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.

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.

Extending epidural analgesia for emergency Caesarean section: a meta-analysis.

There is no high-level evidence supporting an optimal top-up solution to convert labour epidural analgesia to surgical anaesthesia for Caesarean section. The aim of this meta-analysis was to identify the best epidural solutions for emergency Caesarean section anaesthesia, with respect to rapid onset and low supplementation of intraoperative block. Eleven randomized controlled trials, involving 779 parturients, were identified for inclusion after a systematic literature search and risk of bias assessment. 'Top-up' boluses were classified into three groups: 0.5% bupivacaine or levobupivacaine (Bup/Levo); lidocaine and epinephrine, with or without fentanyl (LE ± F); and 0.75% ropivacaine (Ropi). Pooled analysis using the fixed-effects method was used to calculate the mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Lidocaine and epinephrine, with or without fentanyl, resulted in a significantly faster onset of sensory block [MD -4.51 min, 95% confidence interval (CI) -5.89 to -3.13 min, P < 0.00001]. Bup/Levo was associated with a significantly increased risk of intraoperative supplementation compared with the other groups (RR 2.03; 95% CI 1.22-3.39; P = 0.007), especially compared with Ropi (RR 3.24, 95% CI 1.26-8.33, P=0.01). Adding fentanyl to a local anaesthetic resulted in a significantly faster onset but did not affect the need for intraoperative supplementation. Bupivacaine or levobupivacaine 0.5% was the least effective solution. If the speed of onset is important, then a lidocaine and epinephrine solution, with or without fentanyl, appears optimal. If the quality of epidural block is paramount, then 0.75% ropivacaine is suggested.

Induction dose of propofol in patients using cannabis.

BACKGROUND AND OBJECTIVE: An estimated 150 million people worldwide use cannabis. The effect of cannabis on anaesthetic requirements in humans does not appear to have been studied. METHODS: In this prospective, randomized, single-blinded study, 30 male patients using cannabis more than once per week (group C) and 30 nonusers (group NC), aged 18-50 years, were induced with propofol 1.5, 2, 2.5, 3 or 3.5 mg kg. Additional doses were given when required. The primary outcome was the 50% effective dose of propofol and successful induction was determined by loss of consciousness with a bispectral index value of less than 60 and satisfactory insertion of a laryngeal mask. Propofol requirements to achieve these outcomes were recorded. RESULTS: The dose required to achieve the target bispectral index value was not significantly higher in group C, but group C required a significantly higher propofol dose to achieve laryngeal mask insertion (314.0 +/- 109.3 vs. 263.2 +/- 69.5 mg, P < 0.04). The estimated effective propofol induction dose in 50-95% of patients did not significantly differ between groups. CONCLUSION: We conclude that cannabis use increases the propofol dose required for satisfactory clinical induction when inserting a laryngeal mask.

Risk factors for severe postoperative nausea and vomiting in a randomized trial of nitrous oxide-based vs nitrous oxide-free anaesthesia.

BACKGROUND: Refractory postoperative nausea and vomiting (PONV) requiring repeated treatment with antiemetic drugs is a miserable experience for the patient that may substantially increase the cost of care. As risk stratification may aid in prophylaxis and treatment, we explored risk factors for severe PONV in patients enrolled in a large international, randomized controlled trial (the ENIGMA trial). METHODS: Two thousand and fifty patients, aged > or =18 yr and undergoing surgery anticipated to exceed 2 h in duration, were recruited. Patients were randomized to nitrous oxide (N(2)O)-based or N(2)O-free anaesthesia. Choice of other anaesthetic, analgesic, and antiemetic drugs was left to the discretion of the anaesthetist. Anaesthetic depth was adjusted according to clinical judgement and, if available, bispectral index (BIS) monitoring. Severe PONV was defined as: (i) two or more episodes of expulsion of gastric contents at least 6 h apart; (ii) received at least three doses of antiemetic medication for treatment of PONV, within 24 h of surgery; or both. We used logistic regression, and classification and regression tree analysis, to define risk factors for severe PONV. RESULTS: Three hundred and thirty-three (16.6%) patients experienced severe PONV. Age <55 yr, female sex, abdominal surgery, N(2)O administration, absence of BIS monitoring, and longer duration of anaesthesia were predictors of severe PONV [area under receiver operating characteristic curve=0.70 (95% confidence interval: 0.67-0.73)]. CONCLUSIONS: Severe PONV was common and risk factors for it were similar to those reported in other studies that included all patients reporting nausea, vomiting, or both.

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.

Hypertrophic cardiomyopathy and caesarean section: intraoperative use of transthoracic echocardiography.

A pregnant woman with severe hypertrophic cardiomyopathy was monitored with transthoracic echocardiography to guide management of fluids and vasopressors during elective caesarean section. After insertion of intravenous, arterial and central venous cannulae, a transthoracic echocardiogram was performed noting left ventricular cavity size and contractility, systolic anterior motion of the mitral valve and left ventricular outflow tract obstruction. Following combined spinal-epidural anaesthesia, serial examinations were made intraoperatively. Short-lived haemodynamic instability ensued just before the incision and with administration of oxytocin. Her postoperative course was complicated by post-partum haemorrhage requiring radiological intervention but she ultimately recovered fully. Maintaining preload to avoid worsening of left ventricular outflow tract obstruction is essential in these patients. A transthoracic echocardiogram is easily performed, of low risk and provides more useful information than a pulmonary artery catheter.

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.

Assessment of wound infiltration with bupivacaine in women undergoing day-case gynecological laparoscopy.

BACKGROUND AND OBJECTIVES: The effectiveness of local anesthetic wound infiltration for treatment of postoperative pain appears to be variable and partly dependent on the surgical procedure. Although evidence was lacking, it was common practice at our institution to infiltrate the trocar wound of patients undergoing day-case laparoscopic procedures with long acting local anesthetic agents. The aim of this study was to investigate the analgesic efficacy, and the influence of the timing, of local anesthetic infiltration into surgical wounds for day-case diagnostic gynecological laparoscopy. METHODS: A double-blind, randomized trial was conducted on 100 women having general anesthesia for day-case gynecological laparoscopy. Ninety-two patients who had been randomized to 1 of 4 groups for trocar wound infiltration with 30 mL of 0.25% bupivacaine or saline either before or after surgery completed the study. Incisional pain, pain on pressing the umbilicus, severity of nausea, and patient satisfaction with anesthetic technique were all assessed postoperatively until discharge and on the following day through a telephone interview. A P value of <.05 was considered significant. RESULTS: There was no difference between groups in the mean pain scores or analgesic requirements for incisional pain, pain on pressing firmly on the umbilicus, or for patient satisfaction. There was a trend for those patients who had received bupivacaine to use less postoperative morphine (P =.079). CONCLUSIONS: Wound infiltration with local anaesthetic did not significantly reduce pain or opioid requirement after gynecological laparoscopy.

Patient-controlled epidural analgesia in labor: the addition of clonidine to bupivacaine-fentanyl.

BACKGROUND AND OBJECTIVES: Epidural clonidine has not been evaluated as a component of patient-controlled epidural analgesia (PCEA) solutions during labor. A randomized, double-blind trial was conducted to investigate the efficacy and side effects of PCEA using bupivacaine and fentanyl, with or without clonidine. METHODS: Seventy-five healthy parturients in active labor were assigned to a PCEA solution of 0.0625% bupivacaine and fentanyl 2 microg/mL (4 mL demand bolus, 15 min lockout), with or without clonidine 4.5 microg/mL. The primary outcome measure was parturient rating of analgesia; others assessments included pain scores, drug utilization, supplementation and side effects. RESULTS: Thirty-one parturients received clonidine (group BFC) and 38 received control solution (group BF). Eight (6 group BF, 2 group BFC, P = .28) failed to achieve satisfactory epidural analgesia. There was a trend for parturient ratings of pain relief to be higher in group BFC, with significantly more reporting excellent first-stage analgesia (81% v. 57%, P<.05). Pain scores were similar. Clonidine (median dose, 28 microg/h) reduced total bupivacaine and fentanyl use (P<.01), and reduced supplementation (P<.01). Maternal blood pressure (BP) and recordings of systolic BP below 100 mm Hg did not differ. Group BFC had higher sedation scores (P<.01), but no one appeared oversedated. Shivering was reduced in group BFC (P<.01). CONCLUSIONS: The addition of clonidine to epidural bupivacaine and fentanyl for PCEA in labor improved analgesia, reduced the supplementation rate, and reduced shivering. Increased sedation and lower BP were not clinically important.

Patient controlled epidural analgesia during labour: choice of solution.

Epidural characteristics, when using different solutions for patient controlled epidural analgesia (PCEA), were compared in a randomised, blinded study in labour. Women in group 1 (n=23) self-administered 0.25% plain bupivacaine, in group 2 (n=23) 0.125% plain bupivacaine plus fentanyl 3 microg/ml and in group 3 (n=20) 0.0625% bupivacaine with adrenaline 1:250,000 plus fentanyl 3 microg/ml. There were no significant differences between groups with respect to the quality of obstetric pain relief or maternal satisfaction, the requirement for supplementary boluses of staff-administered solution or the incidence of side effects. There was more intense motor block after 3 hours of PCEA (odds ratio 3.33 for score 0 versus 1, 2 or 3) and a significantly higher ratio of demands received to demands made (P<0.03) in group 1 compared groups 2 and 3. The rate of bupivacaine utilisation was significantly higher in group 1 compared to groups 2 and 3 and lower in group 3 compared to 1 and 2 (median+interquartile range: 16+11-21 vs 9+6-11 vs 4+3-8 mg/hr, P<0.0002). Although all solutions provided effective pain relief for PCEA during labour, the use of a low-dose bupivacaine-fentanyl combination offers clinical advantages and further evaluation of such solutions is warranted.

Patient-controlled epidural analgesia in obstetrics.

PCEA is an attractive concept with special benefits in the obstetric population. It provides a safe and valuable alternative to other approaches to labour analgesia, with demonstrable advantages when used appropriately by motivated women. It also appears to be useful for management of pain after caesarean section. It may occasionally be of benefit in other acute and chronic pain settings in the obstetric population. Despite promising initial results, the full potential of PCEA remains to be explored, and this may be encouraged by ongoing developments in PCA pump technology. Comprehensive comparative studies and large prospective clinical series, further defining its role and safety in various settings, are awaited.

Convulsions in a healthy parturient due to intrapartum water intoxication.

Water intoxication during pregnancy is an uncommon event, usually associated with iatrogenic fluid overload, the prolonged administration of high doses of oxytocin or psychiatric disorder. This case report describes water intoxication presenting as the sudden onset of grand mal convulsions in the immediate postpartum period, after a normal delivery in a healthy parturient. The most likely explanation was an excessive voluntary ingestion of large quantities of water and hypotonic fluids during labour.