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Multiple pregnancy is associated with higher risk of uterine atony, postpartum hemorrhage (PPH), blood transfusion, hysterectomy, and death. The optimal dose of oxytocin at cesarean delivery in people with twin pregnancy is unknown. We sought to determine the effective bolus dose of oxytocin required to initiate adequate uterine tone in 90% of people (ED90) with twin pregnancy undergoing elective cesarean delivery. Our hypothesis was that the dose of oxytocin would be higher than 0.5 international units (IU) but lower than 5 IU.A double-blind dose-finding study using the biased coin up-down method was undertaken in people with twin pregnancy ≥36 weeks gestational age undergoing elective cesarean delivery under neuraxial anesthesia. Those with additional risk factors for PPH, apart from twin pregnancy, were excluded. Oxytocin was administered as an intravenous bolus over 1 minute on delivery of the second fetus. The first patient received 0.5 IU, and subsequent oxytocin doses were administered according to a sequential allocation scheme. The actual doses administered were 0.5, 1, 2, 3, 4, and 5 IU of oxytocin. The primary outcome was the response defined as the satisfactory uterine tone at 2 minutes after completion of administration of the oxytocin bolus, as assessed by the operating obstetrician. Secondary outcomes included need for rescue uterotonic drugs, adverse effects, and estimated blood loss. The ED90 was estimated using the Dixon-Mood and the isotonic regression methods.Thirty patients were included in study. The estimated ED90 of oxytocin was 4.38 IU (95% confidence interval [CI], 3.68-4.86 IU) and 3.41 IU (95% CI, 2.83-3.98 IU) by the isotonic regression and Dixon-Mood methods, respectively. Seven patients had inadequate tone at the 2-minute evaluation point and required rescue uterotonic drugs. The median (interquartile range [IQR]) estimated blood loss was 1031 mL (732-1462 mL) calculated by the change in 24-hour hematocrit. Incidence of hypotension after oxytocin administration was 27%, nausea 30%, and vomiting 17%.Our results demonstrated that people with twin pregnancy require a much higher dose of oxytocin than those with singleton pregnancies. We recommended people with twin pregnancies should receive an initial 5 IU bolus over at least 1 minute when undergoing elective cesarean delivery under neuraxial anesthesia.

Infants undergoing cardiac surgery are at risk for bleeding and massive transfusion due to an immature coagulation system, complex surgeries, and cardiopulmonary bypass (CPB) effects. Hemodilution from CPB promotes an acquired hypofibrinogenemia that results in impaired fibrin formation, inadequate clot formation, and increased bleeding. In North America, the current standard of care to supplement fibrinogen is cryoprecipitate. An alternative option is the off-label use of fibrinogen concentrate (FC; RiaSTAP; CSL Behring, Marburg, Germany), a purified fibrinogen. Because perioperative allogenic transfusions are associated with increased morbidity and mortality, we sought to determine whether FC would be an acceptable alternative to cryoprecipitate in a post-CPB transfusion algorithm in infants undergoing open-heart surgery.We randomized 60 infants (12 months) undergoing nonemergent cardiac surgery with CPB at 2 tertiary care children's hospitals to receive either cryoprecipitate or FC in a post-CPB transfusion algorithm. Infants underwent a stratified randomization based on institution and surgical complexity. The primary outcome was the difference in number of intraoperative allogenic blood product transfusions. Secondary outcomes included 24-hour chest tube output (CTO), mechanical ventilation time, adverse events (AEs), intensive care unit (ICU) length of stay (LOS), hospital LOS, postoperative thrombosis, and death within 30 days of surgery. The primary analysis followed the intent-to-treat (ITT) principle and was performed using linear regression adjusted for institution and complexity of surgery. A per-protocol (PP) analysis was also performed.Between June 2016 and January 2018, we enrolled 60 patients with complete data available for 25 patients who received cryoprecipitate and 29 patients who received FC. Patients in the cryoprecipitate group (median age: 4 months [2-6 months]) received 5.5 (4.0-7.0) allogeneic blood units in the ITT analysis and 6.0 units (5.0-7.0 units) in the PP analysis. Patients in the FC group (median age: 4 months [2-5]) received 4 units (3.0-5.0 units) in the ITT analysis and 4.0 units (3.0-5.0 units) in the PP analysis. In the adjusted ITT analysis, the FC group received 1.79 units (95% confidence interval [CI], 0.64-2.93; P = .003) less than the cryoprecipitate group. In the adjusted PP analysis, the FC group received 2.67 units (95% CI, 1.75-3.59; P.001) less than the cryoprecipitate group. There were no significant differences in secondary outcomes or AEs.Our findings suggest that FC may be considered as an alternative to cryoprecipitate for the treatment of hypofibrinogenemia in infants with bleeding after CPB. Although we found no significant differences between secondary outcomes or AEs, further studies are needed to assess safety.

Phenylephrine (PE) is currently the vasopressor of choice to prevent and treat spinal-induced hypotension at cesarean delivery (CD). However, its use is often associated with reflex bradycardia. Norepinephrine (NE) has been put forward as an alternative vasopressor during CD due to its ability to treat hypotension while maintaining heart rate (HR). Recent studies have focused on the role of NE used as an infusion with favorable results compared to PE. No studies have compared equipotent bolus doses of PE and NE at CD. We hypothesized that when used in equipotent doses as an intermittent bolus regimen to prevent and treat spinal-induced hypotension, NE would result in a reduction in the incidence of bradycardia compared to PE.This was a double-blind, randomized clinical trial of women undergoing elective CD under spinal anesthesia. Women were randomized to receive either PE 100 µg or NE 6 µg when the systolic blood pressure (SBP) was below baseline. In addition to the randomized treatment, ephedrine was given intravenously to both groups if the SBP was below baseline and the HR60 bpm or if the SBP was80% of baseline for 2 consecutive readings. The primary outcome was bradycardia (HR50 bpm) in the predelivery period. Secondary outcomes included hypotension (SBP80% of baseline), hypertension (SBP120% of baseline), tachycardia (HR120% of baseline), ≥2 episodes of bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar scores.One hundred twelve patients were randomized. The incidence of bradycardia was lower in the NE group compared to the PE group (10.7% vs 37.5%; P.001; difference [95% confidence interval {CI}], -26.8% [-41.8% to -11.7%]), implying an estimated 71% relative reduction (95% CI, 35%-88%). The distribution of the number of bradycardia episodes was also different between the 2 groups (P = .007). Further testing showed that the patients in the PE group had a higher risk of multiple bradycardia episodes (≥2 episodes) compared to the NE group (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring rescue boluses of ephedrine was lower in the NE group compared to the PE group (7.2% for NE versus 21.4% for PE; P.03; difference [95% CI], -14.3% [-27.0% to -1.6%]). No differences were observed between the 2 groups in the incidence of other secondary outcomes.When used as an intermittent bolus regimen to prevent and treat spinal-induced hypotension during CD, NE resulted in a significant reduction in the incidence of bradycardia as compared to an equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered by NE during CD is superior to that of PE due to less fluctuations in HR and possibly cardiac output.

Recombinant factor VIIa (rFVIIa) is routinely used as an off-label hemostatic agent in children undergoing cardiac surgery. Despite evidence that rFVIIa use is associated with an increased incidence of thrombotic complications in adult cardiac surgery, the safety of rFVIIa as a rescue hemostatic agent in the pediatric cardiac surgical population is less definitively delineated. In this retrospective study, we used propensity score matching to compare the incidence of thrombotic complications between children treated with rFVIIa and their matched controls.We retrospectively reviewed medical records and pharmacy data from all neonates and children who underwent congenital cardiac surgery between May 1, 2011, and October 31, 2013, at Boston Children's Hospital, and identified those who received rFVIIa during the perioperative period. Using existing knowledge, we chose 10 factors associated with bleeding after cardiac surgery to be used in our propensity score: age, sex, body weight, neonates, prematurity, previous sternotomy, cardiopulmonary bypass time, deep hypothermic circulatory arrest time, aortic cross-clamp time, and the operative surgeon. We then used propensity-matched analysis to match children treated with rFVIIa with 2 controls. The primary outcome was thrombotic complications. Secondary outcomes included reexploration for bleeding, length of cardiac intensive care unit stay, length of hospital stay, and 30-day mortality.One hundred forty-nine patients received perioperative rFVIIa during the study period. Propensity matching yielded 143 rFVIIa patients matched to 2 control patients each (n = 286). Three control patients were found to have received rFVIIa during the perioperative course and were removed from the analysis, for a total of 283 control patients. The administration of rFVIIa was associated with an increased incidence of thrombotic complications (20% vs 8%; odds ratio [OR]: 3.9 [95% confidence interval {CI}: 2.6-5.9], P.001). Administration of rFVIIa was associated with a prolonged median length of cardiac intensive care unit stay (8 days [interquartile range {IQR}: 4-24] vs 5 days [IQR: 2-10], P.001) and prolonged length of hospital stay (20 [IQR: 9-44] vs 11 days [IQR: 7-23], P.001). No difference in reexploration for bleeding (rFVII = 14% vs controls = 9%; OR: 1.7 [95% CI, 0.92-3.1], P = .12) or 30-day mortality was observed (8% vs 6%; OR 1.3 [95% CI, 0.60-2.89], P = .51).This retrospective analysis confirmed that perioperative administration of rFVIIa is associated with an increased incidence of postoperative thrombotic complications in neonates and children undergoing cardiac surgery, without increase in 30-day mortality. In conclusion, rFVIIa should be used with extreme caution in pediatric patients undergoing cardiac surgery.

Most studies that have compared programmed intermittent epidural bolus (PIEB) with continuous epidural infusion regimens have included patient-controlled epidural analgesia and/or manual bolus as rescue analgesia for breakthrough pain. Consequently, the optimal time interval between PIEB is yet to be determined. We designed a study to establish the optimal time interval between PIEB of 10 mL of bupivacaine 0.0625% with fentanyl 2 μg/mL to produce effective analgesia in 90% of women during first stage of labor without breakthrough pain.We conducted a double-blind sequential allocation trial with a biased-coin up-down design to obtain the effective interval 90% for the PIEB regimen. We included American Society of Anesthesiologists physical status 2-3 nulliparous women at term undergoing spontaneous or induced labor requesting epidural analgesia. An ultrasound-assisted epidural catheter placement was performed at L2/3 or L3/4. A test dose of 3 mL of bupivacaine 0.125% plus fentanyl 3.3 μg/mL was followed by a loading dose of 12 mL of the same solution. PIEB was then started in women whose pain scores achieved Verbal Numerical Rating Score ≤1/10 within 20 minutes after the end of the loading dose. In all subjects, the programmed bolus dose was fixed at 10 mL of bupivacaine 0.0625% with fentanyl 2 μg/mL. The first bolus was delivered 1 hour after the loading dose. The PIEB interval was set at 60 minutes for the first patient and at varying time intervals (60, 50, 40, and 30 minutes; groups 60, 50, 40 and 30, respectively) for the subsequent patients, according to a biased-coin design. The primary outcome was effective analgesia, defined as no requirement for a patient-controlled epidural analgesia or a manual bolus for 6 hours after the initiation of the epidural analgesia or until the patient presented with full cervical dilatation, whichever event occurred first. Pain scores, sensory block levels to ice, degree of motor block, and blood pressure were assessed hourly.We studied 40 women. The estimated effective interval 90% was 42.6 minutes (95% confidence interval 38.9-46.4) using the truncated Dixon and Mood method and 36.8 minutes (95% confidence interval 31.0-49.0) using the Isotonic Regression analysis. Almost 70% of the patients in group 30 presented with sensory block above T6, compared with 44%, 22%, and 11% in groups 40, 50, and 60, respectively. Only patients in group 30 presented with motor blockade. The incidence of hypotension was low in all groups with no treatment required.The optimal time interval between PIEB of 10 mL of bupivacaine 0.0625% with fentanyl 2 μg/mL is approximately 40 minutes. Further studies to determine the efficacy of this regimen throughout the entire duration of labor are warranted.

BACKGROUND The transcatheter electric stimulation test (Tsui test) can be performed at the bedside to confirm the correct placement of a wire-reinforced epidural catheter within the epidural space. The most commonly observed motor response with a uniport epidural catheter placed in the lumbar area is the unilateral contraction of the lower limbs. Wire-reinforced multiport catheters have recently been introduced into clinical practice; however, the characteristics of the Tsui test with such catheters are unknown. We designed a randomized controlled trial to test the hypothesis that the incidence of a bilateral response to the Tsui test would be higher with a multiport catheter, with all other characteristics of the test remaining unchanged. METHODS We recruited laboring women requesting epidural analgesia. The epidural catheter placement was performed in a standard fashion, assisted by ultrasound, aiming at the L3-L4 interspace. Patients were randomly allocated for the placement of either a 19-G uniport or a 19-G multiport wire-reinforced catheter. The Tsui test (frequency 2 Hz; pulse width 0.2 millisecond) was performed immediately after securing the catheter (baseline) and at 5 minutes after a test dose with 3 mL lidocaine 2%. The current output was increased from zero until motor activity was detected up to a maximum of 20 mA. Subsequently, an initial loading dose of 10 mL bupivacaine 0.125% and 50 μg fentanyl was administered. The sensory block level to ice was assessed bilaterally at 20 minutes after injection of the loading dose. The primary outcome was the motor response pattern to the electric stimulation of the epidural catheter, either unilateral or bilateral; secondary outcomes included minimal current intensity needed to elicit a motor response at baseline and 5 minutes after the test dose, sensory block level and incidence of symmetrical sensory block at 20 minutes after injection of the loading dose, pain scores before the test dose and at 20 minutes after the loading dose, and need for catheter replacement within 2 hours of completion of the loading dose. RESULTS Sixty-three women were assessed for eligibility and 46 were randomly allocated equally to each group. Three patients were excluded, resulting in 21 subjects in the multiport group and 22 subjects in the uniport group. Patient characteristics in both groups were similar. The incidence of unilateral motor response to the Tsui test was 95.2% (20/21) and 95.5% (21/22) in the multiport and uniport groups, respectively (rate difference 0.22%; 95% confidence interval, for the difference -29.2 to 29.2%; P = 0.99). The minimal current intensity (mean ± SD) required to produce a motor response at baseline was 5.4 ± 3.5 mA and 5.4 ± 4.1 mA in the multiport and uniport groups, respectively (P = 0.98). The sensory block levels to ice on the left and right, as well as pain scores at 20 minutes, were similar in both groups. No epidural catheters were resited. CONCLUSIONS The Tsui test produced a high percentage of unilateral motor response in women with both uniport and multiport wire-embedded catheters. A larger study is necessary to confirm that there is no clinically significant difference in the motor response patterns between the 2 catheter types.

BACKGROUND: A single preoperative dose of 600 mg gabapentin, combined with multimodal analgesia, has previously been shown to reduce postcesarean pain and improve maternal satisfaction but was associated with increased maternal sedation. We hypothesized that a lower dose of gabapentin may be effective with less sedation. METHODS: We conducted a doubleblind, randomized, placebo-controlled study. Women undergoing elective cesarean delivery were randomized into 3 groups to receive 300 or 600 mg oral gabapentin, or placebo, 1 hour before surgery. Temporal summation (TS) testing was performed at the time of study drug administration, and a visual analog scale (0 to 100 mm) difference ≥10 mm between the 1st and 10th stimuli was considered TS+. Spinal anesthesia and postoperative analgesia were instituted, including intrathecal fentanyl and morphine, oral diclofenac and acetaminophen, and systemic morphine as required. Pain assessments at rest and on movement (visual analog scale 0 to 100 mm) were conducted at 6, 12, 24, and 48 hours after surgical incision. The primary outcome was pain on movement at 24 hours. Secondary outcomes included satisfaction with analgesia, supplemental opioid consumption, lactation difficulties, neonatal outcomes, maternal sedation, and other adverse effects. Three months after delivery, patients were contacted for assessment of chronic pain. RESULTS: One hundred thirty-two women were randomized and 6 were excluded. The difference in mean pain scores at 24 hours (95% confidence intervals [CI]) were as follows: 600 mg versus 300 mg mean difference: 5 mm (95% adjusted CI, −7 to 17); 600 mg versus placebo: 3 mm (−9 to 15); 300 mg versus placebo: −2 mm [−14 to 10]; overall P value = 0.61. There was no apparent benefit of gabapentin in TS+ women, although overall pain scores were significantly higher in these women irrespective of the study group. CONCLUSION: Given the wide confidence intervals of the differences in mean pain scores, the current study did not allow us to determine whether a single preoperative dose of gabapentin (300 mg and 600 mg) improved postcesarean analgesia compared to placebo in the context of a multimodal analgesic regimen. A larger study is required.

INTRODUCTION Phenylephrine is used to prevent and treat hypotension during spinal anesthesia for cesarean delivery. The optimal administration regimen is undetermined. We used a Non-invasive cardiac output monitor to test the hypothesis that a fixed-rate phenylephrine infusion regimen would cause a smaller reduction in maternal cardiac output, and result in less maternal hypotension, as compared to a phenylephrine bolus regimen. METHODS This was a double-blind, randomized clinical trial of women undergoing elective cesarean delivery under spinal anesthesia. Patients were randomized to an intermittent bolus (120 μg) or a fixed-rate infusion (120 μg/min) regimen of phenylephrine. Any decrease in systolic blood pressure from baseline was treated. The primary outcome was the maximum change in cardiac output in the predelivery period, assessed using bioreactance technology. Secondary outcomes included the maximum change in heart rate, incidence of hypo- and hypertension, nausea/vomiting and bradycardia, total dose of phenylephrine, umbilical blood gases, and Apgar scores. The hemodynamic profiles over time in each treatment arm were compared. RESULTS Sixty patients were studied. There was no significant difference in the maximum change in cardiac output between the 2 treatment arms: mean (SD) maximum change in cardiac output in the bolus group was 1.87 (1.68) L/min versus 1.9 (1.46) L/min in the infusion group (P = 0.94) (95% confidence intervals of difference in means: -0.84 to 0.78 L/min). The infusion group received significantly more phenylephrine (1740 (613) versus 964 (454) μg) (P < 0.001). In the initial 6 min after intrathecal injection, there was a significant decrease in blood pressure in the infusion group compared to the bolus group (P = 0.007). There was no significant difference in the other secondary outcomes. CONCLUSION There were no clinical benefits to administering phenylephrine as an infusion versus a bolus regimen. The bolus regimen maintained maternal arterial blood pressure closer to baseline in the initial minutes after spinal injection but this had no clinical benefits. The infusion regimen required a higher total dose of phenylephrine to maintain maternal arterial blood pressure at baseline during the predelivery period.

The management of postoperative pain with continuous epidural fentanyl infusion was compared with continuous intravenous fentanyl infusion. In a randomized, doubleblind protocol we prospectively studied 20 patients undergoing repair of the anterior cruciate ligament of the knee. The quality of analgesia and the incidence of side effects were documented. Compared with patients receiving continuous intravenous fentanyl infusion, at 18 h postoperatively patients given continuous epidural fentanyl infusion reported similar pain scores both at rest (22 +/- 25 vs 27 +/- 21, P = 0.52) and with ambulation (59 +/- 18 vs 56 +/- 22, P = 0.82). Plasma fentanyl levels were 1.8 +/- 0.4 and 1.7 +/- 0.4 ng/mL (P = 0.91) for the intravenous and epidural groups, respectively. There were no significant differences in the incidence of nausea, pruritus, or urinary retention. There was no respiratory depression in either group. We conclude that when compared with continuous intravenous fentanyl infusion, continuous epidural fentanyl infusion offers no clinical advantages for the management of postoperative pain after knee surgery.