin thrombi were demonstrable in 50-75% of glomeruli. [9] The histological findings and the coagulation abnormalities observed in these animals were similar to those seen in human victims of snake bite. [2]
The strongest evidence supporting direct nephrotoxicity is a dose-dependent decrease in inulin clearance and an increase in fractional excretion of sodium in the isolated perfused rat kidney, following Russell's viper envenomation. [38] However, this study did not include the morphological analysis of the perfused kidneys. To obtain further information about direct toxicity of Russell's viper venom (RVV) in renal tissue, Willinger et al [17] studied the combined functional and morphologic changes in isolated perfused rat kidney, complemented by studies in renal epithelial and mesangial cell cultures.
Isolated male Sprague-Dawley rat kidneys were perfused in single-pass for 120 minutes with 10 and 100 ng/ml of RVV administered 60 and 80 minutes respectively after perfusion. Furthermore, cultured mesangial cells and renal epithelial cells were exposed to RVV for five minutes to 48 hrs. RVV administration induced changes in renal plasma flow, glomerular filtration rate; filtration fraction and tubular reabsorption of sodium were reduced, and fractional excretion of sodium and water showed an increase. Both oliguria and a subsequent polyuric phase, could be demonstrated. On morphological analysis, the most prominent structural lesions were observed in the renal cortex. Extensive damage and loss of glomerular epithelial cells and endothelium was detected with only the basement membrane remaining. Ballooning and even rupture of glomerular capillaries could be seen.
Another prominent feature of RVV action on renal cortex, and likewise on all other renal zones, concerned vessels with muscular walls (arteries, veins, arterioles, venules). The venom led to complete lysis of vascular smooth muscle cells leaving behind only the basement membrane. Varying degrees of epithelial injury occurred in all tubular segments. In cell culture studies, RVV induced a complete disintegration of confluent mesangial cell layers at lower concentration. In epithelial cell cultures however, only extremely high doses of RVV led to microscopically discernible damage. Willinger et al, thus, demonstrated a direct dose dependent toxic effect of RVV on the isolated perfused rat kidney, directed primarily against glomerular and vascular structures and on cultured mesangial cells.
In addition myoglobinuria, sepsis, and hypersensitivity to venomous or anti-venomous protein may also contribute towards renal failure. Crescentic nephritis in patients bitten by puff adder has been attributed to hypersensitivity to antisnake venom. [39] Myoglobinuria generally occurs following sea snake envenomation, which results in necrosis of striated muscles and muscular paralysis. [40]
| Clinical Manifestations | | |
The clinical profile of viper envenomed patients may vary from minor local symptoms to extensive systemic manifestations that, at times, may prove fatal soon after the bite. The severity of the symptoms and signs is related to the type of venom, as well as the dose injected during the bite. Severely envenomed patients develop DIC, frequently resulting in spontaneous bleeding and incoagulable blood. [6],[41] The latter features often dominate the clinical course until coagulation abnormalities revert to normal. Many viper envenomed patients develop hypotensive shock as a consequence of hypovolemia from significant blood loss. [6] Blood can ooze continuously from the fang marks, or severe hemorrhage may manifest as hematemesis, melena, hemoptysis, or bleeding into the muscles, fascial compartments, serous cavities and the subarachnoid space.
Pain and swelling of the bitten part are generally the earliest symptoms and appear within a few minutes. The swelling may spread to involve the whole limb and is due to exudation of plasma or extravasation of blood into the subcutaneous tissues. Blistering or local necrosis is observed in onethird to one-half of the patients.
In patients with ARF, oliguria often develops rapidly within the first 24 hrs, but may be delayed till 2-3 days after the bite. Some patients become anuric, whereas occasional patients remain non-oliguric. Urine may show gross or microscopic hematuria. Some patients complain of pain in the renal angle preceding oliguria, which may be a useful clue to impending renal failure. [41] Jaundice and hemoglobinuria resulting from intravascular hemolysis are not infrequent following Russell's viper or E. carinatus bites and have been reported from India and Sri Lanka. [2],[9],[23] However, this has been conspicuously absent in victims of Russell's viper bite in Burma. [41] Daily urine protein concentration may exceed one gram, and erythrocyte casts may also be seen. Hypertension has been infrequently recorded after both viper [41] and sea snake bites. [40]
Extrarenal manifestations of hydrophid envenomation include myalgia, muscle stiffness, glossopharyngeal palsy, ptosis, ophthalmoplegia, and a generalized flaccid paresis. [23]
Laboratory investigations reveal varying degrees of anemia, resulting from a combination of intravascular hemolysis and blood loss. Hemolysis results in unconjugated hyperbilirubinemia, reticulocytosis, elevated plasma free hemoglobin, and hemoglobinnuria. [2] In some patients, the peripheral blood film may show fragmented erythrocytes, suggesting microangiopathic hemolysis. [22] The blood is incoagulable and features of DIC are often present. [6],[42] Thrombocytopenia, however, may occur, even in the absence of a consumptive coagulopathy. In bites by sea snakes or Australian land snakes, the serum aspartate aminotransferase levels are markedly elevated. [43] Hyperkalemia may occur, even in the absence of renal failure in these patients because of marked muscle necrosis. Myoglobinemia and myoglobinuria are consistently present. [43]
The mortality of patients with renal failure varies with the nature of the renal lesion. Although only 16% of those with acute tubular necrosis, in whom uremia was controlled with dialysis, died, as many as 80% of those with cortical necrosis had a fatal outcome. [2],[9]
| Renal Histology | | |
Renal histology shows predominantly either acute tubular or cortical necrosis. A number of glomerular changes have been described but their significance is not known.
Acute Tubular Necrosis
Acute tubular necrosis is the predominant lesion seen in 70-80% of patients with ARF. [2],[9] On light microscopy, the tubules appear dilated and lined by flattened epithelium. Severe cases exhibit cell necrosis and desquamation of necrotic cells from the basement membrane. Hyaline, granular or, pigment casts are seen in tubular lumina. Varying degrees of interstitial edema, hemorrhage, and inflammatory cell infiltration are present. Later biopsies reveal regenerating tubular epithelium. Intrarenal blood vessels are usually unaffected.
On ultrastructural examination, proximal tubules show dense intra-cytoplasmic bodies representing degenerating organelles or protein resorption droplets. Small areas of basement membrane are denuded. Distal tubular cells have a dilated endoplasmic reticulum and many degenerating organelles. Apoptosis is a prominent feature in the distal tubules, indicating a high cell turnover. In the interstitium, fibroblasts appear active, with increased numbers of organelles and cytoplasmic processes. Mast cells and eosinophils show both granulated and partially degranulated forms. [44]
Although the blood vessels appear normal under light microscopy, ultrastructural abnormalities are notable in both large and small caliber vessels. [44] Medullary vessels are severely affected, with markedly swollen, focally necrotic, endothelial cells obliterating the lumen. Smooth-muscle cells show cytoplasmic vacuoles, which are empty or are filled with granular material. The severe vascular lesions, distal tubular apoptosis, and presence of mast cells, eosinophils, and active fibroblasts in the interstitium are features that have not been observed in acute tubular necrosis from other causes. [44]
Acute Cortical Necrosis
Bilateral diffuse or patchy cortical necrosis has been observed following bites by E. carinatus. Cortical necrosis appears to be more common among Indian patients than among patients in Thailand, for unknown reasons. [2] The presence of fibrin thrombi in the arterioles is a prominent feature in these patients. A narrow subcapsular rim of cortex often escapes necrosis. The area underlying this, however, shows necrosis of glomerular as well as tubular elements. The necrotic zone is often bordered by an area of hyperemia and leukocytic infiltration. Calcification of necrotic areas may occur at a later stage. Varying numbers of glomeruli are spared in patients with patchy cortical necrosis. With healing, fibroblastic proliferation and organization of thrombi are seen. Renal ultrastructure in cortical necrosis following Russell's viper bite has been studied in only two patients. 45 In one patient, the biopsy taken 10 days after the bite showed glomeruli with collapsed capillary basement membrane, and denuded foot processes. No viable endothelial or mesangial cell could be identified, but swollen rounded cells, possibly of endothelial origin, were seen in some capillary lumina. Endothelial swelling of small arterioles and necrosis of peritubular capillaries were also seen. The tubular basement membrane was intact, but the epithelium showed degenerative changes. In the second patient, the biopsy was done 31 days after envenomation. In this patient, the urinary space contained unidentified cells with large cytoplasmic vacuoles. The tubular basement membrane was thickened, and the cortical tubules were lined by flattened epithelium, with large nuclei and a dilated endoplasmic reticulum. Fibroblastic proliferation was seen in the interstitium.
Glomerular Lesions
Whether or not specific glomerular lesions really occur is still controversial. Sant and Purandare [46] reported a "proliferative glomerulonephritis" in patients bitten by E. carinatus. Later, Seedat et al [39] reported two patients with crescentic glomerulonephritis, following puff adder bites, presenting as ARF. Because renal lesions of proliferative nephritis with crescents had developed with in 24-48 hours, these workers ascribed these lesions to an allergic reaction to snake venom. Sitprija and Boonpucknavig [47] described two patients with crescentic glomerulonephritis after Russell's viper bites. In another study of 38 patients bitten by the green pit viper or Russell's viper, the authors observed thickening of the mesangial areas and mild mesangial proliferation in most of their patients, and diffuse glomerular hypercellularity (ascribed to marked mesangial proliferation) in two patients. Other glomerular changes observed are ballooning of capillaries, endothelial swelling, mesangiolysis and splitting of the glomerular basement membrane; however, the significance of these is difficult to ascertain. [48] Immunofluorescence microscopy showed IgM, C3, and fibrin deposits. [47]
In occasional instances, a diffuse and intense mononuclear cell infiltrate has been noted in the interstitium, suggesting the occurrence of an acute interstitial nephritis. [49]
| Management | | |
In recent years, first aid measures for snake bites have been radically revised to exclude methods that were found to worsen a patient's condition, such as tight (arterial) tourniquets, aggressive wound incisions, and application of ice. Initial treatment measures should include avoiding excessive activity, immobilizing the bitten extremity, and quickly transporting the victim to the nearest hospital. A wide, flat constriction band may be applied proximal to the bite to block only superficial venous and lymphatic flow (typically, with about 20 mm Hg pressure) and should be left in place until antivenom therapy, if indicated, is begun. One or two fingers should easily slide beneath this band, since any impairment of arterial blood flow could increase tissue death. Upper extremities should be splinted as close to a gravityneutral position as possible, preferably at heart level. No study has shown any benefit in survival or out come from incision and suction. However, a venom extractor can be beneficial if applied within five minutes of the bite and left in place for 30 minutes. [50]
Wounds should be cleaned, and administration of tetanus toxoid or tetanus immune globulin should be considered for underimmunized or non-immunized patients. Patients should be given intravenous fluid, and blood should be drawn from an unaffected extremity.
The absence of any major symptoms and signs at presentation should not lead to the conclusion that no further care is required. Signs of systemic envenomation often do not develop until several hours after the bite. It is, therefore, prudent to carefully observe the patient for up to 24 hrs after the bite. During this period, the pulse, blood pressure, and respiratory rate should be followed hourly. Urine color and output should be recorded. The site of the bite should be watched for the development of local swelling, blisters, bleeding, or necrosis.
It is safe and also desirable, however, to wait for clear evidence of systemic poisoning to emerge before giving the antivenom because of the risk of untoward reactions. Allergic reactions are known to occur in about 15% of patients. More dreaded is the acute anaphylactic reaction, although fatal anaphylaxis is, undoubtedly, a rare occurrence. Performing a skin test with horse serum is a matter of controversy because it delays therapy, has itself caused anaphylaxis and serum sickness and has been demonstrated to have a 10 to 36% false-negative rate and a 33% false positive rate. Some physicians bypass skin testing altogether, relying instead on premedication with antihistamines and a trial dose of 5 ml of antivenom administered intravenously. Unstable patients (i.e. those with hypotension, severe coagulopathy, respiratory distress) must receive antivenom because no other treatment can reverse the venom's effect. [50],[51] Prolonged clotting time is an indication for anti-snakevenom administration as this suggests systemic envenomation even in the absence of other systemic features. [6]
The dose of the anti-snake-venom required depends upon the type of anti-snake-venom used. Polyvalent antivenom is less effective, and higher dosages have to be employed. The dose of monovalent antivenom depends upon the grade of envenomation. [50] In India, where polyvalent (cobra-krait-viper) antivenom is used, the average dose is 120 ml. [2]
Careful monitoring should continue until all the signs of envenomation have receded. In viperine bites, bleeding may recur after an initial improvement following antivenom. A second dose of antivenom is then indicated. Normal blood coagulability is usually restored within six hrs after antivenom administration, but coagulation studies should be repeated for at least three days to detect recurrence of defects caused by delayed absorption of venom. [6] Antivenom should also be given to patients who present with incoagulable blood, several days after the bite. [2] Blood losses should preferably be replaced with fresh blood. Hypotension in the absence of blood loss may be treated with volume expansion and inotropic agents coupled with central venous pressure monitoring.
Although the aforementioned measures may help in preventing renal failure, they do not always succeed. However, if an adequate dose of antivenom is given within 2-5 hrs of a bite, renal failure may be prevented. In Russell's viper envenomation, antivenom given as early as one hour after the bite does not invariably prevent renal failure. 41 In patients exhibiting massive intravascular hemolysis or myoglobinuria, maintenance of a high urine output and alkalinization of the urine may be useful.
Patients who develop oliguria or biochemical evidence of renal failure should be shifted to centers equipped with dialysis facilities. Both peritoneal and hemodialysis have been used successfully in several centers. Peritoneal dialysis has reduced the mortality of ARF due to snake bite to 27% in Burma [41] and 13% in Sri Lanka. [20] One of the major determinants of the prognosis of renal failure is the nature of the underlying renal lesion. Fatal outcome is seen in 80% of patients with diffuse cortical necrosis. [9] Surviving patients with patchy cortical necrosis are known to develop cortical calcification and go into end-stage renal failure after several months or years. [2] Dialysis may sometimes be required in the absence of renal failure to correct hyperkalemia, secondary to muscle necrosis, particularly in sea snake envenomation. [4],[43]
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Correspondence Address:
V Sakhuja
Department of Nephrology, Postgraduate Institute of Medical, Education and Research, Chandigarh 160012
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 18209442 
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