Four years' experience of a ROTEM® -guided algorithm for treatment of coagulopathy in obstetric haemorrhage.

We report four years of observational data from a large UK hospital and tertiary referral unit, following the introduction of a rotational thromboelastometry-guided algorithm for treatment of coagulopathy in major obstetric haemorrhage. Fibrinogen concentrate was used to treat acquired hypofibrinogenaemia as defined by a FibTEM A5 value of < 7 mm, or 7-12 mm with ongoing or high risk of haemorrhage. Of 32,647 deliveries over 4 years, 893 (2.7%) women had an estimated blood loss ≥ 1500 ml. Two-hundred and three (23%) of these had a FibTEM A5 ≤ 12 mm and 110 received fibrinogen concentrate. We compared clinical outcomes and blood product use with 52 patients who met the same criteria, over a 12-month pre-intervention period during which shock packs were used. In the algorithm group, there was a significant reduction in the number of units (p < 0.0001) and total volume (p = 0.0007) of blood products transfused, with a reduction in transfusion-associated circulatory overload (p = 0.002). Women with placental abruption exhibited more severe coagulopathy and required higher doses of fibrinogen concentrate than women who bled due to other causes. Analysis of rotational thromboelastometry results demonstrated that coagulopathy is not observed in all women who suffer obstetric haemorrhage and cannot be predicted solely by blood loss. Therefore, formulaic treatment with blood products is not justified. When coagulopathy does occur, it appears to be multifactorial and can be severe. Point-of-care testing allows early identification and individualised treatment of coagulopathy. This is supported by the improved outcomes reported.

Measuring fluorescence into a nanofiber by observing field quadrature noise.

We perform balanced homodyne detection of the electromagnetic field in a single-mode tapered optical nanofiber surrounded by rubidium atoms in a magneto-optical trap. Resonant fluorescence of atoms into the nanofiber mode manifests itself as increased quantum noise of the field quadratures. The autocorrelation function of the homodyne detector's output photocurrent exhibits exponential fall-off with a decay time constant of 26.3±0.6 ns, which is consistent with the theoretical expectation under our experimental conditions. To the best of our knowledge, this is the first experiment in which fluorescence into a tapered optical nanofiber has been observed and measured by balanced optical homodyne detection.

Integrated waveguides and deterministically positioned nitrogen vacancy centers in diamond created by femtosecond laser writing.

Diamond's nitrogen vacancy (NV) center is an optically active defect with long spin coherence times, showing great potential for both efficient nanoscale magnetometry and quantum information processing schemes. Recently, both the formation of buried 3D optical waveguides and high-quality single NVs in diamond were demonstrated using the versatile femtosecond laser-writing technique. However, until now, combining these technologies has been an outstanding challenge. In this Letter, we fabricate laser-written photonic waveguides in quantum grade diamond which are aligned to within micron resolution to single laser-written NVs, enabling an integrated platform providing deterministically positioned waveguide-coupled NVs. This fabrication technology opens the way toward on-chip optical routing of single photons between NVs and optically integrated spin-based sensing.

Coagulopathy and placental abruption: changing management with ROTEM-guided fibrinogen concentrate therapy.

Placental abruption may cause significant haemorrhage and coagulopathy that can progress rapidly due to simultaneous consumption and depletion of clotting factors. Plasma fibrinogen levels are predictive of further haemorrhage. Rapid detection and treatment of hypofibrinogenaemia is essential in the evolving clinical and haematological situation. The use of near-patient testing of coagulation using rotational thromboelastometry (ROTEM) allows dynamic monitoring of coagulopathy. Following the introduction of fibrinogen concentrate into our unit, a ROTEM-guided algorithm was developed for use in obstetric haemorrhage. We describe four cases of placental abruption, haemorrhage and severe coagulopathy that span the introduction of the algorithm. Three cases were associated with intrauterine death and the fourth with delivery of an extremely premature neonate. Rotational thromboelastometry was used in all cases but methods of fibrinogen replacement differ, illustrating evolving management of the condition in our unit.

Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage.

We compared blood component requirements during major obstetric haemorrhage, following the introduction of fibrinogen concentrate. A prospective study of transfusion requirements and patient outcomes was performed for 12 months to evaluate the major obstetric haemorrhage pathway using shock packs (Shock Pack phase). The study was repeated after the pathway was amended to include fibrinogen concentrate (Fibrinogen phase). The median (IQR [range]) number of blood components given was 8.0 (3.0-14.5 [0-32]) during the Shock Pack phase, and 3.0 (2.0-5.0 [0-26]) during the Fibrinogen phase (p = 0.0004). The median (IQR [range]) quantity of fibrinogen administered was significantly greater in the Shock Pack phase, 3.2 (0-7.1 [0-20.4]) g, than in the Fibrinogen phase, 0 (0-3.0 [0-12.4]) g, p = 0.0005. Four (9.5%) of 42 patients in the Shock Pack phase developed transfusion associated circulatory overload compared with none of 51 patients in the Fibrinogen phase (p = 0.038). Fibrinogen concentrate allows prompt correction of coagulation deficits associated with major obstetric haemorrhage, reducing the requirement for blood component therapy and the attendant risks of complications.

Accuracy and precision of the ultrasound cardiac output monitor (USCOM 1A) in pregnancy: comparison with three-dimensional transthoracic echocardiography.

BACKGROUND: Cardiac output (CO) monitoring is helpful in the assessment of critically ill pregnant women, but invasive monitors are often unsuitable for use. We aimed to measure agreement between the non-invasive ultrasound cardiac output monitor (USCOM) and three-dimensional transthoracic echocardiography (3D-TTE) in pregnant women. METHODS: Healthy pregnant women from 25 weeks gestation onwards participated. In the left lateral position at rest, CO was measured with the USCOM and 3D-TTE. A single operator performed all USCOM measurements, with a different operator performing all echocardiography. Both were blinded to results from the other device. Each USCOM trace was analysed using two modes: flowtrace (FT) and touchpoint (TP). A second, blinded USCOM reading was taken to assess reproducibility. RESULTS: USCOM readings were obtained in 92, and 3D-TTE images in 85 participants. The mean CO was 5.7, 7.7, and 6.2 litre min(-1) measured by 3D-TTE, USCOM FT, and USCOM TP, respectively. USCOM bias was +2.0 litre min(-1) (FT) and +0.4 litre min(-1) (TP). Limits of agreement were -0.2 to +4.2 litre min(-1) (FT) and -1.4 to +2.3 litre min(-1) (TP). The mean percentage difference was 32.6% (FT) and 31.4% (TP) for CO and 27.0% (FT) and 27.5% (TP) for stroke volume. Intraclass correlation between repeated USCOM readings was 0.9 (FT) and 0.86 (TP). CONCLUSIONS: USCOM has acceptable agreement with 3D-TTE for the measurement of CO in pregnancy. The positive bias of the USCOM, particularly in the FT mode, may be due to the hyperdynamic cardiovascular state in pregnancy. We suggest using the TP mode in this patient population.

Automated control of end-tidal inhalation anaesthetic concentration using the GE Aisys Carestation™.

BACKGROUND: Automated control of end-tidal inhalation anaesthetic concentration is now possible. The EtControl™ module of an Aisys Carestation Anaesthetic machine digitally adjusts fresh gas flow and plenum vaporizer output to achieve a target end-tidal concentration. METHODS: We evaluated EtControl in clinical practice by measuring volatile agent consumption and the need for user input. We compared these values with contemporaneous controls using manual control of fresh gas flow rates. RESULTS: A total of 321 patients were anaesthetized with EtControl and 168 with manual control of fresh gas flow. The mean [95% confidence interval (CI)] sevoflurane usage for cases of 20-40 min duration was 14 (13-16) ml h(-1) with EtControl and 30 (26-35) ml h(-1) with manual control. For cases of the same duration, the mean (95% CI) desflurane consumption was 27 (21-33) ml h(-1) with EtControl and 45 (29-62) ml h(-1) with manual control. The average number of keypresses per case was 6.5 with EtControl and 13.6 during manual control of fresh gas flow. CONCLUSIONS: Automatic implementation of low-flow anaesthesia using EtControl allows the user to set and maintain a desired end-tidal volatile concentration while using less volatile agent.

The economic benefits of cell salvage in obstetric haemorrhage.

BACKGROUND: Cell salvage is increasingly used in the management of major obstetric haemorrhage. Its financial considerations were evaluated over a 5-year period. METHOD: Cell salvage was introduced in the Liverpool Women's NHS Foundation Trust in 2006. Data were collected from all cases in which it was set-up and included the volume of blood processed and returned and whether surgery was elective or emergency. RESULTS: Between 1st January 2006 and 30th June 2011, cell salvage for collection was set-up 587 times and blood was returned in 137 patients. Total volume of blood returned was 47143mL, equivalent to 189 units of packed red cells. The return rate was higher for emergency than elective cases (P=0.03). As the use of cell salvage has extended over time to include a greater proportion of patients, return rates have decreased (P<0.0001). The volume of blood returned from cell salvage was significantly related to the estimated blood loss (P<0.00001), with a best fit line described by estimated blood loss=3.45x+454, where x was the volume of blood returned. In 2011 total costs of cell salvage were £9245 for the equivalent of 83 units of blood. At the current price of £125 per unit of allogeneic blood this would have cost £10375: a saving of £1130. No intraoperative or postoperative complications associated with cell salvage were seen. CONCLUSION: The routine use of cell salvage was associated with more salvaged blood being returned to patients, which offset the cost of collection sets when compared to the cost of using allogeneic blood. Cell salvage is an appropriate expenditure to reduce the use of allogeneic blood.

Public reporting of health care-associated infections (HAIs): approach to choosing HAI measures.

OBJECTIVE: To develop a method for selecting health care-associated infection (HAI) measures for public reporting. CONTEXT: HAIs are common, serious, and costly adverse outcomes of medical care that affect 2 million people in the United States annually. Thirty-seven states have introduced or passed legislation requiring public reporting of HAI measures. State legislation varies widely regarding which HAIs to report, how the data are collected and reported, and public availability of results. DESIGN: The Maryland Health Care Commission developed an HAI Technical Advisory Committee (TAC) that consisted of a group of experts in the field of healthcare epidemiology, infection prevention and control (IPC), and public health. This group reviewed public reporting systems in other states, surveyed Maryland hospitals to determine the current state of IPC programs, performed a literature review on HAI measures, and developed six criteria for ranking the measures: impact, improvability, inclusiveness, frequency, functionality, and feasibility. The committee and experts in the field then ranked each of 18 proposed HAI measures. A composite score was determined for each measure. RESULTS: Among outcome measures, the rate of central line-associated bloodstream infections ranked highest, followed by the rate of post-coronary artery bypass grafting surgical-site infections. Among process measures, perioperative antimicrobial prophylaxis, compliance with central-line bundles, compliance with hand hygiene, and healthcare-worker influenza vaccination ranked highest. CONCLUSIONS: Our qualitative criteria facilitated consensus on the HAI TAC and provided a useful framework for public reporting of HAI measures. Validation will be important for such approaches to be supported by the scientific community.

Rocuronium and sugammadex for rapid sequence induction of obstetric general anaesthesia.

BACKGROUND: Many anaesthetists use rocuronium in place of suxamethonium for rapid sequence induction (RSI). This is less common in obstetric anaesthesia as the duration of action of an effective dose of rocuronium exceeds most obstetric procedures. Sugammadex offers the possibility of rapidly reversing profound rocuronium neuromuscular blockade at the end of surgery. We aimed to determine whether rocuronium 1.2 mg/kg used for RSI in the obstetric population would provide good intubating conditions at 60 s and would be effectively reversed by sugammadex at the end of surgery. METHODS: We present a prospective series of 18 patients who received rocuronium 1.2 mg/kg at induction of anaesthesia, monitored with a train-of-four ratio (TOF)-Watch SX(®) , and reversed using sugammadex 4 mg/kg. RESULTS: The mean (95% CI) onset time of rocuronium was 71 (56-86) s, and the mean (95% CI) time to recovery of the TOF to ≥90%, after the administration of sugammadex 4 mg/kg at the end of surgery, was 86 (69-104) s. CONCLUSION: Rocuronium 1.2 mg/kg reversed by sugammadex appears to be effective in the obstetric population.

Drug approval processes in Australian Paediatric Hospitals.

OBJECTIVE: To describe and evaluate the decision-making processes for drug approval in Australian paediatric hospitals. DESIGN: Multicentre descriptive study involving face-to-face interviews of drug and therapeutics committee chairs and secretaries, review of committee documents and drug submissions for all Australian paediatric hospital drug and therapeutics committees over a 1-year period. SETTING: All eight paediatric hospitals in Australia. PARTICIPANTS: Eight committee chairs and seven secretaries or delegates. MAIN OUTCOME MEASURES: Total drug expenditure, number of formulary submissions, individual-patient use approvals and approval rates for each hospital from 1 July 2006 to 30 June 2007, stratified by therapeutic class. Qualitative description of the approval processes. RESULTS: Total drug expenditure varied from $A1.7 million (US$1.5 million) to $A11.1 million (US$9.8 million) per hospital. The number of formulary submissions also varied, from 7 to 21, but approval rate was high (76%-100%) and not significantly different among hospitals (p=0.17). Several committees approved identical submissions for five drugs. The number of individual-patient use applications varied considerably, ranging from 10 to 456 per hospital. Where estimable, individual-patient use approval was 76%-100% and variable (p=0.03). Quality of evidence relating to safety and efficacy of drugs being considered was regarded as the most important factors influencing decision making, with the cost less important. Most committees had poor infrastructural support for approval processes. No committee formally included a pharmaco-economic evaluation. CONCLUSIONS: Most drug submissions in tertiary paediatric hospitals are approved; however, workload, drug expenditure and individual-patient use schemes vary considerably. Duplication of effort occurs, and few committees are resourced sufficiently given their terms of reference.

Nanophotonics for quantum optics using nitrogen-vacancy centers in diamond.

Optical microcavities and waveguides coupled to diamond are needed to enable efficient communication between quantum systems such as nitrogen-vacancy centers which are known already to have long electron spin coherence lifetimes. This paper describes recent progress in realizing microcavities with low loss and small mode volume in two hybrid systems: silica microdisks coupled to diamond nanoparticles, and gallium phosphide microdisks coupled to single-crystal diamond. A theoretical proposal for a gallium phosphide nanowire photonic crystal cavity coupled to diamond is also discussed. Comparing the two material systems, silica microdisks are easier to fabricate and test. However, at low temperature, nitrogen-vacancy centers in bulk diamond are spectrally more stable, and we expect that in the long term the bulk diamond approach will be better suited for on-chip integration of a photonic network.

Difficult and failed intubation in 3430 obstetric general anaesthetics.

A retrospective audit was performed of all obstetric general anaesthetics in our hospital over an 8 year period to determine the incidence of difficult and failed intubation. Data was collected from a number of sources to ensure accuracy. A total of 3430 rapid sequence anaesthetics were given. None of the patients had a failed or oesophageal intubation (95% CI, 0-1:1143). There were 23 difficult intubations (95% CI, 1:238-1:100). This was anticipated in nine cases, requiring awake fibreoptic intubation in three cases. Consultants or specialist registrars were involved in the management of all cases. We attribute the low incidence of airway complications to the above average rate of general anaesthesia in our hospital, senior cover and specialised anaesthetic operating department assistants.

Pharmacokinetic, pharmacodynamic, and safety profile of a new cholesteryl ester transfer protein inhibitor in healthy human subjects.

A new cholesteryl ester (CE) transfer protein (CETP) inhibitor (CP-800,569) was evaluated. Doses of 30-1,800 mg were administered once daily to healthy subjects for 14 days. Serum CP-800,569 levels increased, and CETP activity decreased, in a dose-related manner. Serum levels of high-density lipoprotein (HDL) increased (by a maximum of 156%), and those of low-density lipoprotein (LDL) decreased (by a maximum of 47%). CP-800,569 also had the effect of lowering postprandial triglyceride levels. Trough concentrations of apolipoprotein E (apoE) increased: the maximum increases were 89% for total plasma apoE and 280% for HDL apoE. By contrast, the postprandial increases in total plasma levels of apoE and non HDL apoE were either diminished by CP-800,569 or reversed to decreases. CP-800,569 was very well tolerated, with some nonserious gastrointestinal adverse events seen only with the 1,800-mg dose. No changes in blood pressure (BP) were observed. The possible effects of higher CP-800,569 doses on aldosterone and cortisol levels could not be excluded. The results of this study may be useful in CP-800,569 dose selection.