Chitosan-covered gauzes for pressure therapy in postpartum haemorrhage
We welcome the review by Chandraharan and Krishna on the diagnostic and management of postpartum haemorrhage (PPH) . We wish to comment on the role of pressure therapy with chitosan-covered gauzes, an innovative uterine packing technique in the management algorithm of PPH, not mentioned in the review.
Recent findings of the WOMAN study, a pragmatic randomised double-blind, placebo-controlled trial, support a reduction of mortality due to PPH in women treated with tranexamic acid, an antifibrinolytic agent, especially when it is given within three hours after childbirth . No significant reduction of hysterectomy rates was observed. Based on these findings, the authors conclude that tranexamic acid, should be given as soon as possible after the onset of bleeding. However, the WOMAN trial was conducted in high-level facilities (i.e. secondary and tertiary hospitals) which have all access to intravenous uterotonics, blood transfusion, and second-line interventions (e.g. uterine balloon tamponade, arterial embolization, uterine compression sutures, or even hysterectomy) through escalation in a timely manner. This is not the case at home or in primary health care centres in low-resource settings where two thirds of childbirths, maternal near-miss events, and maternal deaths occur , despite improved education of the health care work force .
In this context, we regret the absence of clear information dedicated to health care workers in low-resource settings in the review of Chandraharan and Krishna . Thus, in the management of the possible causes of PPH and the infographic summarizing their guidelines (http://bmj.com/content/bmj/suppl/2017/09/27/bmj.j3875.DC1/chae036081.wi.pdf), most of proposed interventions can be implemented only within high-level facility hospitals. The aim of PPH management in rural areas should be primarily to stop the bleeding to allow sufficient time to transport to hospital where more extensive treatment options are available.
In this context, chitosan-covered gauzes offer a ready-to-use solution that is easy to handle in the primary care setting [5-13]. Based on our collective experience in treating more than one hundred cases of severe PPH with chitosan-covered gauzes (CeloxTM) [5-8], we want to draw attention to this low-cost intervention and initiate further research in its use in PPH.
Chitosan is a hydrophilic polysaccharide made by deacetylation of chitin, the structural component of crustacean shells [5-9]. It has widespread applications and is highly biocompatible. Its haemostatic properties are independent of clotting cascades. Chitosan coagulates blood through electrostatic interactions with red blood cell membranes and it is bioactive even in the presence of heparin. Interestingly, it has also antibacterial properties that may reduce the risk of infection. Based on a strong experimental rationale, it has been used for years by the British and American armies to achieve rapid and efficient haemostasis onto the battlefield, to control bleeding from to gunshot wounds .
Furthermore, it has been used as lifesaving intervention in uncontrollable haemothorax after cardiothoracic surgery (e.g. dissection of left anterior coronary artery, subclavian wound by stabbing) , or as an adjunct to packing in uncontrollable pelvic haemorrhage secondary to penetrating trauma (e.g. transpelvic gunshot wound, bilateral lower limb amputations) .
In clinical studies, it has been proven effective against conventional pressure bandages in achieving haemostasis within five minutes and reducing blood losses among civilians treated for penetrating limb trauma . Recently, the combined treatment with chitosan-based pads and a rotary compression device was shown to achieve local haemostasis after radial artery access more rapidly than rotary compression device alone for coronary angiography in a single-centre open-label randomized controlled trial . Several other uses are currently developed, including the maintenance of haemostasis during surgical procedures, prevention of recalcitrant epistaxis, and different uses in nanomedicine. In all these different uses, the authors underscore the safety of chitosan-coated devices and the absence of side-effect.
To our knowledge, chitosan use for haemostasis exists in six different forms: granules (powder), gauzes, nasal plugs, gel, sponges, and pads. Interestingly, for obstetric care purposes, chitosan medical devices, are less expensive than Bakri intrauterine balloons [5-8].
Importantly, in a recent model of pregnant ewe delivered by caesarean section, chitosan-embedded mini-sponge dressing was shown to fil the uterine cavity and maintain contact pressure over 24 hours without causing adverse systemic or local tissue effects, which supports the potential use and safety of chitosan in the uterine cavity .
In PPH, CeloxTM gauzes have been used in the obstetric ward of the Mariankrankenhaus hospital in Hamburg, Germany, since 2011 [5,6]. Uterine packing with chitosan-covered gauzes was successful alone or together with uterotonics infusion, curettage, or uterine compression suture, in a wide range of aetiologies including uterine atony, abnormal placental insertion (e.g. accreta, percreta, or increta), heparin-related coagulopathy, and bleeding after curettage . Chitosan-covered gauzes were removed from the uterine cavity after 24-36 hours without observed side-effect. Most importantly, after introduction of haemostatic dressings, the number of postpartum hysterectomies dropped significantly (0.18% before, 0.05% after, relative risk reduction 72%, P-value = 0.0183) . The experience on the effectiveness and safety on CeloxTM is collected in an international registry . Recently, chitosan as haemostatic has been successfully used in French Guiana in a massive hemoperitoneum after hysterectomy, multiple vaginal lacerations and another hemoperitoneum, the two latter being treated with chitosan granules . In Reunion, it was used with success in an invasive molar pregnancy with massive bleeding (unpublished data).
In conclusion, given actual restrictions in the use of tranexamic acid and barriers to successful implementation of uterine balloon tamponade in low-resource settings , and given the low cost and easy use of chitosan-covered gauzes, we emphasise the role for chitosan haemostatic dressings in the management algorithm of PPH proposed by Chandraharan and Krishna. Aim for the future is to add more evidence to the role of chitosan-covered gauze in PPH and randomized clinical trials are underway [16,17].
The authors thank their colleagues for their support.
Conflict of interest
Dr Mohammed Khairy Ali is the recipient of a grant from Assiut University.
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Competing interests: No competing interests