Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.

How general anesthetics work remains a topic of ongoing study. A parallel field of research has sought to identify methods to reverse general anesthesia. Reversal agents could shorten patients' recovery time and potentially reduce the risk of postoperative complications. An incomplete understanding of the mechanisms of general anesthesia has hampered the pursuit for reversal agents. Nevertheless, the search for reversal agents has furthered understanding of the mechanisms underlying general anesthesia. The study of potential reversal agents has highlighted the importance of rigorous criteria to assess recovery from general anesthesia in animal models, and has helped identify key arousal systems (e.g., cholinergic, dopaminergic, and orexinergic systems) relevant to emergence from general anesthesia. Furthermore, the effects of reversal agents have been found to be inconsistent across different general anesthetics, revealing differences in mechanisms among these drugs. The presynapse and glia probably also contribute to general anesthesia recovery alongside postsynaptic receptors. The next stage in the search for reversal agents will have to consider alternate mechanisms encompassing the tripartite synapse.

Supraglottic Airway Devices: Present State and Outlook for 2050.

Correct placement of supraglottic airway devices (SGDs) is crucial for patient safety and of prime concern of anesthesiologists who want to provide effective and efficient airway management to their patients undergoing surgery or procedures requiring anesthesia care. In the majority of cases, blind insertion of SGDs results in less-than-optimal anatomical and functional positioning of the airway devices. Malpositioning can cause clinical malfunction and result in interference with gas exchange, loss-of-airway, gastric inflation, and aspiration of gastric contents. A close match is needed between the shape and profile of SGDs and the laryngeal inlet. An adequate first seal (with the respiratory tract) and a good fit at the second seal of the distal cuff and the gastrointestinal tract are most desirable. Vision-guided insertion techniques are ideal and should be the way forward. This article recommends the use of third-generation vision-incorporated-video SGDs, which allow for direct visualization of the insertion process, corrective maneuvers, and, when necessary, insertion of a nasogastric tube (NGT) and/or endotracheal tube (ETT) intubation. A videoscope embedded within the SGD allows a visual check of the glottis opening and position of the epiglottis. This design affords the benefit of confirming and/or correcting a SGD's position in the midline and rotation in the sagittal plane. The first clinically available video laryngeal mask airways (VLMAs) and multiple prototypes are being tested and used in anesthesia. Existing VLMAs are still not perfect, and further improvements are recommended. Additional modifications in multicamera technology, to obtain a panoramic view of the SGD sitting correctly in the hypopharynx and to prove that correct sizes have been used, are in the process of production. Ultimately, any device inserted orally-SGD, ETT, NGT, temperature probe, transesophageal scope, neural integrity monitor (NIM) tubes-could benefit from correct vision-guided positioning. VLMAs also allow for automatic recording, which can be documented in clinical records of patients, and could be valuable during teaching and research, with potential value in case of legal defence (with an airway incident). If difficulties occur with the airway, documentation in the patient's file may help future anesthesiologists to better understand the real-time problems. Both manufacturers and designers of SGDs may learn from optimally positioned SGDs to improve the design of these airway devices.

Finger cuff versus invasive and noninvasive arterial pressure measurement in pregnant patients with obesity.

BACKGROUND: Pregnant patients with obesity may have compromised noninvasive blood pressure (NIBP) measurement. We assessed the accuracy and trending ability of the ClearSight™ finger cuff (FC) with invasive arterial monitoring (INV) and arm NIBP, in obese patients having cesarean delivery. METHODS: Participants were aged ≥18 years, ≥34 weeks gestation, and body mass index (BMI) ≥ 40 kg m-2. FC, INV, and NIBP measurements were obtained across 5-min intervals. The primary outcome was agreement of FC measurements with those of the reference standard INV, using modified Bland-Altman plots. Secondary outcomes included comparisons between FC and NIBP and NIBP versus INV, with four-quadrant plots performed to report discordance rates and evaluate trending ability. RESULTS: Twenty-three participants had a median (IQR) BMI of 45 kg m-2 (44-48). When comparing FC and INV the mean bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 16 mmHg (17, -17.3 to 49.3 mmHg), for diastolic blood pressure (DBP) -0.2 mmHg (10.5, -20.7 to 20.3), and for mean arterial pressure (MAP) 5.2 mmHg (11.1, -16.6 to 27.0 mmHg). Discordance occurred in 54 (26%) pairs for SBP, 41 (23%) for DBP, and 41 (21.7%) for MAP. Error grid analysis showed 92.1% of SBP readings in Zone A (no-risk zone). When comparing NIBP and INV, the mean bias (95% limits of agreement) for SBP was 13.0 mmHg (16.7, -19.7 to 29.3), for DBP 5.9 mmHg (11.9, -17.4 to 42.0), and for MAP 8.2 mmHg (11.9, -15.2 to 31.6). Discordance occurred in SBP (84 of 209, 40.2%), DBP (74 of 187, 39.6%), and MAP (63 of 191, 33.0%). CONCLUSIONS: The FC and NIBP techniques were not adequately in agreement with INV. Trending capability was better for FC than NIBP. Clinically important differences may occur in the setting of the perfusion-dependent fetus.

Profound Properties of Protein-Rich, Platelet-Rich Plasma Matrices as Novel, Multi-Purpose Biological Platforms in Tissue Repair, Regeneration, and Wound Healing.

Autologous platelet-rich plasma (PRP) preparations are prepared at the point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate), and variable leukocyte bioformulation and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and, ultimately, functional and structural repair. Normally, after PRP preparation, the PPP fraction is discarded. One of the less well-known but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside of the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation and fibrosis, and they promote keratinocyte migration and support tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating, in a fast and efficient manner, plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein-rich, platelet-rich plasma (PR-PRP) biological preparation. After the activation of proteins, mainly fibrinogen, the PR-PRP matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), as well as the embedded concentrated PRP cells and molecules. The administered PR-PRP biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PR-PRP matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of the PR-PRP matrix.

Diversity in medical PhD curricula: a call for harmonisation.

BACKGROUND: Globalisation has increased human movements around the world, spurring greater connectiveness and opportunities to collaborate. In an increasingly connected world, quality assurance among professionals is paramount, particularly in medical research where PhD (Doctor of Philosophy) degree holders are expected to be at the peak of their field and play advanced-level research, education and leadership roles. While some regional efforts have been made to ensure comparability in the standards of advanced degree training, no previous study has compared these standards for a PhD in medicine across the globe. AIMS: To explore the structural diversity of medical PhD degrees and identify which aspects benefit from greater harmonisation. METHODS: In 2021, the 10 best-ranked universities from each of the top five Western countries, and the top Asian country, were identified based on Quacquarelli Symonds World University Ranking. Data were collected for each university based on individual website information regarding the level of degree required to gain entry into a PhD programme in medicine and requirements for completion of coursework, journal publication and oral defence. RESULTS: Significant variations exist in the requirements for medical PhDs across the world in terms of prerequisite degree and inclusion of coursework. Oral defence is near universal, but a mandatory requirement for publication is largely absent. CONCLUSIONS: Harmonisation of medical PhD degrees through international standards should be considered to encourage quality improvement and benchmarking between institutions, as well as to facilitate greater ease of movement within the medical research community, improving international collaboration and individual career opportunities accordingly.

Transcutaneous carbon dioxide measurements in anesthetized apneic patients with BMI > 35 kg/m2.

Transcutaneous carbon dioxide measurement (TcCO2) offers the ability to continuously and non-invasively monitor carbon dioxide (CO2) tensions when end-tidal monitoring is not possible. The accuracy of TcCO2 has not been established in anesthetized apneic patients with obesity. In this secondary publication, we present a methods comparison analysis of TcCO2 with the gold standard arterial PCO2, in adult patients with body mass index (BMI) > 35kg/m2 who were randomized to receive high flow or low flow nasal oxygenation during post-induction apnea. Agreement between PaCO2 and TcCO2 at baseline, the start of apnea and the end of apnea were assessed using a non-parametric difference plot. Forty-two participants had a median (IQR) BMI of 52 (40-58.5) kg/m2. The mean (SD) PaCO2 was 33.9 (4.0) mmHg at baseline and 51.4 (7.5) mmHg at the end of apnea. The bias was the greatest at the end of apnea median (95% CI, 95% limits of agreement) 1.90 mmHg (-2.64 to 6.44, -7.10 to 22.90). Findings did not suggest significant systematic differences between the PaCO2 and TcCO2 measures. For a short period of apnea, TcCO2 showed inadequate agreement with PaCO2 in patients with BMI > 35 kg/m2. These techniques require comparison in a larger population, with more frequent sampling and over a longer timeframe, before TcCO2 can be confidently recommended in this setting.

Plasma and Interstitial Fluid Pharmacokinetics of Prophylactic Cefazolin in Elective Bariatric Surgery Patients.

Guidelines for surgical prophylactic dosing of cefazolin in bariatric surgery vary in terms of recommended dose. This study aimed to describe the plasma and interstitial fluid (ISF) cefazolin pharmacokinetics in patients undergoing bariatric surgery and to determine an optimum dosing regimen. Abdominal subcutaneous ISF concentrations (measured using microdialysis) and plasma samples were collected at regular time points after administration of cefazolin 2 g intravenously. Total and unbound cefazolin concentrations were assayed and then modeled using Pmetrics. Monte Carlo dosing simulations (n = 5,000) were used to define cefazolin dosing regimens able to achieve a fractional target attainment (FTA) of >95% in the ISF suitable for the MIC for Staphylococcus aureus in isolates of ≤2 mg · L-1 and for a surgical duration of 4 h. Fourteen patients were included, with a mean (standard deviation [SD]) bodyweight of 148 (35) kg and body mass index (BMI) of 48 kg · m-2. Cefazolin protein binding ranged from 14 to 36% with variable penetration into ISF of 58% ± 56%. Cefazolin was best described as a four-compartment model including nonlinear protein binding. The mean central volume of distribution in the final model was 18.2 (SD 3.31) L, and the mean clearance was 32.4 (SD 20.2) L · h-1. A standard 2-g dose achieved an FTA of >95% for all patients with BMIs ranging from 36 to 69 kg · m-2. A 2-g prophylactic cefazolin dose achieves appropriate unbound plasma and ISF concentrations in obese and morbidly obese bariatric surgery patients.

The effect of transnasal humidified rapid-insufflation ventilator exchange (THRIVE) versus nasal prongs on safe apnoea time in paralysed obese patients: a randomised controlled trial.

BACKGROUND: Evidence is lacking regarding the efficacy of Optiflow transnasal humidified rapid-insufflation ventilator exchange (THRIVE™) in obese patients. We compared the impact of this technique at 70 L min-1 with 4 L min-1 oxygen via nasal prongs on safe apnoea times of paralysed obese patients. METHODS: We randomised adults with a BMI >35 kg m-2 undergoing elective bariatric surgery. While apnoeic and paralysed, Group T received 70 L min-1 oxygen via Optiflow THRIVE™. Group N received nasal prong oxygen at 4 L min-1. The primary outcome was time to SpO2 ≤95% while apnoeic, with a 360 s cut-off. This was analysed by applying a time-to-event analysis. RESULTS: Forty-two patients were included. The median (inter-quartile range) BMI was 44.8 kg m-2 (40.0-50.0) in Group T and 42.0 kg m-2 (39.3-45.1) in Group N. Median (inter-quartile range) time to SpO2 ≤95% in Group T was 356 (165 to ≥360) s and in Group N, 210 (160-270) s. Using a survival analysis framework, median time-to-event in Group T was 356 s (95% confidence interval 165 s-upper limit not defined) and 210 s (95% confidence interval 160-242 s) (P=0.049) in Group N. CONCLUSIONS: Compared with oxygen delivered via nasal prongs at 4 L min-1, oxygen delivery via Optiflow THRIVE™ at a flow rate of 70 L min-1 can prolong safe apnoea time, however, the results are statistically inconclusive. Optiflow THRIVE™ did decrease the rate of reduction in Pao2 during apnoea. CLINICAL TRIAL REGISTRATION: ANZCTR 12618000445279.

Oddities in the Evolution of Syringes in Anesthesia.

Many procedures in science and medicine involve the use of a syringe, and its invention is a key milestone in general and regional anesthesia history. The end of the 19th century brought major changes in syringe production. An industry that initially manually crafted syringes to individual physicians' instructions saw the introduction of a large variety of syringes, sometimes with odd and unique modifications. For many of these unique syringes, there was no proven evidence that these modifications were effective or safe to use. This article provides examples of "odd" syringe designs for use in medicine, general anesthesia, and regional anesthesia. Some designs proved functional and have stood the test of time; others quickly disappeared and ended up in dusty collections.

Rotational thromboelastometry (ROTEM® ) in gestational diabetes mellitus and coagulation in healthy term pregnancy: A prospective observational study in Australia.

BACKGROUND: Rotational thromboelastometry (ROTEM® ) is a point-of-care test of coagulation. ROTEM® -defined hypercoagulability has been identified in pregnant women and in non-pregnant patients with diabetes mellitus. Pregnancy is known to be a hypercoagulable state, but the influence of gestational diabetes mellitus (GDM) on coagulation is unknown. AIM: The aim of this study was to assess the combined effect of pregnancy and GDM on coagulation using ROTEM® and to compare this to healthy pregnant women presenting for elective caesarean delivery. MATERIALS AND METHODS: Ethics approval was granted for recruitment of women presenting for elective caesarean delivery. Women with pre-existing conditions affecting coagulation were excluded. Group N included health pregnant women at term and Group G included pregnant women at term with GDM. Data regarding GDM management and glycaemic control were collected. Poor glycaemic control was defined by markers of accelerated fetal growth and elevated fasting or postprandial blood glucose levels. The ROTEM® parameters (extrinsically activated thromboelastometric test (EXTEM) / fibrin polymerisation test (FIBTEM) amplitude at five minutes, coagulation time, maximum clot firmness and clot formation time) were compared between the two groups using Student's t-test. RESULTS: There were 75 women in Group N and 21 women in Group G. Mean age and median body mass index values were comparable for both groups. There were no statistical differences found between the EXTEM and FIBTEM parameters analysed for the two groups. CONCLUSIONS: There was no association between GDM and increased hypercoagulability as demonstrated by ROTEM® parameters in healthy pregnant women presenting for elective caesarean delivery at term.

Features of new vision-incorporated third-generation video laryngeal mask airways.

Numerous studies have shown that blindly inserted supraglottic airway devices (SADs) are sub-optimally placed in 50 to 80% of all cases. Placement under direct vision has been recommended. We describe the very first two new SADs of the third generation that incorporate a videoscope with flexible tip. Both devices are made up of two interlocking components-the SAD and a videoscope. The 3rd generation, direct vision SADs allow vision-guided insertion, corrective manoeuvres, if needed, and correct placement in the hypopharynx and possess additional features which permit insertion of a gastric tube and endotracheal intubation should the need arise. This article describes the two new devices' physical characteristics, features, rationale for use, advantages and limitations in comparison to existing devices. Each of the two new devices-the Video Laryngeal Mask (VLMTM, UE Medical®) and the SafeLM® Video Laryngeal Mask System (SafeLMTM VLMS, Magill Medical Technology®) consist of two parts: (a) a disposable 2nd generation SAD with a silicone cuff and an anatomically curved tube; and (b) a reusable patient-isolated videoscope and monitoring screen, with the flexible scope located into a specially-designed, blind-end channel terminating in the bowl of the SAD, preventing the videoscope from contacting patient body fluids in the SAD bowl. Third generation placement-under-direct-vision supraglottic airway devices possess several theoretical safety and ease of use advantages which now need to be validated in clinical use.

Time to consider supraglottic airway device oropharyngeal leak pressure measurement more objectively.

Oropharyngeal leak pressure (OLP) is considered a measure of successful placement, adequate performance and is a useful comparator between supraglottic airway devices (SADs). OLP measurement is based on the premise that the SAD is sited properly in the hypopharynx after blind placements, but the evidence suggests otherwise. Several limitations and controversies surround OLP. This editorial addresses the uses and pitfalls of OLP, the rationale for and methods of ascertaining OLP, the pros and cons of OLP measurement and newer modalities to improve its accuracy.

ClearSight™ finger cuff versus invasive arterial pressure measurement in patients with body mass index above 45 kg/m2.

BACKGROUND: Measuring blood pressure in patients with obesity is challenging. The ClearSight™ finger cuff (FC) uses the vascular unloading technique to provide continuous non-invasive blood pressure measurements. We aimed to test the agreement of the FC with invasive radial arterial monitoring (INV) in patients with obesity. METHODS: Participants had a body mass index (BMI) ≥45 kg/m2 and underwent laparoscopic bariatric surgery. FC and INV measurements were obtained simultaneously every 5 min on each patient, following induction of anesthesia. Agreement over time was assessed using modified Bland-Altman plots and error grid analysis permitted clinical interpretation of the results. Four-quadrant plots allowed assessment of concordance in blood pressure changes. RESULTS: The 30 participants had a median (IQR) BMI of 50.2 kg/m2 (IQR 48.3-55.3). The observed bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 14.3 mmHg (14.1, -13.4 - 42.0), 5.2 mmHg (10.9, -16.0 - 26.5) for mean arterial pressure (MAP) and 2.6 mmHg (10.8, -18.6 - 23.8) for diastolic blood pressure (DBP). Error grid analysis showed that the proportion of readings in risk zones A-E were 90.8, 6.5, 2.7, 0 and 0% for SBP and 91.4, 4.3, 4.3, 0 and 0% for MAP, respectively. Discordance occurred in ≤8% of pairs for consecutive change in SBP, MAP and DBP. CONCLUSIONS: The vascular unloading technique was not adequately in agreement with radial arterial monitoring. Evaluation in a larger sample is required before recommending this technique for intraoperative monitoring of patients with BMI ≥45 kg/m2.

Techniques to select site of insertion for a peripheral intravenous catheter with vessel locating devices using light, sounds or tactile actions (or palpations).

BACKGROUND: Approximately 80% of patients admitted to acute hospitals have at least one peripheral intravenous catheter inserted during their admission, for the administration of fluids and medicines, and/or diagnostic tests, so the failure rate is concerning. New technology may decrease these rates even when used by inexperienced inserters. The choice of insertion site for an intravenous catheter is a known predictor of catheter failure. Therefore, the objective for this study was to evaluate the utility of vessel locating devices for novice clinicians to select catheter insertion sites in the forearm. METHODS: An inter-subject incomplete counterbalanced research design was employed with healthy volunteers. Novice clinicians used either a vessel locating device using light or sound waves or they used palpation to identify relatively superficial veins in the forearm. This was compared to site selection performed by an expert clinician using palpation method only. Measurements of differences were analysed from photos of chosen sites. Bland-Altman agreement analysis was used to plot novice expert agreement. The STROBE checklist was followed in reporting this study (Techniques to select site of insertion for a peripheral intravenous catheter with vessel locating devices (Appendix S1)). RESULTS: A total of 32 novice clinicians used three vessel locating devices and a palpation technique. Novice clinicians did not choose more veins for optimum catheter placement when assisted with vessel locating devices compared to palpation techniques. All methods had a similar mean difference between novice and expert measurements and a similar percentage difference in distance from the expert choice. Bland-Altman agreement analysis did not identify any advantage for the novice with vessel locating devices over palpation. CONCLUSION: Vessel locating devices do not enhance the ability of novice clinicians any greater than palpation when selecting suitable forearm veins. If vessel locating device approaches are to be adopted in clinical practice to support better insertion outcomes then current PIVC teaching techniques should include structured vessel locating devices theory and practice. RELEVANCE TO CLINICAL PRACTICE: Successful insertion of a peripheral intravenous catheter (PIVC) on the first attempt is a challenging procedure for nurses. Careful consideration of the selected site of insertion could modify this risk factor for catheter failure. The choice of PIVC insertion site by a novice clinician compared to an expert does not necessarily improve with the use of vein locating technology. While there is a range of technological devices available to assist with locating vessels, there needs to be more emphasis from educators on how to select an appropriate insertion site for intravenous therapy.

The case for a 3rd generation supraglottic airway device facilitating direct vision placement.

Although 1st and 2nd generation supraglottic airway devices (SADs) have many desirable features, they are nevertheless inserted in a similar 'blind' way as their 1st generation predecessors. Clinicians mostly still rely entirely on subjective indirect assessments to estimate correct placement which supposedly ensures a tight seal. Malpositioning and potential airway compromise occurs in more than half of placements. Vision-guided insertion can improve placement. In this article we propose the development of a 3rd generation supraglottic airway device, equipped with cameras and fiberoptic illumination, to visualise insertion of the device, enable immediate manoeuvres to optimise SAD position, verify whether correct 1st and 2nd seals are achieved and check whether size selected is appropriate. We do not provide technical details of such a '3rd generation' device, but rather present a theoretical analysis of its desirable properties, which are essential to overcome the remaining limitations of current 1st and 2nd generation devices. We also recommend that this further milestone improvement, i.e. ability to place the SAD accurately under direct vision, be eligible for the moniker '3rd generation'. Blind insertion of SADs should become the exception and we anticipate, as in other domains such as central venous cannulation and nerve block insertions, vision-guided placement becoming the gold standard.

End-tidal to Arterial Gradients and Alveolar Deadspace for Anesthetic Agents.

BACKGROUND: According to the "three-compartment" model of ventilation-perfusion ((Equation is included in full-text article.)) inequality, increased (Equation is included in full-text article.)scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (VDA/VA) customarily measured using end-tidal to arterial (A-a) partial pressure gradients for carbon dioxide. A-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment VDA/VA calculated using partial pressures of four inhalational agents (VDA/VAG) is different from that calculated using carbon dioxide (VDA/VACO2) measurements, but similar to predictions from multicompartment models of physiologically realistic "log-normal" (Equation is included in full-text article.)distributions. METHODS: In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. VDA/VA was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (PAG) and end-capillary partial pressure (Pc'G) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. RESULTS: Calculated VDA/VAG was larger (mean ± SD) for halothane (0.47 ± 0.08), isoflurane (0.55 ± 0.09), sevoflurane (0.61 ± 0.10), and desflurane (0.65 ± 0.07) than VDA/VACO2 (0.23 ± 0.07 overall), increasing with lower blood solubility (slope [Cis], -0.096 [-0.133 to -0.059], P < 0.001). There was a significant difference between calculated ideal PAG and Pc'G median [interquartile range], PAG 5.1 [3.7, 8.9] versus Pc'G 4.0[2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated VDA/VAG. CONCLUSIONS: Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment (Equation is included in full-text article.)scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace.

Prophylactic Cefazolin Dosing in Women With Body Mass Index >35 kg·m-2 Undergoing Cesarean Delivery: A Pharmacokinetic Study of Plasma and Interstitial Fluid.

BACKGROUND: Obesity is a risk factor for surgical site infection after cesarean delivery. There is inadequate pharmacokinetic data available regarding prophylactic cefazolin dosing in obese pregnant women. We aimed to describe the plasma and interstitial fluid (ISF) pharmacokinetics of cefazolin in obese women undergoing elective cesarean delivery and use dosing simulations to predict optimal dosing regimens. METHODS: Eligible women were scheduled for elective cesarean delivery at term, with a body mass index (BMI) of >35 kg·m. Plasma and ISF samples were collected following 2 g of intravenous cefazolin. Concentrations were determined using liquid chromatography-mass spectrometry. Population pharmacokinetic modeling and Monte Carlo dosing simulations were performed using Pmetrics. Total and unbound cefazolin concentrations in plasma and ISF were compared with the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) of cefazolin for Staphylococcus aureus, 2 mg·L. The fractional target attainment (FTA) of dosing regimens to achieve a pre-established target of 95% unbound ISF concentrations >2 mg·L throughout a 3-hour duration of the surgery was calculated. RESULTS: The 12 women recruited had a median (interquartile range [IQR]) BMI of 41.5 (39.7-46.6) kg·m and a median (IQR) gestation of 38.7 weeks (37.9-39.0). For each timepoint up to 180 minutes, the median across subjects of total and unbound plasma concentration of cefazolin remained above 2 mg·L. The minimum observed total plasma concentration was 31.7 mg·L and plasma unbound concentration was 7.7 mg·L (observed in the same participant). For each timepoint up to 150 minutes, the median across subjects of unbound ISF concentrations remained above 2 mg·L. The minimum observed unbound ISF concentration was 0.7 mg·L (observed in 1 participant). In 2 participants, the ISF concentration of cefazolin was not maintained above 2 mg·L. The mean (± standard error [SE]) penetration of cefazolin (calculated as area under the concentration-time curve for the unbound fraction of drug [fAUC]tissue/fAUCplasma) into the ISF was 0.884 ± 1.11. Simulations demonstrated that FTA >95% was achieved in patients weighing 90-150 kg by an initial 2 g dose with redosing of 2 g at 2 hours. FTA was improved to >99% when an initial 3 g dose was repeated at 2 hours. CONCLUSIONS: To maintain adequate ISF antibiotic concentrations in obese pregnant women, our results suggest that redosing of cefazolin may be required. When wound closure has not occurred within 2 hours, redosing is suggested, following either a 2 or 3 g initial bolus. These preliminary results require validation in a larger population.

The influence of obesity on coagulation in healthy term pregnancy as assessed by rotational thromboelastometry.

BACKGROUND: Rotational thromboelastometry (ROTEM® ) is a point-of-care coagulation test which has been used to demonstrate hypercoagulability in pregnant populations and obese populations. AIM: The aim of this study was to assess the combined effect of pregnancy and obesity on coagulation using ROTEM® in healthy pregnant women of varying body mass indices (BMIs) presenting for elective caesarean delivery. MATERIALS AND METHODS: Ethics approval was granted for recruitment of women presenting for elective caesarean delivery. Women with any condition affecting coagulation were excluded. The ROTEM® parameters of extrinsically activated thromboelastometric test / fibrin polymerisation test (EXTEM/FIBTEM) amplitude at five minutes (A5), coagulation time (CT), maximum clot firmness (MCF) and clot formation time (CFT) were compared between three different groups: normal weight, overweight and obese women. RESULTS: One hundred and eighty-five women presenting for elective caesarean delivery met inclusion criteria and were divided into three groups; normal weight (BMI < 25 kg/m2 , n = 86), overweight (BMI 25-29.9 kg/m2 , n = 54) and obese (BMI ≥ 30 kg/m2 , n = 45). They had a mean (SD) age of 32.7 ± 5.0 years and the median (interquartile range) BMI of 21.9 kg/m2 (20.5-23.0), 27.0 kg/m2 (26.0-28.5), 36.0 kg/m2 (32.2-41.8) for the normal weight, overweight and obese groups respectively. Forty-one (22.2%) women were nulliparous. Across the three groups for FIBTEM A5 (P = 0.018), FIBTEM MCF (P = 0.032), FIBTEM CFT (P = 0.047) and EXTEM MCF (P = 0.015) there was evidence of increasing coagulability with increasing BMI. However, following Bonferroni correction, this was no longer significant. CONCLUSIONS: There is no association between BMI and ROTEM® parameters in pregnant women presenting for elective caesarean delivery at term.

A prospective randomized comparison of airway seal using the novel vision-guided insertion of LMA-Supreme® and LMA-Protector®.

The laryngeal mask airways supreme (LMA-Supreme™) and protector (LMA-Protector™) are generally placed blindly, often resulting in a less than optimal position and vision-guided placement has been recommended. This prospective, randomized controlled study compared the efficacy of airway seal by measuring the oropharyngeal leak pressure in 100 surgical patients who underwent a variety of non-thoracic surgery under general anaesthesia, suitable with a supraglottic airway device. Patients were allocated to either the LMA-Supreme (n = 50) or LMA-Protector (n = 50) group. All insertions were performed under vision of a videolaryngoscope using an 'insert-detect-correct-as-you-go' technique with standardized corrective measures. Our primary endpoint, mean oropharyngeal leak pressure, was significantly higher in the LMA-Protector (31.7 ± 2.9 cm H2O) compared to the LMA-Supreme (27.7 ± 3.5 cm H2O) group (mean difference 4.0 cm H2O, 95% confidence interval (CI) 2.7-5.3 cm H2O, p < 0.001) after achieving a near-optimal fibreoptic position in the LMA-Protector (94%) and LMA-Supreme (96%) groups. No statistically significant differences were shown for secondary outcomes of alignment, number of insertion attempts and malpositions, and final anatomical position as scored by fibreoptic evaluation. Corrective manoeuvres were required in virtually all patients to obtain a correct anatomically positioned LMA. Position outcomes of the two devices were similar except for the proportion of procedures with folds in the proximal cuff (90% LMA-Supreme vs. 2% LMA-Protector, p < 0.001), the need for intracuff pressure adjustments (80% LMA-Supreme vs. 48% LMA-Protector, p = 0.001) and size correction (18% LMA-Supreme vs. 4% LMA-Protector, p = 0.025). In conclusion, a higher oropharyngeal leak pressure can be achieved with LMA-Protector compared to LMA-Supreme with optimal anatomical position when insertion is vision-guided.