Indian Journal of Critical Care Medicine June 2014 Vol 18 Issue 6
Unusual causes of anaphylaxis during surgery: Gelofusin-induced Kounis syndrome Sir, In the very interesting report[1] published recently in IJCCM, a 48-year-old female patient, who was planned to have laparoscopic donor nephrectomy, developed atrial premature complexes, flushing of both hands, falling blood pressure, and rising pulse rate after gelofusin infusion. Intravenous hydrocortisone, chlorpheniramine, mephentermine, adrenaline, vasopressors, ipratropiume with salbutamol nebulization and positive pressure ventilation improved her condition. The scheduled surgery was postponed, and the allergic skin tests for antibiotics, anesthetics and gelofusin showed positive skin reaction to gelofusin. This case raises some important points concerning the cause and the type of this reaction and its pathophysiology. Gelofusin is a macromolecule made from succinylated bovine gelatin. Gelatins are proteins derived from collagen and are obtained from cow and pig bones and hides and fish skin. A similar case diagnosed as Type II variant of Kounis hypersensitivity-associated syndrome with peri-operative cardiac arrest due to gelofusin anaphylaxis, confirmed with skin prick tests, has been published recently.[2] It concerned a 57-year-old patient who developed anaphylactic shock during anesthesia and despite initial management with bolus doses of metaraminol and epinephrine intravenously, hypotension worsened, and cardiac output was reduced. The patient recovered gradually with intravenous antihistamines, steroids and myocardial ischemia protocol, thus supporting our view that anaphylactic shock is a manifestation of Kounis syndrome. In another report, anaphylaxis with cardiovascular symptoms such as profound hypotension, tachycardia, and elevated airway pressures have been reported following intraosseous gelatin administration.[3] Drug capsules, suppositories, plasma expanders, and vaccine stabilizers including diphtheria-tetanus-pertussis, measles, mumps, rubella, varicella, yellow fever, rabies, and some influenza vaccines contain bovine and porcine gelatins as heat stabilizers. Since gelatin is contained in various vaccines given in children, then vaccination is regarded as a primary route of
Figure 1: Improvized arrangement
improvized arrangement, a T-adaptor with jet nebulizer assembly is attached to the above mentioned connection port [Figure 1]. A one-way valve [Direction, Figure 1] is attached to the free end of the T-adaptor to prevent aerosol loss and direct airflow to the bag inlet when it is re-expanding. Presence of resuscitation bag next to the jet nebulizer and addition of 3-4 mL of normal saline to the drug can help in effective delivery of aerosol. The tidal and minute volumes can be controlled manually to deliver aerosol safely to the ventilator dependent patients where compatible aerosol device is not available.
Ashish Saraogi
Department of Anaesthesiology, NIMS Hospital and Medical College, Jaipur, Rajasthan, India
Correspondence: Dr. Ashish Saraogi, B6, Faculty B Block, NIMS University Campus, Shobha Nagar, Jaipur-Delhi Highway, Jaipur - 303 121, Rajasthan, India. E-mail: [email protected]
References 1. 2.
3. 4.
Rubin BK. Air and soul: The science and application of aerosol therapy. Respir Care 2010;55:911-21. Guerin C, Fassier T, Bayle F, Lemasson S, Richard JC. Inhaled bronchodilator administration during mechanical ventilation: How to optimize it, and for which clinical benefit? J Aerosol Med Pulm Drug Deliv 2008;21:85-96. Dhand R. Aerosol delivery during mechanical ventilation: From basic techniques to new devices. J Aerosol Med Pulm Drug Deliv 2008;21:45-60. Dorsch JA, Dorsch SA. Manual resuscitators. In: Understanding Anaesthesia Equipments. 5th ed. New Delhi: Lippincott William’s and Wilkins; 2008. p. 282-93. Access this article online Quick Response Code: Website: www.ijccm.org
DOI: 10.4103/0972-5229.133955
410
78
Indian Journal of Critical Care Medicine June 2014 Vol 18 Issue 6
sensitization. Indeed, specific gelatin antibodies have been detected in patients following vaccination[4] and Type I hypersensitivity reactions to gelatin have been even reported with specific IgE levels as low as 0.8 kUA/L. When, gelatins are used intravenously as modified fluid gelatins and as plasma substitutes and expanders they can induce severe allergic reactions such as in the described case.
George D. Soufras, Nicholas G. Kounis1, George Hahali2
Department of Cardiology, Saint Andews State General Hospital, Department of Medical Sciences, Patras Highest Institute of Education and Technology, 2Department of Cardiology, University of Patras Medical School, Patras, Achaia, Greece 1
Correspondence: Prof. Nicholas G. Kounis, Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece. E-mail: [email protected]
References
The described patient had received, before gelofusin administration, a total 10 different drugs in an effort to induce anesthesia. Despite negative skin tests, substances such as lactated ringer, ranitidine, fentanyl, ondansetron, cefotaxine, thiopentone, suxamethonium, isoflurane, vecuronium, and mannitol, could have acted as antigens and have joined forces with gelofusin in order to induce anaphylaxis and Kounis syndrome. It is known that anaphylaxis resulting in Kounis syndrome occurs when 2000 nearby antibodies attached to mast cell surface are bridged by corresponding antigens and make the critical number of 1000 bridges. On the other hand, IgE antibodies with different specificities can have additive effects and small, even subthreshold numbers of them can join forces and trigger the cells to release their mediators.[5]
1. 2.
3. 4. 5.
Parikh G, Shah V, Singh D, Kadam P, Kharadi N. An unusual cause of anaphylaxis during surgery. Indian J Crit Care Med 2013;17:396-7. Shah G, Scadding G, Nguyen-Lu N, Wigmore T, Chenzbraun A, Wechalekar K, et al. Peri-operative cardiac arrest with ST elevation secondary to gelofusin anaphylaxis-Kounis syndrome in the anaesthetic room. Int J Cardiol 2013;164:e22-6. Luhmann SJ, Sucato DJ, Bacharier L, Ellis A, Woerz C. Intraoperative anaphylaxis secondary to intraosseous gelatin administration. J Pediatr Orthop 2013;33:e58-60. Sakaguchi M, Nakayama T, Fujita H, Toda M, Inouye S. Minimum estimated incidence in Japan of anaphylaxis to live virus vaccines including gelatin. Vaccine 2000;19:431-6. Nopp A, Johansson SG, Lundberg M, Oman H. Simultaneous exposure of several allergens has an additive effect on multisensitized basophils. Allergy 2006;61:1366-8.
Access this article online Quick Response Code: Website:
Therefore, anesthetic drugs used during surgery can join forces with substances acting as antigens and can induce anaphylaxis and Kounis anaphylaxis-associated syndrome. Anesthetists and surgeons should be aware of this consequence in order to timely receive protective, preventive, and therapeutic measures.
www.ijccm.org
DOI: 10.4103/0972-5229.133956
79
411
Copyright of Indian Journal of Critical Care Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Unusual causes of anaphylaxis during surgery: Gelofusin-induced Kounis syndrome Sir, In the very interesting report[1] published recently in IJCCM, a 48-year-old female patient, who was planned to have laparoscopic donor nephrectomy, developed atrial premature complexes, flushing of both hands, falling blood pressure, and rising pulse rate after gelofusin infusion. Intravenous hydrocortisone, chlorpheniramine, mephentermine, adrenaline, vasopressors, ipratropiume with salbutamol nebulization and positive pressure ventilation improved her condition. The scheduled surgery was postponed, and the allergic skin tests for antibiotics, anesthetics and gelofusin showed positive skin reaction to gelofusin. This case raises some important points concerning the cause and the type of this reaction and its pathophysiology. Gelofusin is a macromolecule made from succinylated bovine gelatin. Gelatins are proteins derived from collagen and are obtained from cow and pig bones and hides and fish skin. A similar case diagnosed as Type II variant of Kounis hypersensitivity-associated syndrome with peri-operative cardiac arrest due to gelofusin anaphylaxis, confirmed with skin prick tests, has been published recently.[2] It concerned a 57-year-old patient who developed anaphylactic shock during anesthesia and despite initial management with bolus doses of metaraminol and epinephrine intravenously, hypotension worsened, and cardiac output was reduced. The patient recovered gradually with intravenous antihistamines, steroids and myocardial ischemia protocol, thus supporting our view that anaphylactic shock is a manifestation of Kounis syndrome. In another report, anaphylaxis with cardiovascular symptoms such as profound hypotension, tachycardia, and elevated airway pressures have been reported following intraosseous gelatin administration.[3] Drug capsules, suppositories, plasma expanders, and vaccine stabilizers including diphtheria-tetanus-pertussis, measles, mumps, rubella, varicella, yellow fever, rabies, and some influenza vaccines contain bovine and porcine gelatins as heat stabilizers. Since gelatin is contained in various vaccines given in children, then vaccination is regarded as a primary route of
Figure 1: Improvized arrangement
improvized arrangement, a T-adaptor with jet nebulizer assembly is attached to the above mentioned connection port [Figure 1]. A one-way valve [Direction, Figure 1] is attached to the free end of the T-adaptor to prevent aerosol loss and direct airflow to the bag inlet when it is re-expanding. Presence of resuscitation bag next to the jet nebulizer and addition of 3-4 mL of normal saline to the drug can help in effective delivery of aerosol. The tidal and minute volumes can be controlled manually to deliver aerosol safely to the ventilator dependent patients where compatible aerosol device is not available.
Ashish Saraogi
Department of Anaesthesiology, NIMS Hospital and Medical College, Jaipur, Rajasthan, India
Correspondence: Dr. Ashish Saraogi, B6, Faculty B Block, NIMS University Campus, Shobha Nagar, Jaipur-Delhi Highway, Jaipur - 303 121, Rajasthan, India. E-mail: [email protected]
References 1. 2.
3. 4.
Rubin BK. Air and soul: The science and application of aerosol therapy. Respir Care 2010;55:911-21. Guerin C, Fassier T, Bayle F, Lemasson S, Richard JC. Inhaled bronchodilator administration during mechanical ventilation: How to optimize it, and for which clinical benefit? J Aerosol Med Pulm Drug Deliv 2008;21:85-96. Dhand R. Aerosol delivery during mechanical ventilation: From basic techniques to new devices. J Aerosol Med Pulm Drug Deliv 2008;21:45-60. Dorsch JA, Dorsch SA. Manual resuscitators. In: Understanding Anaesthesia Equipments. 5th ed. New Delhi: Lippincott William’s and Wilkins; 2008. p. 282-93. Access this article online Quick Response Code: Website: www.ijccm.org
DOI: 10.4103/0972-5229.133955
410
78
Indian Journal of Critical Care Medicine June 2014 Vol 18 Issue 6
sensitization. Indeed, specific gelatin antibodies have been detected in patients following vaccination[4] and Type I hypersensitivity reactions to gelatin have been even reported with specific IgE levels as low as 0.8 kUA/L. When, gelatins are used intravenously as modified fluid gelatins and as plasma substitutes and expanders they can induce severe allergic reactions such as in the described case.
George D. Soufras, Nicholas G. Kounis1, George Hahali2
Department of Cardiology, Saint Andews State General Hospital, Department of Medical Sciences, Patras Highest Institute of Education and Technology, 2Department of Cardiology, University of Patras Medical School, Patras, Achaia, Greece 1
Correspondence: Prof. Nicholas G. Kounis, Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece. E-mail: [email protected]
References
The described patient had received, before gelofusin administration, a total 10 different drugs in an effort to induce anesthesia. Despite negative skin tests, substances such as lactated ringer, ranitidine, fentanyl, ondansetron, cefotaxine, thiopentone, suxamethonium, isoflurane, vecuronium, and mannitol, could have acted as antigens and have joined forces with gelofusin in order to induce anaphylaxis and Kounis syndrome. It is known that anaphylaxis resulting in Kounis syndrome occurs when 2000 nearby antibodies attached to mast cell surface are bridged by corresponding antigens and make the critical number of 1000 bridges. On the other hand, IgE antibodies with different specificities can have additive effects and small, even subthreshold numbers of them can join forces and trigger the cells to release their mediators.[5]
1. 2.
3. 4. 5.
Parikh G, Shah V, Singh D, Kadam P, Kharadi N. An unusual cause of anaphylaxis during surgery. Indian J Crit Care Med 2013;17:396-7. Shah G, Scadding G, Nguyen-Lu N, Wigmore T, Chenzbraun A, Wechalekar K, et al. Peri-operative cardiac arrest with ST elevation secondary to gelofusin anaphylaxis-Kounis syndrome in the anaesthetic room. Int J Cardiol 2013;164:e22-6. Luhmann SJ, Sucato DJ, Bacharier L, Ellis A, Woerz C. Intraoperative anaphylaxis secondary to intraosseous gelatin administration. J Pediatr Orthop 2013;33:e58-60. Sakaguchi M, Nakayama T, Fujita H, Toda M, Inouye S. Minimum estimated incidence in Japan of anaphylaxis to live virus vaccines including gelatin. Vaccine 2000;19:431-6. Nopp A, Johansson SG, Lundberg M, Oman H. Simultaneous exposure of several allergens has an additive effect on multisensitized basophils. Allergy 2006;61:1366-8.
Access this article online Quick Response Code: Website:
Therefore, anesthetic drugs used during surgery can join forces with substances acting as antigens and can induce anaphylaxis and Kounis anaphylaxis-associated syndrome. Anesthetists and surgeons should be aware of this consequence in order to timely receive protective, preventive, and therapeutic measures.
www.ijccm.org
DOI: 10.4103/0972-5229.133956
79
411
Copyright of Indian Journal of Critical Care Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
