Kristi Downey

Phenylephrine infusion versus bolus regimens during cesarean delivery under spinal anesthesia: a double-blind randomized clinical trial to assess hemodynamic changes.

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 &mgr;g) or a fixed-rate infusion (120 &mgr;g/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) &mgr;g) (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.

A single preoperative dose of gabapentin does not improve postcesarean delivery pain management: a randomized, double-blind, placebo-controlled dose-finding trial.

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.

A randomized, double-blind, placebo-controlled trial of epidural morphine analgesia after vaginal delivery

BACKGROUND: Pain after vaginal delivery can interfere with the activities of daily living. We hypothesized that epidural medication administered after delivery would be of benefit for acute postpartum pain management. The objective of this study was to assess whether epidural morphine after vaginal delivery would reduce the analgesic requirements for perineal pain. METHODS: This randomized, double-blind, placebo-controlled trial included 228 parturients who received epidural morphine, 2.5 mg, or epidural saline within 1 h of delivery. The primary outcome was the proportion of women who received additional analgesics in the first 24 h postpartum. We also evaluated the time to first request for analgesia, pain and satisfaction scores, and the incidence of side effects due to epidural morphine. RESULTS: The majority of the 228 women participating in the study were Caucasian, primiparous patients >30 yr old. The proportion of women requiring additional analgesics was less among those who received epidural morphine (8 of 113; 7%) compared with saline (37 of 115; 32%), regardless of the degree of perineal trauma (RR = 0.22, 95% CI: 0.12–0.41). The relative risk reduction in receiving additional analgesics for primiparous patients receiving epidural morphine compared with saline was 0.25 (95% confidence interval [CI]: 0.13–0.49) and for multiparous women was 0.12 (95% CI: 0.02–0.63). The time to first request for analgesics was later for those who received morphine (mean 22.9 h, 95% CI: 22.2–23.7) compared with saline (mean 18.9 h, 95% CI: 17.4–20.4) (P < 0.0001). The side-effect incidence (pruritus, nausea and vomiting, and sedation) was not different between the 2 groups. CONCLUSION: There was a 78% reduction in analgesic requirements in women given epidural morphine after vaginal delivery compared with placebo for both primiparous and multiparous patients. Women who receive epidural labor analgesia for vaginal deliveries and stay in the hospital for 24 h after delivery may benefit from postpartum administration of epidural morphine.

A Perioperative Course of Gabapentin Does Not Produce a Clinically Meaningful Improvement in Analgesia after Cesarean Delivery: A Randomized Controlled Trial.

Background:Studies examining the efficacy of a single preoperative dose of gabapentin for analgesia after cesarean delivery (CD) have been inconclusive. The authors hypothesized that a perioperative course of gabapentin would improve analgesia after CD. Methods:This single-center, randomized, double-blind, placebo-controlled, parallel-group, superiority trial was designed to determine the analgesic efficacy of a perioperative course of gabapentin when added to a multimodal analgesic regimen. Women scheduled for elective CD during spinal anesthesia were randomized to receive a perioperative oral course of either gabapentin (600 mg preoperatively followed by 200 mg every 8 h for 2 days) or placebo. Postoperative pain was measured at 24 and 48 h, at rest and on movement, on a visual analogue scale (VAS, 0 to 100 mm). The primary outcome was pain on movement at 24 h. Neonatal outcomes, opiate consumption, VAS satisfaction (0 to 100 mm), adverse effects, and persistent pain were also assessed. Results:Baseline characteristics were similar between groups. There was a statistically significant but small reduction in VAS pain score (mean [95% CI]) on “movement” (40 mm [36 to 45] vs. 47 mm [42 to 51]; difference, −7 mm [−13 to 0]; P = 0.047) at 24 h in the gabapentin (n = 100) compared with control group (n = 97). There was more sedation in the gabapentin group at 24 h (55 vs. 39%, P = 0.026) but greater patient VAS satisfaction (87 vs. 77 mm, P = 0.003). Conclusions:A perioperative course of gabapentin produces a clinically insignificant improvement in analgesia after CD and is associated with a higher incidence of sedation.

Non-invasive monitoring based on bioreactance reveals significant hemodynamic instability during elective cesarean delivery under spinal anesthesia

BACKGROUND AND OBJECTIVES Blood pressure monitoring offers a limited understanding of the hemodynamic consequences of spinal anesthesia for cesarean delivery. The purpose of this study was to assess, with the aid of a non-invasive cardiac output monitor based on bioreactance, the hemodynamic changes during elective cesarean delivery under spinal anesthesia in which intermittent boluses of phenylephrine were used to prevent and treat hypotension. METHODS This observational study was conducted with the Research Ethics Board approval, and all participants provided written informed consent. Healthy patients undergoing elective cesarean delivery under spinal anesthesia were enrolled. Intermittent boluses of phenylephrine were administered in an attempt to maintain systolic blood pressure at baseline levels, and patients were assessed with a non-invasive cardiac output monitor based on bioreactance. Hemodynamic data was collected continuously at baseline, and during the postspinal and postdelivery periods. Data was analyzed using a mixed model ANOVA, and a p < 0.05 was considered significant. RESULTS Systolic blood pressure was maintained within 79.2 ± 14.2 and 105.8 ± 10.0 percent of baseline during the postspinal period, and 78.4 ± 11.3 and 100.9 ± 10.7 percent of baseline in the postdelivery period (mean ± SD) There were significant fluctuations in systolic blood pressure, heart rate, and cardiac output during the postspinal period, and significant fluctuations in systolic blood pressure and cardiac output in the postdelivery period. CONCLUSIONS A new non-invasive monitor based on bioreactance reveals significant hemodynamic fluctuations during cesarean delivery under spinal anesthesia, despite attempts to maintain blood pressure at baseline levels with intermittent boluses of phenylephrine.

Programmed Intermittent Epidural Bolus for Labor Analgesia During First Stage of Labor: A Biased-Coin Up-and-Down Sequential Allocation Trial to Determine the Optimum Interval Time Between Boluses of a Fixed Volume of 10 mL of Bupivacaine 0.0625% With Fentanyl 2 μg/mL.

BACKGROUND: 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 &mgr;g/mL to produce effective analgesia in 90% of women during first stage of labor without breakthrough pain. METHODS: 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 &mgr;g/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 &mgr;g/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. RESULTS: 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. DISCUSSION: The optimal time interval between PIEB of 10 mL of bupivacaine 0.0625% with fentanyl 2 &mgr;g/mL is approximately 40 minutes. Further studies to determine the efficacy of this regimen throughout the entire duration of labor are warranted.

Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-finding Study

BACKGROUND: The use of phenylephrine as the first-line agent for prevention and treatment of maternal hypotension during cesarean delivery (CD) may reduce cardiac output, posing a theoretical risk to mother and fetus. Norepinephrine has been suggested as a potential alternative, because its &bgr;-adrenergic effects might result in greater heart rate and cardiac output than phenylephrine. The use of norepinephrine to prevent and treat hypotension during CD is new, and its use as a bolus has not been fully determined in this context. The purpose of this study was to determine the effective norepinephrine dose, when given as intermittent intravenous (IV) boluses, to prevent postspinal hypotension in 90% of women undergoing elective CD (ED90). METHODS: This was a prospective, double-blind sequential allocation dose-finding study, using the biased coin up-and-down design. Forty-term pregnant women undergoing elective CD under spinal anesthesia received a set intermittent norepinephrine bolus of either 3, 4, 5, 6, 7, or 8 µg every time their systolic blood pressure (SBP) fell to below 100% of baseline. The primary outcome was the success of the norepinephrine regimen to maintain SBP at or above 80% of baseline, from induction of spinal anesthesia to delivery of the fetus. Secondary outcomes included nausea, vomiting, hypertension (SBP > 120% of baseline), bradycardia (<50 bpm), upper sensory level of anesthesia to ice cold and umbilical artery and vein blood gases. The ED90 and 95% confidence intervals (CIs) were estimated using both truncated Dixon and Mood and isotonic regression methods. RESULTS: The estimated ED90 of norepinephrine was 5.49 µg (95% CI, 5.15–5.83) using the truncated Dixon and Mood method and 5.80 µg (95% CI, 5.01–6.59) using the isotonic regression method. CONCLUSIONS: The use of intermittent IV norepinephrine boluses to prevent spinal-induced hypotension in elective CD seems feasible and was not observed to be associated with adverse outcomes. Practically, we suggest an ED90 dose of 6 µg. Further work is warranted to elucidate the comparative effects of intermittent IV bolus doses of phenylephrine and norepinephrine, in terms of efficacy and safety.

Intraperitoneal Instillation of Lidocaine Improves Postoperative Analgesia at Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND: Cesarean delivery is a commonly performed procedure worldwide. Despite improvements in balanced multimodal analgesia, there remains a proportion of women for whom postoperative pain relief and patient satisfaction are still inadequate. Intraperitoneal instillation of local anesthetic has been shown to be effective in reducing postoperative pain after abdominal surgery. We sought to investigate the effect of intraperitoneal instillation of lidocaine on postcesarean delivery pain as part of a multimodal analgesia regimen. METHODS: We studied women scheduled for elective cesarean delivery under spinal anesthesia. Spinal anesthesia was performed with 0.75% hyperbaric bupivacaine, fentanyl, and morphine. At the end of the cesarean delivery, immediately before parietal peritoneum or fascia closure, patients were randomized to receive either lidocaine (20 mL 2% lidocaine with epinephrine) or placebo (20 mL normal saline) instilled into the peritoneal cavity. The primary outcome was pain score on movement at 24 hours. Secondary outcomes were pain score at rest and on movement at 2, 24, and 48 hours; maternal satisfaction score; analgesic consumption; incidence of nausea, vomiting, and itching; and return of bowel function. RESULTS: Two hundred four women were recruited. Baseline characteristics were similar between the lidocaine and placebo groups. Pain scores at 24 hours postcesarean delivery on movement (parameter estimate 0.02 [95% confidence interval {CI} −0.14 to 0.18]; P = .823) and at rest (parameter estimate 0.00 [95% CI −0.32 to 0.33]; P = .986) were similar in both groups. Pain scores at 2 hours postcesarean delivery on movement (parameter estimate −0.58 [95% CI −0.90 to −0.26]; P = .001) and at rest (parameter estimate −1.00 [95% CI −1.57 to −0.43]; P = .001) were lower in the lidocaine group. Subgroup analysis of patients with peritoneum closure revealed significantly lower pain scores at 24 hours on movement (parameter estimate −0.33 [95% CI −0.64 to −0.03]; P = .032) in the lidocaine group. The number of women requesting postoperative opioids for breakthrough pain was significantly lower in the lidocaine group compared with that of the placebo (40 [40%] vs 61 [65%], respectively, relative risk 0.59 [95% CI 0.43–0.81]; P = 0.001). CONCLUSIONS: The use of intraperitoneal instillation of lidocaine improves early postoperative pain management after cesarean delivery. Furthermore, it reduces the number of women requesting systemic opioids in the immediate postpartum period. Women undergoing peritoneal closure may particularly benefit from this intervention.

Response Patterns to the Electric Stimulation of Epidural Catheters in Pregnant Women: A Randomized Controlled Trial of Uniport Versus Multiport Catheters.

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 &mgr;g 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.

Monitoramento não invasivo baseado na biorreatância revela instabilidade hemodinâmica significativa durante cesárea eletiva sob raquianestesia

JUSTIFICATIVA Y OBJETIVOS: La monitorizacion de la presion arterial ofrece una comprension limitada de las consecuencias hemodinamicas de la raquianestesia para la cesarea. El objetivo de este estudio fue evaluar, con la ayuda del monitor de debito cardiaco no invasivo y con base en la biorreactancia, las alteraciones hemodinamicas durante la cesarea electiva bajo raquianestesia, en la cual bolos intermitentes de fenilefrina fueron utilizados para prevenir y tratar la hipotension. METODOS: Este estudio observacional fue realizado posterior a la aprobacion de la comision de etica en investigacion y de la firma del consentimiento informado. Se evaluaron los pacientes sanos con cesarea electiva programada bajo raquianestesia. Bolos intermitentes de fenilefrina fueron administrados para mantener la presion arterial sistolica en los niveles basales, y las pacientes fueron evaluadas con la ayuda del monitor de debito cardiaco no invasivo con base en la biorreactancia. Los datos hemodinamicos se recopilaron continuamente en el momento basal y durante los periodos postraquianestesia y despues del nacimiento del feto. Los datos se analizaron usando ANOVA para modelos mixtos, y un p < 0,05 fue considerado significativo. RESULTADOS: La presion arterial sistolica se mantuvo entre 79,2 (14,2) y 105,9 (10,0) por ciento de los valores basales durante el periodo postraquianestesia, y 78,4 (11,13) y 100,9 (10,7) por ciento de los valores basales en el periodo postparto promedio ± de. Las fluctuaciones significativas se observaron en la presion arterial sistolica, en la frecuencia cardiaca y en el debito cardiaco en el periodo postparto. CONCLUSIONES: Un nuevo monitor no invasivo, con base en la biorreactancia, revelo fluctuaciones hemodinamicas significativas durante la cesarea bajo la raquianestesia, pese a los intentos de mantener la presion arterial a niveles basales con bolos intermitentes de fenilefrina.