|Year : 2017 | Volume
| Issue : 4 | Page : 119-124
Living donor hepatectomy in female donors with ongoing menstruation: Safety and ethical issues
Horng-Ren Yang1, Ashok Thorat2, Kin-Shing Poon3, Chun-Chieh Yeh1, Yi-Ying Chiang3, Te-Hung Chen1, Shih-Chao Hsu1, Long-Bin Jeng1
1 Organ Transplantation Center, China Medical University Hospital; Department of Surgery, China Medical University Hospital; China Medical University, Taichung, Taiwan
2 Organ Transplantation Center, China Medical University Hospital; China Medical University, Taichung, Taiwan
3 China Medical University; Department of Anaesthesiology, China Medical University Hospital, Taichung, Taiwan
|Date of Submission||03-May-2016|
|Date of Decision||09-Jul-2016|
|Date of Acceptance||17-Nov-2016|
|Date of Web Publication||19-Jul-2017|
Organ Transplantation Center, China Medical University Hospital, 2, Yuh-Der Road, Taichung
Source of Support: None, Conflict of Interest: None
Purpose: The purpose of this study was to study the safety of the major hepatectomy in female donors with ongoing menstruation in situations where the recipient needs urgent liver transplantation and its impact on menstrual bleeding and subsequent menstrual cycles.
Materials and Methods: Fifty-eight female donors that underwent adult-to-adult living donor liver transplantation were enrolled in this study and were categorized into two groups. Group A comprised 49 female donors with normal physiological state and Group B comprised nine female donors with ongoing menstruation during the surgery. All the donors in the cohort underwent right hepatectomy including the middle hepatic vein without any blood transfusion in perioperative period.
Results: Preoperative international normalized ratio (INR) in Group A and B was 1.05 ± 0.08 and 1.07 ± 0.08, respectively, while INR at postoperative day 7 in Group A donors was 1.72 ± 0.22 while in Group B donors, it was 1.75 ± 0.26. Perioperative hemoglobin drop in Group A and B was statistically insignificant (1.59 ± 0.83 g% vs 1.68 ± 1.51 g%, P = 0.78). The menstrual blood loss in both the groups was statistically comparable.
Conclusions: Our study shows safety of right lobe living donation in female donors with ongoing menstruation with no increased risk of intraoperative excessive bleeding and postoperative physiological impact on their general health.
Keywords: Blood loss, coagulopathy, hepatectomy, living donor liver transplantation, menstruation
|How to cite this article:|
Yang HR, Thorat A, Poon KS, Yeh CC, Chiang YY, Chen TH, Hsu SC, Jeng LB. Living donor hepatectomy in female donors with ongoing menstruation: Safety and ethical issues. Formos J Surg 2017;50:119-24
|How to cite this URL:|
Yang HR, Thorat A, Poon KS, Yeh CC, Chiang YY, Chen TH, Hsu SC, Jeng LB. Living donor hepatectomy in female donors with ongoing menstruation: Safety and ethical issues. Formos J Surg [serial online] 2017 [cited 2017 Nov 20];50:119-24. Available from: http://www.e-fjs.org/text.asp?2017/50/4/119/211081
| Introduction|| |
Living donor liver transplantation (LDLT) is adopted as one of the solutions to overcome the graft shortage in adult patients with end-stage liver disease waiting for liver transplantation, especially in Asia, where the cadaveric donation is scarce. In some urgent medical conditions such as patients with acute liver failure or acute decompensation in underlying cirrhotic liver with worsening encephalopathy, living donation is the only available and quick option for life-saving liver transplantation. When any further delay may lead to mortality in recipients, donor's safety is also a concern that transplant team has to keep in mind all the time. Especially when female donors are in altered physiological states such as ongoing menstrual period, a lot of factors need to be considered as any anxiety and stress may alter the menstrual cycle and increased menstrual blood loss which may add to operative morbidity and increased risk of donor complications.
The liver disorders and any associated coagulopathy are the known risks factors for increased menstrual blood loss. Living donor hepatectomy is associated with postoperative deranged coagulation profile. Transient hepatic dysfunction after major hepatic resection can cause temporary state of synthetic insufficiency of the remnant liver. Furthermore, there is consumption and half-life dependent decay of the coagulation factors which is usually reflected as prolonged prothrombin time (PT). Borromeo et al. found that PT required 3–6 days to return to normal values because of transiently impaired hepatic synthesis after donor right hepatectomy for LDLT.
Furthermore, long anesthesia duration, low body mass index, and small remnant liver volume are additional risk factors for postoperative coagulopathy. This altered coagulative state may further accentuate the underlying physiological stress by causing increased amount of menstrual blood loss., Furthermore, any need for blood transfusion in perioperative period is associated with increased risk of complications, such as bile leaks and infection.,
However, because of the urgency of the underlying condition of the recipient, any further delay may prove fatal to the recipient, and hence, liver donation from female donor can be considered with ongoing menstruation. The balance between the benefit to the recipient and the risk to the donor plays a central role in justifying LDLT in such situations.
As there is no previous study to evaluate the correlation of the hepatectomy and its impact on menstrual blood loss, our analysis in this context attempts to highlight the safety of such major surgery in donors when they are already in altered physiological state with an additional psychological stress due to ailing family member.
| Materials and Methods|| |
From January 2011 to December 2012, 194 adult-to-adults' LDLT were performed at our institute of China medical university hospital, Taiwan. Fifty-eight females (n = 58) were enrolled in this retrospective analysis. Database was analyzed for demographic, perioperative, and postoperative characteristics of all the enrolled patients. The physical status was determined by American society of Anesthesiologists Class I or Class II.
In our donor survey protocol, we exclude the donors with fatty change >30%, with a history of medication in the recent past that may influence the coagulation profile, with preoperative anemia (hemoglobin [Hb] <9 g/dl).
The female donors were stratified into two broad groups:
- Group A: Female donors without ongoing menstruation (n = 49).
- Group B: Female donors with onset of menstruation during the surgery (n = 9).
Clinical data such as age, pre- and post-operative international normalized ratio (INR), Hb, and liver function profile that included aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and alkaline phosphatase (ALP), and operative blood loss were documented.
All the donors in the cohort underwent right hepatectomy including the middle hepatic vein without any blood transfusion in perioperative period. The operating surgeon performing the donor hepatectomy was same for the entire donor hepatectomies performed in this study cohort.
Anesthetic induction was done with 2 μg/kg fentanyl and 2 mg/kg propofol with 0.6 mg/kg rocuronium as muscle relaxant. After tracheal intubation, the general anesthesia was maintained with sevoflurane in 50% oxygen and air while controlled ventilation was adjusted to maintain the end-tidal CO2 level of 35–40 mm of Hg. During surgery, central venous pressure was consistently kept below 5 cm of H2O for all the donors that underwent hepatectomy. Postoperative management included daily renal and hepatic function tests and abdominal hepatic ultrasound as required. After surgery, all donors received patient-controlled analgesia by pump infusion for 48 h. Early ambulation and incentive spirometry were encouraged to minimize atelectasis.
Before each operation, the donor, recipient, and their families were fully informed about liver donation, liver transplantation, and the possible risks involved in both donors as well as recipients.
The study was approved by internal review board of the institution before LDLT.
Assessment of menstruation and menstrual blood loss
Menstrual blood loss was assessed by face-to-face interviews and self-applied questionnaires. With this, the pattern of menstruation in terms of days and blood loss was recorded and correlated to their previous and subsequent menstrual cycles. Every female donor of study cohort that experienced excess menstrual loss as compared to her previous menstrual cycles was asked to report to coordinating nurse. The assessment continued postoperatively for 1–2 regular menstrual cycles to see whether any alteration of the cycle and amount of bleeding.
This is to state that the data for the present retrospective study were analyzed with PASW statistics version 18.0 (SPSS Inc.,). Descriptive statistics were computed for age, height, weight, preoperative INR and Hb, intraoperative blood loss, postoperative INR, Hb, and perioperative Hb drop in each group. Group comparisons were done utilizing two-tailed t-test for continuous variables and Chi-square test for categorical variables. Results were presented as mean values ± standard deviation. All tests were two-sided and P < 0.05 was considered as statistically significant.
The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.
| Results|| |
Group A comprised 49 and Group B had nine patients. The age (years), height (cm), and weight (kg) in Group A and B were 33.22 ± 9.00 versus 33.10 ± 8.58 (P = 0.97), 159.39 ± 6.12 versus 160.8 ± 6.68 (P = 0.52), and 59.05 ± 9.41 versus 58.06 ± 7.10 (P = 0.75), respectively, as shown in [Table 1]. Preoperative INR in Group A and B was comparable and did not appear statistically significant (1.05 ± 0.08 vs. 1.07 ± 0.08, P = 0.48). Mean Hb in preoperative period in Group A cohort was 13.03 ± 1.13 g% while the same in patients of Group B was 12.64 ± 1.51 g% with P = 0.35.
|Table 1: Variables in Group A and B examined with two tailed independent t-tests before donor surgery|
Click here to view
The platelet count of Group A and B patients was 245.40 ± 55.15 and 230.22 ± 37.12 103/mm 3, respectively, which was statistically insignificant (P = 0.47). Liver function profile of the donors of both the groups was normal and shown in [Table 1].
The average intraoperative blood loss in Group A patients was 364 ml while menstruating females in Group B had 470 ml blood loss. Although this was not statistically significant (P = 0.11), the overall blood loss during hepatectomy was definitely more for Group B donors as compared to the Group A donors [Table 2]. Although 100 ml extra blood loss was not significant in statistical point of view, it surely shows altered physiological responses in menstruating females. However, none of the donors in Group B had prolonged hospital stay and the postoperative recovery was uneventful. The increased blood loss intraoperatively had no significant impact on the perioperative Hb drop [Table 2]. Postoperative INR in both the groups was increased which is often expected due to loss of normal functioning hepatocytes. The mean INR value at postoperative day 7 in Group A and Group B patients was 1.72 ± 0.22 and 1.75 ± 0.26, respectively, with P = 0.68. The postoperative Hb showed slight drop in both the groups, but Group B female donors showed slightly increased postoperative Hb drop. The mean postoperative Hb in Group A was 11.44 g% and in Group B donors, the postoperative Hb was 10.96 g%. The perioperative Hb drop in Group A and B was statistically insignificant (1.59 ± 0.83 g% vs. 1.68 ± 1.51 g%, P = 0.78). The comparison of Hb and INR values in Group A and B in postoperative period is depicted in [Figure 1] and [Figure 2]. There was no significant difference of Hb INR levels between Group A and Group B in any perioperative day.
|Table 2: Postoperative variables in Group A and B with two-tailed independent t-tests|
Click here to view
|Figure 1: Comparison of hemoglobin levels in postoperative period between Group A and B|
Click here to view
|Figure 2: Comparison of INR value in postoperative period between Group A and B. Hb: Hemoglobin, INR: International normalized ratio, postoperative D1, D3, D7, and D15-postoperative day 1, day 3, day 7, and day 15|
Click here to view
The liver function profile of Group A patients at 7th postoperative day was AST 41 ± 13.62 IU/ml, ALT 64.26 ± 25.8 IU/ml, total bilirubin 1.31 ± 0.78 mg/dl and ALP 50.8 ± 16.25 IU/ml. The donors of Group B showed following liver function profile at 7th postoperative day: AST 47.22 ± 10.66 IU/ml, ALT 74.44 ± 29.69 IU/ml, total bilirubin 1.44 ± 0.22 mg/dl, and ALP 41.88 ± 11.35 IU/ml. Statistical comparison of liver function profile in both the groups was not significant [Table 2].
Postoperative course in all the donors in both the groups was uneventful with average hospital stay of 7 days. As per questionnaire for the pattern of menstruation, the mean duration for which menstruation persisted was 4.2 ± 1.2 days in donors of both the groups. One of the donors of the Group A had oligomenorrhea while rest of donors in Group A as well as B had no change in amount of blood loss subjectively [Table 3]. None of the female donors had any impact on their subsequent menstrual cycles which were regular. None of the donors suffered from any hepatic or extra-hepatic complications in this study.
| Discussion|| |
This is the first study that analyzed the safety of major hepatic surgery in female donors with altered physiological state such as ongoing menstruation. The impaired coagulation and altered metabolic functions are expected immediately after major hepatic resection. Decreased synthetic functions of the liver remnant and consumption of coagulation factors postoperatively can cause increase in INR with corresponding decrease in platelets and fibrinogen. This alteration in coagulation profile is more significant after right lobe hepatectomy. This can further increase chances of menorrhagia in females with already ongoing menstruation. However, no significant increased menstrual blood loss was noted in all the studied donors. Furthermore, in subsequent menstrual cycles, no irregularities were found in any of the donors.
However, there was increased intraoperative blood loss in menstruation Group B which was although statistically insignificant as compared to Group A, shows impact of altered physiological state on surgery. This may be further stressful as any increased intraoperative blood loss further increases the morbidity which is another important concern for the potential donor and the physicians involved in the procedure. As living donation is not free of complications and in worldwide reports of LDLTs, donor morbidity ranges between 0% and 67%, a thorough preoperative assessment and selection of donors should be the strict protocol of all transplant centers., In any situation, the concern for the safety of healthy living donors should not be undermined due to overwhelming benefit of LDLT for critically ill patients with end-stage liver disease. Hence, given recipient's deteriorating condition and altered physiological status of donor put us in moral dilemma to select such person as donor or not. Our first experience of such situation was in 2009 when the recipient had to receive emergency transplantation on account of his worsening hepatic encephalopathy due to underlying liver disease. The donor got her menstrual periods a day before surgery and when no definitive answer was yielded even after consulting gynecologist, we proceeded with planned donor surgery due to medical urgency of the recipient. The donor was meticulously managed in postoperative ward and recovered without any complication or increased menstrual blood loss. After judging the safety of the procedure, we performed subsequent donor surgeries while their menstrual periods were ongoing although with bit concern of chances of increased morbidity. However, none of the donors of the study cohort suffered any ill effects due to procedure. As high volume centers that deal with more emergency cases like this center where recipients often have high MELD score, it is unwise to do delay the transplantation surgery on account of donor's altered physiological profile with no other contraindications for donor surgery.
In all the cases, after medical evaluation and psychological assessment, donors and their families were explained about possible risks after donor hepatectomy and especially in such physiologically altered state where chances of morbidities were high due to ongoing bleeding during menstruation. However, none of the donors from both the groups suffered any complication and postoperative recovery among all patients was smooth. Days of menstruation remained same in study group with respect to their previous menstrual cycles. The Hb level in postoperative period showed no drop although INR continued to be elevated for average 1–5th postoperative day.
In general, the average menstrual blood loss is under 80 ml in healthy females. The prolonged INR after hepatectomy and ongoing menstruation may have significant impact on hemostasis. As it is difficult to assess the exact amount of menstrual blood loss during the menstruation, we developed face-to-face interviews and self-questionnaire in which every menstruation female donors were asked about their patterns of cycles as well as amount of blood loss they experienced and if they would account it as heavy blood loss, normal quantity, or less blood loss as compared to their previous cycles. These interviews were carried out by trained coordinating nurse. However, the patterns of menstruation remained unaltered in postoperative period. Even if the INR is expected to increase after donor hepatectomy, there was no significant change noted in the menstrual pattern. In usual circumstances, we would delay any operative intervention till the menstrual periods get over. However, when recipient is in critical condition due to acute liver failure or worsening encephalopathy in end-stage liver disease and in the absence of any other suitable donor, we preferred to accept the female donor during her periods as any further delay can cause mortality in recipients. Postoperative recovery was smooth in both the groups and major hepatectomy had no significant impact on menstrual bleeding and/or subsequent menstrual cycles. Average hospital day for all the donors in both the groups was 7 days.
With this experience, we would like to raise the issue: in unavoidable circumstances with medical urgency, whether to do surgery for females with ongoing menstruation or not? As there were no prior studies providing evidence of outcome of surgery in female patients with ongoing menstruation, our experience in this regard highlights the application as well as safety of major surgery in such females. Moreover, operative procedures with less chance of postoperative coagulopathy are thus safe to be performed. Hence, in an unavoidable situation, female patients can undergo major surgery even during ongoing menstruation without any additional risk.
| Conclusion|| |
In emergency situation due to lack of suitable donor, female donor can be accepted for living donation with altered physiological state such as ongoing menstrual bleeding without increased risk of excessive intraoperative blood loss. Although donor safety always remains a concern and postoperative coagulopathy can have impact on present hemostasis leading to increased amount of blood loss during menstruation, major hepatectomy practically proved safe in our series. However, coagulation derangement was worth considering. In the absence of other risk factors such as fatty liver >30% and very low body mass index, living donor hepatectomy is safe during menstruation without significantly altering the normal physiological milieu. As for any other procedure, careful donor evaluation, intense preoperative planning, and meticulous surgical techniques are imperative in avoiding complications.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jeng LB, Thorat A, Li PC, Li ML, Yang HR, Yeh CC, et al.
Raising-flap technique for outflow reconstruction in living donor liver transplantation. Liver Transpl 2014;20:490-2.
Sevmis S, Karakayali H, Karakayali F, Savas NA, Akkoc H, Haberal M. Postsurgical complications in living-related liver donors. Transplant Proc 2008;40:245-7.
Siniscalchi A, Begliomini B, De Pietri L, Braglia V, Gazzi M, Masetti M, et al.
Increased prothrombin time and platelet counts in living donor right hepatectomy: Implications for epidural anesthesia. Liver Transpl 2004;10:1144-9.
Borromeo CJ, Stix MS, Lally A, Pomfret EA. Epidural catheter and increased prothrombin time after right lobe hepatectomy for living donor transplantation. Anesth Analg 2000;91:1139-41.
Kim YK, Shin WJ, Song JG, Jun IG, Kim HY, Seong SH, et al.
Factors associated with changes in coagulation profiles after living donor hepatectomy. Transplant Proc 2010;42:2430-5.
Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011;113:3-13.
Shapley M, Croft PR, McCarney R, Lewis M. Does psychological status predict the presentation in primary care of women with a menstrual disturbance? Br J Gen Pract 2000;50:491-2.
Ghobrial RM, Freise CE, Trotter JF, Tong L, Ojo AO, Fair JH, et al.
Donor morbidity after living donation for liver transplantation. Gastroenterology 2008;135:468-76.
Abecassis MM, Fisher RA, Olthoff KM, Freise CE, Rodrigo DR, Samstein B, et al.
Complications of living donor hepatic lobectomy – A comprehensive report. Am J Transplant 2012;12:1208-17.
Helling TS. Liver failure following partial hepatectomy. HPB (Oxford) 2006;8:165-74.
Thorat A, Lee WC. Critical care issues after major hepatic surgery. In: Abdeldayem H, editor. Hepatic Surgery. InTech Open; 2013. p. 83-103.
van Eijkeren MA, Christiaens GC, Haspels AA, Sixma JJ. Measured menstrual blood loss in women with a bleeding disorder or using oral anticoagulant therapy. Am J Obstet Gynecol 1990;162:1261-3.
Brown RS Jr., Russo MW, Lai M, Shiffman ML, Richardson MC, Everhart JE, et al.
A survey of liver transplantation from living adult donors in the United States. N Engl J Med 2003;348:818-25.
Adam R, McMaster P, O'Grady JG, Castaing D, Klempnauer JL, Jamieson N, et al.
Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry. Liver Transpl 2003;9:1231-43.
Poon KS, Chen TH, Jeng LB, Yang HR, Li PC, Lee CC, et al.
A high model for end-stage liver disease score should not be considered a contraindication to living donor liver transplantation. Transplant Proc 2012;44:316-9.
Warrilow G, Kirkham C, Ismail KMK, et al
. “Quantification of menstrual blood loss,” The Obstetrician and Gynaecologist 2004;6:88-92.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]