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Is There Any Role for Intravenous Antivenom for Snake Venom Ophthalmia?
The Journal of Emergency Medicine
of all the aforementioned needle types, including blunt spinal needles of the same size. The Atraucan needle has a combined bevel that cuts an ultrafine channel that is expanded bluntly by the rest of the tip. Their investigations, which included electron microscopy analysis, suggest that perhaps a modified cutting needle like the Atraucan needle will provide the least amount of damage to the dura, and thus decrease the incidence of spinal headaches. In terms of the treatment options listed in Table 3 of the article, it is true that epidural blood patch is contraindicated in the setting of cellulitis. This makes sense if you are attempting to place the blood patch over the cellulitic area. However, Szeinfeld and colleagues demonstrated that 12–15 cc of technetium-labeled red blood cells injected into the epidural space can travel 8 –10 disc spaces from the point of injection, most commonly 6 above and 3 below the site of injection (9). As such, I would submit that in patients who are highly symptomatic, attempting an epidural blood patch a few disc spaces away is still a reasonable option as long as the cellulitis is not so extensive as to preclude such a procedure. Lastly, I wanted to thank the author, Dr. Robert Frank, for such an extensive review of the literature. This is a common problem seen in the emergency department and we must continue to explore methods to mitigate the occurrence of PDPH, as well as explore treatment options for our patients. Bradley N. Younggren, MD, FAAEM Major, Medical Corps Associate Program Director Department of Emergency Medicine Madigan Army Medical Center Ft. Lewis, Washington doi:10.1016/j.jemermed.2008.12.018
REFERENCES 1. Frank RL. Lumbar puncture and post-dural puncture headaches: implications for the emergency physician. J Emerg Med 2008;35:149 –57. 2. Collier BB. Treatment for postdural puncture headache. Br J Anaesth 994;72:366 –7. 3. Foster P. ACTH treatment for post-lumbar puncture headaches. Br J Anaesth 1994;73:429. 4. Carter BL, Pasupuleti R. Use of intravenous cosyntropin for the treatment of postdural puncture headaches. Anesthesia 2000;92: 272– 4. 5. Canovas L, Barros C, Gomez A, Castro M, Castro A. Use of intravenous tetracosactin in the treatment of postdural puncture headache: our experience in forty cases. Anesth Analg 2002;94: 1369. 6. Younggren BN, Zeger W, Nolan R. Cosyntropin vs. caffeine for post-dural puncture headaches. Acad Emerg Med 2005;12(5 Suppl 1): 52–3. 7. Crul BJ, Gerritse BM, van Dongen RT, et al. Epidural fibrin glue injection stops persistent postdural puncture headache. Anesthesiology 1999;92:576 –7.
659 8. Holst D, Mollmann M, Ebel C, et al. In vitro investigation of cerebrospinal fluid leakage after dual puncture with various spinal needles. Anesth Analg 1998;87:1331–5. 9. Szeinfeld M, Ihmeidan IH, Moser MM, et al. Epidural blood patch: evaluation of the volume and spread of blood injected into the epidural space. Anesthesiology 1986;64:820 –2.
e IS THERE ANY ROLE FOR INTRAVENOUS ANTIVENOM FOR SNAKE VENOM OPHTHALMIA? e To the Editor: We read with interest the article entitled “Ophthalmic Exposure to Crotalid Venom,” which presented the first reported case involving the use of intravenous (i.v.) antivenom (CroFab®; BTG International Inc., West Conshohocken, PA) in the management of pit viper ocular accidental contact irritation (1). Virtually all published experience with snake venom ophthalmia relates to spitting cobras (family Elapidae), where both fangs and venom have evolved to specifically target the eye, yet there is no evidence that this results in systemic envenoming, the prime indication for antivenom therapy. In spitting cobra-induced ocular envenoming, antivenom has been used only topically, but the most current published expert advice does not recommend this treatment (2,3). With this background, the use of i.v. antivenom in the Johnson case is puzzling and difficult to support. Intravenous antivenoms are used for clinically significant venomous snakebites in the United States, and indications for use of antivenom have been delineated previously, typically determined by expanding local effects accompanied by laboratory abnormalities (e.g., prolonged international normalized ratio), marked systemic envenoming, or a notable single abnormality (e.g., systolic blood pressure ⬍ 80 mm Hg) (4–6). Antivenom therapy presents potential risk and should be used with caution, as adverse reactions such as anaphylaxis, anaphylactoid reactions, or delayed serum sickness can occur (6–8). These adverse reactions are more common for the older Antivenom (Crotalidae) Polyvalent in comparison with the newer Crotalidae polyvalent immune Fab (ovine) (Fab AV [CroFab®]). The reduced adverse reaction rate for Fab AV antivenom has been attributed to the absence of the Fc portion in the Fab AV antivenom. A recent retrospective article reported the incidence of acute hypersensitivity reaction to be 5.4% (5 out of 93 patients) when a mean dose of 12 vials of Fab AV antivenom were used (9). In the case reported by Johnson, four vials of Fab AV were initially used, and this was followed by an unspecified amount of the same antivenom, despite the absence of systemic envenoming (1). Intravenous Fab AV was used due to concerns regarding direct corneal protein denaturation, direct central nervous system absorption, and the theoretical risk of ocular
660
Letters to the Editor
intake with ocular instillation of antivenom. Published case reports of venom ophthalmia contain no evidence that supports the above as likely risks, against which the known risks of i.v. antivenom must be considered. Although topical antivenoms have been previously employed in the management of ocular envenoming by spitting cobras, and recovery occurred for a majority of patients, the role of antivenom in recovery is unclear (10). In recent publications, topical antivenoms are not recommended due to their potential irritating effects and the lack of evidence for beneficial effects (2,3). Other reported cases involving pit vipers in ocular envenoming have resulted in only transient mild ocular irritation, with irrigation as the sole treatment (11,12). In addition, irrigation alone has prevented further ocular complications (11,12). Having considered the following factors: the relatively mild sequelae sustained from ocular envenoming by pit vipers, the immediate resolution of symptoms with irrigation, the adverse effects that can occur with i.v. antivenom, and the lack of evidence for any systemic effects from ocular envenoming; the risks of i.v. antivenom (including Fab AV) outweigh the benefits in the management of pit viper venom ophthalmia. In addition to copious irrigation, a recent review of the management of snake venom ophthalmia recommended urgent medical attention, topical cycloplegics, topical antibiotics, and topical adrenaline (Chu ER, Weinstein S, White J, Warrell DA. A review of ocular envenoming [venom ophthalmia]: pathophysiology and management. Toxicon, accepted for publication). Until there is clear evidence of systemic abnormalities resulting from ocular envenomation, antivenom should not be used, either topically or intravenously. Instead, copious irrigation should be administered, as in previous cases of pit viper ocular envenomation. Edward Rickie L. Chu, MBBS Royal Adelaide Hospital Adelaide, South Australia Julian White, MBBS, MD Department of Toxinology Women’s and Children’s Hospital North Adelaide, South Australia Scott Weinstein, MSC, PHD, MBBS Royal Adelaide Hospital Adelaide, South Australia Department of Toxinology Women’s and Children’s Hospital North Adelaide, South Australia doi:10.1016/j.jemermed.2009.06.128
REFERENCES 1. Johnson R. Ophthalmic exposure to crotalid venom. J Emerg Med 2009;36:37– 8. 2. Warrell DA. Management of cobra spit ophthalmia. In: Warrell DA, ed. Guidelines for the clinical management of snake bite in the South-East Asia Region. New Delhi, India: World Health Organization, Regional Office for South-East Asia; 2005:49. 3. Warrell DA. Clinical toxicology of snakebite in Asia. In: Meier J, White J, eds. Handbook of clinical toxicology of animal venoms and poisons. Boca Raton, FL: Informa HealthCare; 1995:579 – 618. 4. Weinstein S, Dart R, Staples A, White J. Envenomations: an overview of clinical toxinology for the primary care physician. Am Fam Physician 2009;80:793– 802. 5. Gold BS, Barish RA, Dart RC. North American snake envenomation: diagnosis, treatment and management. Emerg Med Clin North Am 2004;22:423– 43. 6. White J, Dart R. Snakebite: a brief medical guide. Stirling, South Australia: White; 2007. 7. Clark RF, McKinney PE, Chase PB, Walter FG. Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom. Ann Emerg Med 2002;39:671– 6. 8. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med 2001;37:181– 8. 9. Cannon R, Ruha AM, Kashani J. Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom. Ann Emerg Med 2008;51:407–11. 10. Warrell DA, Ormerod LD. Snake venom ophthalmia and blindness caused by the spitting cobra (Naja nigricollis) in Nigeria. Am J Trop Med Hyg 1976;25:525–9. 11. Cantrell FL. Ocular exposure to rattlesnake venom. J Toxicol Clin Toxicol 2003;41:605– 6. 12. Troutman WG, Wilson LE. Topical ophthalmic exposure to rattlesnake venom. Am J Emerg Med 1989;7:307– 8.
e RESPONSE TO DRS. CHU, WHITE, AND WEINSTEIN e To the Editor: I appreciate Drs. Chu, White, and Weinstein’s interest in my article, “Ophthalmic Exposure to Crotalid Venom” (1). Their comments are not only complete but also give a brief overview of the treatment of crotalid envenomation and describe what is thought to be the standard of care for crotalid ocular envenomations. Dr. Chu and colleagues assert that there is no evidence to support the theory of absorption past the eye in pure ocular envenomations. I agree with that assertion; however, as the authors mention, “virtually all published experience with snake venom ophthalmia relates to spitting cobras.” This report was not advocating an actual concern but rather a theoretical concern for systemic absorption. As is stated in the manuscript, “although there is insufficient evidence to conclude that intravenous CroFab had any effect, it is interesting that our patient had early intravenous CroFab and delayed irrigation with rapid recovery and no complications.” What the report did lack was specifics on the amount of eye irrigation that was initially performed and the total quan-
of all the aforementioned needle types, including blunt spinal needles of the same size. The Atraucan needle has a combined bevel that cuts an ultrafine channel that is expanded bluntly by the rest of the tip. Their investigations, which included electron microscopy analysis, suggest that perhaps a modified cutting needle like the Atraucan needle will provide the least amount of damage to the dura, and thus decrease the incidence of spinal headaches. In terms of the treatment options listed in Table 3 of the article, it is true that epidural blood patch is contraindicated in the setting of cellulitis. This makes sense if you are attempting to place the blood patch over the cellulitic area. However, Szeinfeld and colleagues demonstrated that 12–15 cc of technetium-labeled red blood cells injected into the epidural space can travel 8 –10 disc spaces from the point of injection, most commonly 6 above and 3 below the site of injection (9). As such, I would submit that in patients who are highly symptomatic, attempting an epidural blood patch a few disc spaces away is still a reasonable option as long as the cellulitis is not so extensive as to preclude such a procedure. Lastly, I wanted to thank the author, Dr. Robert Frank, for such an extensive review of the literature. This is a common problem seen in the emergency department and we must continue to explore methods to mitigate the occurrence of PDPH, as well as explore treatment options for our patients. Bradley N. Younggren, MD, FAAEM Major, Medical Corps Associate Program Director Department of Emergency Medicine Madigan Army Medical Center Ft. Lewis, Washington doi:10.1016/j.jemermed.2008.12.018
REFERENCES 1. Frank RL. Lumbar puncture and post-dural puncture headaches: implications for the emergency physician. J Emerg Med 2008;35:149 –57. 2. Collier BB. Treatment for postdural puncture headache. Br J Anaesth 994;72:366 –7. 3. Foster P. ACTH treatment for post-lumbar puncture headaches. Br J Anaesth 1994;73:429. 4. Carter BL, Pasupuleti R. Use of intravenous cosyntropin for the treatment of postdural puncture headaches. Anesthesia 2000;92: 272– 4. 5. Canovas L, Barros C, Gomez A, Castro M, Castro A. Use of intravenous tetracosactin in the treatment of postdural puncture headache: our experience in forty cases. Anesth Analg 2002;94: 1369. 6. Younggren BN, Zeger W, Nolan R. Cosyntropin vs. caffeine for post-dural puncture headaches. Acad Emerg Med 2005;12(5 Suppl 1): 52–3. 7. Crul BJ, Gerritse BM, van Dongen RT, et al. Epidural fibrin glue injection stops persistent postdural puncture headache. Anesthesiology 1999;92:576 –7.
659 8. Holst D, Mollmann M, Ebel C, et al. In vitro investigation of cerebrospinal fluid leakage after dual puncture with various spinal needles. Anesth Analg 1998;87:1331–5. 9. Szeinfeld M, Ihmeidan IH, Moser MM, et al. Epidural blood patch: evaluation of the volume and spread of blood injected into the epidural space. Anesthesiology 1986;64:820 –2.
e IS THERE ANY ROLE FOR INTRAVENOUS ANTIVENOM FOR SNAKE VENOM OPHTHALMIA? e To the Editor: We read with interest the article entitled “Ophthalmic Exposure to Crotalid Venom,” which presented the first reported case involving the use of intravenous (i.v.) antivenom (CroFab®; BTG International Inc., West Conshohocken, PA) in the management of pit viper ocular accidental contact irritation (1). Virtually all published experience with snake venom ophthalmia relates to spitting cobras (family Elapidae), where both fangs and venom have evolved to specifically target the eye, yet there is no evidence that this results in systemic envenoming, the prime indication for antivenom therapy. In spitting cobra-induced ocular envenoming, antivenom has been used only topically, but the most current published expert advice does not recommend this treatment (2,3). With this background, the use of i.v. antivenom in the Johnson case is puzzling and difficult to support. Intravenous antivenoms are used for clinically significant venomous snakebites in the United States, and indications for use of antivenom have been delineated previously, typically determined by expanding local effects accompanied by laboratory abnormalities (e.g., prolonged international normalized ratio), marked systemic envenoming, or a notable single abnormality (e.g., systolic blood pressure ⬍ 80 mm Hg) (4–6). Antivenom therapy presents potential risk and should be used with caution, as adverse reactions such as anaphylaxis, anaphylactoid reactions, or delayed serum sickness can occur (6–8). These adverse reactions are more common for the older Antivenom (Crotalidae) Polyvalent in comparison with the newer Crotalidae polyvalent immune Fab (ovine) (Fab AV [CroFab®]). The reduced adverse reaction rate for Fab AV antivenom has been attributed to the absence of the Fc portion in the Fab AV antivenom. A recent retrospective article reported the incidence of acute hypersensitivity reaction to be 5.4% (5 out of 93 patients) when a mean dose of 12 vials of Fab AV antivenom were used (9). In the case reported by Johnson, four vials of Fab AV were initially used, and this was followed by an unspecified amount of the same antivenom, despite the absence of systemic envenoming (1). Intravenous Fab AV was used due to concerns regarding direct corneal protein denaturation, direct central nervous system absorption, and the theoretical risk of ocular
660
Letters to the Editor
intake with ocular instillation of antivenom. Published case reports of venom ophthalmia contain no evidence that supports the above as likely risks, against which the known risks of i.v. antivenom must be considered. Although topical antivenoms have been previously employed in the management of ocular envenoming by spitting cobras, and recovery occurred for a majority of patients, the role of antivenom in recovery is unclear (10). In recent publications, topical antivenoms are not recommended due to their potential irritating effects and the lack of evidence for beneficial effects (2,3). Other reported cases involving pit vipers in ocular envenoming have resulted in only transient mild ocular irritation, with irrigation as the sole treatment (11,12). In addition, irrigation alone has prevented further ocular complications (11,12). Having considered the following factors: the relatively mild sequelae sustained from ocular envenoming by pit vipers, the immediate resolution of symptoms with irrigation, the adverse effects that can occur with i.v. antivenom, and the lack of evidence for any systemic effects from ocular envenoming; the risks of i.v. antivenom (including Fab AV) outweigh the benefits in the management of pit viper venom ophthalmia. In addition to copious irrigation, a recent review of the management of snake venom ophthalmia recommended urgent medical attention, topical cycloplegics, topical antibiotics, and topical adrenaline (Chu ER, Weinstein S, White J, Warrell DA. A review of ocular envenoming [venom ophthalmia]: pathophysiology and management. Toxicon, accepted for publication). Until there is clear evidence of systemic abnormalities resulting from ocular envenomation, antivenom should not be used, either topically or intravenously. Instead, copious irrigation should be administered, as in previous cases of pit viper ocular envenomation. Edward Rickie L. Chu, MBBS Royal Adelaide Hospital Adelaide, South Australia Julian White, MBBS, MD Department of Toxinology Women’s and Children’s Hospital North Adelaide, South Australia Scott Weinstein, MSC, PHD, MBBS Royal Adelaide Hospital Adelaide, South Australia Department of Toxinology Women’s and Children’s Hospital North Adelaide, South Australia doi:10.1016/j.jemermed.2009.06.128
REFERENCES 1. Johnson R. Ophthalmic exposure to crotalid venom. J Emerg Med 2009;36:37– 8. 2. Warrell DA. Management of cobra spit ophthalmia. In: Warrell DA, ed. Guidelines for the clinical management of snake bite in the South-East Asia Region. New Delhi, India: World Health Organization, Regional Office for South-East Asia; 2005:49. 3. Warrell DA. Clinical toxicology of snakebite in Asia. In: Meier J, White J, eds. Handbook of clinical toxicology of animal venoms and poisons. Boca Raton, FL: Informa HealthCare; 1995:579 – 618. 4. Weinstein S, Dart R, Staples A, White J. Envenomations: an overview of clinical toxinology for the primary care physician. Am Fam Physician 2009;80:793– 802. 5. Gold BS, Barish RA, Dart RC. North American snake envenomation: diagnosis, treatment and management. Emerg Med Clin North Am 2004;22:423– 43. 6. White J, Dart R. Snakebite: a brief medical guide. Stirling, South Australia: White; 2007. 7. Clark RF, McKinney PE, Chase PB, Walter FG. Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom. Ann Emerg Med 2002;39:671– 6. 8. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med 2001;37:181– 8. 9. Cannon R, Ruha AM, Kashani J. Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom. Ann Emerg Med 2008;51:407–11. 10. Warrell DA, Ormerod LD. Snake venom ophthalmia and blindness caused by the spitting cobra (Naja nigricollis) in Nigeria. Am J Trop Med Hyg 1976;25:525–9. 11. Cantrell FL. Ocular exposure to rattlesnake venom. J Toxicol Clin Toxicol 2003;41:605– 6. 12. Troutman WG, Wilson LE. Topical ophthalmic exposure to rattlesnake venom. Am J Emerg Med 1989;7:307– 8.
e RESPONSE TO DRS. CHU, WHITE, AND WEINSTEIN e To the Editor: I appreciate Drs. Chu, White, and Weinstein’s interest in my article, “Ophthalmic Exposure to Crotalid Venom” (1). Their comments are not only complete but also give a brief overview of the treatment of crotalid envenomation and describe what is thought to be the standard of care for crotalid ocular envenomations. Dr. Chu and colleagues assert that there is no evidence to support the theory of absorption past the eye in pure ocular envenomations. I agree with that assertion; however, as the authors mention, “virtually all published experience with snake venom ophthalmia relates to spitting cobras.” This report was not advocating an actual concern but rather a theoretical concern for systemic absorption. As is stated in the manuscript, “although there is insufficient evidence to conclude that intravenous CroFab had any effect, it is interesting that our patient had early intravenous CroFab and delayed irrigation with rapid recovery and no complications.” What the report did lack was specifics on the amount of eye irrigation that was initially performed and the total quan-