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.

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.

Mental health and welfare in Australian anaesthetists.

This survey was designed to evaluate the factors affecting mental health and welfare in Australian anaesthetists and to investigate current sources of support. An electronic survey was sent to 500 randomly selected Fellows and trainees of the Australian and New Zealand College of Anaesthetists. Questions were related to: anxiety, stress, depression, substance misuse, self-medication, suicide, reporting illness, and help-seeking. Current psychological wellbeing was assessed using the Kessler Psychological Distress Scale (K10). A total of 191 completed surveys were received (a response rate of 38%): 26% had attended their general practitioner for mental health issues, of whom half had been diagnosed with a mental illness; 7% of all respondents were currently prescribed medication for this; 25% had previously self-prescribed psychoactive medication; 17% admitted to using alcohol to deal with stress, anxiety or depression; and 8% responded that mental illness had at some point impaired clinical care. Sixteen percent of all respondents reported previous suicidal ideation. Despite a low response rate, and the possibility of responder bias, the mental health of Australian anaesthetists would appear to be subject to common and persistent risk factors, many of which are well described in previous studies. We identify general practitioners as particularly valuable in targeting initiatives for improvements in mental health and welfare. The significant prevalence of suicidal ideation and reluctance to approach senior colleagues with concerns about mental health or welfare issues are specific causes for concern and suggest that further investigation, education and a potential review of support networks is required.

Spontaneous coronary artery dissection in pregnancy requiring emergency caesarean delivery followed by coronary artery bypass grafting.

Spontaneous coronary artery dissection is a rare and often fatal condition of pregnancy. The long-term morbidity is unknown, but a small cohort of patients develop severe ventricular dysfunction as a consequence. We describe a 37-week gestation parturient who presented with cardiogenic shock secondary to spontaneous left main coronary artery dissection. Despite rapid diagnosis, stabilisation with an intra-aortic balloon pump and prompt transfer to a tertiary centre for emergency caesarean delivery and coronary artery bypass grafting, the patient developed a severe postoperative dilated ischaemic cardiomyopathy. There is little information about the long-term outcomes and the specific anaesthesia management of combined emergency caesarean delivery and cardiac surgery in pregnancy for spontaneous coronary artery dissection. Therefore, we outline our multidisciplinary management of this critically ill pregnant woman.

Hyperfibrinolysis diagnosed by rotational thromboelastometry in a case of suspected amniotic fluid embolism.

Rotational thromboelastometry is a viscoelastomeric, point-of-care method for testing haemostasis in whole blood which can be visualised rapidly, in real time, in the operating theatre. Advantages over traditional coagulation tests relate to the rapid feedback of results and the ability to visualise hyperfibrinolysis. We present a case of suspected amniotic fluid embolism that presented with sudden respiratory arrest associated with haemodynamic compromise during a non-elective caesarean delivery. Soon after the collapse, coagulopathy developed. Rotational thromboelastometry showed hyperfibrinolysis and hypofibrinogenaemia, which allowed targeted coagulation factor replacement therapy and the use of tranexamic acid. Hyperfibrinolysis may be a contributor to the coagulopathy associated with amniotic fluid embolism but has been infrequently reported, perhaps due to limited diagnosis with traditional coagulation tests. Treatment of the coagulopathy associated with a suspected amniotic fluid embolism with antifibrinolytic agents may deserve greater consideration.

The cyclodextrin sugammadex and anaphylaxis to rocuronium: is rocuronium still potentially allergenic in the inclusion complex form?

Rocuronium, a non-depolarizing neuromuscular blocking drug has a rapid onset of action, a comparatively low potency and, with a more favourable side effects profile than succinylcholine, it has become a popular alternative to that drug for rapid sequence inductions in anaesthesia. The rocuronium-binding cyclodextrin derivative sugammadex, prepared by per-6 substitution of the primary hydroxyls of γ-cyclodextrin with thiol ether-linked propionic acid side chains to extend the hydrophobic cavity to accommodate rocuronium, is used to reverse neuromuscular blockade by encapsulating the drug as an inclusion complex and removing it from the neuromuscular junction to the plasma. It has recently been suggested that sugammadex might also be of value in the management of rocuronium-induced anaphylaxis and this has been potentially supported by recent case reports. However, before sugammadex can be recommended for this purpose, it is important to establish whether or not the allergenic substituted ammonium groups at each end of the rocuronium molecule in the inclusion complex are masked within the cavity or left exposed for interaction with rocuronium-reactive IgE antibodies in the sera of rocuronium-allergic patients. Detailed experimental strategies and experimental protocols to investigate the allergenic potential of the sugammadex-rocuronium inclusion complex are presented and a possible explanation of the apparently rapid and successful reversal of anaphylaxis by administration of sugammadex is advanced and discussed.

Obesity and obstetric anaesthesia.

Obesity is increasing in the population as a whole, and especially in the obstetric population, among whom pregnancy-induced physiological changes impact on those already present due to obesity. In particular, changes in the cardiovascular and respiratory systems during pregnancy further alter the physiological effects and comorbidities of obesity. Obese pregnant women are at increased risk of diabetes, hypertensive disorders of pregnancy, ischaemic heart disease, congenital malformations, operative delivery postpartum infection and thromboembolism. Regional analgesia and anaesthesia is usually preferred but may be challenging. Obese pregnant women appear to have increased morbidity and mortality associated with caesarean delivery and general anaesthesia for caesarean delivery in particular, and more anaesthesia-related complications. This article summarises the physiological and pharmacological implications of obesity and pregnancy and describes the issues surrounding the management of these women for labour and delivery.

Drug-specific cyclodextrins with emphasis on sugammadex, the neuromuscular blocker rocuronium and perioperative anaphylaxis: implications for drug allergy.

Cyclodextrins, oligosaccharides linked in a circular arrangement around a central cavity, are used extensively in the pharmaceutical industry to improve drug delivery. Their usefulness depends on their capacity to form a drug inclusion, or host-guest, complex within the cavity. In an attempt to improve the delivery of the widely used neuromuscular blocking drug (NMBD) rocuronium, a rocuronium inclusion complex was formed with a chemically modified γ-cyclodextrin. The high binding affinity and specificity of the modified carrier (named sugammadex) for rocuronium (and other aminosteroid NMBDs) led to its use in anaesthesia as an innovative and useful agent for rapid reversal of rocuronium-induced neuromuscular block by sequestering the drug as an inclusion complex. This, in turn, led to the suggestion that sugammadex might be useful to remove the NMBD from the circulation of patients experiencing rocuronium-induced anaphylaxis, a suggestion subsequently supported in case reports where traditional treatment had failed. Successful resuscitations suggested that sugammadex might be a valuable new treatment for such intractable cases but, given the inappropriateness of clinical trials, confirmation or refutation will have to await the slow accumulation of results of individual case reports. Important questions related to antibody accessibility of drug allergenic structures on the rocuronium-sugammadex inclusion complex, and the competition between sugammadex and IgE antibodies (both free and cell bound) for rocuronium, also remain and can be investigated in vitro. The sugammadex findings indicate that the use of carrier molecules such as the cyclodextrins to improve drug delivery will sometimes give rise to changed immunologic and allergenic behaviour of some drugs and this will have to be taken into account in preclinical drug safety assessments of drug-carrier complexes. The possibility of encapsulating and removing other allergenic drugs, e.g., penicillins and cephalosporins, in cases of difficult-to-reverse anaphylaxis to these drugs is discussed.

Sugammadex in the management of rocuronium-induced anaphylaxis.

Anaphylaxis during anaesthesia is a rare event that in ∼60-70% of cases is secondary to neuromuscular blocking agents. It has been suggested previously that the recent introduction of sugammadex may provide a novel therapeutic approach to the management of rocuronium-induced anaphylaxis. We describe the case of a 33-yr-old female who suffered a severe anaphylactic reaction to rocuronium, presenting with cardiovascular collapse on induction of anaesthesia. After 19 min of traditional management, she was given a bolus of sugammadex 500 mg. This was associated with an improvement in the adverse haemodynamic state. The underlying reasons for this are unclear, but sugammadex may potentially be a useful adjunct in the management of rocuronium-induced anaphylaxis.

The development and implementation of an obstetric cell salvage service.

Cell salvage in obstetric haemorrhage is now endorsed by a number of organisations. Most of the literature has focused on isolated case series and safety. We describe how cell salvage, including a quality assurance process conducted prior to clinical implementation, was introduced to our stand-alone obstetric hospital which had no previous experience of this technique. An implementation committee was established and 25 quality assurance and familiarisation cases were initially conducted. As part of this process the alpha fetoprotein, haematocrit, free plasma haemoglobin, potassium and Kleihauer tests were performed when enough blood was available for processing. Our guidelines for clinical use included women at greatly increased risk of obstetric haemorrhage and women at increased risk of haemorrhage who refused traditional transfusion. After the successful completion of this process, cell salvage was signed off for clinical use in March 2007 and was used on 51 occasions between March 2007 and July 2009. Twenty-one patients had salvaged blood re-transfused and for seven patients this was their only red blood cell replacement. The median blood loss in patients re-transfused was 3000 ml (range <500 to 8500 ml), with the median volume re-transfused 359 mi (range 60 to 1300 ml). There was one episode of unexplained hypotension associated with administration of salvaged blood. We have successfully introduced obstetric cell salvage into clinical practice. A quality assurance process prior to implementation was beneficial for the staff involved. Despite targeting a high-risk obstetric population, our re-transfusion rates are approximately 40%. No serious adverse events have been recorded. We recommend that in units that already provide intraoperative cell salvage in a non-obstetric setting, extending the service into obstetric situations should be considered. Units that routinely care for high-risk obstetric patients should also consider the introduction of such a service. Post transfusion Kleihauer testing should be performed as soon as possible in Rhesus-negative mothers who deliver a Rhesus-positive foetus, so that appropriate anti-D prophylaxis can be administered.

A randomised comparison of parecoxib versus placebo for pain management following minor day stay gynaecological surgery.

At therapeutic concentrations, parecoxib selectively inhibits the cyclo-oxygenase-2 enzyme. We investigated the impact of a single preoperative dose of parecoxib on pain relief following minor gynaecological surgery. Ninety women undergoing uterine dilatation and curettage, with or without hysteroscopy, were randomised to receive either 40 mg of parecoxib intravenously or a saline placebo prior to induction of standardised general anaesthesia. Exclusion criteria included a preoperative history of renal dysfunction or hypertension and the preoperative use of anti-inflammatory or opioid medication. The primary endpoint was the pain score during recovery. There was no difference in global pain scores or area under the curve for pain scores in the recovery area. Pain scores with coughing one hour after surgery were low in both groups but significantly lower after parecoxib (median 2 [interquartile range 0 to 4] parecoxib group vs. 2 [interquartile range 0 to 6] placebo group, P = 0.037). The 24 hour Quality of Recovery score did not differ significantly between groups but the parecoxib group was less likely to experience headache at 24 hours postoperatively (12 vs. 38%, P = 0.007) and reported complete satisfaction more frequently (78 vs. 57%, P = 0.042). The preoperative administration of parecoxib was associated with a significant but small decrease in dynamic pain scores one hour postoperatively. Women who received preoperative parecoxib had a lower incidence of postoperative headache and higher satisfaction.

Acute magnesium toxicity in an obstetric patient undergoing general anaesthesia for caesarean delivery.

Magnesium is commonly used in the prevention of eclampsia. Reports of acute toxicity are rare and we are not aware of detailed management algorithms. We present a case of acute magnesium toxicity presenting as ventilatory impairment and failure to rouse adequately from general anaesthesia. The patient was managed with controlled ventilation, further sedation, intravenous calcium gluconate, forced diuresis and dextrose-insulin infusion. We present a guideline for the management of life-threatening magnesium toxicity and discuss measures that may prevent future similar occurrences.

A randomised comparison of regular oral oxycodone and intrathecal morphine for post-caesarean analgesia.

BACKGROUND: Primary post-caesarean analgesia based on oral opioid has not been adequately studied. This approach may show a good side-effect profile and high satisfaction and avoid neuraxial complications. METHODS: In a double-blind, double-dummy, placebo-controlled clinical trial 120 women were randomised to receive either sustained-release oral oxycodone 20mg in the recovery room followed by immediate-release oxycodone 10mg 6-hourly for the first 24h (group O) or intrathecal morphine 100mug at the time of spinal anaesthesia (group I). All women received regular postoperative diclofenac, paracetamol and standardised supplemental analgesia. RESULTS: One hundred and eleven women completed the study. The area under the curve for pain scores to 24h did not differ significantly between groups for pain at rest (P=0.465) or on movement (P=0.533). Numerical pain scores were low and similar, except at rest at 12h (group I 1 [0-2] vs. group O 2 [1-3]; P=0.030). The time to first analgesic request was similar but additional postoperative analgesics were required more often in group O (82% vs. 63%, P=0.034). Group O more frequently reported high worst pain scores (score 4-10 in 87% vs. 64%, P=0.007). Pruritus was more common and more severe in group I (87% vs. 56%, P=0.001). At 24h maternal satisfaction with the analgesic regimen was lower in group O (P=0.010). CONCLUSION: Oral oxycodone produced comparable postoperative pain relief to intrathecal morphine with a lower incidence of pruritus, but was associated with a lower satisfaction score.

Analgesia after caesarean delivery.

As the number of women giving birth by caesarean increases throughout most of the developed world, so too is research into postoperative pain relief for these women. Like most other post-surgical populations, the new mother needs effective pain relief so that she can mobilise early but she also has the added responsibility of needing to care for her newborn baby. There is no 'gold standard' for post-caesarean pain management; the number of options is large and the choice of method is at least partly determined by drug availability, regional and individual preferences, resource limitations and financial considerations. Most methods rely on opioids, supplemented with anti-inflammatory analgesics, nerve blocks or other adjunctive techniques. The aim of this review is to detail commonly used opioid-based methods and to review the evidence supporting non-opioid methods, when incorporated into a multimodal approach to post-caesarean pain management. Areas of promising research are also discussed.