Recovery characteristics of patients receiving either sugammadex or neostigmine and glycopyrrolate for reversal of neuromuscular block: a randomised controlled trial.

Sugammadex more rapidly and reliably reverses rocuronium-induced neuromuscular block compared with neostigmine, but it is not known if subsequent patient outcomes, including nausea, vomiting and other aspects of recovery are modified. In this study, we compared the recovery characteristics of sugammadex and neostigmine/glycopyrrolate following reversal of neuromuscular block. This was a single-centre, randomised, blinded, parallel-group clinical trial in women undergoing elective day-surgical laparoscopic gynaecological surgery, with a standardised general anaesthesia regimen that included rocuronium. Neuromuscular block was reversed with either sugammadex 2 mg.kg-1 or neostigmine 40 µg.kg-1 and glycopyrrolate 400 µg. The primary outcome was the incidence of nausea and vomiting during the first six postoperative hours. Secondary outcomes included other measures of postoperative recovery such as patient symptoms and recovery scores. Three-hundred and four women were analysed by intention-to-treat (sugammadex n = 151, neostigmine n = 153), which included four major protocol violations. There was no significant difference between sugammadex and neostigmine groups in the incidence of early nausea and vomiting (49.0% vs. 51.0%, respectively; OR 0.92, 95%CI 0.59-1.45; p = 0.731). Double vision (11.5% vs. 20.0%; p = 0.044) and dry mouth (71.6% vs. 85.5%; p = 0.003) were less common after sugammadex. Sedation scores at 2 h were also lower after sugammadex (median (IQR [range]) 0 (0-3 [0-10]) vs. 2 (0-4.[0-10]); p = 0.021). Twenty-four-hour recovery scores were not significantly different between groups. Reversal with sugammadex in this patient population did not reduce postoperative nausea or vomiting compared with neostigmine/glycopyrrolate.

Immediate postpartum neurological deficits in the lower extremity: a prospective observational study.

BACKGROUND: Neurological deficits noted immediately after childbirth are usually various obstetric neuropathies, but prospective studies are limited. The main study aim was to quantify and describe immediate postpartum neurological deficits of the lower extremity, including the buttocks. METHODS: A prospective observational study of postpartum women delivering in a single maternity hospital during three months of 2016. Among 1147 eligible women, 1019 were screened for symptoms of lower extremity numbness or weakness within eight to 32hours of delivery. Consent to undergo a detailed neurological evaluation was sought from those reporting symptoms. Risk factors were identified using logistic regression. RESULTS: Thirty five women (3.4%) reported symptoms, 27 entered the study and 23 (2.0%) had objective signs of a neurological deficit. The most common injuries were mild lumbosacral plexopathies and cluneal nerve compression. Most deficits were sensory, half of these also having a motor deficit that did not impact functionally. Based on analysis of 22 cases involving a likely intrapartum deficit, no association was found with parity, body weight, duration of labour, mode of delivery or neuraxial block. A past history of a neurological condition or a back injury was associated with odds ratios of 7.98 and 4.82 respectively. There were no neurological deficits that were clinically concerning or that were likely a complication of a neuraxial block. CONCLUSION: Transient neurological complications after labour and delivery are infrequent, mainly sensory involving multiple lumbosacral nerve roots or specific sacral cutaneous nerves, and they typically resolve within a short time.

A randomised double-blind trial of phenylephrine and metaraminol infusions for prevention of hypotension during spinal and combined spinal-epidural anaesthesia for elective caesarean section.

Prophylactic vasopressor administration is commonly recommended to reduce maternal hypotension during spinal anaesthesia for caesarean section. Metaraminol has undergone limited investigation in obstetric anaesthesia for this purpose, particularly in comparison with phenylephrine. In this multicentre, randomised, double-blind, non-inferiority study, we compared prophylactic phenylephrine or metaraminol infusions, started immediately after spinal anaesthesia, in 185 women who underwent elective caesarean section. Phenylephrine was initially infused at 50 µg.min-1 , and metaraminol at 250 µg.min-1 . The primary outcome was the difference in umbilical arterial pH between groups; secondary outcomes included other neonatal acid-base measures, and maternal haemodynamic changes. The mean (SD) umbilical arterial pH was 7.28 (0.06) in the phenylephrine group vs. 7.31 (0.04) in the metaraminol group (p = 0.0002). The estimated mean (95%CI) pH difference of 0.03 (0.01-0.04) was above the pre-determined lower boundary of clinical non-inferiority, and also met the criterion for superiority. Umbilical artery lactate concentration was 2.8 (1.2) mmol.l-1 in the phenylephrine group vs. 2.3 (0.7) mmol.l-1 in the metaraminol group (p = 0.0018). Apgar scores did not significantly differ between groups. There was a higher incidence of hypotension, defined as systolic arterial pressure < 90% baseline, in the phenylephrine group; there was a higher incidence of hypertension and severe hypertension (systolic arterial pressure > 110% and > 120% baseline, respectively) in the metaraminol group. There was no significant difference between groups in the incidence of nausea, vomiting or maternal bradycardia. We conclude that, when used as an infusion to prevent hypotension after spinal anaesthesia for elective caesarean section, metaraminol is at least non-inferior to phenylephrine with respect to neonatal acid-base outcomes.

Chronic postsurgical pain in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II trial.

BACKGROUND: Previous animal and clinical studies showed that nitrous oxide may produce long-term analgesia. The aim of this study was to evaluate the effect of nitrous oxide in preventing chronic postsurgical pain. We also explored whether methylenetetrahydrofolate reductase gene polymorphisms (1298A>C, 667C>T) would enhance nitrous oxide analgesia. METHODS: We conducted a telephone interview at 12 months after surgery on 2924 (41.1%) patients enrolled in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia-II trial. Pain at the wound site was recorded using the modified brief pain inventory and the neuropathic pain questionnaire. General health status was measured using the EQ-5D questionnaire. Genotyping was performed in a subset of 674 Asian patients in Hong Kong. RESULTS: At 12 months after surgery, 356 (12.2%) patients reported chronic postsurgical pain at the wound site and 112 (3.8%) patients had severe pain and required regular analgesic interventions. Nitrous oxide did not affect the rate of chronic postsurgical pain (11.8% nitrous oxide group; 12.5% no nitrous oxide group), relative risk (95% confidence intervals): 0.94 (0.75-1.17), P=0.57. However, in a planned subgroup analysis, nitrous oxide reduced the risk of chronic postsurgical pain in Asian patients, relative risk (95% confidence intervals): 0.70 (0.50-0.98), P=0.031. Patients who were homozygous for either gene polymorphism and who received nitrous oxide during surgery were less likely to report chronic postsurgical pain. CONCLUSIONS: Nitrous oxide administration had no impact on chronic postsurgical pain, but benefits may still be possible in Asian patients and patients with variants in methylenetetrahydrofolate reductase gene. CLINICAL TRIAL REGISTRATION: NCT00430989.

Postoperative analgesia with transversus abdominis plane catheter infusions of levobupivacaine after major gynecological and obstetrical surgery. A case series.

Transversus abdominis plane block has become an important method of postoperative pain management for patients undergoing abdominal surgery but the modest duration is a major limitation. We report the successful use of a novel TAP catheter technique for continuous infusion of levobupivacaine in six gynecologic and obstetric patients. Bilateral TAP catheters were inserted at the end of surgery by ultrasound imaging using a Contiplex® C needle (B. Braun, Melsungen, Germany) in the Triangle of Petit or in a postero-subcostal level based on the location of the surgical incision. Following negative aspiration, 0.25% levobupivacaine 5 mL was injected. After withdrawing the needle, while holding the over-the-needle catheter in place, bilateral continuous infusion of 0.125% levobupivacaine at 2 mL/h from elastomeric pumps (INfusor SV2, Baxter, France) was started and continued for up to 50h. Before removal of the catheter, a bolus of 10 mL levobupivacaine 0.25% was administered. Successful analgesia was achieved in all six cases utilizing continuous infusion of levobupivacaine, minimizing the volume required. TAP infusions produce significant opioid sparing and better patient mobility. This technique may be a reliable alternative to neuraxial analgesia in major gynecological and obstetrical surgery.

The relationship between body mass index and post-dural puncture headache in obstetric patients.

BACKGROUND: Difficult epidural insertion and accidental dural puncture are more likely in the obese pregnant population. Low-level evidence suggests that the risk of post-dural puncture headache declines as body mass index increases. METHODS: We retrospectively reviewed prospective data on 18315 obstetric epidural and combined spinal-epidural insertions, identifying 125 (0.7%) accidental dural punctures or post-dural puncture headaches between 2007 and 2012. The audit record and patient medical record were examined to determine patient body mass index, headache characteristics and use of a therapeutic epidural blood patch. Women were classified into two groups: non-obese (body mass index <30 kg/m2, Group <30) or obese (body mass index ⩾30 kg/m2, Group ⩾30). Statistical analysis was by chi-square or Fisher exact tests, with P<0.05 considered significant. RESULTS: Compared to Group <30 (n=65), women in Group ⩾30 (n=60) did not significantly differ in the incidence of post-dural puncture headache (82% vs. 80%, P=0.83); its intensity (severe 36% vs. 23%, P=0.34); or the need for epidural blood patch (57% vs. 54%, P=0.81). Groups also did not differ significantly when confining analysis to those who had a witnessed accidental dural puncture (n=93) or to women with a body mass index >40 kg/m2 (n=10) vs. Group <30. CONCLUSION: This retrospective study found no evidence that women of higher body mass index are less likely to develop a post-dural puncture headache or that the characteristics of the headache and use of epidural blood patch were different.

A randomised controlled trial of parecoxib, celecoxib and paracetamol as adjuncts to patient-controlled epidural analgesia after caesarean delivery.

The benefit of combining non-opioid analgesics with neuraxial opioids for analgesia after caesarean delivery has not been clearly established. Larger doses of paracetamol or cyclooxygenase-2 inhibitors have not been evaluated. A randomised, double blind, double-dummy, parallel group placebo-controlled clinical trial was conducted among women having elective caesarean delivery under spinal anaesthesia, followed by pethidine patient-controlled epidural analgesia. Patients received placebos (group C); intravenous parecoxib 40 mg then oral celecoxib 400 mg at 12 hours (group PC); intravenous paracetamol 2 g then oral 1 g six-hourly (group PA); or these regimens combined (group PCPA). The primary outcome was 24-hour postoperative patient-controlled epidural pethidine use and the main secondary outcome was postoperative pain. One hundred and thirty-eight women were recruited but 27 subsequently met exclusion criteria, leaving 111 who were randomised, allocated and analysed by intention-to-treat (n=23, 30, 32 and 26 in groups C, PC, PA and PCPA respectively). There were no differences between groups for pethidine consumption, based on either intention-to-treat (median 365, 365, 405 and 360 mg in groups C, PC, PA and PCPA respectively, P=0.84) or per protocol analysis (17 major violations). Dynamic pain scores did not differ between groups but requirement for, and dose of, supplementary oral tramadol was least in group PCPA (incidence 23% versus 48%, 70% and 58% in groups C, PC and PA respectively, P=0.004). The addition of regular paracetamol, cyclooxygenase-2 inhibitors or both to pethidine patient-controlled epidural post-caesarean analgesia did not provide a pethidine dose-sparing effect during the first 24 hours.

Parecoxib and paracetamol for pain relief following minor day-stay gynaecological surgery.

Paracetamol and non-steroidal anti-inflammatory drugs are often administered for postoperative analgesia. Dilatation and curettage, with or without hysteroscopy, is a common day-stay procedure that is associated with pain that is partly mediated by prostaglandins. This study aimed to investigate the analgesic efficacy of adjunctive paracetamol and parecoxib in this setting. A randomised, blinded, placebo-controlled, single-centre trial was conducted among 240 women undergoing dilatation and curettage. Patients were randomised intraoperatively into one of four groups, to receive either intravenous paracetamol 2 g, intravenous parecoxib 40 mg, both in combination, or placebos, post-induction and with intravenous fentanyl. The primary endpoints were pain score one hour postoperatively and the Overall Benefit of Analgesia Score. There were no statistically significant differences in primary outcomes across groups. The area under the curve for pain scores to two hours postoperatively was significantly lower in the group receiving paracetamol (P=0.018) and the need for rescue analgesia with tramadol was less in the combination group (P=0.02). There were no significant differences in patient satisfaction or recovery. We conclude that paracetamol or parecoxib does not produce a clinically important reduction in pain in this setting. Women having uterine curettage and receiving intravenous fentanyl do not appear to benefit from administration of these non-opioid analgesics.

Amniotic fluid embolism: a leading cause of maternal death yet still a medical conundrum.

Amniotic fluid embolism is a rare and potentially catastrophic condition that is unique to pregnancy. The presentation may range from relatively subtle clinical events to sudden maternal cardiac arrest. Despite an increased awareness of the condition, it remains a leading cause of maternal mortality. The underlying mechanisms of amniotic fluid embolism are poorly understood, but current theories support an immune-based mechanism which is triggered by potentially small amounts of amniotic fluid gaining access to the maternal circulation. This can result in a wide spectrum of clinical findings, with cardiovascular and haematological disturbances being prominent. The management of a suspected episode of amniotic fluid embolism is generally considered to be supportive, although in centres with specific expertise, echocardiography may assist in guiding management. Whilst outcomes after an episode of amniotic fluid embolism are still concerning, mortality would appear to have decreased in recent times, likely secondary to an improved awareness of the condition, advances in acute care and the inclusion of less severe episodes in case registries.

Efficacy and safety of intraoperative intravenous methadone during general anaesthesia for caesarean delivery: a retrospective case-control study.

BACKGROUND: Most patients undergoing caesarean delivery with general anaesthesia require systemic opioid administration. Due to its rapid onset and long duration of action, intravenous methadone may make it suitable for analgesia after caesarean delivery. Intraoperative methadone combined with postoperative intravenous patient-controlled analgesia with fentanyl or morphine has recently been introduced in our unit. METHODS: A retrospective case-control study of 25 patients who had received methadone was performed. Fifty control patients undergoing elective or emergency caesarean delivery were matched for the use of postoperative intravenous patient-controlled analgesia, transversus abdominis plane (TAP) block and regular non-steroidal anti-inflammatory drugs. Exclusion criteria included preoperative neuraxial analgesia or pre-delivery opioid consumption greater than 10 mg of intravenous morphine equivalents. RESULTS: Patients in the methadone group had lower pain scores and were less likely to require intravenous opioid supplementation in the post-anaesthetic care unit (P<0.001). Opioid consumption over 48 h was significantly lower in the methadone group. Delayed discharge from the post-anaesthesia care unit was due to sedation in one patient in the methadone group compared to three control patients in whom it was due to sedation and inadequate analgesia. CONCLUSION: A single intraoperative bolus of intravenous methadone appeared to provide effective analgesia with an acceptable side-effect profile.

New formulations of fentanyl for acute pain management.

Intravenous fentanyl citrate has stood the test of time as a valuable formulation for pain management. The desirable physicochemical properties of fentanyl have allowed the development of several alternative formulations for delivery using less invasive routes, for example, transmucosal (intranasal, oral buccal and oral sublingual) and transdermal. These new formulations have been applied to clinical settings in which rapid onset of analgesia is desired, using convenient but noninvasive methods. Recent commercialization of various formulations has been driven largely by the needs of cancer patients, for whom severe but self-limiting "breakthrough" pain is less suitably treated by parenteral or oral routes of opioid administration. However, these formulations are also used for acute analgesia in prehospital and in-hospital emergency department care, and for pediatric acute pain management. Finally, they are increasingly used by patients with chronic pain of nonmalignant origin, although there is considerable debate about their merit in this group. We searched the databases MEDLINE, PubMed, EMBASE, CINAHL and Cochrane up to October 2011, using search terms "fentanyl AND nasal; intranasal; transmucosal; buccal; sublingual; oral; inhaled; inhalation; transdermal". The characteristics of several formulations of fentanyl are reviewed, detailing their pharmacokinetics, pharmacodynamics and clinical experience with their use for acute pain management.