Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

BACKGROUND: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia. METHODS AND FINDINGS: This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age ≥18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered. CONCLUSIONS: Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting. TRIAL REGISTRATION: The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016).

Comparing volumetric and biochemical assessment of intravasation caused by hysteroscopic surgery.

BACKGROUND: During hysteroscopic surgery intravasation of irrigation fluid occurs, leading to potentially dangerous intravascular fluid overload. Currently, intravasation is usually measured volumetrically as fluid deficit. Intravasation could also be calculated using the decrease in hemoglobin or increase in chloride ion concentration, both phenomena known to result from intravasation. We compared the values of intravasation measured volumetrically as fluid deficit versus calculated from the biochemical change in hemoglobin and chloride. We expected that these values would show strong correlation and agreement. METHODS: In a retrospective data analysis of 51 patients who underwent hysteroscopic resection of myomas or endometrium a pre and post procedure concentration of haemoglobin and chloride was available. The fluid deficit was plotted against the two versions of calculated intravasation. Furthermore, we put the data into Bland-Altman plots to scrutinize their relationship. RESULTS: The volumetric assessed fluid deficit and both versions of biochemically assessed intravasation, either using the change in hemoglobin or chloride ion concentration, turned out to be three totally different entities with weak correlation. Bland-Altman plots show too wide limits of agreement, and a striking difference between the two methods of calculated intravasation. CONCLUSION: Our study shows significant differences and poor agreement between volumetric and biochemically assessed intravasation. Based on this study, routinely assessing intravasation by biochemical methods does not have additional benefit compared to the volumetric fluid deficit. It remains unclear which method resembles true intravasation.

The (cost) effectiveness of procedural sedation and analgesia versus general anaesthesia for hysteroscopic myomectomy, a multicentre randomised controlled trial: PROSECCO trial, a study protocol.

BACKGROUND: In women with abnormal uterine bleeding, fibroids are a frequent finding. In case of heavy menstrual bleeding and presence of submucosal type 0-1 fibroids, hysteroscopic resection is the treatment of first choice, as removal of these fibroids is highly effective. Hysteroscopic myomectomy is currently usually performed in the operating theatre. A considerable reduction in costs and a higher patient satisfaction are expected when procedural sedation and analgesia with propofol (PSA) in an outpatient setting is applied. However, both safety and effectiveness - including the necessity for re-intervention due to incomplete resection - have not yet been evaluated. METHODS: This study is a multicentre randomised controlled trial with a non-inferiority design and will be performed in the Netherlands. Women > 18 years with a maximum of 3 symptomatic type 0 or 1 submucosal fibroids with a maximum diameter of 3.5 cm are eligible to participate in the trial. After informed consent, 205 women will be randomised to either hysteroscopic myomectomy using procedural sedation and analgesia with propofol in an outpatient setting or hysteroscopic myomectomy using general anaesthesia in a clinical setting in the operating theatre. Primary outcome will be the percentage of complete resections, based on transvaginal ultrasonography 6 weeks postoperatively. Secondary outcomes are cost effectiveness, menstrual blood loss (Pictorial blood assessment chart), quality of life, pain, return to daily activities/work, hospitalization, (post) operative complications and re-interventions. Women will be followed up to one year after hysteroscopic myomectomy. DISCUSSION: This study may demonstrate comparable effectiveness of hysteroscopic myomectomy under procedural sedation and analgesia versus general anaesthesia in a safe and patient friendly environment, whilst achieving a significant cost reduction. TRIAL REGISTRATION: Dutch trial register, number NTR5357 . Registered 11th of August 2015.

Gas embolism during hysteroscopic surgery using bipolar or monopolar diathermia: a randomized controlled trial.

OBJECTIVE: The objective of the study was to determine the incidence and amount of gas embolism during hysteroscopic surgery using either monopolar or bipolar diathermia and to investigate the relationship between the severity of gas embolism and the amount of intravasation of distension fluid. STUDY DESIGN: This was a randomized, observer-blinded trial. Fifty patients, scheduled for hysteroscopic surgery, were assigned to either monopolar or bipolar diathermia. Transesophageal echocardiography was used to detect and classify gas embolism (grade 0-IV). Intravasation of distension fluid was measured. RESULTS: Venous gas embolism was observed in all but 1 patient. A higher incidence of more extensive (grade IV) was seen during bipolar diathermia (42% vs 13%; P = .031). Paradoxical embolism was observed in 2 patients. When intravasation exceeded 1000 mL, significantly more grade IV venous gas embolism was seen (P = .049). CONCLUSION: During hysteroscopic surgery, gas embolism was equally observed irrespective of the type of diathermia. However, more extensive embolism was observed when intravasation of distension fluid exceeded 1 L. These results question the acceptance of up to 2500 mL intravasation of distension fluid if bipolar diathermia is used.

The HYSTER study: the effect of intracervically administered terlipressin versus placebo on the number of gaseous emboli and fluid intravasation during hysteroscopic surgery: study protocol for a randomized controlled clinical trial.

BACKGROUND: Transcervical resection of myoma or endometrium is a safe, hysteroscopic, minimally invasive procedure. However, intravasation of distension fluid is a common phenomenon during these procedures. In a previous study we observed venous gas emboli in almost every patient. The severity of hysteroscopic-derived embolization has been shown to be correlated to the amount of intravasation. In addition, paradoxical gas embolism, which is potentially dangerous, was observed in several patients. Studies have shown a reduction of intravasation by using intracervically administered vasopressin during hysteroscopy. We think that its analog, terlipressin, should have the same effect. In our previous research we observed more gaseous emboli as intravasation increased. Whether or not the insertion of intracervically administered terlipressin leads to a lower incidence and severity of gas embolism is unknown. We hypothesize that intracervically administered terlipressin leads to a reduction of intravasation with a lower incidence and severity of gas embolism. Terlipressin may be of benefit during hysteroscopic surgery. METHODS/DESIGN: Forty-eight patients (ASA 1 or 2) scheduled for transcervical resection of large, types 1-2 myoma or extensive endometrium resection will be included. In a double-blind fashion patients will be randomized 1:1 according to surgical treatment using either intracervically administered terlipressin or placebo. Transesophageal echocardiography will be used to observe and record embolic events. A pre- and post-procedure venous blood sample will be taken to calculate intravasation based on hemodilution. Our primary endpoint will be how terlipressin influences the severity of embolic events. Secondary endpoints include the effect of terlipressin on the amount of intravasation and on hemodynamic parameters. DISCUSSION: If terlipressin does indeed reduce the number of gaseous emboli and intravasation occurring during hysteroscopic surgery, it would be a simple method to minimize potential adverse events. It also allows for prolonged operating time before the threshold of intravasation is reached, thereby reducing the need for a second operation. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), ID: NTR5577 . Registered retrospectively on 18 December 2015.