The Journal of Maternal-Fetal & Neonatal Medicine ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20 Fetal Response to Intramuscular Epinephrine for Anaphylaxis during Maternal Penicillin Desensitization for Secondary Syphilis Shan Shan Wu, Tina Abraham, Chelsea Michaud, Brian Peppers, Andrea Ward, Stacey Ehrenberg Buchner, Catalina V Teba, Haig Tcheurekdjian, Robert Hostoffer & Devi Jhaveri To cite this article: Shan Shan Wu, Tina Abraham, Chelsea Michaud, Brian Peppers, Andrea Ward, Stacey Ehrenberg Buchner, Catalina V Teba, Haig Tcheurekdjian, Robert Hostoffer & Devi Jhaveri (2017): Fetal Response to Intramuscular Epinephrine for Anaphylaxis during Maternal Penicillin Desensitization for Secondary Syphilis, The Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.1080/14767058.2017.1336221 To link to this article: http://dx.doi.org/10.1080/14767058.2017.1336221 Accepted author version posted online: 31 May 2017. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalinformation?journalcode=ijmf20 Download by: [The UC San Diego Library] Date: 01 June 2017, At: 11:58
Fetal Response to Intramuscular Epinephrine for Anaphylaxis during Maternal Penicillin Desensitization for Secondary Syphilis Dr Shan Shan Wu D.O. (Corresponding Author) Email: shanshan.wu@uhhospitals.org University Hospitals Regional Hospitals, Internal Medicine Residency Program, 27100 Chardon Road, Richmond Heights, 44143 United States Dr Tina Abraham Email: Tina.Abraham@UHhospitals.org University Hospitals Regional Hospitals, Allergy-Immunology Fellowship Program, Richmond Heights, United States Dr Chelsea Michaud Email: Chelsea.Michaud@UHhospitals.org University Hospitals Regional Hospitals, Allergy-Immunology Fellowship Program, Richmond Heights, United States Dr Brian Peppers Email: Brian.Peppers@UHhospitals.org University Hospitals Regional Hospitals, Allergy-Immunology Fellowship Program, Richmond Heights, United States Dr Andrea Ward Email: Andrea.Ward@UHhospitals.org ACCEPTED University Hospitals Cleveland Medical, Obstetrics and Gynecology Residency Program, Cleveland, United States JUST
Dr Stacey Ehrenberg Buchner Email: stacey.ehrenberg@gmail.com University Hospitals Cleveland Medical Center, Departments of Obstetrics and Gynecology, Cleveland, United States Dr Catalina V Teba Email: Catalina.Teba@UHhospitals.org University Hospitals Cleveland Medical Center, Department of Medicine, Division of Pulmonary/Critical Care, Cleveland, United States Dr Haig Tcheurekdjian Email: Haig.Tcheurekdjian@UHhospitals.org Allergy/Immunology Associates, Inc., Mayfield Heights, United States Dr Robert Hostoffer Email: Robert.Hostoffer2@UHhospitals.org Allergy/Immunology Associates, Inc., Mayfield Heights, United States Dr Devi Jhaveri Email: Devi.Jhaveri@UHhospitals.org Allergy/Immunology Associates, Inc., Mayfield Heights, United States
Penicillin desensitization is indicated in pregnant patients with severe allergies to penicillin with syphilis. The immediate effects of intramuscular epinephrine on the fetus during desensitization remain unreported. We describe a pregnant patient with secondary syphilis and penicillin allergy who developed anaphylaxis during penicillin desensitization. Anaphylaxis resolved after administration of intramuscular epinephrine. Throughout the procedure, continuous electronic fetal monitoring showed a stable fetus without a decrease in variability, tachycardia, decelerations or signs of fetal distress. This case showed that intramuscular epinephrine is effective in treatment of anaphylaxis in a pregnant patient with little to no immediate effects on the fetus. Keywords: epinephrine, desensitization, anaphylaxis, fetus, syphilis Introduction Syphilis is a bacterial infection caused by Treponema pallidum. This disease is quite prevalent in low socioeconomic environments and aside from its direct morbidity, it poses a lifelong morbidity to infants born to infected mothers [1]. Penicillin is the primary treatment for maternal syphilis and prevention of congenital syphilis [2-4]. Penicillin desensitization is indicated in pregnant patients with severe allergies to penicillin who have contracted syphilis. The literature describes successful oral and intravenous (IV) desensitization in pregnant patients with syphilis and penicillin allergy [2,3,5]. Epinephrine given intravenously for anaphylaxis in obstetric patients has been described [6-8]. There is no documentation regarding the immediate effects of intramuscular (IM) epinephrine on the fetus during penicillin desensitization of the mother. We present a case of continuous electronic fetal monitoring (CEFM) in a pregnant patient with secondary syphilis who required IM epinephrine for anaphylaxis during penicillin desensitization. Case Report The patient is a 22-year-old G4P1203 at 24.3 weeks, with a pertinent past medical history of asthma, and a previous anaphylactic reaction to amoxicillin at age 9. Her diagnosis was established by both the hallmark maculopapular rash on her palms and soles and a repeatedly positive Syphilis IgG (nonreactive TP-PA and VDRL). Skin prick and intradermal testing for
penicillin-g, Pre-Pen, and minor determinant mixture (MDM) were all positive. Based on these objective findings with a concomitant appropriate clinical history, oral penicillin desensitization with a protocol adapted by Wendel et al [5] was initiated in the medical intensive care unit (ICU). The protocol started the patient with 100 Units of penicillin. After the second step of desensitization with 200 Units of penicillin (total of 300 Units of penicillin), the patient developed anaphylaxis which was exhibited by oxygen desaturation and hypotension along with dizziness and pruritus of the palms [Table 1]. She was given IM epinephrine 0.3 ml (1:1000), IV diphenhydramine, and supplemental oxygen. She required a second dose of IM epinephrine 0.3 ml (1:1000) and additional second-line anaphylaxis treatments with IV methylprednisolone and nebulized albuterol before the anaphylaxis resolved. The desensitization resumed with an adjusted protocol. The adjusted protocol started at 12.5 Units with the dose doubled every 15 minutes to a completion of 640,000 Units. The patient received a cumulative dose of 1,296,700 units of penicillin and was successfully desensitized without additional adverse reactions. Throughout the procedure, the CEFM showed a stable fetus. Fetal heart tones during and after the desensitization revealed a baseline of 130 beats per minute (bpm), moderate baseline fetal heart (FHR) variability, 10 x 10 accelerations and no decelerations. These findings are consistent with a category I tracing. Discussion Obtaining a thorough history with particular emphasis on known allergies, reactions, and avoidance of known triggers such as food, stinging insects, medications and natural rubber latex are recommended in the pregnant patient [4]. Due to the increased risk of anaphylaxis during desensitization, the procedure is usually recommended post-parturition to avoid anaphylaxis-
related detrimental maternal and fetal events such as maternal cardiac arrests and fetal demise. Desensitization in the case of untreated syphilis during pregnancy is always appropriate to prevent congenital syphilis [3,4]. Close monitoring in the ICU with an integrated team is warranted in pregnant patients undergoing desensitization should an anaphylactic event arise necessitating the use of epinephrine. Epinephrine was thought to decrease uterine blood flow by increasing uterine vascular resistance, yet the overall effect of epinephrine increases uteroplacental perfusion by increasing vascular systemic resistance, blood pressure, and cardiac output [6,8]. IM epinephrine to the middle outer thigh is the first line treatment for anaphylaxis regardless of pregnancy status [4]. IV epinephrine is recommended for patients who do not respond to IM epinephrine injections and with symptoms of or high risk of progression to cardiovascular collapse [9]. When the IV route is indicated, IV infusion of epinephrine is recommended as opposed to IV boluses given the latter s increased risks of cardiovascular events of arrhythmia, cardiac ischemia, stroke, angina, and hypertension [9]. Additional care and attention to the health of the fetus is assessed by using CEFM, which is most often used during the third trimester of pregnancy before or during the course of labor in cases of anaphylaxis [8]. There are no studies to our knowledge using CEFM during penicillin desensitization and no reported literature showing the immediate effects of IM epinephrine on the fetus for anaphylaxis during desensitization. In our case, the fetus remained stable without a decrease in variability, signs of tachycardia, decelerations, or other markers of fetal distress as portrayed by CEFM Category I tracing during the desensitization procedure in conjunction with the use of IM epinephrine. Category I tracing is defined as normal and predictive of normal fetal acid-base balance at the time of observation and fulfills all of these criteria: baseline rate
110 to 160 bpm, moderate baseline fetal heart rate variability, no late or variable decelerations, early decelerations may be present or absent and accelerations may be present or absent [10]. The fetal heart rate tracing remained category I throughout the entire desensitization procedure. Conclusion Intramuscular epinephrine is recommended over IV administration when signs of shock are absent. This case demonstrates that the administration of IM Epinephrine had little to no immediate effects on a second trimester fetus. We described the first case of intramuscular epinephrine and its lack of clinically significant effects on the CEFM during penicillin desensitization in a pregnant patient with syphilis.
References 1. Hook, EW. Syphilis. Lancet. 2016 Dec 16 [Mar 2017]; S0140-6736(16)32411-4. doi: 10.1016/S0140-6736(16)32411-4 2. Ziaya PR, Hankins GDV, Gilstrap LC III, et al. Intravenous penicillin desensitization treatment during pregnancy. JAMA. 1986 Nov;256(18):2561-2562. 3. Chisholm, CA, Katz VL, McDonald TL, et al. Penicillin desensitization in the treatment of syphilis during pregnancy. Amer J Perinatol. 1997 Oct;14(9):553-554. 4. Simons FE, Schatz M. Anaphylaxis during pregnancy. J Allergy Clin Immunol. 2012 Sept;130(3):597-606. 5. Wendel GD Jr, Stark BJ, Jamison RB, et al. Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med. 1985 May;312(19):1229-1232. 6. Gei AF, Pacheco LD, Vanhook JW, et al. The use of a continuous infusion of epinephrine for anaphylactic shock during labor. Obstet Gynecol. 2003 Dec;102(6):1332-1335. 7. Chaudhuri K, Gonzales J, Jesurun CA, et al. Anaphylactic shock in pregnancy: a case study and review of the literature. Int J Obstet Anesth. 2008 Oct;17(4):350-357. 8. Hepner DL, Castells M, Mouton-Faivre C, et al. Anaphylaxis in the clinical setting of obstetric anesthesia: a literature review. Anesth Analg. 2013 Dec;117(6):1357-67. 9. Campbell RL, Li JT, Nicklas RA, et al. Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. 2014 Dec;113(6):599-608. 10. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol. 2008 Sep; 112(3):661-666.
Table 1. Maternal hemodynamic parameters at time of anaphylaxis during penicillin desensitization. Time Relative to Onset of Anaphylaxis (minute) Blood Pressure (units/ml) Heart Rate (beats/minute) Respiratory Rate (breaths/minute) Oxygen saturation (% O2) Temperature (Celsius, Fahrenheit) -122 95/57 82 16 95% 36.7, 98-22 a 103/64 103 26 99% -7 b 94/64 95 21 100% 0 c 88/64 80 17 87% 15 d 115/78 69 19 93% * 30 e 95/65 75 22 96% * 45 100/60 84 17 100% * 60 f 96/67 91 18 93% 35.3, 95.5 75 93/54 91 18 96% a 1 st dose of penicillin administered. b 2 nd dose of penicillin administered. c Onset of anaphylaxis. 1 st dose of intramuscular epinephrine 0.3 ml (1:1000) and intravenous diphenhydramine 25mg were administered. d 2 nd dose of intramuscular epinephrine 0.3 ml (1:1000) was administered. e Intravenous methylprednisolone 60 mg and nebulized albuterol were administered f Anaphylaxis resolved. * Supplemental oxygen with 2 liters of oxygen via nasal cannula Data not available
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