Prevention of postpartum haemorrhage in Hong Kong: Risk and cost considerations

Currently, oxytocin is the agent of choice for postpartum haemorrhage (PPH) prevention at Hong Kong’s public hospitals. Although carbetocin, a synthetic analogue of oxytocin with a longer half-life, has been shown to be more effective at preventing PPH in a large-scale meta-analysis, it is also substantially more expensive than oxytocin. In an interview with MIMS Doctor, Professor Tak-Yeung Leung of the Department of Obstetrics & Gynaecology, Chinese University of Hong Kong (CUHK), discussed potential risks associated with PPH and whether the more expensive agent can offer greater savings to the public healthcare system.

PPH: Rare but burdensome
PPH, defined as blood loss of ≥500 mL following vaginal birth and ≥1,000 mL following Caesarean section (C-section), is a major cause of maternal morbidity and may lead to organ failure, shock, oedema, compartment syndrome, transfusion complications, thrombosis, acute respiratory distress syndrome, sepsis, anaemia, intensive care, and prolonged hospitalization. [BMC Pregnancy and Childbirth 2019;19:438; Comparative Effectiveness Reviews #151, Agency for Healthcare Research and Quality (US), 2015]

According to the latest data for Hong Kong, PPH prevalence was at 6.2 percent in 2017. [PLoS One 2022;doi:10.1371/journal.pone.0279130] “Although relatively rare, if PPH occurs, its consequences are of considerable burden to both the patient and the healthcare system,” said Leung. “First-line management is with a uterotonic drug, followed by balloon tamponade, compression sutures and artery embolization in the second line, and in very rare, life-threatening cases, hysterectomy may be performed.” [Hong Kong Med J 2020;26:370-371]

PPH prophylaxis: What’s it worth?
“As management of acute PPH may require transfusions and even surgery under general anaesthesia, followed by intensive care and a prolonged hospital stay, the medical costs are high. As a result of the risks associated with PPH, prophylactic treatment with a uterotonic agent is given to all mothers giving birth in Hong Kong,” explained Leung.

In Hong Kong’s public hospitals, oxytocin is currently the agent of choice for first-line prophylaxis of PPH in low-risk mothers. “Oxytocin is a very safe, well-researched and long-used drug, which is effective in the majority of cases. However, it has a short half-life and, as a result, its effect is not sustainable, meaning that in a minority of cases, it fails to prevent PPH, necessitating the administration of a second dose of oxytocin or possibly additional [costly] interventions,” commented Leung.

Carbetocin is a synthetic analogue of oxytocin, which has enhanced half-life, duration of action and heat stability. [Eur J Obstet Gynecol Reprod Biol 2009;147:15-20] It was found to be more effective at preventing PPH of ≥500 mL than oxytocin in a meta-analysis of 140 randomized trials involving a total of 88,947 women, which compared multiple uterotonics. [Cochrane Database Syst Rev 2018;doi:10.1002/14651858. CD011689.pub3] At the same time, the risks of headache, tremor, hypotension, flushing, nausea, abdominal pain, pruritus, and feeling of warmth are similar for women receiving carbetocin or oxytocin. [Eur J Obstet Gynecol Reprod Biol 2009;147:15-20] In Hong Kong, however, the cost per course of PPH prevention with carbetocin is 12–25 times higher than with oxytocin. [PLoS One 2022;doi:10.1371/journal.pone.0279130]

Carbetocin cost-effectiveness analysis
To examine whether use of carbetocin for PPH prevention is cost-effective in a Hong Kong public hospital setting, a decision-analytic model was developed, which simulated clinical and economic outcomes of carbetocin and oxytocin for PPH prevention in a hypothetical cohort of women in the third stage of labour following vaginal birth or C-section. Primary model outcomes included PPH-related direct medical cost, PPH, hysterectomy, maternal death, and quality-adjusted life-year (QALY) loss. [PLoS One 2022;doi:10.1371/journal.pone.0279130]

The CUHK researchers used inputs from a global literature search to create a base-case vaginal or C-section scenario and applied local data, such as drug acquisition costs, proportion of C-sections among all births, incidence of PPH, and need for emergency hysterectomy, to ensure their findings were relevant to Hong Kong. The model-simulated incidence of PPH (4.88 percent) and emergency hysterectomy (0.06 percent) was validated against the incidence of PPH (4.8–5.2 percent) and emergency hysterectomy (0.04–0.07 percent) reported in Hong Kong’s public hospitals in 2013–2016 (prior to the introduction of carbetocin in public hospitals), and found to be highly similar.

Up to 30 percent of all births in Hong Kong’s public hospitals are delivered via C-section. The probability of PPH with ≥500 mL blood loss using oxytocin as PPH prophylactic agent in 120 vaginal births (2.2 percent) and C-sections (1.1 percent) were approximated using 2013–2016 data from Hong Kong’s public hospitals, while the probability of the same occurring with carbetocin as the prophylactic agent were calculated using the 0.72 relative risk estimate for carbetocin vs oxytocin acquired from the aforementioned meta-analysis. [Cochrane Database Syst Rev 2018;doi:10.1002/14651858.CD011689.pub3] The proportion of cases with blood loss ≥1,500 mL among all PPH cases following vaginal birth (12 percent) and C-section (15 percent) were estimated from Hong Kong public hospital data.

PPH prevention with carbetocin during vaginal or C-section delivery appeared to reduce total direct medical cost and QALY loss in the public healthcare setting in Hong Kong. Compared with oxytocin, PPH-related cost with carbetocin was reduced by USD 29 per birth, while incidence of PPH with ≥500 mL and ≥1,500 mL blood loss was reduced by 13.7 cases and 1.9 cases per 1,000 births, respectively. It was also found that use of carbetocin would be associated with 15 fewer hysterectomies and 2 fewer maternal deaths for every 100,000 births vs oxytocin. In addition, the model showed that carbetocin saves 0.00059 QALY per birth. (Table) The study’s authors noted that while the cost analysis included direct medical cost, it did not consider indirect cost, such as loss of productivity, meaning that their findings may underestimate the economic benefits of PPH prevention with carbetocin.

“According to our research, carbetocin was the preferred cost-effective option for PPH prevention from the perspective of public healthcare provider in Hong Kong,” summarized Leung. “From patients’ perspective, the main advantages of using carbetocin would be reduced risk of adverse health outcomes and minimal hospital stay.”

Key take-away
“The primary objective for clinicians is to provide the best care through ensuring the highest level of safety for their patients. For administrators, it is to reduce costs while fostering better health across the entire population. Using carbetocin instead of oxytocin for every birth in Hong Kong would satisfy both goals due to carbetocin’s cost-effectiveness at preventing PPH without additional side effects,” concluded Leung.