Postoperative Opioid Prescribing After Female Pelvic Medicine and Reconstructive Surgery.

OBJECTIVE: This study aimed to provide female pelvic medicine and reconstructive surgery (FPMRS) providers with evidence-based guidance on opioid prescribing following surgery. METHODS: A literature search of English language publications between January 1, 2000, and March 31, 2021, was conducted. Search terms identified reports on opioid prescribing, perioperative opioid use, and postoperative pain after FPMRS procedures. Publications were screened, those meeting inclusion criteria were reviewed, and data were abstracted. Data regarding the primary objective included the oral morphine milligram equivalents of opioid prescribed and used after discharge. Information meeting criteria for the secondary objectives was collected, and qualitative data synthesis was performed to generate evidence-based practice guidelines for prescription of opioids after FPMRS procedures. RESULTS: A total of 6,028 unique abstracts were identified, 452 were screened, and 198 full-text articles were assessed for eligibility. Fifteen articles informed the primary outcome, and 32 informed secondary outcomes. CONCLUSIONS: For opioid-naive patients undergoing pelvic reconstructive surgery, we strongly recommend surgeons to provide no more than 15 tablets of opioids (roughly 112.5 morphine milligram equivalents) on hospital discharge. In cases where patients use no or little opioids in the hospital, patients may be safely discharged without postoperative opioids. Second, patient and surgical factors that may have an impact on opioid use should be assessed before surgery. Third, enhanced recovery pathways should be used to improve perioperative care, optimize pain control, and minimize opioid use. Fourth, systemic issues that lead to opioid overprescribing should be addressed. Female pelvic medicine and reconstructive surgery surgeons must aim to balance adequate postoperative pain control with individual and societal risks associated with excess opioid prescribing.

Is a Postvoid Residual Necessary? A Randomized Trial of Two Postoperative Voiding Protocols.

OBJECTIVES: This study aimed to compare a backfill-assisted voiding trial (VT) with and without a postvoid residual (PVR) after pelvic reconstructive surgery. METHODS: This was a nonblinded randomized controlled trial of women undergoing pelvic organ prolapse and/or stress incontinence surgery. Participants were randomized immediately after surgery to either a PVR VT or a PVR-free VT. Our primary outcome was the rate of VT failure at discharge. Secondary outcomes included days of catheterization, urinary tract infection (UTI), and prolonged voiding dysfunction. With a power of 80% and an α of 0.05, we needed 126 participants to detect a 25% difference in VT failure (60% in PVR VT vs 35% in PVR-free VT). RESULTS: Participants were enrolled from March 2017 to October 2017. Of the 150 participants, mean age was 59 years, and 33% underwent vaginal hysterectomy, 48% underwent anterior repair, and 75% underwent midurethral sling. Seventy-five (50%) were randomized to PVR VT and 75 (50%) to PVR-free VT, with no differences in baseline demographic or intraoperative characteristics between the 2 groups. Our primary outcome, VT failure, was not significantly different (53% PVR VT vs 53% PVR-free VT, P = 1.0). There were no significant differences in days of postoperative catheterization (1 [0, 4] in PVR VT vs 1 [0, 4] in PVR-free VT, P = 0.90), UTI (20% PVR VT vs 20% PVR-free VT, P = 1.0), or postoperative voiding dysfunction (4% PVR VT vs 5% PVR-free VT, P = 1.0). CONCLUSIONS: When performing a backfill-assisted VT, checking a PVR does not affect VT failure, postoperative duration of catheterization, UTI, or voiding dysfunction.

Lidocaine Use in Vaginal Surgery and Risk of Toxicity.

OBJECTIVES: The primary objective of this study was to compare the amount of lidocaine administered for vaginal reconstruction with versus without hysterectomy. The secondary objective was to assess the risk of lidocaine toxicity. METHODS: This retrospective cohort study compares lidocaine dose in 2 cohorts: women who underwent vaginal hysterectomy with additional vaginal reconstruction (VH + VR) versus those who underwent vaginal reconstruction without hysterectomy (VR only). Total intraoperative lidocaine dose included the intravenous dose from anesthesia and the vaginally injected dose from the surgeon. The risk of toxicity was defined as total dose greater than 7 mg/kg. The primary outcome was the difference in total lidocaine dose for VH + VR versus VR only. RESULTS: Among 372 women included, 140 (37.6%) were in the VH + VR group, and 232 (62.4%) in the VR-only group. For the primary outcome of total lidocaine dose between groups, VH + VR received more total lidocaine than did VR only (228 ± 105 vs 168 ± 78 mg, P < 0.001). This difference was due to the vaginal lidocaine dose (P < 0.001), with no significant difference in the intravenous lidocaine dose (P = 0.68). In a logistic regression model controlling for age, anesthesia type, sling, and anterior repair, posterior repair, and anesthesia type, VH remained an independent risk factor for increased lidocaine dose (P < 0.001). Two women received a toxic dose of lidocaine, and both were in the VH + VR group. CONCLUSIONS: Women undergoing vaginal hysterectomy with additional vaginal reconstructive procedures are more likely to receive a higher dose of lidocaine compared with women undergoing vaginal reconstruction alone. The risk of lidocaine toxicity is increased with concomitant procedures.

Transfusion Rates and the Utility of Type and Screen for Pelvic Organ Prolapse Surgery.

OBJECTIVES: Limited data exist directly comparing the likelihood of blood transfusion by route of apical pelvic organ prolapse (POP) surgery. In addition, limited evidence is available regarding the risk of not ordering preoperative type and screen (T&S) in apical POP surgery. The objectives of the study are to (1) provide baseline data regarding the current need for preoperative T&S by comparing perioperative blood transfusion rates between 3 routes of apical POP surgery and (2) determine the rate of a positive preoperative antibody screen in women who underwent apical POP surgery. METHODS: This was a retrospective cohort study of women who underwent apical POP surgery by 3 different routes: abdominal (abdominal sacrocolpopexy), robotic (robotic sacrocolpopexy), or vaginal (uterosacral or sacrospinous ligament fixation). RESULTS: Among 610 women who underwent apical POP surgeries between May 2005 and May 2016, 24 women (3.9%) received a perioperative blood transfusion. The rate of transfusion was higher in the abdominal group (11.1%) compared with robotic (0.5%, P < 0.001) and vaginal (0.5%, P < 0.001). In a logistic regression model, abdominal route of POP surgery remained significantly associated with transfusion (odds ratio, 20.7; 95% confidence interval, 2.7-156.6). Among the 572 women who had a preoperative T&S performed, 9 (1.5%) had a positive antibody screen. CONCLUSIONS: Blood transfusion was significantly more common in abdominal compared with robotic and vaginal apical POP surgeries. The rate of a positive antibody screen was low, suggesting that type O blood is low risk if cross-matched blood is not available. Thus, it may be reasonable to not order a preoperative T&S prior to robotic or vaginal apical POP surgery.

Concomitant Sacral Neuromodulation and Gynecologic Surgery: A Single-Institution Experience.

AIMS: Sacral Neuromodulation (SNM) is a safe and minimally invasive treatment for urinary and fecal pelvic floor disorders (PFDs). With a high prevalence of women reporting multiple PFDs, knowledge regarding concomitant surgery may inform optimal patient care. Our literature search did not identify any published data on this topic, thus we sought to report our experience with concomitant SNM and gynecologic surgery. Our primary objective was to identify the rate of adverse events among cases. Secondarily, we reviewed the anesthetics used to identify potential associations when performing combined surgery. MATERIALS AND METHODS: This was retrospective case series of women undergoing SNM at a single academic center from 2012 to 2018. Cases were identified using current procedural terminology codes for SNM and common gynecologic procedures. These electronic medical records were reviewed to identify cases that occurred concomitantly in addition to obtaining demographics, adverse events, type of anesthesia, and overnight hospital stay. Descriptive data analysis was performed with Excel. RESULTS: Of 200 identified cases of SNM, 15 (7.5%) were concomitantly performed with another procedure. Most concomitant surgeries occurred with insertion of implantable pulse generator. Three minor adverse events occurred: two urinary tract infections and one occurrence of urinary retention. Eight (53%) cases were performed under general anesthesia while seven (46%) received monitored sedation. CONCLUSIONS: No serious adverse events or anesthesia-related complications were identified in this series. While general anesthesia was used more often, it was in accordance with our standard practice for the gynecologic procedures. This study supports the safety of concomitant gynecologic and SNM surgery.

Association of Anticholinergic Risk Score With Functional Status in Patients Preparing for Pelvic Reconstructive Surgery.

OBJECTIVES: Anticholinergic medication use has been associated with cognitive impairment and other functional limitations, particularly in older patients. The anticholinergic risk score (ARS) can be used to measure a patient's cumulative exposure to medications with anticholinergic properties. Our primary objective was to evaluate the correlation between ARS and functional status, as measured by instrumental activities of daily living (IADL), in patients preparing to undergo urogynecologic surgery. The secondary objective was to examine the correlation between ARS and physical function in this same cohort. METHODS: This was a planned cross-sectional analysis of a prospective cohort study to evaluate the impact of urogynecologic surgery on functional status. The ARS was calculated by summing the ARSs of each patient's medications and classified as high (ARS > 5) or low (ARS ≤ 5). A patient's ability to live independently was determined using the IADL questionnaire. The patient's physical function status was determined using the functional comorbidity index. RESULTS: One hundred twenty-two patients were evaluated. A total of 89.3% of subjects had a low and 10.7% had a high ARS score. For our primary outcome, high ARS was associated with low IADL in logistic regression controlling for age and formal education level (odds ratio, 8.0; 95% confidence interval, 1.4-46.9). For our secondary outcome, ARS was not associated with the functional comorbidity index (P = 0.24). CONCLUSIONS: These data support recognition of ARS as a potential risk factor for low functional status in patients planning urogynecologic surgery.

Predictors of Opioid Administration in the Acute Postoperative Period.

OBJECTIVES: Our primary objective was to evaluate age as a predictor of postanesthesia care unit (PACU) opioid administration in women undergoing reconstructive pelvic surgery. Our secondary objective was to identify additional predictors of PACU opioid administration. METHODS: We conducted a retrospective cohort study of women undergoing outpatient urogynecologic surgery for pelvic organ prolapse and/or stress urinary incontinence between September 2015 to October 2016 at 1 academic medical center. We compared 2 cohorts (1) women older than 65 years and (2) women older than 65 years. Our primary outcome was any opioid medication administered during the PACU admission. RESULTS: A total of 183 women were included in the study; 124 (68%) were younger than 65 years, and 59 (32%) were 65 years or older. For our primary outcome, women younger than 65 years were more likely to be given any opioids in PACU than women 65 years (70% vs 54%, P = 0.04, respectively). Women younger than 65 years were also given higher total amounts of opioid narcotics postoperatively (9.0 ± 8.3 vs 5.1 ± 6.0 mg, P < 0.05). For our secondary outcome, we found that PACU opioid administration was associated with midurethral sling (MUS) surgery (70% MUS vs 30% no MUS, P = 0.04) and high maximum PACU pain score (97% high vs 3% low, P < 0.01). CONCLUSIONS: In women undergoing urogynecologic surgery, age younger than 65 years is a predictor of high PACU pain score and resultant PACU opioid dispensation. This population should be targeted in future studies addressing the use of nonopioid multimodal therapies in the treatment of postoperative pain.

Toll-like receptor 8: augmentation of innate immunity in platinum resistant ovarian carcinoma.

Ovarian cancer is the most deadly gynecologic cancer, with 15,000 anticipated deaths within the United States alone in 2012, and new treatment strategies are needed. Ovarian cancer tumors are known to host an immunosuppressive microenvironment. This suppression may be reversible via activation of the innate immune response. Toll-like receptor 8 activates innate immunity while simultaneously inhibiting the effects of regulatory T cells within the ovarian cancer tumors. VTX-2337 is a novel small molecule ligand of Toll-like receptor 8 and is currently the subject of a Phase II randomized, double-blind, placebo-controlled trial Gynecologic Oncology Group (GOG)-3003 for patients with recurrent platinum-resistant ovarian cancer. We look forward to the results of this trial as support for the paradigm of process therapy in the treatment of ovarian cancer.

Ischiorectal fossa abscess after pelvic floor injection of botulinum toxin.

Botulinum toxin is used to treat pelvic floor tension myalgia; however, its safety profile is poorly understood. We report an ischiorectal fossa abscess after pelvic floor injections of botulinum toxin. Physicians need to be aware of this possible complication, consider alternate injection techniques and antiseptic preparation before injection.

Use of fluorescence to determine the effects of cholesterol on lipid behavior in sphingomyelin liposomes and erythrocyte membranes.

The purpose of this study was to generate the equivalent of a cholesterol/temperature phase map for a biological membrane using fluorescence spectroscopy. The pseudo-phase map was created using human erythrocytes treated with various concentrations of methyl-beta-cyclodextrin to remove defined amounts of cholesterol and a trio of fluorescent probes that assess different membrane properties (laurdan, diphenylhexatriene, and merocyanine 540). Parallel experiments with two-photon microscopy suggested that changes in cellular cholesterol content affected the entire membrane rather than being localized to specific macroscopic domains. The various regions of the composite erythrocyte pseudo-phase map were interpreted using analogous data acquired from multilamellar vesicles that served as simplified models of cholesterol-dependent phases. The vesicles consisted of various concentrations of cholesterol (0 to 50 mol%) with either palmitoyl sphingomyelin, 1:1 dipalmitoylphosphatidylcholine and dioleoylphosphatidylcholine, or phospholipid mixtures intended to simulate either the inner or outer leaflet of erythrocyte membranes. Four distinguishable regions were observed in sphingomyelin phase maps corresponding to the traditional solid-ordered and liquid-disordered phases and two types of liquid-ordered behavior. Physical properties were less diverse in the mixed phospholipid vesicles, as expected, based on previous studies. Erythrocytes displayed five regions of different combinations of membrane properties along the phase map. Some of the observations identified similarities between the cells and liquid-ordered behavior observed in the various types of liposomes as well as some interesting differences.

Effects of cholesterol on physical properties of human erythrocyte membranes: impact on susceptibility to hydrolysis by secretory phospholipase A2.

The ability of secretory phospholipase A(2) (sPLA(2)) to hydrolyze cell membranes is highly dependent on the physical properties of the membrane. The effects of cholesterol on these properties have been characterized in artificial bilayers and found to alter sPLA(2) activity significantly. It is hypothesized that the natural difference in cholesterol content between erythrocytes and leukocytes is in part responsible for their differing susceptibility to hydrolysis by sPLA(2). To test this hypothesis, defined amounts of cholesterol were removed from erythrocyte membranes using methyl-beta-cyclodextrin. Treatment of cells with methyl-beta-cyclodextrin increased the hydrolysis rate and total substrate hydrolyzed by sPLA(2). In general, this effect of cholesterol removal was more pronounced at higher temperatures. Comparison of the level of membrane order (assessed with the fluorescent probe laurdan) with hydrolysis rate revealed that sPLA(2) activity was greatly enhanced upon significant reductions in lipid order. Additional treatment of the cells with calcium ionophore further enhanced the hydrolysis rate and altered the relationship with membrane order. These data demonstrated that interactions with sPLA(2) observed in artificial bilayers apply to biological membranes. It is also proposed that the high level of cholesterol in erythrocyte membranes is a protective mechanism to guard against hydrolytic enzymes.

Relationship between membrane physical properties and secretory phospholipase A2 hydrolysis kinetics in S49 cells during ionophore-induced apoptosis.

During apoptosis, changes occur in lymphocyte membranes that render them susceptible to hydrolysis by secretory phospholipase A(2) (sPLA(2)). To study the relevant mechanisms, a simplified model of apoptosis using a calcium ionophore was applied. Kinetic and flow cytometry experiments provided key observations regarding ionophore treatment: the initial rate of hydrolysis was elevated at all enzyme concentrations, the total amount of reaction product was increased fourfold, and adsorption of the enzyme to the membrane surface was unaltered. Analysis of these results suggested that susceptibility during calcium-induced apoptosis is limited by availability of substrate rather than adsorption of enzyme. Fluorescence experiments identified three membrane alterations during apoptosis that might affect substrate access to the sPLA(2) active site. First, intercalation of merocyanine 540 into the membrane was improved, suggesting an increase in lipid spacing. Second, laurdan detected increased solvation of the lower headgroup region of the membrane. Third, the rate at which fluorescent lipids could be removed from the membrane by albumin was enhanced, implying greater vertical mobility of phospholipids. Thus, it is proposed that the membranes of apoptotic cells become susceptible to sPLA(2) through a reduction in lipid-neighbor interactions that facilitates migration of phospholipids into the enzyme active site.

A new hat for an old enzyme: waste management.

The history of research regarding secretory phospholipase A(2) (sPLA(2)) has often focused in one of two directions. Originally, the enzyme was studied biophysically in terms of its fundamental structure, enzymology, and the relationship between membrane physics and catalytic activity. More recently, a large and growing body of information has accumulated concerning regulatory factors, tissue distribution, and physiological/pathological roles of sPLA(2). Evidence is presented that suggests an additional function for the protein in which it helps to clear dead and damaged cells while avoiding digestion of those that are healthy. Apparently, the ability of the enzyme to discriminate between susceptible and resistant cells depends on physical properties of membrane lipids related to order, distribution, and neighbor/neighbor interactions. Investigations into this action of the enzyme offer the rare opportunity to apply biophysical approaches and principles to a physiological setting.