Report from the Maternal Death Exploratory Committee

J. Obstet. Gynaecol. Res. 2016

doi:10.1111/jog.13136

Recommendations for saving mothers’ lives in Japan: Report from the Maternal Death Exploratory Committee (2010–2014) Junichi Hasegawa6, Tomoaki Ikeda1, Akihiko Sekizawa2, Hiroaki Tanaka1, Masamitsu Nakamura2, Shinji Katsuragi3, Kazuhiro Osato1, Kayo Tanaka1, Takeshi Murakoshi4, Masahiko Nakata7, and Isamu Ishiwata5 on behalf of the Maternal Death Exploratory Committee in Japan and the Japan Association of Obstetricians and Gynecologists 1

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, 2Department of Obstetrics and Gynecology, Showa University School of Medicine, 3Department of Obstetrics and Gynecology, Sakakibara Heart Institute, 7Department of Obstetrics and Gynecology, Toho University, Tokyo, 4Obstetrics and Gynecology, Maternal and Perinatal Care Center, Seirei Hamamatsu General Hospital, Shizuoka, 5Ishiwata Obstetrics and Gynecology Hospital, Ibaraki and 6Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kanagawa, Japan

Abstract To make recommendations for saving mothers’ lives, issues related to maternal deaths including diseases, causes, treatments, and hospital and regional systems are analyzed by the Maternal Death Exploratory Committee in Japan. In this report, we present ten clinical important recommendations based on the analysis of maternal deaths between 2010 and 2014 in Japan. Key words: blood transfusion, emergency medicine, maternal death, maternal mortality rate, postpartum hemorrhage.

Recommendations to prevent maternal death 1. Remind the importance of vital signs. 2. Obtain diagnostic skills and hemostasis for postpartum hemorrhage. 3. Do not hesitate to perform immediate blood transfusion or maternal transport during shock. 4. Use not only red blood cell, but also fresh frozen plasma primarily for postpartum hemorrhage. 5. Leave from bed within a day after cesarean section to prevent pulmonary embolism. 6. Keep amniotic fluid embolism in mind. 7. Consider pre-eclampsia and HELLP syndrome as risk factors for cerebral stroke. 8. Develop the emergency response system and cooperate with emergency physicians, anesthesiologists, and other medical providers.

9. Obtain maternal resuscitation skills. 10. Recommend autopsy and report case to the Japan Society of Obstetrics and Gynecology when maternal death occurs.

Introduction In Japan, approximately 2500 facilities provide delivery services for approximately one million pregnant women per year. However, more than half of all deliveries are managed in private clinics organized by one or sometimes two obstetricians because of pregnant women’ accessibility and comfort of the delivery facilities. Besides, anesthesiologists are not present full time, and obstetricians usually administer anesthetics during cesarean section (CS) in most of such clinics. Nevertheless, the perinatal mortality rate in Japan, which was 8.8 and 4.0 per 100 000 births in 1992 and

Received: June 27 2016. Accepted: July 17 2016. Correspondence: Dr Junichi Hasegawa, Associate Professor, St. Marianna University School of Medicine, Department of Obstetrics and Gynecology, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan, Tel. +81-44 (977) 8111 ext. 3332 Email: [email protected]

© 2016 Japan Society of Obstetrics and Gynecology

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2012, respectively, has halved over the last two decades, and Japan is one of the countries in the world with the lowest perinatal mortality rate.1 However, the Japan Association of Obstetricians and Gynecologists (JAOG) established a registration system and the Maternal Death Exploratory Committee in 2010 to reduce the number of maternal deaths. Furthermore, to reduce the number of maternal deaths due to similar causes, several analyses associated with maternal death in Japan were demonstrated in the previous studies.2–6 To provide information that could lead to the prevention of maternal deaths, and to improve the quality of obstetric health care in Japan almost all cases resulted in maternal death has been reported to JAOG wherein the Committee conducted causal analysis for each maternal death, since the registration system has started. The problems in maternal deaths between 2010 and 2014, including diseases, causes, treatments, and hospital and regional systems, were reported in the previous article.2 We reviewed maternal death cases between 2010 and 2014 and extracted ten recommendations that were important and vital reminders to prevent maternal death.

Review and analysis of maternal deaths Between January 2010 and June 2014 in Japan, 213 women, who died during pregnancy or within a year after delivery and whose detailed reports were submitted to the JAOG, were analyzed by the Maternal Death Exploratory Committee. Detailed methods of the cases analyzed were described in the previous report.2 Among these subjects, 59% (125) and 23% (49) were categorized as direct and indirect pregnancy-associated deaths, respectively. Ten cases were accidental deaths, and 29 cases were not evaluable.

Interpretation of recommendations The Maternal Death Exploratory Committee strongly recommends that the following points be incorporated into the management of pregnancies and deliveries in daily clinical settings. 1. Remind the importance of vital signs. a) One-fourth of maternal deaths are due to postpartum hemorrhage. The most frequent cause of maternal deaths between 1992 and 2014 was PPH although the maternal mortality rate associated with PPH reduced from 38 to 23%2,7 (Fig. 1). Of all maternal deaths, 52% occurred after transvaginal delivery or Cesarean section. More than half of the maternal deaths that were caused by PPH were associated with atonic bleeding2 (Fig. 2). b) Interval between postpartum hemorrhage and cardiopulmonary arrest is not too short. Interval between initial symptoms and cardiopulmonary arrest is not too short, and its peak duration was 1–3 h2. No cases of PPH were recorded wherein cardiopulmonary arrest occurred within 30 min2. Therefore, the committee considers that improvement of the management of PPH can reduce the maternal mortality rate.

Ethics statement This study was approved by the ethics board of the National Cerebral and Cardiovascular Center (No. N18–34), Osaka, Japan and the JAOG (No. 294), Tokyo, Japan. This investigation was conducted according to the principles expressed in the Declaration of Helsinki. Informed consent was not obtained from patients or their families because this study was based on the analysis of institutional forms, and the patient records/information was anonymized before the analysis.

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Figure 1 Causes of maternal deaths between 2010 and 2014 (n = 213).


For saving mothers’ lives

to account for 3.7% of all maternal deaths. The initial symptoms of high fever and abdominal or chest pain are characteristics and are attributable to a common cold syndrome or viral infection8; they are associated with early onset and rapid progression resulting in disseminated intravascular coagulopathy (DIC) and death within a day. Administration of antibiotics (clindamycin with beta-lactam) for pregnant women might be recommended even for treatment of initial symptoms9 because postpartum females have a 20-fold increased incidence of GAS compared with non-pregnant females.10 GAS infection also should be suspected when spontaneous abortion and strong uterine contractions associated with infections are noted. 2. Obtain diagnostic skills and hemostasis for postpartum hemorrhage. Figure 2 Causes of postpartum hemorrhage in maternal deaths (n = 49).

c) Think of emergency condition when shock index is >1. Vital signs and the amount of bleeding should be immediately determined; efficient primary care, including hemostasis, vital care, and primary resuscitation are required in cases of PPH. Treatment was delayed until the onset of sudden obvious severe symptoms such as impaired consciousness and cardiopulmonary arrest, when caregivers often chose expectant management over an extended time in cases with unimproved continuous small bleeding after delivery, even though the shock index was greater than 1.

a) Prompt diagnosis and hemostasis are required. The initial symptoms occurred during or after delivery in most maternal deaths. The committee emphasized that the immediate detection, interpretation of abnormal conditions, and efficient provision of primary care for PPH were required to prevent maternal deaths. Sufficient primary care with diagnostic strategies is recommended (Fig. 3). Bimanual compression of the uterus is effective not only for hemostasis of atonic bleeding, but also for circulation improvement in the inferior vena cava (IVC). Balloon tamponade may also control massive bleeding temporarily. At the

d) Hypotension is a final condition because of homeostasis. The vital signs in pregnant women are likely to remain relatively stable due to homeostasis even during massive hemorrhage, but the blood pressure suddenly deteriorates thereafter. e) Suspect sepsis in pregnant women with high fever or shock vital signs. Maternal deaths due to infectious diseases were reported in 7% of all maternal deaths. Septic shock should be considered in pregnant women with high fever. Serious group A streptococcal (GAS) toxic shock syndrome is still one of the significant causes of maternal death, estimated


Figure 3 Primary care with diagnostic strategies for postpartum hemorrhage.

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same time, immediate evaluation of PPH is required for complete hemostasis. Obstetricians should consider carrying out the next procedure (operation, transport, etc.) during bimanual compression of the uterus and tamponade. When PPH occur during CS, obstetricians should obtain hemostasis techniques such as compression suture and hysterectomy. b) Focused assessment obstetrics (FASO).

with

sonography

for

The FASO technique (a modified version of focused assessment with sonography for trauma; FAST) allows us to differentially evaluate the status of the patient with PPH because primary obstetric survey is a quick diagnostic method for PPH.11,12 A transabdominal ultrasound transducer is used in a FASO assessment to examine the uterine cavity, Morrison’s pouch, spleen region, pouch of Douglas, and IVC diameter within one minute. This assessment leads to the evaluation of retained placenta, intraabdominal bleeding, and hypovolemia. 3. Do not hesitate immediate blood transfusion or maternal transport during shock. a) 20% of deaths were associated with delay in blood transfusion. We assessed preventability in each case. A majority of PPH cases were classified to be preventable with some probability.2 Diagnosis and treatment, including not only primary care, medications, and surgical interventions, but also blood transfusion should not be delayed b) In a primary hospital, maternal transport should be considered during shock. The initial symptoms occurred inside and outside a medical facility in 71% and 29% of patients, respectively. Maternal transport was required in 58% of cases because of medical management limitations in small-scale facilities although the initial cardiopulmonary arrest occurred at a clinic, hospital, and midwifery home in 12%, 70%, and 1% of deaths. c) 10% of transported patients suffered cardiopulmonary arrest in the ambulance. Cardiopulmonary arrest occurred during transportation in 10% of patients between medical facilities

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d) Strong lines of regional communication should be established. The committee considers that more than half of all maternal deaths are still not preventable due to the severity of the patients’ conditions. On the other hand, in cases wherein maternal death was considered to be preventable, delay in maternal transport, intervention, and blood transfusion were associated with death. Enhanced regional communication and cooperation system should be established at both the inter- and intra-hospital levels; stronger ties are required among the caregivers in primary delivery services such as clinics that engage a single obstetrician and doctors in regional tertiary center hospitals. 4. Use not only red blood cell, but also fresh frozen plasma primarily for PPH. In cases of hemorrhagic shock, blood transfusion (fresh frozen plasma and red blood cell) should be immediately prepared; if it is not possible to obtain a blood supply, patient should be immediately transported to the center hospital. Massive fluid replacement is also required during preparation of blood transfusion and transportation. 5. Leave from bed within a day after cesarean section to prevent pulmonary embolism. The incidence of maternal deaths associated with pulmonary embolism in Japan was estimated to be 7%.1,13 Most patients with pulmonary embolism after CS had delayed first walking after CS. The committee strongly recommends that postpartum women leave from bed within a day after CS. 6. Keep amniotic fluid embolism in mind. a) Almost all patients with amniotic fluid embolism (AFE) result in death. The initial cardiopulmonary arrest occurred within 30 min in most patients with AFE. The Maternal Death Exploratory Committee considered deaths associated with AFE to be difficult to prevent. b) Prepare to encounter AFE in each hospital. Deaths associated with AFE were the most difficult to prevent due to the severity of DIC and the rapidly progressive condition of the disease itself. Mothers need high levels of intensive medical treatment and management when



complicated with AFE. Therefore, AFE treatment and management should be reconsidered in each hospital. Pathological examination (including autopsy) and maternal serum analysis are useful for diagnosis and also important as evidence of AFE complication. 7. Consider pre-eclampsia and HELLP syndrome as risk factors for cerebral stroke.

pregnant has increased due to advances in pharmaceutical and surgical therapies for CVD, which correlates with the increase in the rate of maternal deaths related to CVD. Women with previous disease history should be counseled cautiously from the beginning of pregnancy on life-threatening pregnancy risks, both for them and for the unborn child.

a) Extreme hypertension should be controlled immediately.

c) Medications for epilepsy and psychiatric disorders should not be stopped because of pregnancy.

The second most frequent cause of death was brain disease, which accounted for 16% of maternal deaths.2 The final diagnosis of the direct cause of maternal death in mothers with hypertensive disorder was cerebral stroke in 50% of the cases. Hepatic hemorrhage, AFE, pulmonary edema, and convulsion were considered to be the other causes of death in patients with hypertensive disorders.4 Recently, the prophylactic use of corticosteroids besides both anti-convulsive and anti-hypertensive drugs in patients with HELLP syndrome, which is called as the Mississippi protocol, has been advocated to prevent severe complications related to maternal death.14

Sudden unexpected death in epilepsy (SUDEP) is defined as the sudden death of a patient with epilepsy caused by its complications.15,16 A number of studies on the mechanism of SUDEP have suggested hypoventilation due to epileptic attack, arrhythmia, central neural dysfunction, and autonomic nervous system dysfunction as possible causes.17–19 It is considered that sudden death risk for pregnant women with epilepsy may be higher than that of the non-pregnant state.20 Not only women with epilepsy, but also women with psychiatric disorder likely discontinued taking their drugs without consulting psychiatrists and obstetricians after pregnancy. Otherwise, blood levels of such drugs may decrease due to pregnancy. To avoid such complications in pregnant women with epilepsy and psychiatric disorders, pre-conception counseling, planning pregnancy, routine clinic visit, and continuing drug therapy during pregnancy are recommended.

b) Immediate termination should be considered. The immediate appropriate management of hypertension during pregnancy and early maternal transport to a tertiary hospital are recommended although half of the deaths due to brain disease are considered to be impossible to prevent. 8. Develop the emergency response system and cooperate with emergency doctors, anesthesiologists, and other medical providers. a) Share the burden of treatment with the other department doctors. The obstetricians should develop a good relationship with not only emergency doctors, but also anesthesiologists, interventional radiologists, pediatricians, and other hospital staff members at the tertiary hospital. All medical providers should work in perfect unison in the event of an emergency. b) Share information of pregnant women with complications between obstetrician and the specialist of the disease. For example, the number of women with cardiovascular disease (CVD) who decide to become


9. Obtain skills for maternal resuscitation. a) Prepare treatments for cardiopulmonary arrest. Resuscitation for pregnant women is very difficult even by anesthesiologists and emergency doctors. Caregivers in delivery services should reconsider the strategies that they apply in dealing with complications in pregnant women. The obstetricians should develop a good relationship with well-skilled doctors and other hospital staff members, not only intra-, but also regional inter-hospital relationship during emergency. b) Obtain skills for maternal resuscitation. Because it is important to consider both changes in vital signs at the early stage and the initial treatment, daily training and simulation enable

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us to take prompt action during real emergencies. To reduce maternal mortality rate, the Japan Council for Implementation of Maternal Emergency Life-Saving System (J-CIMELS) was established in October 2015 by the JAOG, Japan Society of Obstetrics and Gynecology (JSOG), Japan Society of Perinatal and Neonatal Medicine, Japanese Society of Anesthesiologists, Japanese Society for Emergency Medicine, Kyoto Society for Emergency Response in Obstetrics and Gynecology, and Maternal Death Exploratory Committee in Japan. The aim of the simulation course organized by J-CIMELS is for all caregivers in delivery service to understand maternal conditions and develop skills regarding primary care for maternal emergency with the help of doctors well trained in emergency medicine. All caregivers in delivery service should participate in this course and improve their skills for safe management of women during pregnancy and labor. 10. Recommend autopsy and report case to JSOG when maternal death occurs. a) Causation of the death in women during or after pregnancy is so complex that we cannot easily recognize it. Epidemiology and methods of treatment and prevention still have not been established in many diseases associated with pregnancy and childbirth, such as pre-eclampsia and PPH. Autopsy is useful to make unknown etiology of the maternal deaths clear. Because the incidence of autopsy in Japan is lower than that in western countries, unknown cause of the maternal deaths was often obliged to be reported from this committee. Complete registration system of maternal deaths to JAOG, increased rate of autopsies, detailed evaluation of each case, and analyses of maternal deaths in Japan could further reduce deaths. b) Autopsy makes unknown cause of deaths clear. Many diseases in pregnant women, such as AFE, pulmonary embolism, cardiac disease, and aneurysm might be revealed by autopsy. It is also difficult to distinguish small placental adherence from incomplete uterine rupture without pathological examination or autopsy. Besides, autopsy is important in the prevention and

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treatment for further similar emergency cases. Inherited disease such as Marfan syndrome might be found by autopsy and this information might be useful for relatives.Recently, the use of autopsy imaging is also considered. Although it is useful for investigations of anatomical disruptive changes, such as stroke and dissection of the artery, use of autopsy imaging for other pathologic conditions has several limitations.21 Thus, autopsy imaging could be selected instead of autopsy, if the family does not provide consent to perform an autopsy.

Acknowledgments Members of the Maternal Death Exploratory Committee in Japan Tomoaki Ikeda (Chair), Tsuyomu Ikenoue, Hiroshi Ishikawa, Isamu Ishiwata, Nobuya Unno, Kazuhiro Osato, Akifumi Kagiya, Shinji Katsuragi, Naohiro Kanayama, Masakiyo Kawabata, Akihiko Kikuchi, Hirokatsu Kitai, Takahiko Kubo, Takao Kobayashi, Shigeru Saito, Shoji Satoh, Yumi Shiina, Akihiko Sekizawa, Tsuneo Takahashi, Satoru Takeda, Yoshiharu Takeda, Kayo Tanaka, Hiroaki Tanaka, Noboru Tanabe, Yuki Tsukahara, Katsuo Terui, Masahiko Nakata, Masao Nakabayashi, Masamitsu Nakamura, Junichi Hasegawa, Toshimitsu Maemura, Hideo Matsuda, Nobuaki Mitsuda, Takeshi Murakoshi, Jun Murotsuki, and Jun Yoshimatsu.

Members of the Maternal Death Case Review Committee Tomaki Ikeda (Chair), Isamu Ishiwata, Nobuya Unno, Kazuhiro Osato, Toshiyuki Okutomi, Shinji Katsuragi, Rie Kato, Naohiro Kanayama, Chizuko Kamiya, Satoshi Kimura, Takahiko Kubo, Tomohito Sadahiro, Yumi Shiina, Hiroyuki Sumikura, Akihiko Sekizawa, Makoto Takeuchi, Kayo Tanaka, Hiroaki Tanaka, Motoshi Tanaka, Katsuo Terui, Masahiko Nakata, Kentaro Nakama, Masamitsu Nakamura, Yoshiya Nishida, Junichi Hasegawa, Hideo Matsuda, Hiroshi Matsumoto, Takeshi Murakoshi, Hidenori Yoshizawa, Jun Yoshimatsu, and Tomoko Wakasa.

Disclosure No author has any potential conflict of interest.



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