The Effect of Intermittent Oxytocin Pretreatment on Oxytocin-Induced Contractility of Human Myometrium In Vitro.

BACKGROUND: Prolonged continuous oxytocin administration during labor may induce oxytocin receptor desensitization, which attenuates the response of the myometrium to further oxytocin, increasing the risk of postpartum hemorrhage. The literature comparing pulsatile (intermittent) versus continuous oxytocin administration for induction and augmentation of labor is inconsistent with regard to maternal outcomes. We aimed to determine the effect of intermittent versus continuous oxytocin preexposure on myometrial responsiveness to subsequent oxytocin. We hypothesized that intermittent oxytocin pretreatment would result in superior subsequent oxytocin-induced contractility than continuous oxytocin pretreatment. METHODS: This in vitro study was undertaken using myometrium obtained from women undergoing elective cesarean deliveries. Each myometrial strip was mounted in an individual organ bath with physiological salt solution under homeostatic conditions and allocated to one of 3 groups: (1) control (no pretreatment); (2) continuous (pretreatment with oxytocin 10(-5) M for 2 hours); or (3) intermittent (pretreatment with alternating oxytocin 10 M and physiological salt solution every 15 minutes, for 2 hours). After pretreatment, dose-response testing to oxytocin 10(-5) to 10(-5) M was performed and contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions. RESULTS: Eighteen women were recruited, and 86 successful experiments were performed (control n = 29, continuous n = 28, intermittent n = 29). The means (standard errors) of MI (√g·contractions/10 min) in the control, continuous, and intermittent groups were 2.34 (0.09), 1.78 (0.09), and 2.13 (0.11), respectively. The MI was significantly reduced in the continuous group when compared to the control (estimated difference [95% confidence interval {CI}], -0.56 [-0.81 to -0.31]; P < .01) and intermittent group (estimated difference [95% CI], -0.35 [-0.62 to -0.08]; P = .01). There was no significant difference in MI between the intermittent and control group (estimated difference [95% CI], -0.21 [-0.51 to 0.09]; P = .17). CONCLUSIONS: Human myometrium remains more responsive to subsequent oxytocin after intermittent compared to continuous exposure to oxytocin, most likely due to reduction in oxytocin receptor desensitization, or facilitation of receptor resensitization in the intermittent group. Hence, intermittent oxytocin administration during labor warrants further investigation as a technique to preserve uterine oxytocin responsiveness.

The Recovery Time of Myometrial Responsiveness After Oxytocin-Induced Desensitization in Human Myometrium In Vitro.

BACKGROUND: Postpartum hemorrhage secondary to uterine atony is a leading cause of maternal morbidity. Prolonged exposure to oxytocin for labor augmentation can result in the desensitization phenomenon, a decrease in the responsiveness of myometrium to further oxytocin. It is currently not known whether waiting for a specific time interval after the cessation of oxytocin allows the oxytocin receptors to resensitize and recover, thereby improving subsequent oxytocin-induced myometrial contractility. We aimed to investigate the effect of a rest period of 30, 60, and 90 minutes after oxytocin administration on the recovery of oxytocin-desensitized human myometrium in vitro. We hypothesized that the longer the rest period, the better the responsiveness and subsequent oxytocin-induced contractility of the myometrium. METHODS: Myometrial tissue was obtained from women undergoing elective cesarean deliveries. The myometrial sample was dissected into 4 strips, and each strip was mounted in a single organ bath with physiological salt solution (PSS) under homeostatic conditions and then pretreated for 2 hours with oxytocin 10 M. After pretreatment, each strip was washed with PSS and allowed to rest in PSS solution for 30, 60, or 90 minutes. At the end of the rest period, dose-response testing to oxytocin 10 to 10 M was performed. A control group consisted of oxytocin dose-response testing without any oxytocin pretreatment. Contractile parameters were measured and compared among the groups after square root transformation. The primary outcome was motility index (frequency × amplitude), and secondary outcomes included frequency, amplitude, and area under the curve. RESULTS: Fifty-five experiments were conducted from samples obtained from 16 women. The mean motility index (√g·contractions/10 min) during the dose-response curve (oxytocin 10 to 10 M) in the control group was significantly greater than all the experimental groups; the mean estimated differences (95% confidence intervals) were -1.33 (-2.50 to -0.15, P = 0.02), -1.59 (-2.68 to -0.50, P = 0.004), and -1.88 (-2.97 to -0.80, P = 0.001) for the 30-, 60-, and 90-minute groups, respectively. When the experimental groups were compared, there were no significant differences in any of the contractility parameters; however, confidence intervals were wide. CONCLUSIONS: Our study shows that oxytocin pretreatment attenuates oxytocin-induced contractility in human myometrium despite a rest period of up to 90 minutes after oxytocin administration. However, we were unable to determine whether increasing the rest period from 30 to 90 minutes results in improvement in myometrial contractility because of our small sample size relative to the variability in the contractile parameters. Further laboratory and clinical in vivo studies are necessary to determine whether a rest period up to 90 minutes results in improvement in myometrial contractility. In addition, further experimental studies are necessary to determine the key mechanisms of oxytocin receptor resensitization.

The Effect of Extracellular Calcium on Oxytocin-Induced Contractility in Naive and Oxytocin-Pretreated Human Myometrium In Vitro.

BACKGROUND: Prolonged exposure to oxytocin during augmentation of labor is a significant risk factor for uterine atony, resulting in the desensitization phenomenon, a decrease in the responsiveness of myometrium to further oxytocin. The importance of extracellular calcium is well established in spontaneous myometrial contractility; however, its significance is unknown in the context of desensitized myometrium. We aimed to investigate the effect of low, normal, and high extracellular calcium concentration on oxytocin-induced contractility in oxytocin-pretreated human myometrium in vitro. We hypothesized that extracellular normocalcemia would provide superior oxytocin-induced contractility in both naive and oxytocin-pretreated myometrium compared with hypocalcemia and hypercalcemia. METHODS: Myometrial tissue was obtained from women undergoing elective cesarean deliveries and was dissected into longitudinal strips. Each strip was mounted in a single organ bath with physiological salt solution (PSS) under homeostatic conditions and then pretreated for 2 hours with either oxytocin 10 M or PSS (control). The tissue was then washed with PSS, and calcium concentrations were altered to reflect low (1.25 mM), normal (2.5 mM), or high (3.75 mM) levels, thereby providing 6 study groups. After equilibration in the desired calcium concentration, a dose-response testing to oxytocin 10 M to 10 M was performed. Contractile parameters were measured and compared among groups after square root transformation. The primary outcome was motility index (frequency × amplitude), and secondary outcomes included frequency, amplitude, and area under the curve. RESULTS: One hundred seventy-four experiments were conducted from samples obtained from 36 women. In the control group, the mean motility index (√g·contractions/10 min) was significantly lower in the hypocalcemic group than in the normocalcemic group (estimated difference, -0.43; 95% confidence interval [CI], -0.82 to -0.04; P = 0.03). In addition, the mean frequency of contractions (√contractions/10 min) was significantly lower in the hypocalcemic (estimated difference, -0.27; 95% CI, -0.46 to -0.09; P = 0.002) and hypercalcemic groups (estimated difference, -0.18; 95% CI, -0.34 to -0.02; P = 0.03) compared with the normocalcemic group. In the oxytocin-pretreated group, there were no significant differences in the values of any of the contractility parameters of the hypocalcemic or hypercalcemic groups compared with the normocalcemic group (mean motility index [√g·contractions/10 min] estimated difference, 0.10; 95% CI, -0.23 to 0.43; P = 0.74 and -0.39; 95% CI, -1.10 to 0.32; P = 0.39, respectively). CONCLUSIONS: In oxytocin-naive myometrium, normocalcemia provides superior oxytocin-induced contractility compared with hypocalcemic and hypercalcemic conditions. We were unable to draw conclusions regarding oxytocin-pretreated myometrium because of the small sample size relative to the large variability of the data. These observations warrant further investigations in laboratory and clinical settings.

Obstetric and Anaesthesia Checklists for the Management of Morbidly Adherent Placenta.

OBJECTIVE: To develop an integrated checklist for the management of patients with suspected morbidly adherent placenta (MAP). METHODS: A checklist process was developed incrementally by clinicians in the disciplines of maternal-fetal medicine, gynaecology, medical imaging, and anaesthesia for management of women with suspected MAP. RESULTS: Over a five-year period of debriefing after individual cases, a comprehensive checklist system was developed. The checklist is activated upon referral if MAP is suspected at an initial maternal-fetal medicine consultation; the process is subsequently guided by a clinical nurse specialist, leading to a standardized program of care. CONCLUSIONS: Having a checklist process facilitates standardized care and optimal communication between specialists, providing team-based care for women with this potentially serious complication of pregnancy.

COVID-19 in Women's health: Pre-operative gynaecological assessment and shared decision making.

The National Health Service (NHS) response to the coronavirus disease 2019 (COVID-19) pandemic brought about rapid and innovative changes to surgical care in gynaecology, shared decision making around operative procedures and pre-operative gynaecological pathways. Short-term changes are linked to the redeployment of resources away from elective gynaecology and long-term changes relate to accelerating the streamlining of treatments, telemedicine and education in patient self-management. The speed and recency of the response does not yet permit the creation of a large evidence base for effective and acceptable interventions, apart from anecdotal observations of 'what works well'' good practice and guidance from the Royal Colleges and the National Institute for Health and Care Excellence (NICE).

The Use of Ultrasonography in Obstetric Anesthesia.

This article provides an overview of the use of ultrasonography in obstetric anesthesia. It discusses the indications, benefits, and techniques of using ultrasonography to optimize the delivery of anesthesia and provide safe and efficacious clinical care. More specifically, it discusses the use of ultrasonography to facilitate neuraxial anesthesia, abdominal field blocks, central and peripheral vascular access, as well as the assessment of the lung fields and gastric contents, and identification of the cricothyroid membrane.

The Monitoring and Management of Severe Traumatic Brain Injury in the United Kingdom: Is there a Consensus?: A National Survey.

BACKGROUND: To survey the current practice of monitoring and management of severe traumatic brain injury (TBI) patients in the critical care units across the United Kingdom. METHODS: A structured telephone interview was conducted with senior medical or nursing staff of all the adult neurocritical care units. Thirty-one neurocritical care units that managed adult patients with severe TBI were identified from the Risk Adjustment in Neurocritical Care (RAIN) study and the Society of British Neurological Surgeons. RESULTS: Intracranial pressure (ICP) monitoring was used in all the 31 institutions. Cerebral perfusion pressure was used in 30 of the 31 units and a Cerebral perfusion pressure target of 60 to 70 mm Hg was the most widely used target (25 of 31 units). Transcranial Doppler was used in 12 units (39%); brain tissue oxygen (PbtO(2)) was used in 8 (26%); cerebral microdialysis was used in 4 (13%); jugular bulb oximetry in 1 unit; and near-infrared spectrometry was not used in any unit. Continuous capnometry was used in 28 (91%) units for mechanically ventilated patients. Mannitol was the most commonly used agent for osmotherapy to treat intracranial hypertension. CONCLUSIONS: We identified that there was no clear consensus and considerable variation in practice in the management of TBI patients in UK neurocritical care units. A protocol-based management has been shown to improve outcome in sepsis patients. Given the magnitude of the problem, we conclude that there is an urgent need for international consensus guidelines for management of TBI patients in critical care units.