Terrence K. Allen

Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis

BACKGROUND The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone on postoperative pain and explore adverse events associated with this treatment. METHODS MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes. RESULTS Forty-five studies involving 5796 patients receiving dexamethasone 1.25-20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) -0.49 [95% confidence interval (CI): -0.83, -0.15]} and 24 h [MD -0.48 (95% CI: -0.62, -0.35)] after surgery. Dexamethasone-treated patients used less opioids at 2 h [MD -0.87 mg morphine equivalents (95% CI: -1.40 to -0.33)] and 24 h [MD -2.33 mg morphine equivalents (95% CI: -4.39, -0.26)], required less rescue analgesia for intolerable pain [relative risk 0.80 (95% CI: 0.69, 0.93)], had longer time to first dose of analgesic [MD 12.06 min (95% CI: 0.80, 23.32)], and shorter stays in the post-anaesthesia care unit [MD -5.32 min (95% CI: -10.49 to -0.15)]. There was no dose-response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h [MD 0.39 mmol litre(-1) (95% CI: 0.04, 0.74)]. CONCLUSIONS A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.

A double-blind, placebo-controlled trial of four fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for cesarean delivery.

BACKGROUND: The administration of prophylactic phenylephrine infusions in combination with fluid cohydration significantly reduces the incidence of hypotension in women having cesarean delivery under spinal anesthesia. The ideal dosing regimen for this purpose is not known. In this study, we investigated the dose of phenylephrine that, when administered as a prophylactic fixed rate infusion, is associated with the least interventions needed to maintain maternal systolic blood pressure (SBP) within 20% of baseline. METHODS: Women undergoing elective cesarean delivery were randomly allocated to receive placebo or prophylactic phenylephrine infusion at 25, 50, 75, or 100 &mgr;g/min immediately after spinal anesthesia in combination with a 2-L fluid coload. Maternal SBP was maintained within the target range using a predetermined algorithm. The number of physician interventions, hemodynamic performance, intraoperative nausea and vomiting, and umbilical cord blood gases were compared among the groups. RESULTS: One hundred one patients were included in the analysis. There were no differences between the placebo and phenylephrine groups in the number of interventions needed to maintain maternal SBP within the target range. Doses of phenylephrine of 25 and 50 &mgr;g/min were associated with significantly fewer interventions when compared with 100 &mgr;g/min (P = 0.004 vs 50 &mgr;g/min, P = 0.02 vs 25 &mgr;g/min). Predelivery hypotension was more frequent in the control group compared with all phenylephrine groups. Phenylephrine 75 and 100 &mgr;g/min groups were associated with a significantly higher incidence of predelivery hypertension compared with control (P < 0.001 vs 75 &mgr;g/min and 100 &mgr;g/min). There was a trend toward an increase in median magnitude of deviations of SBP above or below baseline (P = 0.006), and the bias of SBP to be above baseline (P < 0.001) with increasing rates of phenylephrine infusion. There were no differences in the incidence and severity of intraoperative nausea and vomiting and umbilical cord blood gases among the groups. CONCLUSIONS: The use of prophylactic fixed rate phenylephrine infusions did not significantly reduce the number of physician interventions needed to maintain maternal predelivery SBP within 20% of baseline compared with placebo. However, prophylactic phenylephrine infusions reduced the incidence and severity of maternal predelivery hypotension. Phenylephrine 25 and 50 &mgr;g/min administered as a prophylactic fixed rate infusion provided greater maternal hemodynamic stability than phenylephrine 75 and 100 &mgr;g/min. Prophylactic fixed rate infusions may have limited application in clinical practice, and future studies assessing the accuracy of hemodynamic control with variable rate phenylephrine infusions are needed.

Intermittent epidural bolus compared with continuous epidural infusions for labor analgesia: a systematic review and meta-analysis.

BACKGROUND:The current standard labor epidural analgesic regimens consist of a local anesthetic in combination with an opioid delivered via continuous epidural infusion (CEI). With CEI local anesthetic, doses may be large with resulting profound motor blockade potentially affecting the incidence of instrumental deliveries. In this systematic review of randomized controlled trials (RCTs), we compared the effect of intermittent epidural bolus (IEB) to standard CEI dosing with or without patient-controlled epidural analgesia on patient satisfaction, the need for manual anesthesia interventions, labor progression, and mode of delivery in healthy women receiving labor epidural analgesia. METHODS:A systematic review of RCTs that compared CEI with IEB for labor analgesia was performed. The articles were evaluated for validity, and data were extracted by the authors and summarized using odds ratios (ORs), mean differences (MDs), and 95% confidence intervals (CIs). RESULTS:Nine RCTs were included in this systematic review. Three hundred forty-four subjects received CEI, whereas 350 subjects received IEB labor analgesia. All 9 studies were deemed to be low risk of bias. There was no statistical difference detected between IEB and CEI in the rate of cesarean delivery (OR, 0.87; 95% CI, 0.56–1.35), duration of labor (MD, −17 minutes; 95% CI, −42 to 7), or the need for anesthetic intervention (OR, 0.56; 95% CI, 0.29–1.06). IEB did result in a small but statistically significant reduction in local anesthetic usage (MD, −1.2 mg bupivacaine equivalent per hour; 95% CI, −2.2 to −0.3). Maternal satisfaction score (100-mm visual analog scale) was higher with IEB (MD, 7.0 mm; 95% CI, 6.2–7.8). CONCLUSIONS:IEB is an appealing concept; current evidence suggests IEB slightly reduces local anesthetic usage and improves maternal satisfaction. Given the wide CIs of the pooled results for many outcomes, definite conclusions cannot be drawn for those outcomes, but there is also a potential that IEB improves instrumental delivery rate and need of anesthesia interventions. More study is required to conceptualize the ideal IEB regimen and investigate its effect on labor analgesia and obstetric outcomes.

Serotonin receptor antagonists for the prevention and treatment of pruritus, nausea, and vomiting in women undergoing cesarean delivery with intrathecal morphine: a systematic review and meta-analysis.

BACKGROUND: We performed a systematic review to determine the overall efficacy of serotonin (5-HT3) receptor antagonists for the prevention and treatment of pruritus, nausea, and vomiting in women receiving spinal anesthesia with intrathecal morphine for cesarean delivery. METHODS: Reports of randomized, controlled trials that compared prophylaxis or treatment of pruritus and/or nausea, and vomiting using one of the 5-HT3 receptor antagonists or placebo in women undergoing cesarean delivery were reviewed. The articles were scored for validity and data were extracted by the authors independently and summarized using relative risks (RR) with 95% confidence intervals (CI). RESULTS: Nine randomized, controlled trials were included in the systematic review. The nine trials had a total of 1152 patients enrolled; 539 received 5-HT3 receptor antagonists, 413 received placebo, and 200 received other antiemetics and were not included in the analysis. The incidence of pruritus was not reduced with 5-HT3 receptor antagonists prophylaxis compared with placebo (80.7% vs 85.8%, RR [95% CI] = 0.94 [0.81–1.09]). However, their use reduced the incidence of severe pruritus and the need for treatment of pruritus (number-needed-to-treat = 12 and 15, respectively). Their use for the treatment of established pruritus showed improved efficacy compared with placebo with a number-needed-to-treat of three. There was a significant reduction in the incidence of postoperative nausea (22.0% vs 33.6%, RR [95% CI] = 0.75[0.58–0.96]) and vomiting (7.7% vs 16.8%, RR [95% CI] = 0.49 [0.30–0.81]), and the need for postoperative rescue antiemetic treatment with the use of 5-HT3 receptor antagonists when compared with placebo (9% vs 23%, RR [95% CI] = 0.38 [0.21–0.68]). CONCLUSIONS: Although prophylactic 5-HT3 receptor antagonists were ineffective in reducing the incidence of pruritus, they significantly reduced the severity and the need for treatment of pruritus, the incidence of postoperative nausea and vomiting, and the need for rescue antiemetic therapy in parturients who received intrathecal morphine for cesarean delivery. They were also effective for the treatment of established pruritus. Although more studies are warranted, the current data suggest that the routine prophylactic use of those drugs should be considered in this patient population.

Dexamethasone for the Prophylaxis of Postoperative Nausea and Vomiting Associated with Neuraxial Morphine Administration: A Systematic Review and Meta-Analysis

BACKGROUND: We performed a systematic review to assess the efficacy of dexamethasone in reducing postoperative nausea, vomiting (PONV), pruritus, and enhancing postoperative analgesia in patients receiving neuraxial anesthesia with neuraxial morphine. METHODS: We searched Medline (1966–2011), the Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science for all randomized controlled trials comparing dexamethasone with placebo for the prevention of PONV and/or pruritus in patients receiving neuraxial morphine as part of a neuraxial anesthetic technique. Data were extracted independently by the authors on the incidence of PONV, pruritus, pain scores at 4 and 24 hours, and use of rescue antiemetics, antipruritics, and analgesics. RESULTS: Eight randomized controlled trials (4 cesarean deliveries, 4 total abdominal hysterectomies) were included. From these trials, 768 patients were analyzed with 473 receiving dexamethasone and 295 receiving placebo. The doses of dexamethasone investigated ranged from 2.5 to 10 mg. Dexamethasone reduced the incidence of postoperative nausea (relative risk, RR [95% confidence interval, CI] = 0.57 [0.45, 0.72]), vomiting (RR [95% CI] = 0.56 [0.43, 0.72]), and the use of rescue antiemetic therapy (RR [95% CI] = 0.47 [0.36, 0.61]) compared with placebo. There was no evidence of dose responsiveness with respect to its antiemetic effect. Dexamethasone also reduced 24-hour visual analog pain scores (measured on an 11-point scale [0–10]) (mean difference [95% CI] = −0.30 [−0.46, −0.13]) and the use of rescue analgesics (RR [95% CI] = 0.72 [0.52, 0.98]). Dexamethasone did not reduce the incidence of pruritus (RR [95% CI] = 0.98 [0.84, 1.15]). Examination of the funnel plots and Eggers test revealed evidence of publication bias in the primary outcomes. CONCLUSION: Dexamethasone is an effective antiemetic for patients receiving neuraxial morphine for cesarean delivery and abdominal hysterectomy. In addition, the doses used for antiemetic prophylaxis enhanced postoperative analgesia compared with placebo. However, dexamethasone was not effective for the prophylaxis against neuraxial morphine–induced pruritus.

A pilot study to compare the Episure Autodetect syringe with the glass syringe for identification of the epidural space in parturients.

The Episure™ AutoDetect™ syringe, a spring-loaded syringe, is a new loss-of-resistance syringe with an internal compression spring that applies constant pressure on the plunger. In this pilot study, we compared the spring-loaded syringe with the standard glass syringe for identification of the epidural space during initiation of epidural analgesia in parturients. The primary outcome was the incidence of failed epidural analgesia. Three-hundred and twenty-five women were enrolled. Eight residents performed 291 procedures (90%) and two attendings performed 34 procedures (10%). Epidural analgesia failed in five subjects in the glass syringe group and in no subject in the spring-loaded syringe group (P = 0.025).

P6 Stimulation for the Prevention of Nausea and Vomiting Associated with Cesarean Delivery Under Neuraxial Anesthesia: A Systematic Review of Randomized Controlled Trials

BACKGROUND: A number of studies investigated the use of P6 stimulation for the prevention of intraoperative and postoperative nausea and vomiting (IONV and PONV) in women having cesarean delivery under neuraxial anesthesia. We performed a systematic review to determine the overall efficacy of these techniques in preventing IONV and PONV in this patient population. METHODS: We performed a literature search of all randomized controlled trials (1966–2007) that compared different methods of P6 stimulation with placebo in women having cesarean delivery under neuraxial anesthesia. Data were extracted on the primary outcomes including the incidence of nausea, vomiting, and the need for rescue antiemetic therapy, both intraoperatively and postoperatively. RESULTS: Six studies involving 649 patients were included in this review. Five studies reported on intraoperative outcomes. Of these, two studies reported a significant reduction in the incidence of intraoperative nausea with P6 stimulation, and one study reported a significant reduction in rescue antiemetic requirement. However, none of the studies reported any differences between the treatment and control groups with respect to vomiting. Four studies reported postoperative outcomes. Of these, one study reported a significant reduction in postoperative nausea, two studies reported a significant reduction in postoperative vomiting, and one study reported a significant reduction in the need for postoperative rescue antiemetic therapy. CONCLUSIONS: While some studies showed a benefit of P6 stimulation, this finding was not consistent. The presence of heterogeneity and inconsistent results among the included trials prevents any definitive conclusions on the efficacy of P6 stimulation in reducing IONV and PONV associated with cesarean delivery performed under neuraxial anesthesia.

A survey of the management of spinal-induced hypotension for scheduled cesarean delivery

BACKGROUND Intravenous fluids and vasopressors are used for managing spinal-induced hypotension during cesarean delivery, but the choice of vasopressor and the type and timing of fluid administration remain controversial. METHODS We conducted an electronic survey of all members of the Society for Obstetric Anesthesia and Perinatology between February and March 2007 to determine their preferences for preventing and treating spinal-induced hypotension with respect to fluid and vasopressor administration. RESULTS The response rate was 292/746 (39%). Fifty percent worked in academic institutions and 56% had >50% of their clinical responsibility to obstetric anesthesia. For prophylaxis, 35% used fluid preloading, 30% fluid preloading with vasopressors, and 12% fluid co-loading with vasopressors. Of those using vasopressors for prophylaxis, 32% used ephedrine, 26% used phenylephrine, and 33% based their choice on heart rate. For treatment, 32% used ephedrine, 23% used phenylephrine, and 41% used either agent based on heart rate. Anesthesiologists in academic practice were less likely to use fluid preloading only (P=0.028) and more likely to use fluid co-loading and vasopressors (P=0.003). They were also more likely to administer phenylephrine for prophylaxis compared with those in private practice (P=0.042). CONCLUSION Significant variations in practice exist in the prevention and treatment of spinal-induced hypotension. Fluid preloading and the prophylaxis and treatment of hypotension with ephedrine continue to be common practices.

A retrospective assessment of the incidence of respiratory depression after neuraxial morphine administration for postcesarean delivery analgesia.

Respiratory depression can occur after neuraxial morphine administration. In the obstetric population, there are little data on respiratory depression after neuraxial morphine administration in women undergoing cesarean delivery. In this single-center, retrospective study in 5036 obstetric patients (mean body mass index = 34 kg/m2) who underwent cesarean delivery and received neuraxial morphine, we did not identify any instances of respiratory depression requiring naloxone administration or rapid response team involvement. Therefore, the upper 95% confidence limit for respiratory depression in our study is 0.07% (1 event per 1429 cases).

Progesterone Receptor Membrane Component 1 as the Mediator of the Inhibitory Effect of Progestins on Cytokine-Induced Matrix Metalloproteinase 9 Activity In Vitro

Progesterone (P4) and the progestin, 17α-hydroxyprogesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical progesterone receptor (PGR) but instead a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyprogesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyprogesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small interfering RNA. Our findings highlight a possible novel role of PGRMC1 in mediating the effects of MPA and in modulating cytokine-induced MMP-9 activity in cytotrophoblast cells in vitro.