Thoracic epidural analgesia as part of an enhanced recovery program in gynecologic oncology: a prospective cohort study.

OBJECTIVE: To evaluate the safety and the effectiveness of thoracic epidural analgesia as part of the enhanced recovery after surgery (ERAS) multimodal analgesic protocol in patients with gynecologic oncology who have undergone laparotomy for suspected or confirmed malignancy. METHODS: We conducted a prospective cohort study, following an enhanced recovery after surgery pathway, among patients who had undergone laparotomy for confirmed or suspected gynecological malignancy between January 2020 and September 2021. All patients who underwent laparotomy at the gynecologic oncology department for the aforementioned reason during that time were considered eligible. Patients (n=217) were divided into two groups: epidural (n=118) and non-epidural (n=99) group. Both groups were treated with the standard ERAS departmental analgesic protocol. The primary outcomes were length of hospital stay, complications, and readmission rates. RESULTS: Data from 217 patients (epidural group, n=118 vs non-epidural group, n=99) with median age of 61 years (IQR 53-68) were analyzed. The most common type of cancer was of ovarian origin (85/217, 39.2%, p=0.055) and median (Aletti) surgical complexity score was 3 (p=0.42). No differences were observed in the patients' demographics, clinical, and surgical characteristics. Primarily, median length of stay was 4 days in both groups with statistically significant lower IQR in the epidural group (3-5 vs 4-5, p=0.021). Complication rates were more common in the non-epidural group (38/99, 38.3% vs 36/118, 30.5%, p<0.001) with similar rates of grade III (p=0.51) and IV (0%) complications and readmission rates (p=0.51) between the two groups. Secondarily, the epidural group showed lower pain scores (p<0.001) on the day of surgery and in the first post-operative day (p<0.001), higher mobilization rates on the day of surgery (94.1% vs 57.6%, p<0.001), faster removal of urinary catheter (p<0.001), shorter time to flatus (p<0.001), and less nausea on the day of surgery (p<0.001). CONCLUSION: In this study we showed that thoracic epidural analgesia, when used as part of an ERAS protocol, is safe and offers more favorable pain relief along with a number of additional benefits, improving the peri-operative experience of patients with gynecologic cancer.

European Society of Gynaecological Oncology guidelines for the peri-operative management of advanced ovarian cancer patients undergoing debulking surgery.

The European Society of Gynaecological Oncology (ESGO) developed and established for the first time in 2016, and updated in 2020, quality indicators for advanced ovarian cancer surgery to audit and improve clinical practice in Europe and beyond. As a sequela of the continuous effort to improve oncologic care in patients with ovarian cancer, ESGO issued in 2018 a consensus guidance jointly with the European Society of Medical Oncology addressing in a multidisciplinary fashion 20 selected key questions in the management of ovarian cancer, ranging from molecular pathology to palliation in primary and relapse disease. In order to complement the above achievements and consolidate the promoted systemic advances and surgical expertise with adequate peri-operative management, ESGO developed, as the next step, clinically relevant and evidence-based guidelines focusing on key aspects of peri-operative care and management of complications as part of its mission to improve the quality of care for women with advanced ovarian cancer and reduce iatrogenic morbidity. To do so, ESGO nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of ovarian cancer (18 experts across Europe). To ensure that the guidelines are evidence based, the literature published since 2015, identified from a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 117 independent international practitioners in cancer care delivery and patient representatives.

Programmed Intermittent Epidural Boluses of 0.1% Ropivacaine Versus 0.2% Ropivacaine for the Maintenance of Epidural Analgesia in Labor.

Objective The gold standard for pain management during labor is epidural analgesia, which can be administered in two different ways to the parturients, either by bolus doses or continuous infusions of local anesthetic solutions with opioids. Recently, programmed intermittent epidural boluses (PIEBs) via a pump are gaining popularity as a very effective method with minimal side effects. The aim of this study was to evaluate the optimum ropivacaine concentration between two different regimens (0.1% or 0.2% both with fentanyl 2 µg/ml) that can provide satisfactory analgesia with the minimum degree of motor blockade, using PIEBs. Methods A prospective randomized controlled study was performed from March 2020 to March 2022. Two different concentrations of ropivacaine 0.1% and 0.2% via PIEBs were equally allocated to two groups of parturients with an additional patient control epidural rescue bolus if needed. Our primary endpoint was motor blockade, as assessed by the modified Bromage scale (MBS). We also recorded visual analog scale (VAS) scores, heart rate, blood pressure, total local anesthetic consumption, labor duration and method of delivery, and APGAR score of the newborns. Results All patients presented Bromage scores equal to 6, and the total consumption of the anesthetic solution was comparable between the two groups. Women in the 0.2% group showed higher pain relief and satisfaction compared to the 0.1% group. Concerning the 0,2% group, diastolic blood pressure and APGAR scores were lower alongside with a lower satisfactory extrusion stage observed by the obstetrician. Conclusion Both ropivacaine regimens provide satisfactory labor epidural analgesia for the expectant mother without any motor blockade.

Propofol Versus Dexmedetomidine for Conscious Sedation During Vaginal Hysterectomy With Pre-emptive Local Anesthesia: A Prospective Cohort Study.

BACKGROUND/AIM: Hysterectomy is the most frequent gynecological surgery. Vaginal hysterectomy (VH) seems to be related to favorable perioperative outcomes compared to abdominal or laparoscopic approaches. As the population ages, anesthesia that is safer for the elderly, such as local anesthesia (LA) with conscious sedation, is gaining popularity and is related to favorable outcomes in patients' recovery compared to general or regional anesthesia. We aimed to evaluate the efficacy of dexmedetomidine versus propofol for women undergoing VH for uterine prolapse under LA and conscious sedation. PATIENTS AND METHODS: A prospective study on 40 women with uterine prolapse stage ≥3 who had VH under LA with conscious sedation under either dexmedetomidine (n=20) or propofol (n=20) was performed. A standardized surgical approach with continuous hemodynamic monitoring and sedation assessment using the Ramsay Sedation Scale (RSS) was conducted. The primary endpoint of the study was to determine the percentage of patients receiving intraoperative fentanyl. RESULTS: Analysis of outcomes demonstrated a significant reduction in the proportion of patients requiring intraoperative rescue fentanyl (35% vs. 5%, respectively, p=0.04) and in postoperative pain scores, with more patients achieving an optimal RSS score of 3 in the dexmedetomidine group. CONCLUSION: Based on the findings of the present study, dexmedetomidine offered superior analgesia and patient comfort compared to propofol, suggesting a favorable anesthetic profile for VH under LA.

Splenectomy as Part of Maximal-Effort Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer.

INTRODUCTION: A splenectomy is frequently performed during debulking surgery for advanced ovarian cancer. Its impact on perioperative and survival outcomes remains questionable as current evidence is conflicting. In the present study, we sought to determine the factors that affect survival rates in ovarian cancer patients that undergo a splenectomy as part of maximal-effort cytoreduction. PATIENTS AND METHODS: A retrospective chart review was conducted that included all epithelial ovarian cancer patients that had surgical cytoreduction for advanced epithelial ovarian cancer. Differences among splenectomized and non splenectomized patients were evaluated as well as the impact of known risk factors on survival outcomes of splenectomized patients. RESULTS: Overall, 245 patients were identified and 223 were included in the present series, of whom 91 had a splenectomy. Recurrence rates as well as death rates were comparable among splenectomized and non-splenectomized patients; however, both the disease-free survival (log-rank = 0.001), as well as the overall survival of splenectomized patients (log-rank = 0.006), was shorter. Thrombotic events as well as rates of pulmonary embolism were comparable. Sepsis was more common among splenectomized patients. The site of splenic metastases did not influence patients' survival. Among splenectomized patients, those offered primary debulking had longer progression-free survival (log-rank = 0.042), although their overall survival did not differ compared to patients submitted to interval debulking. Complete debulking significantly improved the overall survival compared to optimal debulking (log-rank = 0.047). Splenectomized patients that developed sepsis had worse overall survival (log-rank = 0.005). DISCUSSION: The findings of our study support the feasibility of splenectomy in advanced epithelial ovarian cancer; however, its impact on patients' survival is considerable. Therefore, every effort should be made to avoid splenic injury which will result in unintended splenectomy for non-oncological reasons.

Inferior vena cava obstruction and collateral circulation as unusual manifestations of hepatobiliary cystadenocarcinoma.

BACKGROUND: Hepatobiliary cystadenocarcinoma represents a rare epithelial malignant tumor derived from the intrahepatic bile duct. METHODS: A 71-year-old woman, who had undergone laparoscopic drainage of a cystic lesion of the right hepatic lobe, was misdiagnosed as having hepatic echinococcal disease, and received intracystic infusion of 95% ethanol four years ago. She was admitted to our hospital for further treatment. RESULTS: Physical examination revealed dilated superficial veins across the right abdominal wall. After mapping the direction of blood flow in these vessels, we assumed that this was a sign of inferior vena cava obstruction. Abdominal ultrasound, computed tomography, magnetic resonance imaging combined with magnetic resonance angiography showed a large cystic mass in the right upper quadrant and epigastrium, displacing the adjacent structures, adherent to the inferior vena cava, which was not patent, resulting in dilation of superficial epigastric veins. The patient underwent an exploratory laparotomy. Total excision of the huge mass measuring 16X15 cm was possible under selective vascular exclusion of the liver. Removal of the tumor resulted in immediate restoration of flow in the inferior vena cava. On the basis of the pathology and findings of immunohistochemical analysis, a hepatobiliary cystadenocarcinoma was diagnosed. CONCLUSIONS: In the present case, hepatobiliary cystadenocarcinoma was accompanied by dilated superficial venous collaterals due to inferior vena cava obstruction. Selective vascular exclusion of the liver allowed a safe oncological resection of the tumor.

Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter.

Background and Goal of Study: Spinal anesthesia for cesarean section is frequently associated with a high incidence of hypotension, which may bring about untoward effects for both the mother and fetus. Recently, norepinephrine has emerged as a promising alternative in maintaining blood pressure in the obstetric setting. Fluid administration is another technique still widely used to prevent maternal hypotension. The optimal fluid strategy to prevent maternal hypotension has not been elucidated yet. It has been recently suggested that the main strategy in the prevention and management of hypotension should be the combination of vasoconstrictive medications and fluid administration. The aim of this randomized study was to compare the incidence of maternal hypotension in parturients receiving either colloid preload or crystalloid co-load in the setting of prophylactic norepinephrine infusion during elective cesarean section under combined spinal-epidural anesthesia. Materials and Methods: After ethics committee approval, 102 parturients with full-term singleton pregnancies were randomly allocated to either 6% hydroxyethyl starch 130/0.4 5 mL/kg before the onset of spinal anesthesia (colloid preload group) or Ringer's lactate solution 10 mL/kg concurrent with the subarachnoid injection (crystalloid co-load group). In both groups, norepinephrine 4 µg/min starting simultaneously with the administration of the subarachnoid solution was also administered. The primary outcome of the study was the incidence of maternal hypotension, defined as systolic arterial pressure (SAP) <80% of baseline. The incidence of severe hypotension (SAP < 80 mmHg), total dose of vasoconstrictive agents administered, as well as the acid-base status and Apgar score of the neonate and any incidence of maternal side effects were also recorded. Results: Data analysis was performed on 100 parturients: 51 in the colloid preload group and 49 in the crystalloid co-load group. No significant differences were demonstrated between the colloid preload group and the crystalloid co-load group in the incidence of hypotension (13.7% vs. 16.3%, p = 0.933) or the incidence of severe hypotension (0% vs. 4%, p = 0.238). The median (range) ephedrine dose was 0 (0-15) mg in the colloid preload group and 0 (0-10) mg in the crystalloid co-load group (p = 0.807). The incidence of bradycardia, reactive hypertension, requirement for modification of vasopressor infusion, time to the first occurrence of hypotension, and maternal hemodynamics did not differ between the two groups. There were no significant differences in other maternal side effects or neonatal outcomes between groups. Conclusions: The incidence of hypotension with a norepinephrine preventive infusion is low and comparable with both colloid preload and crystalloid co-load. Both fluid-loading techniques are appropriate in women undergoing cesarean delivery. It appears that the optimal regimen for prevention of maternal hypotension is a combined strategy of a prophylactic vasopressor such as norepinephrine and fluids.

Reply to Akça, B.; Bilotta, F. Time and Type of Administered Fluids during Cesarean Section Might Not Matter for Hemodynamic Outcomes, but There Are Significant Patient Safety Concerns Regarding Colloid Use in Parturients. Comment on "Theodoraki et al. Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter. J. Clin. Med. 2023, 12, 1333".

We would like to take this opportunity to thank Drs Akça and Bilotta for their interest and their insightful comments [...].

Maximal Effort Cytoreduction in Epithelial Ovarian Cancer: Perioperative Complications and Survival Outcomes from a Retrospective Cohort.

Background: Rates of maximal effort cytoreductive surgery in ovarian cancer patients increase gradually the last decade. The purpose of the present study is to evaluate factors that contribute to survival and morbidity outcomes in this group of patients. Methods: We retrospectively reviewed patient records of epithelial ovarian cancer patients with an intermediate and high Mayo Clinic surgical complexity score, operated between January 2010 and December 2018. Results: Overall, 107 patients were enrolled in the present study with a median age of 62 years (23-84) and a follow-up of 32 months (2-156). Thirteen Clavien-Dindo grade IIIa complications were documented in 10 patients (9.3%). Of all the investigated factors, only stage IVb (p = 0.027) and interval debulking surgery (p = 0.042) affected overall survival rates. Overall survival outcomes of patients operated on a primary setting started to differentiate compared to those that received neo-adjuvant chemotherapy after the 4th postoperative year. Conclusions: Maximal effort cytoreductive procedures should be considered feasible in the modern surgical era, as they are accompanied by acceptable rates of perioperative morbidity. Hence, every effort should be made to perform them in the primary setting, rather than following neoadjuvant chemotherapy as current evidence favor increased survival rates of patients that will likely surpass an interval of observation of more than 4 years.

Enhanced Recovery After Surgery Protocols in Obese Gynecological Oncology Patients: A Single-Center Experience.

Objective The aim of this study is to present our experience and evaluate the safety and outcomes of the implementation of Enhanced Recovery After Surgery (ERAS) protocols in obese patients who underwent surgery for suspected or confirmed gynecological malignancies. Method From January 2020 to September 2021, 217 patients underwent laparotomy for a confirmed or suspected gynecological malignancy following a 19-element ERAS pathway. The patients were divided into two groups: obese (BMI ≥ 30 kg/m2, n = 104) and non-obese (BMI < 30, n = 113). Both groups were treated with a 19-element ERAS protocol. Results After dividing the 217 patients into two groups, significantly more comorbidities were observed in the obese group (diabetes mellitus: 23% vs. 8%, p = 0.004; ASA score grade 3: 25.0% vs. 6.2%, p < 0.001), as well as higher rates of endometrial cancer (51.9% vs. 17.7%, p < 0.001) compared to the non-obese group. The overall ERAS compliance rates when matched element by element were similar. Postoperatively, complication rates of all grades were significantly higher in the obese group (46.1% vs. 27.4%, p < 0.001) without differences in the length of stay, readmission, and reoperation rates. Conclusion In this retrospective study, we showed that obese gynecological oncology patients can be safely managed with ERAS protocols perioperatively while potentially minimizing the adverse outcomes in these otherwise high-risk patients.

The Use of Vigileo® Monitor in a Parturient With Severe Mitral Valve Stenosis and Severe Pulmonary Hypertension Undergoing Cesarean Section Under General Anesthesia: A Case Report and Literature Review.

We report a case of a 35-year-old pregnant female of Afghan origin who was admitted to the intensive care unit (ICU) because of pulmonary edema development when she was in the 30th week of gestation. During the bedside examination, the transthoracic echocardiogram (TTE) revealed severe mitral valve stenosis and pulmonary hypertension. The patient went into treatment with metoprolol for the control of tachycardia and furosemide for the prevention of fluid overload. During the 32nd week of gestation, the medical council decided on a cesarean section (CS) to be carried out under general anesthesia. The anesthesiologists decided to use the Vigileo monitor (Edwards Lifesciences, Irvine, CA, USA) as it is vitally important to approach fluid administration as fluid management is challenging concerning the obstetric patient. Vigileo monitoring is based on the invasive measurement of cardiac output (CO), cardiac index (CI), stroke volume (SV), and stroke volume variation (SVV). Fluid resuscitation based on hemodynamic parameters is a key component of patient care, especially in scenarios such as cardiovascular disease. This is the first case report where a Vigileo monitor was applied to a patient with severe mitral valve stenosis and severe pulmonary hypertension undergoing a cesarean section, which was accomplished without any complications. The patient was discharged from the hospital on the 12th postoperative day, hemodynamically stable. Each immigrant woman, regardless of her financial, social, cultural, or any other situation, has the fundamental right to receive complete perinatal healthcare. Nevertheless, the most recent statistical data show that those women's access to public healthcare is insufficient, leading to high rates of maternal mortality. The international medical community has to adapt to the new multicultural environment, and health services must be provided to this vulnerable population with the appropriate level of safety.

Pelvic exenteration for gynecologic malignancies: The experience of a tertiary center from Greece.

BACKGROUND: Pelvic exenteration is an ultraradical procedure that is performed for locally advanced pelvic malignancies. Despite its rarity, the rates of the procedure increase during the last years due to the gain of surgical expertise. Data on survival rates remain; however, scarce in the literature. METHODS: We retrospectively reviewed the records of all patients who underwent exenterative procedures for advanced gynecologic malignancies between 2006 and 2020. Major and minor perioperative complications were documented according to the Clavien-Dindo classification only when they occurred during a time limit of 30 days from the operation. Cox regression analysis and Kaplan-Meier survival curves were used for the analysis of survival outcomes. RESULTS: Overall, we identified 138 patients who were offered a pelvic exenteration procedure that were followed up for a median of 42 months (range 6-60 months). Seventy-five patients recurred (54.3%) during the follow-up period within 35.04 months (95% CI 31.01, 39.07 months). After examining several potential factors that might influence survival rates, we observed that only patients with positive margins had increased risk of recurrence (HR 1.66, 95%CI 1.10, 2.56 p = .016), although this was not associated with a decrease in overall survival. Overall survival outcomes were available for 112 patients of whom 62 died (55.4%) within 38.84 months (95% CI 35.02, 42.67). Major complications were detected in 21 patients. Reoperation was required in 18 patients. Anastomotic leakage was observed in 7 cases (5%) of whom 4 patients required reoperation. CONCLUSION: In summary, the findings of our study suggest that women undergoing pelvic exenteration for gynecologic malignancies have a significant survival probability that is accompanied by acceptable rates of operative morbidity.

Deep versus Moderate Neuromuscular Blockade in Gynecologic Laparoscopic Operations: Randomized Controlled Trial.

Background: To investigate whether deep neuromuscular blockade (NMB) improves surgical conditions and postoperative pain compared to moderate block, in patients undergoing gynecologic laparoscopic surgery. Methods: A single blind, randomized, controlled trial was undertaken with laparoscopic gynecologic surgical patients, who were randomly assigned to one of the following two groups: patients in the first group received deep NMB (PTC 0-1) and in the other, moderate NMB (TOF 0-1). Primary outcomes included assessing the surgical conditions using a four-grade scale, ranging from 0 (extremely poor) to 3 (optimal), and patients' postoperative pain was evaluated with a five-grade Likert scale and the analgesic consumption. Results: 144 patients were analyzed as follows: 73 patients received deep NMB and 71 moderate NMB. Mean surgical field scores were comparable between the two groups (2.44 for moderate vs. 2.68 for deep NMB). Regarding postoperative pain scores, the patients in the deep NMB experienced significantly less pain than in the group of moderate NMB (0.79 vs. 1.58, p < 0.001). Moreover, when the consumption of analgesic drugs was compared, the moderate NMB group needed more extra opioid analgesia than the deep NMB group (18.3% vs. 4.1%, p = 0.007). From the secondary endpoints, an interesting finding of the study was that patients on deep NMB had significantly fewer incidents of subcutaneous emphysema. Conclusions: Our data show that, during the performance of gynecologic laparoscopic surgery, deep NMB offers no advantage of operating filed conditions compared with moderate NMB. Patients may benefit from the deep block as it may reduce postoperative pain.

Application of J-Plasma in the excision of diaphragmatic lesions as part of complete cytoreduction in patients with advanced ovarian cancer.

For the resection of diaphragmatic disease in patients with advanced ovarian cancer (OC), a plethora of ablative methods have been utilized. The present study aimed to present preliminary data on the use of J-Plasma in OC with diaphragmatic involvement via a retrospective review of patients who had diaphragmatic stripping with of J-Plasma® from January 2016 to September 2020. A total of 12 patients (median age, 65 years) were analyzed. Median operative time was 240 min while median estimated blood loss was 400 ml. Median operative time for diaphragmatic resection was 25 min. During a median follow-up of 12 months, two recurrences were noted while none of the patients died of the disease. Median disease free survival was 12 months. Overall, the preliminary outcomes of the present study indicated that J-Plasma could be safely used in diaphragmatic resection and it was associated with low rates of short-term morbidity. However, further studies are warranted to reach to safe conclusions.

Peripartum Ηysterectomy: A Four-Year Obstetric and Anesthetic Experience in a Tertiary Referral Hospital in Greece.

Background Although peripartum hysterectomy (PH) is a life-saving procedure in cases of abnormal placentation and postpartum hemorrhage, it can be associated with major obstetric and anesthetic complications. This retrospective study aimed to evaluate the incidence, etiology, perioperative anesthetic and obstetric management, complications, and fetal outcomes in women undergoing PH in a single tertiary referral hospital in Greece. Methodology This was a retrospective analysis of medical records of women who underwent emergency or elective PH in our hospital between January 2015 and December 2018. Results During the study period, 69 women who underwent a PH were identified. The incidence rate of elective and emergency PH was 4 and 1.2 per 1,000 deliveries, respectively. The main indication for PH was abnormal placentation (81.2%), followed by uterine atony (13%). Conversion to general anesthesia (GA) was performed in 21 (30.4%) cases. Conclusions This study showed a high prevalence of PH in our hospital compared to high-income countries. A neuraxial-only technique may be a safe alternative in individual cases of abnormal placentation. Conversion to GA can be reserved for complex surgical cases when massive hemorrhage is anticipated and, if possible, after the neonate has been delivered.

Role of Critical Care Units in the management of obstetric patients (Review).

Pregnancy is considered a natural process for the majority of women. However, a limited proportion of pregnancies and deliveries can present with a broad variety of complications that may require admission to a Critical Care Unit (CCU). In the present review, the indications of admission of obstetrical and postpartum patients to CCUs were critically evaluated with a particular focus on the management of their complications. The management of critically ill obstetric patients remains challenging due to the physiological changes that occur during pregnancy, pregnancy-related diseases and the need to carefully consider the well-being of the fetus before any intervention can be recommended/performed. Indications for admission to CCUs include both obstetric and non-obstetric conditions that may require continuous monitoring and further interventions. Hypertensive disorders of pregnancy and mass hemorrhage are amongst the most common causes of admission to CCUs in pregnant and postpartum women. The establishment of a diagnostic and care algorithm based on the contribution of a multidisciplinary team is of critical importance to aid in the determination of which patients will require intensive care, and to assist in deciding what type of critical care each critically ill patients receives.

A novel laparoscopic pulse oximeter device. An easy, efficient and cost- effective way of detecting arterial structures.

The introduction of laparoscopy has revolutionized surgery. However, these new techniques have brought new problems into the surgical field. Due to the loss of depth and tactile sensation, time- consuming efforts must be made in order to identify normal anatomy and detect any aberrations. Even well experienced surgeons could face difficulties during demanding procedures, such as operations on inflammatory conditions. Therefore, there is still a strong need for developing additional tools to help mapping the anatomy. We designed a laparoscopic pulse oximeter device, which offers an easy, efficient and cost- effective way of using pulse oximetry in combination with a standard laparoscopic clamp in order to identify arterial structures.

Prevention of hypotension during elective cesarean section with a fixed-rate norepinephrine infusion versus a fixed-rate phenylephrine infusion. Α double-blinded randomized controlled trial.

BACKGROUND: Spinal anesthesia for cesarean section can be complicated by hypotension, with untoward effects for both the mother and fetus. Frequently used phenylephrine can lead to baroreceptor-mediated reflex bradycardia. The aim of the present study was to compare a fixed-rate prophylactic norepinephrine infusion to a fixed-rate prophylactic phenylephrine infusion during elective cesarean section under combined spinal-epidural anesthesia. MATERIALS AND METHODS: Eighty-two parturients were randomized to either norepinephrine 4 µg/min or phenylephrine 50 µg/min fixed-rate infusions, starting simultaneously with the administration of the subarachnoid solution. The primary endpoint was the incidence of maternal bradycardia. Maternal hemodynamics at specific timepoints, the incidence of hypotension or hypertension, the requirement for ephedrine or atropine bolus administration as well as the acid-base status and Apgar score of the neonate were recorded. RESULTS: The incidence of bradycardia as well as the requirement for atropine administration was lower in the norepinephrine group (4.8% vs. 31.7%, p = 0.004 and 2.4% vs. 24.3%, p = 0.01, respectively). Fetal pH, and fetal blood glucose concentration were higher in the norepinephrine group (p = 0.027 and 0.019, respectively). No difference in the occurrence of hypotension, hypertension, in the requirement for bolus vasoconstrictive medication or in Apgar scores was demonstrated. CONCLUSIONS: A fixed-rate infusion of norepinephrine is as effective in the management of hypotension during regional anesthesia for cesarean section as a fixed-rate infusion of phenylephrine, with the avoidance of phenylephrine-induced bradycardia. The more favourable neonatal acid-base profile of noradrenaline might be due to better maintenance of placental blood flow in the noradrenaline group due to its beta action, while the higher fetal glucose concentration in the same group might result from a catecholamine-stimulated glucose metabolism increase and a ß-receptor mediated insulin decrease.

Biomarker assessment of tobacco smoking exposure and risk of dementia death: pooling of individual participant data from 14 cohort studies.

BACKGROUND: While there is a suggestion that self-reported tobacco smoking may be a risk factor for dementia, to date, it has not been possible to explore the thresholds at which this exposure elevates risk. Accordingly, our aim was to relate cotinine, a biomarker of tobacco smoking, to risk of dementia death. METHODS: We pooled 14 prospective cohort studies that held data on cotinine (plasma or saliva), covariates and death records. RESULTS: In the 33 032 study members (17 107 women) with salivary cotinine data, a mean duration of 8.3 years of follow-up gave rise to 135 deaths ascribed to dementia; while in 15 130 study members (7995 women) with plasma cotinine data, there were 119 dementia deaths during 14.3 years of mortality surveillance. After multiple adjustment, both plasma cotinine (per 1 SD higher cotinine; 95% CI 1.29; (1.05 to 1.59)) and salivary cotinine (1.10 (0.89 to 1.36)) were positively related to dementia risk, with stronger effects apparent for plasma. CONCLUSION: Our finding that plasma cotinine was related to an elevated risk of dementia death warrants testing in studies with measures of disease onset as opposed to just mortality.