J Am Board Fam Med: first published as 10.3122/jabfm.19.6.621 on 7 November 2006. Downloaded from

Appendicitis in Pregnancy

Patricia A. Pastore, MSN, RN, FNP, Dianne M. Loomis, MSN, RN-CS, FNP, and John Sauret, MD, FAAFP

Background: Our urban practice had two incidences of documented appendicitis in pregnancy in a 24-hour period with two unique outcomes that prompted an inquiry. Appendicitis in pregnancy is relatively rare, but it has significant morbidity and is a cause of maternal and infant mortality. Ab- dominal pain is the most common presenting symptom, and the consideration of multiple patho- logic disorders should be entertained. Accurate diagnosis of appendicitis in pregnancy is the larg- est challenge since the signs and symptoms may vary depending on the trimester in which the patient presents. Methods: We undertook a systematic review of English-language articles from 1975 to 2005 us- ing the key words “appendicitis,” and “pregnancy” using MEDLINE, CINAHL, and Cochrane Con- trolled Trials Register databases. Results and Conclusions: The accurate diagnosis of appendicitis during pregnancy requires a high level of suspicion and clinical skills, and not merely relying on the classic signs and diagnos- tic testing. Primary care providers play an important role in recognizing potential signs and symp- toms of appendicitis in pregnancy to initiate prompt action and reduce negative maternal and fetal outcomes. (J Am Board Fam Med 2006;19:621–6.)

Case 1 office for increasing abdominal pain. She was re- A 22-year-old G1P0 of 16 weeks gestation awoke ferred back to the ER with a chief complaint of about midnight with periumbilical abdominal pain increasing pain localized to the RLQ. Now she had and presented to the hospital for evaluation. Phys- nausea and emesis but denied fever, chills, consti- ical examination showed mild abdominal tender- pation, or diarrhea. ness, and an ultrasound showed a viable fetus. The On examination, her temperature was 37.6°C, patient was discharged from the hospital with the heart rate 117, and blood pressure 133/76. Physical diagnosis of round ligament pain. Persistent peri- examination revealed gravid abdomen with RLQ umbilical and right lower quadrant (RLQ) pain tenderness with deep palpation along with guard- http://www.jabfm.org/ prompted her to seek care at her primary care ing but without rebound tenderness. Pertinent lab- office. She reported nausea but denied vomiting, oratory results were: white blood cell count, 17.5; vaginal discharge, bleeding, fever, or constipation. hemoglobin, 13; hematocrit, 37; platelets, 191,000; Examination revealed a gravid abdomen of 16 fibrinogen, 446 (170–410), liver function tests, weeks, tenderness, and guarding in the RLQ. Com- normal; electrolytes, normal; urinalysis, normal. plete blood count, complete metabolic profile, uri- Obstetrical and surgical consultations were ob- on 1 October 2021 by guest. Protected copyright. nalysis, and urine culture were sent to the lab. The tained. Ultrasound showed a normal appendix and patient was sent for repeat ultrasound, which was intrauterine pregnancy at 16 weeks. She was admit- negative for appendicitis and showed a viable fetus ted to the hospital for observation, where she de- of 16 weeks. Later that day, the patient called the veloped worsening pain and low-grade fever. A repeat ultrasound in the morning showed appendi- This article was externally peer-reviewed. citis. An open appendectomy was performed under Submitted 30 March 2006; accepted 17 April 2006. general anesthesia showing an acutely inflamed From the Department of Family Medicine, The State University of New York at Buffalo, Buffalo, NY (PAP, JS); nonperforated appendix. Postoperative course was Kaleida Health, Buffalo, NY (PAP, DML); and Niagara initially unremarkable with fetal heart tones Falls Memorial, Niagara Falls, NY (JS). Conflict of interest: none declared. present. However, 7 days postdischarge, she pre- Corresponding author: Patricia A. Pastore, Department of sented to labor and delivery with premature labor Family Medicine, The State University of New York at Buffalo, 462 Grider Street, Buffalo, NY 14215 (E-mail: and spontaneous vaginal delivery of a nonviable [email protected]). fetus. http://www.jabfm.org Appendicitis in Pregnancy 621 J Am Board Fam Med: first published as 10.3122/jabfm.19.6.621 on 7 November 2006. Downloaded from

Case 2 and “pregnancy.” Studies included in this review A 39-year-old G7P6 at 20 weeks gestation reported were English-language and applicable to US clini- to an urban hospital ER with complaint of perium- cal practice. No articles were found that focused bilical abdominal pain that began about 9 hours specifically on appendicitis in pregnancy in the pri- prior. The pain intensified throughout the day, mary care setting. The bibliographies of all in- with localization to the right lower abdominal re- cluded articles were reviewed and selected for in- gion. She had associated nausea and slight fever. clusion. These case studies were approved by the She denied any emesis, dysuria, frequency, diar- Health Sciences Institutional Review Board of the rhea, or vaginal symptoms, including irregular vag- State University of New York at Buffalo. inal bleeding or back pain. Her previous medical history was unremarkable except for six full-term Epidemiology vaginal births. The patient had no surgical history Although a rare presentation, appendicitis is one of or allergies and was on prenatal vitamins and iron the most common causes of an acute abdomen in supplementation for anemia. pregnancy, occurring in approximately 1 in 1500 On admission, her temperature was 36.3°C, pregnancies.1,2 This represents an overall incidence heart rate 102, respiratory rate was 16/min, and of 0.05% to 0.07% and does not appear to be any blood pressure 121/63. She appeared in moderate difference in the nongravid population.3,4 One re- distress. On physical examination, head, ears, eyes, port of a reduced incidence of appendicitis during nose and throat was normal; neck supple; lungs pregnancy suggested a possible protective effect, clear; cardiac rate regular; gravid abdomen; fundal and the mean age is 28 years.5 height at 21 cm; hypoactive bowel sounds, RLQ Incidence rates in the first trimester range from tenderness with mild palpation, positive rebound, 19% to as high as 36%.2,3,6,7 There is a higher psoas, and voluntary guarding. Pelvic examination incidence of appendicitis in the second trimester, was normal. Labs revealed white blood count of ranging from 27% to 60%.2,3,6 Although incidence 13.7, neutrophils 11.3, u/a with bacteria 26–100, decreases from 15% to 33% in the third trimester; epithelial cells, and trace hematuria. Sonogram in- some studies reported a 59% incidence in the third dicated gestational age at 20 weeks, 6 days consis- trimester.2,3,6,7 Perforation rates for pregnant pa- tent with last menstrual period, adequate fetal heart tients have been reported as high as 55% of cases, tones, and equivocal for acute appendicitis. compared with 4% to 19% of the general popula- Surgery was consulted and felt that she should tion.3,8,9

be transferred to a local hospital specializing in Due to the lack of specificity of the preoperative http://www.jabfm.org/ pediatrics and obstetrics for emergency appendec- evaluation; the pathologic diagnosis of appendicitis tomy secondary to clinical history and physical ex- is confirmed in only 30% to 50% of cases.2,6,7 The amination. Obstetrical consult was in agreement, first trimester yields a greater accuracy, but more and surgery was planned for the following morn- than 40% of patients in the second and third tri- ing. The second ultrasound was positive for acute mester will have a normal appendix. 10Overall, nor- appendicitis, while her pain improved slightly. mal histology was reported to be 11% to 50%.11,12 Open laparotomy under general anesthesia was Appendicitis was correctly diagnosed 50% to 86% on 1 October 2021 by guest. Protected copyright. performed the day following onset of symptoms. of the time.3,6,7,11 The risk of delay in diagnosis is Pathology established acute suppurative appendici- associated with a greater risk of complications such tis. Postoperative recovery was uneventful, and the as perforation, infection, preterm labor, and risks of patient delivered a healthy infant at term without fetal or maternal loss.6,8 Maternal mortality has complications. been reported from none to 2%.2,3,6,7 An unrup- tured appendix carries a fetal loss of 1.5% to 9%, while this rate increases up to 36% with perfora- Methods tion.2,6,13 Electronic review of the literature from 1975 to The risk of perforation increases with gesta- 2005 using MEDLINE, CINAHL, and Cochrane tional age, and perforation in the third trimester Controlled Trials Register databases was con- often results in preterm labor.3 Delay in surgical ducted by two family nurse practitioners and a intervention carries increased fetal loss.14 The risk family physician using the key words “appendicitis” for premature delivery is the greatest during the

622 JABFM November–December 2006 Vol. 19 No. 6 http://www.jabfm.org J Am Board Fam Med: first published as 10.3122/jabfm.19.6.621 on 7 November 2006. Downloaded from

Table 1. Obstetrical and Gynecological Differential Diagnoses of RLQ Pain in Pregnancy

Ruptured ovarian cyst Hemorrhagic ovarian cyst Appendicitis Idiopathic Ectopic pregnancy Ovarian torsion Pelvic inflammatory disease Tubo-ovarian abscess Threatened abortion Placental abruption Chorioamnionitis Degenerating leiomyoma Ventral hernia Pyelonephritis Salpingitis Adnexal torsion Ruptured corpus luteum cyst Round ligament syndrome Figure 1. Changes in position of the appendix as Preeclampsia pregnancy advances (MO, month, PP, postpartum). As modified from Baer and associates. With permission from The McGraw-Hill Companies. signs of appendicitis such as positive Rovsing’s and psoas sign have not been shown to be of any clinical significance in diagnosing an acute appendicitis in first week after surgery. However, maternal mor- pregnancy.6 Rectal pain and vaginal tenderness es- 2,6,7 tality is very low. This may be due to rapid pecially in the first trimester may be evident. administration of antibiotics, close perioperative monitoring, improved cooperation between gen- Differential Diagnosis eral surgeons, obstetricians, and anesthesiologists Both obstetrical and gynecological conditions can and improved perioperative care. present with abdominal pain and mimic appendici- 6,8,15

tis (Table 1). A thorough history and a careful http://www.jabfm.org/ Diagnosis physical examination should lead the evaluating cli- The most common presenting symptoms include nician to formulate a differential diagnosis that is anorexia, nausea, vomiting, and right lower quad- appropriate for the individual. Nonobstetrical/non- rant pain.2,8,15 Fever and tachycardia may not be gynecological conditions include gastroenteritis, present during pregnancy.8,15 Right upper quad- urinary tract infections, pyleonephritis, cholecysti- rant pain, uterine contractions, dysuria, and diar- tis, cholelithiasis, pancreatitis, nephrolithiasis, her- rhea can also be present.1,3,6 It is believed that the nia, bowel obstruction, carcinoma of the large on 1 October 2021 by guest. Protected copyright. appendix changes its location during pregnancy bowel, mesenteric adenitis, and rectus hematoma, with an upward displacement toward the costal pulmonary embolism, right-lower-lobe pneumo- margin in the later stages of pregnancy (Figure nia, and sickle cell disease.18,19 Gynecologic and 1).16,17 Patients may then present with right upper obstetric conditions include ovarian cyst, adnexal quadrant pain or entire right-sided pain, although torsion, salpingitis, abruptio placenta, chorioam- the relocation of the appendix during the later nionitis, degenerative fibroid, ectopic pregnancy, stages of pregnancy and right upper quadrant pain preeclampsia, round ligament syndrome, and pre- was not reproduced in some patients.1 A presenta- term labor.18,19 One study demonstrated that ap- tion with right upper quadrant pain can be highly pendicitis occurred in approximately half of their variable with an incidence as high as 55%.3 sample; ovarian cysts, mesenteric adenitis, fibromy- It is important to note that there is no one oma uteri, varicose veins in the parametria, ileus, reliable sign or symptom that can aid in the diag- salpingitis, and torsion were the other pathologies nosis of appendicitis in pregnancy, and the classic identified.2 http://www.jabfm.org Appendicitis in Pregnancy 623 J Am Board Fam Med: first published as 10.3122/jabfm.19.6.621 on 7 November 2006. Downloaded from

Diagnostic Testing bility; however their efficacy has not been demon- Accurately identifying acute appendicitis in preg- strated.2,6 nancy can be a diagnostic dilemma. The reluctance Antibiotic use during or after surgery may ex- to operate in pregnancy adds to delays, yet diag- pose the developing fetus to potentially teratogenic nostic imaging techniques have shown promise in substances.10 Pregnancy related pharmacodynamic facilitating and supporting the diagnosis. Graded changes result in reduced maternal plasma levels of compression ultrasound has shown to be highly antibiotics.23 Gentamycin and related aminoglyco- sensitive and specific although to a lesser degree sides have been associated with nephrotoxicity and after a gestational age of 35 weeks due to technical ototoxicity, while tetracyclines may cause perma- difficulties. This noninvasive procedure should be nent tooth discoloration and long bone malforma- considered first in working up suspected acute ap- tion. Fluoroquinolones may cause dysplasia of car- pendicitis.20 Although considerations regarding tilage and arthropathies in children so are not operator technique, large body habitus and possible currently recommended in pregnancy. If perfora- obscuring bowel and gas may not allow for a con- tion, peritonitis, or gangrenous appendix has oc- clusive preoperative diagnosis.21 curred, broad-spectrum antibiotics with anaerobic Selective imaging of the appendix using Helical coverage such as the second-generation cephalo- Computed Tomography has recently shown to be a sporins would be appropriate.12 Perioperative (pro- safe and potentially reliable tool to accurately iden- phylactic) antibiotics were administered to 94% of tify appendiceal changes in appendicitis. Radiation the patients undergoing appendectomies of which exposure using this test is 300 mrad, which is below 60% were second-generation cephalosporins.9 Am- an accepted safe level of radiation exposure in preg- picillin or cephalosporins are used in combination nancy of 5 rad. Reliance on radiographic studies with metronidazole in cases with perforated or gan- may not be cost-effective, and may deter from care- grenous appendix.6 ful and timely serial physical exams.22 Chest radiograph may be useful in identifying Laparotomy versus Laparoscopic Surgery right lower lobe pneumonia from appendicitis in Assessment for open laparotomy is dependent on pregnant patients with right-sided abdominal pain. gestational age since the appendix progressively A plain abdominal radiograph can be used to iden- relocates. This is typically from McBurney’s point, tify air fluid levels or free air but offers little diag- and then rising above the iliac crest at about mid- nostic value. Radiation exposure to the fetus is less gestation, then upward to the gallbladder.16

than 300 mrad. McBurney’s point is the point situated about one- http://www.jabfm.org/ Laboratory evaluation may not be helpful and third the distance between the right anterior-supe- cannot be relied on.11 Leukocytosis in pregnancy rior iliac spine and the umbilicus. This area pro- can be as high as 16,000 cells/mL with bandemia vides effective access for appendectomy throughout present and still considered a normal variant and pregnancy, even in the third trimester.24 not a clear indicator of appendicitis. During labor, Pregnancy is not considered to be a contraindi- it may rise to 30,000 cells/mL, and not all pregnant cation for laparoscopic approach to appendecto- patients with appendicitis have leukocytosis. It is my.25 Fetal health complicates the management of on 1 October 2021 by guest. Protected copyright. not a reliable marker, as up to 33% of cases may the gravida patient with acute abdominal pain. have a leukocyte count greater than 15,000/mm4,8 When appendicitis is suspected, timely obstetric as well as a general surgical consult is necessary. Lapa- roscopic surgery in the pregnant patient has not Management and Treatment been broadly accepted in the latter second and Early surgical intervention, with less than a 24- third trimester due to the concern regarding fetal hour delay, has shown to be vital in minimizing wastage, the effects of carbon dioxide on the devel- both maternal and fetal morbidity and mortality. oping fetus and the long-term effects of this expo- Surgical delays of more than 24 hours from the sure.26 Laparoscopy procedures take approximately time of presentation have been associated with ap- 50% longer with conflicting studies showing de- pendiceal perforation and significant fetal loss and creased length of stay and hospitalization.9,27 Ques- cases of maternal mortality.8,14 Various tocolytic tions arise regarding the risk for decreased uterine agents are used prophylactically for uterine irrita- blood flow due to increased intraabdominal pres-

624 JABFM November–December 2006 Vol. 19 No. 6 http://www.jabfm.org J Am Board Fam Med: first published as 10.3122/jabfm.19.6.621 on 7 November 2006. Downloaded from sures from insufflation and the possibility of fetal after appendectomy. Int J Gynaecol Obstet 1999;65: carbon dioxide absorption.28 Use of nitrous oxide 129–35. pneumoperitoneum has been advocated25 although 3. Tracey M, Fletcher HS. Appendicitis in pregnancy. technical difficulties arise with the gravid uterus. Am Surg 2000;66:555–9:discussion 559–60. 4. Liu C, McFadden D. Acute abdomen and appendix. Blind placement of the Veress needle, or primary In: Surgery: Scientific Principles and Practice, 2nd port, has resulted in puncturing and subsequent ed. Edited by Grennfield L, Mulholland M, Oldham 27,29 pneumoamnion. K. Philadelphia: Lippincott-Raven 1997; p. 1246– With improved technique, laparoscopy surgery 61. has been shown to offer some advantages over open 5. Andersson RE, Lambe M. Incidence of appendicitis laparatomy: decreased postoperative pain, reduced during pregnancy. Int J Epidemiol 2001;30:1281–5. hospital, and wound morbidity.29 Postoperatively, 6. Al-Mulhim AA. Acute appendicitis in pregnancy. A early mobilization is advantageous for prevention review of 52 cases. Int Surg 1996;81:295–7. of thromboembolism as occurrence rates of deep 7. Andersen B, Nielsen TF. Appendicitis in pregnancy: diagnosis, management and complications. Acta Ob- vein thrombosis are higher in pregnancy. Early stet Gynecol Scand 1999;78:758–62. mobilization also reduces the occurrence of inci- 8. Tamir IL, Bongard FS, Klein SR. Acute appendicitis sion scars, hernias, and decreases fetal depression in the pregnant patient. Am J Surg 1990;160:571–6. 30 secondary to pain and narcotic use. 9. Hale DA, Molloy M, Pearl RH, et al. Appendec- tomy: a contemporary appraisal. Ann Surg 1997;225: 252–61. Conclusions 10. Stone K. Acute abdominal emergencies associated The accurate diagnosis of appendicitis during preg- with pregnancy. Clin Obstet Gynecol 2002;45:553– nancy requires a high level of suspicion and clinical 61. skills, and not merely relying on the classic signs 11. Maslovitz S, Gutman G, Lessing JB, et. The signif- and diagnostic testing. Delay of operation corre- icance of clinical signs and blood indices for the lates to more inflammatory changes in the appendix diagnosis of appendicitis during pregnancy. Gynecol Obstet Invest 2003;56:188–91. and to higher maternal and fetal complication rates. 12. Musselman RC, Nunnelee JD, Ware DB. Appendi- Early surgical intervention is essential. Suspected citis during pregnancy. Clin Excell Nurse Pract cases of this condition require serial physical exams 1998;2:338–42. as well as general surgery and obstetric consulta- 13. Al-Fozan H, Tulandi T. Safety and risks of laparos- tion, since they are most qualified to evaluate all copy in pregnancy. Curr Opin Obstet Gynecol 2002; aspects of a gravid patient and maternal physiology. 14:375–9. It remains to be determined which diagnostic test is 14. Horowitz MD, Gomez GA, Santiesteban R, Burkett http://www.jabfm.org/ best suited to facilitate or determine a diagnosis of G. Acute appendicitis during pregnancy. Diagnosis acute appendicitis in pregnancy and often the cor- and management. Arch Surg 1985;120:1362–7. rect diagnosis is determined only at surgical inter- 15. Nunnelee JD, Musselman R, Spaner SD. Appendec- tomy in pregnancy and postpartum: analysis of data vention. Primary care providers must assume a re- from a large private hospital. Clin Excell Nurse Pract sponsible role in recognizing potential signs and 1999;3:298–301.

symptoms of appendicitis in pregnancy and initiate 16. Baer J, Reis R, Arens R. Appendicitis in pregnancy on 1 October 2021 by guest. Protected copyright. prompt action to reduce negative outcomes. with changes in position and axis of nomal appendix in pregnancy. JAMA 98:1359, 1932. 17. Nathan L, Huddleston JF. Acute abdominal pain in We gratefully acknowledge the assistance of Angela Henke in pregnancy. Obstet Gynecol Clin North Am 1995;22: the preparation of this manuscript. We also thank Dr. Mark 55–68. Lema, Dr. Kim Griswold, and Dr. John Brewer for their exper- 18. Coleman MT, Trianfo VA, Rund DA. Nonobstetric tise and guidance. emergencies in pregnancy: trauma and surgical con- ditions. Am J Obstet Gynecol 1997;177:497–502. References 19. Sharp HT. Gastrointestinal surgical conditions dur- 1. Mourad J, Elliott JP, Erickson L, Lisboa L. Appen- ing pregnancy. Clin Obstet Gynecol 1994;37:306– dicitis in pregnancy: new information that contra- 15. dicts long-held clinical beliefs. Am J Obstet Gynecol 20. Lim HK, Bae SH, Seo GS. Diagnosis of acute ap- 2000;182:1027–9. pendicitis in pregnant women: value of sonography. 2. Hee P, Viktrup L. The diagnosis of appendicitis AJR 1992;159:539–42. during pregnancy and maternal and fetal outcome 21. Nguyen H, Le K, Le C. Concurrent ruptured ec- http://www.jabfm.org Appendicitis in Pregnancy 625 J Am Board Fam Med: first published as 10.3122/jabfm.19.6.621 on 7 November 2006. Downloaded from

topic pregnancy and appendicitis. J Am Board Fam 26. Rizzo AG. Laparoscopic surgery in pregnancy: long- Pract 2005;18:63–6. term follow-up. J Laparoendosc Adv Surg Tech A 22. Old J, Dusing R, Yap W, Dirks J. Imaging for Sus- 2003;13:11–15. pected Appendicitis. Am Fam Phys 2005;71:71–8. 27. Lachman E, Schienfeld A, Voss E, et al. Pregnancy and laparoscopic surgery. J Am Assoc Gynecol Lapa- 23. Niebyl JR. Antibiotics and other anti-infective rosc 1999;6:347–51. agents in pregnancy and lactation. Am J Perinatol 28. Sharp HT. The acute abdomen during pregnancy. 2003;20:405–14. Clin Obstet Gynecol 2002;45:405–13. 24. Popkin CA, Lopez PP, Cohn SM, et al. The incision 29. Friedman JD, Ramsey PS, Ramin KD, Berry C. of choice for pregnant women with appendicitis is Pneumoamnion and pregnancy loss after second- through McBurney’s point. Am J Surg 2002;183: trimester laparoscopic surgery. Obstet Gynecol 20–2. 2002;99:512–3. 25. Danso D, Dimitry ES. Perforated 26 weeks pregnant 30. Bisharah M, Tulandi T. Laparoscopic surgery in uterus at appendicectomy. BJOG 2004;111:628–9. pregnancy. Clin Obstet Gynecol 2003;46:92–7. http://www.jabfm.org/ on 1 October 2021 by guest. Protected copyright.

626 JABFM November–December 2006 Vol. 19 No. 6 http://www.jabfm.org