Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.

Comparative dose-response study of intrathecal hyperbaric ropivacaine for cesarean delivery in preterm singleton versus twin pregnancies.

INTRODUCTION: Previously, we demonstrated that patients with full-term singletons and preterm twins require similar dose of intrathecal hyperbaric ropivacaine. However, these findings may be attributable to enrolled patients with preterm twin pregnancies. In this study, we aimed to determine the intrathecal dose requirements of hyperbaric ropivacaine for twins and singletons at equal gestational ages. METHODS: We enrolled 75 patients with preterm singletons and 75 patients with preterm twins scheduled for cesarean delivery under combined spinal-epidural anesthesia in this two-arm parallel, randomized, double-blind, dose-response study. Patients with singletons and twins were randomly assigned to receive one of five different doses of hyperbaric ropivacaine: 10, 12, 14, 16, or 18 mg. A probit regression model was used to determine the dose effective in 50% of patients (ED50) and dose effective in 90% of patients (ED90) values. The relative median potency was calculated to compare the ED50 between patients with twins and singletons. RESULTS: Intrathecal ropivacaine ED50 and ED90 (with 95% CI) in patients with preterm singletons were 9.9 (7.2 to 11.5) mg and 16.8 (14.5 to 22.9) mg, respectively. In patients with preterm twins, these values were 9.2 (95% CI 6.4 to 10.8) mg and 15.6 (95% CI 13.6 to 20.6) mg. Between patients with preterm twins and preterm singletons, the relative potency (ED50 ratios) was 0.933 (95% CI 0.72 to 1.15). CONCLUSIONS: During preterm gestation, intrathecal hyperbaric ropivacaine dose requirements for scheduled cesarean delivery were not different between patients with twins and singletons. TRIAL REGISTRATION NUMBER: ChiCTR2100051382.

Comparative study on the manually-controlled variable-rate versus fixed-rate infusion of norepinephrine for preventing hypotension during spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: Previous studies have shown that prophylactic norepinephrine infusion is superior to intermittent bolus administration in preventing post-spinal hypotension. Nevertheless, it is still controversial whether manually-controlled variable-rate infusion is more effective than fixed-rate infusion. The purpose of the present study was to compare the efficacy of variable-rate infusion and fixed-rate infusion of norepinephrine for prophylaxis against maternal hypotension and maintaining hemodynamic stability during spinal anesthesia for cesarean delivery to determine more effective mode for clinical practice. DESIGN: A prospective randomized, controlled study. SETTING: Operating room, Women's Hospital, Zhejiang University School of Medicine. PATIENTS: A total of 161 parturients scheduled for elective cesarean delivery with spinal anesthesia were randomized into Group F (fixed-rate infusion) and Group V (variable-rate infusion). INTERVENTIONS: Parturients received prophylactic norepinephrine infusion concurrent with the intrathecal injection at rate started at 0.05 µg/kg/min. In Group F, norepinephrine was administered continuously at a fixed (on-off) rate, and a bolus of norepinephrine 5 µg or 10 µg was given when systolic blood pressure (SBP) decreased by 20% or more of baseline. In Group V, manually adjusted norepinephrine infusion within the range 0-0.14 µg/kg/min, according to SBP at 1-min intervals until delivery, aim to maintain values close to the baseline. MEASUREMENTS: During the study period, the incidence of maternal hypotension, hemodynamic performance, the number of physician interventions, reactive hypertension, bradycardia, nausea, vomiting, norepinephrine cumulative dose (before delivery), and neonatal outcomes were recorded. MAIN RESULTS: The incidence of maternal hypotension was significantly lower in Group V than that in Group F (9% versus 30%) (P < 0.001). No significant difference was found in the serial changes in SBP and heart rate (HR) for the first 15 min. Group V showed higher frequency of physician interventions compared with the Group F (P < 0.001). The incidence of hypertension, severe hypotension, nausea, vomiting, bradycardia, norepinephrine cumulative dose, and neonatal outcome were comparable between the two groups. CONCLUSION: When norepinephrine was infused at an initial dose of 0.05 µg/kg/min for preventing hypotension during spinal anesthesia for cesarean delivery, due to technical limitations of inadequate dose design in this study, neither a variable-rate infusion (need more physician intervention) nor a fixed-rate infusion regimen (experience more transient hypotension) was optimal. However, in terms of clinical importance, how to prevent the parturients from experiencing more incidence of hypotension might be a greater concern for anesthesiologists.

Comparative Dose-Response Study of Phenylephrine Bolus for the Treatment of the First Episode of Spinal Anesthesia-Induced Hypotension for Cesarean Delivery in Severe Preeclamptic versus Normotensive Parturients.

Background: It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED50 and ED90 of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension. Methods: Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 µg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 µg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed. Results: The ED50 and ED90 (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) µg and 107 (95.9-128.6) µg in parturients with normotension. The ED50 and ED90 values in parturients with severe preeclampsia were 47.6 (41.3-52.7) µg and 70.7 (62.9-86.7) µg. The relative median potency was 1.51 (1.16-2.61). Conclusion: Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED50 of phenylephrine dose compared with normotensive parturients.

2,2',4,4'-tetrabromodipheny ether (BDE-47) disrupts gonadal development of the Africa clawed frog (Xenopus laevis).

Previous studies have shown that BDE-47, one of the most abundant polybrominated diphenyl ethers (PBDEs) congeners, has a weak estrogenic activity, but it has remained unclear whether BDE-47 disrupts gonadal development and causes male-to-female sex reversal in lower vertebrates, with limited and controversial data. The present study aimed to determine the effects of BDE-47 on gonadal development in Xenopus laevis, a model amphibian species for studying adverse effects of estrogenic chemicals on reproductive development. X. laevis at stage 45/46 were exposed to BDE-47 (0.5, 5, 50 nM) in semi-static system, with 1 nM 17ß-estradiol (E2) as the positive control. When reaching stage 53, tadpoles were examined for gonadal morphology, histology and sex-dimorphic gene expression. The phenotypic sex (gonadal morphology and histology) of each BDE-47-treated tadpole matched its genetic sex, showing no sex-reversal, whereas one half of genetic males treated with E2 displayed ovarian-like features. However, some genetic males (26%) in the 50 nM BDE-47 treatment group were found to contain more germ cells clumping together in the medulla, along with an increasing tendency of the gonad length/kidney length ratio in males, resembling feminizing outcomes of E2. These observations seem to suggest that BDE-47 exerted weak feminizing effects. However, BDE-47 induced increases in expression of both female-biased genes and male-biased genes in two sexes, which disagrees with feminizing outcomes, suggesting complicated effects of BDE-47 on gonadal development. Taken together, all results demonstrate that nanomolar BDE-47 disrupted gonadal development and exerted weak feminizing effects, but not resulted in male-to-female sex reversal in X. laevis.

Clinical feasibility of imaging with indocyanine green combined with carbon nanoparticles for sentinel lymph node identification in papillary thyroid microcarcinoma.

BACKGROUND: Although several previous studies demonstrated the feasibility and efficacy of indocyanine green (ICG) for thyroid cancer surgery, ICG was administered through venous injection and focused on parathyroid gland protection. We thus aimed to study the feasibility of imaging using ICG combined with carbon nanoparticles (CNs) in the identification of sentinel lymph nodes (SLNs) in patients diagnosed with papillary thyroid microcarcinoma (PTMC). METHODS: Two approaches were applied to detect lymph nodes in PTMC surgery. Patients were randomized into 2 groups. ICG and CNs were injected into the thyroid in Group A. In Group B, only CNs was injected. Black-stained or fluorescent nodes observed using near-infrared fluorescence imaging systems were defined as SLNs. SLN and central lymph node (CLN) dissection was completed in both groups. The pathological and postoperative outcomes were compared between 2 groups. RESULTS: There were 40 patients in Group A and 60 in Group B. A total of 138 SLNs were identified; 72 and 66 SLNs were detected and dissected in Groups A and B, respectively. The number of SLNs identified (per patient) in Group A was higher than that in Group B (P = .027). The number of harvested CLNs was 161 and 192 in Groups A and B, respectively, out of which 45 and 48 lymph nodes with metastasis were confirmed by permanent pathology. The CLN metastatic rate in Group A was higher than that in Group B (P = .048). CONCLUSION: Imaging using ICG combined CNs is feasible and safe for SLN identification in PTMC patients. Compared with using only CNs, more SLNs can be removed and more metastatic lymph nodes can be confirmed when using the combined method. Although the combined method appears to accurately stage tumors, further research is needed.