Cardiac arrest during pregnancy is a catastrophic condition that can lead to major morbidity and mortality for both mother and baby. In addition, there may be dire consequences, on both medicolegal and psychological grounds, for health care personnel. Therefore, it is important that appropriate resources are available and prompt resuscitative measures are undertaken to improve maternal and neonatal outcomes in such situations.
The information on the incidence of maternal cardiac arrest reported in the literature has been variable; it has been cited as 1 in 30,000 pregnancies.1 According to the 2006 to 2008 triennial report from the Confidential Enquiries into Maternal deaths from the United Kingdom, the incidence was estimated as 1 in 50,000 births.2 The 10th annual report of Scottish Confidential Audit of severe maternal morbidity, which included data from 2003 to 2012, quoted the incidence of arrest as 1 in 25,000 births.3 A retrospective cohort study from the Netherlands identified 55 cases of maternal cardiac arrest in its 15-year review during 1993 to 2008, corresponding to an incidence of 1:53,260 deliveries.4 Maternal and neonatal case fatality rates in this study were found to be 83% and 58%, respectively.4 The only population-based study of maternal cardiac arrest conducted in the United States reviewed a nationwide inpatient sample of more than 50 million hospitalizations for delivery between 1998 and 2011.5 Cardiac arrest complicated 1:12,000 hospitalizations for delivery, of which 58.9% of women survived to hospital discharge. The rarity of cardiac arrest in pregnancy and high fatality from this condition, even in large maternity units, implies the importance of sharing knowledge and practices in various institutions/countries in managing this complication.
Recently, the Society for Obstetric Anesthesia and Perinatology committee developed a consensus statement to disseminate information and strategies to improve knowledge of and adherence to maternal cardiac arrest guidelines to optimize maternal and neonatal outcomes.6 This consensus statement is based on existing guidelines, multidisciplinary expert opinion, literature reviews, simulation data, and case reports.
The epidemiology of cardiac arrest in pregnancy in Canada is unknown, which could potentially limit the ability to develop national guidelines and policies on the management of maternal cardiac arrest.7 The objective of this study was to generate information about cardiac arrest during hospitalization for delivery in Canada by examining the frequency, temporal incidence, associated conditions, maternal, and neonatal survival rates.
This retrospective population-based cohort study used hospitalization data from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database relating to obstetric deliveries in Canada for 13 fiscal years from April 1, 2002, to March 31, 2015. Data from all jurisdictions in Canada (except the province of Quebec) were included in the study. The records include approximately 75% of all obstetric deliveries during the study period and are fairly representative of births in Canada.8
CIHI data, prepared under strict confidentiality guidelines, contain information extracted from the medical records of women admitted for delivery. The data were accessed through the Public Health Agency of Canada’s (PHAC) Canadian Perinatal Surveillance System. This study is based on secondary analyses, and the data source involved denominalized information from all hospitals in Canada (excluding Quebec), hence, ethics review board approval was not required.
The study population consisted of all pregnant women with gestational age of 20 weeks or more with cardiac arrest during hospitalization for childbirth, excluding early pregnancies with abortive outcome and ectopic and molar pregnancies. Diagnoses were coded according to the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems for diagnoses.9 Procedures were coded according to the Canadian Classification of Health Interventions.10 Cardiac arrest was defined based on the presence of diagnostic (I46.0, I46.1, I46.9, I49.00, and I49.01)9 and/or intervention codes (1.HZ.30.^^, 1.HZ.09.JA-FS, 1.HZ.09.LA-FS, and 1.HZ.09.LA-CJ) (Supplemental Digital Content 1, Supplemental Appendix 1, http://links.lww.com/AA/B640).10
Data on patient demographics, medical conditions, obstetrical complications during labor and delivery, and potential etiologies of cardiac arrest were retained. The definitions of medical and obstetric conditions are listed in Supplemental Appendix 1 (Supplemental Digital Content 1, http://links.lww.com/AA/B640). Temporal trend in the incidence of cardiac arrest was examined in addition to the provincial occurrence of cases. The primary outcome was the population-based incidence of cardiac arrest in pregnant women hospitalized for childbirth in Canada from April 1, 2002, to March 31, 2015. The secondary outcomes included rates of survival to hospital discharge, the association between cardiac arrest and medical and obstetric conditions, as well as neonatal survival rates.
Population demographics and the incidence of cardiac arrest by year and province were summarized using descriptive statistics. Rates were expressed per 100,000 deliveries. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to examine bivariate associations, and the Cochran-Armitage test for trend was used to examine temporal trends. Multivariable logistic regression analysis was used to identify medical and obstetrical conditions independently associated with maternal cardiac arrest after adjusting for maternal age, gestational age, parity, as well as all medical and obstetric conditions. A sensitivity analysis was done including cesarean delivery and stillbirth in the model because their sequential relationship with cardiac arrest could not be determined from our database. Statistical analyses were undertaken with SAS Version 9.2 (SAS Institute, Cary, NC) software.
We identified 286 cases of maternal cardiac arrest among 3,568,597 hospitalizations for childbirth between 2002 and 2015. The overall incidence was 8.0 per 100,000 deliveries (95% CI, 7.1–9.0 per 100,000 deliveries). The annual incidence varied between 4.6 and 10.5 per 100,000 deliveries; however, there was no statistically significant difference in the incidence over time (P = .42) (Figure 1). Provincial variation also failed to reach statistical significance (P = .47) (Figure 2). A total of 204 women (71.3%; 95% CI, 65.7–76.5%) survived to hospital discharge. The survival rate was not significantly different over time (Figure 3) and among the provinces. Among those with cardiac arrest, 82 women (29%) died, giving a fatality rate of 2.3 per 100,000 deliveries.
Table 1 shows the distribution of demographic characteristics in cases of cardiac arrest in pregnant women hospitalized for delivery. The odds of developing cardiac arrest were higher in women older than 35 years of age (OR, 2.34; 95% CI, 1.69–3.26), pregnant for the 5th or higher order (OR, 2.08; 95% CI, 1.15–3.75), and <37 weeks gestational age (OR, 6.22; 95% CI, 4.87–.95).
Among the obstetrical conditions complicating pregnancy, morbidly adherent placenta, placenta previa and abruption, and polyhydramnios were associated with maternal cardiac arrest. Hypertensive disorders of pregnancy, gestational diabetes, malignancy, and diseases of the respiratory and nervous systems were the preexisting maternal medical conditions found to be significantly associated with cardiac arrest (Table 2).
Several acute conditions were significantly associated with cardiac arrest, including intrapartum and postpartum hemorrhage, heart failure, amniotic fluid/obstetric embolism, complications of anesthesia, trauma, sepsis, eclampsia, pulmonary edema, obstetric trauma, aortic aneurysm, or dissection (Table 3).
Twenty-eight (10%) women had a diagnostic code of cardiac arrest/failure during pregnancy, labor and delivery, or puerperium as a result of complications from anesthesia. However, we were unable to distinguish cases of cardiac arrest from cardiac failure because of combined coding for those conditions. Three patients had aspiration pneumonitis, and 2 patients had failed/difficult intubation during labor and delivery.
Cesarean delivery (OR, 5.72; 95% CI, 3.79–8.62) and stillbirth (OR, 6.87; 95% CI, 4.09–11.52) were significantly associated with cardiac arrest. However, even after repeating the analysis including these 2 variables in the model, the level of significance of associated medical, obstetric, and acute conditions with cardiac arrest remained unchanged (Supplemental Appendix 2 and 3, Supplemental Digital Content 2, http://links.lww.com/AA/B641).
When examining survival from arrest by potential etiologies, conditions such as eclampsia, pulmonary edema, heart failure, antepartum and postpartum hemorrhage, and obstetric embolism including amniotic fluid embolism, sepsis, and trauma have a fairly good survival rate of more than 50%, with complications from anesthesia having the most favorable outcome (Figure 4).
Basic neonatal outcome data were available on 268 neonates. A total of 23 neonates survived to hospital discharge (86%), 10 neonates died (4%), and 28 were stillborn (10%); 135 neonates (50%) were admitted to the neonatal intensive care unit.
This is the first Canadian population-based cohort study on the epidemiology of cardiac arrest in pregnant women hospitalized for delivery. Our analysis shows that during a period of 13 years, 1 in 12,500 hospitalizations for delivery in Canada was complicated by cardiac arrest. Preexisting conditions such as hypertensive disorders of pregnancy and gestational diabetes were found to be the most common diagnoses associated with cardiac arrest, whereas postpartum hemorrhage, heart failure, amniotic fluid embolism, and complications of anesthesia were identified as the most common potential etiologies. The overall survival to hospital discharge rate was high, at 71%; however, it varied as per the etiology, with 100% survival for anesthesia-related complications.
Our literature search revealed a lack of studies on the true incidence, maternal outcome, predisposing comorbid conditions, and prognostic factors after maternal cardiac arrest in Canada. A recent study of maternal mortality by Lisonkova et al11 estimated the maternal mortality rate and evaluated temporal trends using hospitalization data from CIHI. However, this study did not provide mortality rates attributable to maternal cardiac arrest. According to the World Health Organization initiative, “Making Pregnancy Safer,”12 the statistics about maternal mortality itself do not help us identify what can be done to prevent or avoid unnecessary deaths, and hence, monitoring at global, regional, and national levels is a prerequisite for providing essential management guidelines. The existing resuscitation guidelines in pregnancy are based on anecdotal sporadic case reports/series and are not supported by robust or high-quality evidence.13 Because of the extremely rare nature of the event, obtaining evidence-based information from randomized controlled trials is impractical. Therefore, the most efficient way to address this global issue is to review and analyze the cases of maternal cardiac arrest to help better understand why women die or survive after such severe events. This will enable health care providers to take necessary actions based on the results.
The event rate in our study was 8:100,000 or 1:12,500 deliveries and is similar to that reported in the United States cohort.5 It is higher than the rate reported by the Scottish Confidential Audit and a cohort from the Netherlands,2–4 likely because of the differences in data acquisition between the studies. The above-mentioned surveillance systems require active reporting of the cases, whereas both the results by Mhyre et al,5 and the current results relied on diagnostic and intervention codes for cardiac arrest from administrative data sets.
We did not observe a temporal trend in rates of maternal cardiac arrest over time, nor any significant variations among provinces. This finding could merely indicate the rarity of the complication (ie, low absolute risk). A total of 85% of cases were from 3 provinces (Ontario, Alberta, and British Columbia), primarily because of high volume of hospitalizations in these provinces. This finding is in contrast with previous studies that have shown substantial provincial variation in the rates of maternal mortality11 and morbidity14 in Canada.
The report by Liu et al14 indicated temporal decline in the incidence of some conditions, such as eclampsia and sepsis, that could potentially cause the arrest. Our analysis of the most common contributing and potentially causative factors indicated that despite the rise in the rates of postpartum hemorrhage, gestational hypertension and diabetes, heart failure, and obesity during the study period (Figure 5), the rates of maternal cardiac arrest have remained the same. One of the possible explanations could be better surveillance and antenatal care of women with these conditions.
The analysis of maternal mortality, based on vital statistics death registration in Canada by Lisonkova et al,11 suggested that the most common causes associated with maternal death from 1981 to 2007 were cardiovascular disorders, hypertensive disorders of pregnancy, postpartum hemorrhage, and obstetric embolism. There was also a significant increase in maternal deaths caused by major puerperal infection over the observed time period. Mhyre et al5 found hemorrhage, heart failure, and amniotic fluid embolism as the most common potential etiologies for cardiac arrest in their review. In our cohort, we identified similar potential precipitating factors. Although hypertensive disorders of pregnancy and gestational diabetes were present in 37% of cases, postpartum hemorrhage, heart failure, amniotic fluid embolism, and complications of anesthesia together accounted for potential etiologies in 95% of cases of cardiac arrest. Similar to our study, a recent population-based cohort study of all hospital deliveries in Canada from 2003 to 2010 by Mehrabadi et al15 revealed a 22% increase in the incidence of postpartum hemorrhage, with a 48% increase in the rate of postpartum hemorrhage with blood transfusion and a 171% increase in postpartum hemorrhage with procedures to control bleeding. This increasing incidence of postpartum hemorrhage is in keeping with findings from other countries.16,17
Heart failure during pregnancy could be either a complication of a preexisting cardiovascular disorder or a manifestation of peripartum cardiomyopathy. In the large worldwide registry of pregnant women with underlying cardiac disease, it was the most common complication, occurring in 13% of patients and found predominantly in women with poor prepregnancy cardiac function, with a diagnosis of cardiomyopathy or pulmonary hypertension.18
Amniotic fluid embolism comprised 13% of the cases in our population cohort. In recent years, several population-based studies have examined its incidence, temporal trends, and risk factors from Canada,19 Australia,20 the United Kingdom,21 and the United States.22 A recent Canadian population-based study that included hospital deliveries from 1991 to 2009 yielded an incidence of 2.5 per 100,000 deliveries for amniotic fluid embolism, with 27% of cases being fatal.23 Significant risk factors included medical induction, cesarean delivery, instrumental vaginal delivery, and uterine or cervical trauma. The most common confirmatory criterion for diagnosing amniotic fluid embolism was cardiac arrest (47%).
The incidence of puerperal sepsis was relatively low in our study; however, the fatality rate was high, at 40%. The 2006 to 2008 confidential inquiries into maternal deaths report from the United Kingdom identified sepsis as a newly emerging leading cause of direct maternal death.2
This study was unique in addressing maternal weight as a contributing factor because most databases do not have this information. Despite not reaching statistical significance, 15 (5%) women with cardiac arrest in this cohort had obesity as a comorbidity, further indicating a potential deleterious effect of this condition on maternal health. Its prevalence was 5 times higher among women who sustained cardiac arrest compared with those who did not. The proportion of overweight and obese women in Canada rose from 34% in 1978 to 40% in 1992, and in 2004, it was 53%.24,25 Obese parturients are at increased risk of developing gestational hypertension, diabetes, thromboembolic event, undergoing cesarean delivery, and experiencing failed intubation compared with parturients with a body mass index less than 30 kg/m2.26
The distribution of risk factors in this study parallels plausible etiology of maternal cardiac arrest. As such, women >35 years of age are at risk of developing eclampsia27 or having a stillbirth.28 Gestational hypertension and diabetes are common in both advanced age and obese women.26,29,30 Similarly, morbidly adherent placenta is an important cause of intrapartum and postpartum hemorrhage.31 Malignancy during pregnancy is a rare occurrence and may pose challenges in obstetric management.32 Other associated medical conditions include diseases of nervous system and lower respiratory tract, hence, patients with these conditions should be closely monitored in the peripartum period.
Although the odds of sustaining cardiac arrest was 6 times higher in women who had cesarean delivery, we were unable to comment on plausibility of this association because cesarean delivery could have been performed as a result of cardiac arrest. Furthermore, the CIHI database cannot distinguish between elective and emergency cesarean delivery.
The high survival rate (71%) reported in this study is very encouraging and suggests that women can survive this rare but potentially fatal event. The survival rate after maternal cardiac arrest reported in the literature varies between 17%4 and 59%.5 Therefore, the survival rate in Canadian women sustaining cardiac arrest in pregnancy is the highest reported in the literature to date. The patients with cardiac arrest who had complications of anesthesia, eclampsia, or pulmonary edema/heart failure had the highest survival rate, whereas those with acute myocardial infarction and aortic aneurysm dissection had the lowest. One of the potential explanations for such a high survival rate from anesthetic complications is the availability of immediate resuscitation in the operating room or labor and delivery room.
This is the only population-based study that addresses neonatal outcome after maternal cardiac arrest. Dijkman et al4 reported a neonatal case fatality rate of 58% in their 15-year audit of perimortem cesarean deliveries. However, we are neither able to determine the temporal relationship between delivery of the infant and maternal arrest, nor the details of delivery to comment whether or not adhering to the 5-minute rule was observed.33
The limitations of this study are similar to any analysis using an administrative data set. The hospitalization records do not directly identify an underlying cause of cardiac arrest. The inability to determine sequential relationship between delivery and cardiac arrest makes it impossible to recommend the safest mode of delivery in women with known risk factors. Survival rates, although important, do not specify whether the woman was neurologically intact at the time of discharge. Furthermore, we could not obtain additional detailed information on the neonatal data, and stillbirth data could not be linked to the maternal records. The nature of the database also does not include out-of-hospital cardiac arrests, which could have a different distribution of risk factors and medical conditions. Finally, we were not able to examine cardiac arrest during hospitalization for delivery in Quebec because data from this province are not available through the CIHI discharge abstract database for administrative reasons. For this reason, the data set for this study captures approximately 75% of obstetric deliveries across the country.
The quality of information in the hospitalization data has been investigated previously.8,34 The number of data errors in terms of illogical or out-of-range values was found to be low, and the estimated prevalence of maternal comorbid conditions was similar to that reported in the literature. The hospitalization data have been successfully used in previous studies of maternal morbidity and infant health outcomes,14,23 which provides reassurance regarding the validity of our findings.
With the significant progress made toward achieving the United Nation Millennium Development Goal number 5, resulting in an overall reduction of the risk of dying from pregnancy-related causes by half, international efforts are now focused on achieving the sustainable development goal of ending maternal deaths by 2030.35 This warrants the need to establish a system for comprehensive maternal health surveillance to ensure that each death or “near-miss” event is captured and the lessons learned are widely disseminated to improve safety in pregnancy in the future. The results from our study could serve as baseline for future investigations based on more comprehensive maternal morbidity and mortality data. Furthermore, as shown in simulation studies, obstetrical care providers are not always up to date with respect to current maternal resuscitation guidelines.36 Therefore, our findings could contribute to guiding content development and delivery of future regular simulation drills in hospitals across Canada caring for pregnant patients so that patient safety can be further improved. Finally, focusing on the effective treatment of the predisposing conditions identified in this review can help prevent the incidence of this dreadful complication.
In conclusion, this was the first Canadian study on the epidemiology of cardiac arrest during hospitalization for delivery. It was most commonly associated with postpartum hemorrhage, heart failure, amniotic fluid embolism, and complications of anesthesia. Survival rate was high overall but varied by etiology.
Name: Mrinalini Balki, MBBS, MD.
Contribution: This author helped design and conduct the study, interpret the data, and write and revise the manuscript.
Name: Shiliang Liu, MB, PhD.
Contribution: This author helped design and conduct the study, analyze the data, and revise the manuscript.
Name: Juan Andrés León, MD.
Contribution: This author helped design and conduct the study, analyze the data, and revise the manuscript.
Name: Leyla Baghirzada, MD.
Contribution: This author helped design and conduct the study, interpret the data, and write and revise the manuscript.
This manuscript was handled by: Jill M. Mhyre, MD.
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