Study of effectiveness of vasopressin as hemostatic agent in laparoscopic myomectomy at tertiary health care center

 

Pradeep Kode¹, Rajesh Varma Alluri^2*, Bariki Santosh Kumar³, Deepraj Singh B⁴, Sherry Mathews⁵

 

Abstract              Background: Myomectomy is an invasive surgical procedure and surgical removal is necessary when the myoma is symptomatic and resistant to medical management or interferes with reproduction. Present study was aimed to A study of effectiveness of vasopressin for the patients undergoing Laparoscopic Myomectomy at tertiary health care center. Material and Methods: Present study was hospital based, comparative, parallel-group study, conducted in patients with uterine fibroid, ASA physical status I/II, posted for elective laparoscopic myomectomy. 60 patients were randomly allocated by sealed envelope method into two equal groups (n = 30 each), into Group V and Group NS. Results: 60 patients were randomly divided into two groups (n=30) each. General Characteristics such as Mean age in years, ASA grade I/II, BMI, Mean maximum diameter of the largest myoma in cm, number of myomas and position of myomas were comparable in both groups and difference was not statistically significant. In operative characteristics, we noted longer duration of surgery, more amount of blood loss, more Intraoperative Blood transfusions and increased Hemoglobin difference between preop and at 3^rd day in NS group as compared to Group V and difference was statistically significant (p<0.05). We monitored Vital parameters and Side effects of all patients. Bradycardia (HR of 41-60 bpm) and. Hypertension (SAP ≥20% above baseline) was more in group V as compared to group NS and difference was statistically significant (p<0.05). All side effects were effectively managed medically and no incidence of myocardial infarction, pulmonary oedema, congestive heart failure, cardiac arrest, mortality was noted in present study. Conclusion: Vasopressin is effective for the patients undergoing Laparoscopic Myomectomy in terms of blood loss, duration of surgery, though few side effects are noted for which caution is needed during surgical procedure.

Keywords: Vasopressin, Laparoscopic Myomectomy, hemorrhage, blood transfusion

 

INTRODUCTION

Uterine myomas are the most frequent tumours of the female genital tract affecting 20–50% of all women, with an increased incidence in the later years of a woman’s reproductive life.¹ Myomectomy is necessary when the myoma is symptomatic and resistant to medical management or interferes with reproduction. Over the 2-3 decades the laparoscopic approach became very popular amongst gynecologic surgeons and patients for the reasons of faster recovery, shorter hospitalization, better cosmetic results and excellent long-term results both in terms of resolution of symptoms and reproductive outcomes.^2,3 Vasopressin is a synthetic analogue of the anti‑diuretic hormone. It causes vasoconstriction through its action on V1 receptors and anti‑diuresis through V2 receptors in the kidney. Intramyometrial injection of vasopressin causes vasoconstriction, stimulates the uterine contractions and therefore it reduces the blood loss during surgery.⁴ Vasopressin produces generalized constriction of blood vessels including coronary vasculature when given at higher doses. The effects include reduced cardiac output and heart rate resulting from vasoconstriction.⁵ When infiltrated, vasopressin reduces hemorrhage, which is the most common complication during gynecological surgery, through its vasoconstrictive and uterine contraction effects, shortens the duration of surgery, and prevents additional complications such as infection.⁶ However, vasopressin was reported to be associated with severe complications such as bradycardia, arrhythmias, pulmonary edema, and cardiac arrest.⁷ Present study was aimed to A study of effectiveness vasopressin for the patients undergoing Laparoscopic Myomectomy at tertiary health care centre.

              

MATERIAL AND METHODS

Present study was hospital based, comparative, parallel-group study, conducted in Department of Anaesthesiology, Bhaskar Medical College & General Hospital, Yenkapally, India. Present study was conducted over 2 years period (January 2019 to December 2020). Study was approved by institutional ethical committee.

Inclusion criteria: Patients with uterine fibroid, ASA physical status I/II, posted for elective laparoscopic myomectomy, willing to participate in study.

Exclusion criteria: Patients with ischaemic heart disease, cardiac valvular disease, hypertension, severe respiratory disease, severe hepatic or renal disease. Patients with BMI > 30 kg/m²

Study was explained to patients and a written informed consent was taken for participation. 60 patients were randomly allocated by sealed envelope method into two equal groups (n = 30 each), into Group V (Vasopressin group) and Group NS (Normal saline group: Patients received 15 ml of normal saline, for each myoma).

The vasopressin was prepared by dilution of 20 units vasopressin in 200 ml normal saline as 0.1 unit/ml, then 15 ml was injected by the surgeon slowly after negative aspiration of blood in the plane between the myometrium and the myoma. A single injection of 15 ml was made for each myoma.

In operation theatre, electrocardiogram (ECG), pulse oximeter, and non‑invasive arterial blood pressure, were monitored. All patients were operated under general anaesthesia with atracurium (0.5 mg/kg) and sevoflurane (2-3%). Intraoperatively, parameters such as amount of blood loss, blood transfusion (the transfusion trigger was the amount of blood loss >20% of the estimated blood volume), heart rate, mean arterial blood pressure, a continuous ECG with automatic ST‑segment analysis (leads II and V), arterial oxygen saturation (SPO2) and the end‑tidal carbon dioxide (ETCO2). The values were collected at preoperatively, just before intramyometrial vasopressin administration, at 15, 30, 45, 60 minute and at the end of surgery.

After extubation patients were monitored in postoperative anaesthesia care unit for next 12 hours and heart rate, mean arterial blood pressure, a continuous ECG with automatic ST‑segment analysis (leads II and V), arterial oxygen saturation (SPO2) were monitored every 30 minutes. Later patients were shifted to respective wards. Patients were interviewed during discharge for any complaints.

Data was collected and compiled using Microsoft Excel, analysed using SPSS 23.0 version. Frequency, percentage, means and standard deviations (SD) was calculated for the continuous variables, while ratios and proportions were calculated for the categorical variables. Difference of proportions between qualitative variables were tested using chi- square test or Fisher exact test as applicable. P value less than 0.5 was considered as statistically significant.

 

RESULTS

60 patients were randomly divided into two groups (n=30) each. General Characteristics such as Mean age in years, ASA grade I/II, BMI, Mean maximum diameter of the largest myoma in cm, number of myomas and position of myomas were comparable in both groups and difference was not statistically significant. In majority of cases mean maximum diameter of the largest myoma was 5-7 cm, 2-3 myomas and intramural position of myomas was noted.

DISCUSSION

Myomectomy is a fairly hemorrhagic operation. Several measures have been tried to achieve a reduction of blood loss during open and laparoscopic myomectomy, including the use of bipolar energy, application of a variety of vasoconstrictive and uterotonic agents, use of tourniquets, temporary clipping of the uterine arteries, and use of barbed sutures.^8,9,10,11 Myomectomy is associated with intraoperative and postoperative complications including excessive haemorrhage, pyrexia, visceral damage, thrombo-embolism, conversion to hysterectomy, blood transfusions, scar dehiscence in future pregnancy and many others.¹²

Intramyometrial infusion of vasopressin causes vasoconstriction, stimulates the uterine contractions and therefore it reduces the blood loss during surgery.⁴ However, vasopressin was reported to be associated with severe complications such as bradycardia, arrhythmias, pulmonary edema, and cardiac arrest.⁶ The variations in heart rate (HR) and blood pressure after intramyometrial vasopressin injection might be correlated to the systemic absorption of vasopressin especially during the surgical excisions of the fibroid and not linked to the direct intravascular injection.¹⁰

Frishman recommended intramyometrial dose of 4–6 U at a concentration 0.2 U/ml to be safe, based on assumption that low dose and low concentration are equally effective in achieving hemostasis without cardiac complications.¹³ Moda, N et al.,¹⁴ found that 20 units intramyometrial vasopressin used dogmatically by surgeons drops blood loss but it is connected with cardiovascular impediments. Hence, 10 units of intramyometrial vasopressin as compared to 20 units is associated with similar blood loss and lesser side effects such as bradycardia, pulmonary edema, hypotension, blood loss, and increased airway pressure.¹⁴ In a study conducted by H. Fletcher et al.¹⁵ there was <800ml blood loss in vasopressin group compared to 1000ml in tourniquet group. Protopapas A et al.,¹⁶ studied 150 patients undergoing laparoscopic myomectomy; 50 were treated without the use of any vasoconstrictivec agent (group 1), and 100 were treated with intraoperative intramyometrial injection of dilute vasopressin (20 IU/100 mL normal saline) (group 2). Overall, the mean estimated blood loss was 321.8 ± 246.0 mL in group 1 compared with 147.8 ± 171.8 mL in group 2, respectively (p <.001). The risk factors for hypercapnea and subcutaneous emphysema included the size and intramural position of the largest myoma. Vasopressin was not associated with serious cardiovascular adverse events. Soliman R et al.,¹⁷ studied 194 patients divided into two groups as Vasopressin group (vasopressin 0.1 unit/ml, 15 ml) and Control group (equal amount of normal saline). The heart rate decreased significantly in both groups, but the decrease was lower with vasopressin than the control group through the time points T3 to T5 (P < 0.05) The mean arterial blood pressure increased significantly in both groups, but the increase was higher with vasopressin than the control group through T3 to T5 (P < 0.05). The amount of blood loss decreased significantly with vasopressin than the control groups (P = 0.001). The number of transfused packed red blood cells was lower with vasopressin than the control group (P = 0.001). The incidence of hypertension, bradycardia and atrial extrasystole was higher with vasopressin than the control group (P = 0.005, P = 0.012, P = 0.033, respectively). Similar findings were noted in present study. Saha MM et al.,¹⁸ compared intraoperative blood loss following abdominal myomectomy after receiving intramyometrial vasopressin or tourniquet application, blood loss in the tourniquet group was significantly higher (p=<0.001). Postoperative haemoglobin and haematocrit were lower in tourniquet group than vasopressin group. There was significant fall in haemoglobin and haematocrit in postoperative period in both group (p=<0.001) but it was more in tourniquet group. Total five patients (three in tourniquet group and two in vasopressin group) had received one unit whole blood transfusion.

The safety of vasopressin has been challenged in the past as a result mainly of case reports of serious and potentially lethal cardiovascular complications associated with its use as a vasoconstrictive agent, including bradycardia, hypotension, arrhythmias, atrioventricular block, pulmonary edema, and even cardiac arrest.^19,20,21

Low concentrations of vasopressin has been considered to be safe, but sometimes it can lead to undesirable effects such as bradycardia with loss of peripheral pulse, non recordable blood pressure further leading to cardiac arrest. Nikhilesh B et al., reported a case of acute onset bradycardia and dyspnea along with loss of peripheral pulse after local infiltration of 5 unit of vasopressin (20units diluted in 100ml NS), patient was revived by successful resuscitation.²²

Severe adverse reactions, such as myocardial infarction and cardiac arrest, have also been reported even after local intramyometrial infiltration of AVP during gynecological surgery under general anesthesia.²³

Bradycardia induced by vasopressin infiltration so, the dose used should range from 0.05-0.3 units/ml and the total administered dose should be as small as possible. In addition, close communication between the anesthesiologist and the gynecologist is also important to identify and treat such rare complications, which can sometimes be induced by the local infiltration of vasopressin.²¹

 

CONCLUSION

Vasopressin is effective for the patients undergoing Laparoscopic Myomectomy in terms of blood loss, duration of surgery, though few side effects are noted for which caution is needed during surgical procedure. An effective communication between the anesthesiologist and gynaecologist is very important for early identification and appropriate treatment of rare complications associated with local vasopressin.

 

REFERENCES

1. Sami Walid M, Heaton RL. The role of laparoscopic myomectomy in the management of uterine fibroids. Curr Opin Obstet Gynecol. 2011;23(4):273-7.
2. Bhave Chittawar P, Franik S, Pouwer AW, Farquhar C. Minimally invasive surgical techniques versus open myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2014;21;(10):CD004638.
3. Buckley VA, Nesbitt-Hawes EM, Atkinson P, Won HR, Deans R, Burton A, Lyons SD, Abbott JA. Laparoscopic myomectomy: clinical outcomes and comparative evidence. J Minim Invasive Gynecol. 2015;22(1):11-25.
4. Shimanuki H, Takeuchi H, Kitade M, Kikuchi I, Kumakiri J, Kinoshita K. The effect of vasopressin on local and general circulation during laparoscopic surgery. J Minim Invasive Gynecol 2006; 13:190- 4.
5. Muthukumar M, Mathews L, Vasantha NS, Anoop S. Intramyometrial vasopressin as a haemostatic agent: Is it really safe? Indian J Anaesth. 2015;59(1):51.
6. Chudnoff S, Glazer S and Levie M. Review of vasopressin use in gynecologic surgery. J Minim Invasive Gynecol 2012; 19: 422–433.
7. Kimura T, Kucui C. Effectiveness of hormonal tourniquet by vasopressin during myomectomy through vasopressin V1a receptor ubiquitously expressed in myometrium. Gynecol Obstet Invest 2002; 54:125-31.
8. Park KS, Yoo KY. Role of vasopressin in current anesthetic practice. Korean J Anesthesiol 2017; 70:245-57.
9. Conforti A, Mollo A, Alviggi C, et al. Techniques to reduce blood loss during open myomectomy: a qualitative review of literature. Eur J Obstet Gynecol Reprod Biol. 2015;192:90–95.
10. Hickman LC, Kotlyar A, Shue S, Falcone T. Hemostatic techniques for myomectomy: an evidence-based approach. J Minim Invasive Gynecol. 2016;23:497–504.
11. Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy for fibroids. Cochrane Database Syst Rev. 2014;8:CD005355.
12. Paul GP, Naik SA, Madhu KN, Thomas T. Complications of laparoscopic [6]myomectomy: A single surgeon's series of 1001 cases. Australian and New Zealand Journal of Obstet and Gynecol. 2010;50:385.
13. Frishman G. Vasopressin: If some is good, is more better? Obstet Gynecol 2009; 113:476-7.
14. Moda, N., S. Das, M. Patro, P. Biswal. “Comparison of hemodynamic status and complications between two different doses of intramyometrial vasopressin during laparoscopic myomectomy: a retrospective study, the lesser the better”. Asian Journal of Pharmaceutical and Clinical Research, vol. 14, no. 10, Oct. 2021, pp. 111-3,
15. Fletche H, Frederick J, Hardie M, Simeon D. A Randomized Comparison of Vasopressin and Tourniquet as Hemostatic Agents During Myomectomy. Obstet Gynecol. 1996;87(6):1014–8.
16. Protopapas A, Giannoulis G, Chatzipapas I, Athanasiou S, Grigoriadis T, Kathopoulis N, Vlachos DE, Zaharakis D, Loutradis D. Vasopressin during Laparoscopic Myomectomy: Does It Really Extend Its Limits? J Minim Invasive Gynecol. 2019 Mar-Apr;26(3):441-449.
17. Soliman R, Yacoub A, Elbiaa AA. Assessment of the perioperative effect of vasopressin in patients undergoing laparoscopic myomectomy: A double‑blind randomized study. Indian J Anaesth 2021;65:139‑45.
18. Saha MM, Khushboo, Biswas SC, Alam H, Kamilya GS, Mukhopadhyay M, Mondal S. Assessment of Blood Loss in Abdominal Myomectomy by Intramyometrial Vasopressin Administration Versus Conventional Tourniquet Application. J Clin Diagn Res. 2016 May;10(5):QC10-3.
19. Hung MH, Wang YM, Chia YY, Chou YM, Liu K. Intramyometrial injection of vasopressin causes bradycardia and cardiac arrest report of two cases. Acta Anaesthesiol Taiwan. 2006;44:243–247.
20. Riess ML, Ulrichs JG, Pagel PS, Woehlck HJ. Case report: severe vasospasm mimics hypotension after high-dose intrauterine vasopressin. Anesth Analg. 2011;113:1103–1105.
21. Butala BP, Shah VR, Parikh BK, Jayaprakash J, Kalo J. Bradycardia and severe vasospasm caused by intramyometrial injection of vasopressin during myomectomy. Saudi J Anaesth. 2014;8:396–398.
22. Nikhilesh B, Vadhanan P, Megha K, Tripaty DK. A case report of vasopressin induced bradycardia and dyspnea after intramyometrial injection during myomectomy. Indian J Clin Anaesth 2020;7(4):698-699.
23. Hobo R, Netsu S, Koyasu Y, Tsutsumi O. Bradycardia and cardiac arrest caused by intramyometrial injection of vasopressin during a laparoscopically assisted myomectomy. Obstet Gynecol 2009;113:484-6.

 

 

 

 

 

 

Policy for Articles with Open Access
Authors who publish with MedPulse International Journal of Anesthesiology (Print ISSN:2579-0900) (Online ISSN: 2636-4654) agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.