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Pulse pressure variation (PPV) is a dynamic cardiac preload variable used to predict fluid responsiveness. PPV can be measured non-invasively using innovative finger-cuff systems allowing for continuous arterial pressure waveform recording, e.g., the Nexfin system [BMEYE B.V., Amsterdam, The Netherlands; now Clearsight (Edwards Lifesciences, Irvine, CA, USA)] (PPVFinger). However, the agreement between PPVFinger and PPV derived from an arterial catheter (PPVART) in obese patients having laparoscopic bariatric surgery is unknown. We compared PPVFinger and PPVART at 6 time points in 60 obese patients having laparoscopic bariatric surgery in a secondary analysis of a prospective method comparison study. We used Bland–Altman analysis to assess absolute agreement between PPVFinger and PPVART. The predictive agreement for fluid responsiveness between PPVFinger and PPVART was evaluated across three PPV categories (PPV 13%) as concordance rate of paired measurements and Cohen’s kappa. The overall mean of the differences between PPVFinger and PPVART was 0.5 ± 4.6% (95%-LoA − 8.6 to 9.6%) and the overall predictive agreement was 72.4% with a Cohen’s kappa of 0.53. The mean of the differences was − 0.7 ± 3.8% (95%-LoA − 8.1 to 6.7%) without pneumoperitoneum in horizontal position and 1.1 ± 4.8% (95%-LoA − 8.4 to 10.5%) during pneumoperitoneum in reverse-Trendelenburg position. The absolute agreement and predictive agreement between PPVFinger and PPVART are moderate in obese patients having laparoscopic bariatric surgery.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

Background The optimal method for blood pressure monitoring in obese surgical patients remains unknown. Arterial catheters can cause potential complications, and noninvasive oscillometry provides only intermittent values. Finger cuff methods allow continuous noninvasive monitoring. The authors tested the hypothesis that the agreement between finger cuff and intraarterial measurements is better than the agreement between oscillometric and intraarterial measurements. Methods This prospective study compared intraarterial (reference method), finger cuff, and oscillometric (upper arm, forearm, and lower leg) blood pressure measurements in 90 obese patients having bariatric surgery using Bland–Altman analysis, four-quadrant plot and concordance analysis (to assess the ability of monitoring methods to follow blood pressure changes), and error grid analysis (to describe the clinical relevance of measurement differences). Results The difference (mean ± SD) between finger cuff and intraarterial measurements was −1 mmHg (± 11 mmHg) for mean arterial pressure, −7 mmHg (± 14 mmHg) for systolic blood pressure, and 0 mmHg (± 11 mmHg) for diastolic blood pressure. Concordance between changes in finger cuff and intraarterial measurements was 88% (mean arterial pressure), 85% (systolic blood pressure), and 81% (diastolic blood pressure). In error grid analysis comparing finger cuff and intraarterial measurements, the proportions of measurements in risk zones A to E were 77.1%, 21.6%, 0.9%, 0.4%, and 0.0% for mean arterial pressure, respectively, and 89.5%, 9.8%, 0.2%, 0.4%, and 0.2%, respectively, for systolic blood pressure. For mean arterial pressure and diastolic blood pressure, absolute agreement and trending agreement between finger cuff and intraarterial measurements were better than between oscillometric (at each of the three measurement sites) and intraarterial measurements. Forearm performed better than upper arm and lower leg monitoring with regard to absolute agreement and trending agreement with intraarterial monitoring. Conclusions The agreement between finger cuff and intraarterial measurements was better than the agreement between oscillometric and intraarterial measurements for mean arterial pressure and diastolic blood pressure in obese patients during surgery. Forearm oscillometry exhibits better measurement performance than upper arm or lower leg oscillometry. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Women laboring with epidural analgesia experience fever much more frequently than do women who chose other forms of analgesia, and maternal intrapartum fever is associated with numerous adverse consequences, including brain injury in the fetus. We developed a model of noninfectious inflammatory fever in the near-term pregnant rat to simulate the pathophysiology of epidural-associated fever and hypothesized that it would produce fetal brain inflammation.Twenty-four pregnant Sprague-Dawley rats were studied at 20 days gestation (term: 22 days). Dams were treated by injection of rat recombinant interleukin (IL)-6 or vehicle at 90-minute intervals, and temperature was monitored every 30 minutes. Eight hours after the first treatment, dams were delivered of fetuses and then killed. Maternal IL-6 was measured at delivery. Fetal brains (n = 24) were processed and stained for ED-1/CD68, a marker for activated microglia, and cell counts in the lateral septal and hippocampal brain regions were measured. Fetal brains were also stained for cyclooxygenase-2 (COX-2), a downstream marker of neuroinflammation. Eight fetal brains were further analyzed for quantitative forebrain COX-2 by Western blotting compared to a β-actin standard. Maternal temperature and IL-6 levels were compared between treatments, as were cell counts, COX-2 staining, and COX-2 levels by Mann-Whitney U test, repeated-measures analysis of variance, or Fisher exact test, as appropriate.Injection of rat IL-6 at 90-minute intervals produced an elevation of maternal temperature compared to vehicle (P.0001). IL-6 levels were elevated to clinically relevant levels at delivery in IL-6 compared to vehicle-treated animals (mean ± standard deviation: 923 ± 97 vs 143 ± 94 pg/mL, P = .0006). ED-1-stained cells were present in significantly higher numbers in fetal brains from IL-6 compared to saline-treated dams (median [interquartile range]: caudal hippocampus, 99 [94-104] and 64 [57-68], respectively, P = .002; lateral septum, 102 [96-111] and 68 [65-69], respectively, P = .002), as well as COX-2 immunostaining (lateral septum, 22 [20-26] and 17 [15-18], respectively, P = .005; dorsal hippocampus, 27 [22-32] and 16 [14-19], respectively, P = .013) and quantitative COX-2 Western blotting activity (mean ± standard error of the mean: vehicle, 0% of β-actin intensity versus IL-6, 41.5% ± 24%, P.001).Noninfectious inflammatory fever is inducible in the near-term pregnant rat by injection of IL-6 at levels comparable to those observed during human epidural labor analgesia. Maternal IL-6 injection causes neuroinflammation in the fetus.

BACKGROUND: Electromagnetic coil overheating, deformation, occlusion, and rupture during rapid infuser use have been previously reported. Although the etiology is unclear, prolonged machine use and reconstitution of citrated blood components with crystalloid solutions in the reservoir have been implicated. Lactated Ringer’s (LR) solution is of particular concern as a diluent because of its calcium content. We sought to reproduce this failure mode using different infusion rates and different combinations of fluids for blood product reconstitution in the reservoir. We also introduced calcium chloride (CaCl2) to the mix to determine its role in macroscopic clot formation. METHODS: In this in vitro study, we conducted 2 series of experiments using the Belmont FMS 2000 rapid infuser and a reservoir. In series I, we submitted a mix of 1 U fresh thawed plasma (FTP) and 1 U red blood cells (RBC) with 500 mL of LR solution, normal saline, Plasma-Lyte A, or albumin 5% to a specific pump flow sequence. If neither a pump failure mode or self-shutoff (primary outcome) nor macroscopic clot (secondary outcome) was observed during a pump flow sequence, the sequences were repeated after first adding an additional 500 mL of the initially used crystalloid or albumin and then CaCl2 beginning with 200 mg and up to 1 g to the reservoir. In series II, 7 different crystalloid-blood product combinations were tested by using a variety of pump flow sequences with the same end points. Descriptive statistics and analysis of variance were used, and data were reported as means ± SD. RESULTS: We did not observe a Belmont pump failure mode (coil deformation, occlusion, or rupture) as previously described. In series I, the addition of CaCl2 200 mg resulted in macroscopic clots in 9 of 10 experiments (95% confidence interval, 0.55–0.99). The time to clot formation was 9.1 ± 2.3 minutes (99% confidence interval, 6.74–11.46) and did not differ between solutions used for component reconstitution. In series II, adding variable amounts of CaCl2 to 4 different combinations of FTP/RBC with Plasma-Lyte A or LR solution led to clot formation. The use of only FTP in 2 experiments with either LR solution or normal saline resulted in formation of a fibrin clot. In 1 experiment of LR solution mixed with RBCs alone, no clot was observed even after addition of 1 g CaCl2. After the observation of clot in the reservoir, the fluid empty alarm occurred once in series I, the overheating alarm occurred once in series II, and the high-pressure alarms occurred 3 times in each series, all accompanied by self-shutoff. CONCLUSIONS: In this in vitro study, we were unable to reproduce the failure mode characterized by coil overheating, deformation, and rupture previously reported with use of the FMS 2000. Addition of CaCl2 in the range of 200 mg caused macroscopic coagulation in the reservoir when added to crystalloids or albumin mixed with different combinations of blood products containing FTP.

Background. Effective 2007, the ACGME required scholarly activity during residency. Although many programs have ongoing research, residents' involvement may be limited. This US anesthesiology residency survey assesses the current scholarly environment, research activity and program support during training. Methods. Following IRB approval, 131 US anesthesiology program directors were invited to participate in a web-based survey. Questions to directors and residents included program structure, research activity, funding and productivity. We categorized residencies threefold based on their size. Results are summarized descriptively. Results. The response rate was 31.3% (n=41) for program directors and 15.3% (n=185) for residents. Residents' responses mirrored those of program directors' regarding the presence of didactic curricula (51% versus 51.9%), research rotations (57% versus 56.2%) and a project requirement (37% versus 40%). Demands of residency (27.0%) and early stage in training (22.2%) were the main obstacles to research cited by trainees. Residents' financial support was available in 94.3% of programs. Medium and large programs had multiple funding sources (NIH, industrial and private). Conclusion. Programs are dedicated to incorporate research into their curriculum. Residents' financial support and mentorship are available, while research time is limited. Systematic improvements are needed to increase trainee research in US anesthesiology residencies.

Background: Changes in donor plasma albumin (Alb) and bilirubin (Tbili) are common following right hepatectomy for liver transplantation. We conducted a retrospective study to determine whether the size of the liver resection and the estimated blood loss (EBL) impact these laboratory values in the first week (early) and third week (late) postoperatively. Methods: Demographics and peri-operative data of 34 donors undergoing right hepatectomy were analysed by Spearman's correlation (data in means±SD, P

To determine separately the effect of corticotropin-releasing hormone (CRH) on analgesia and on inflammation, rats were assigned to receive CRH 60 microg/kg, CRH 300 microg/kg, morphine 4 mg/kg, or normal saline intravenously 15 min before a burn injury. Two mesh chambers that allowed collection of fluid had been previously implanted subdermally in each rat. The skin overlying the right chamber was subject to thermal injury. The left chamber served as a control. We assessed systemic analgesia, and levels of beta-endorphin and corticosterone in plasma and in chamber fluid before, 1, 4 and 24 h after drug administration. The CRH groups exhibited longer tail flick latencies than the control group (P=0.0001) although the increase in latency was of smaller magnitude than in the morphine group. We did not observe a CRH dose response for analgesia. Plasma corticosterone levels were higher in the CRH 300 microg/kg group than in the normal saline group at 4 h (P=0.03). Levels of beta-endorphin in plasma as well as the levels of corticosterone and beta-endorphin in chambers were similar in the CRH 300 microg/kg group and in the normal saline group (all P values0.1). Thus, systemically administered CRH produces analgesia in thermal injury independent of its effect on these two markers of local or systemic inflammation.

The use of “multimodal” combination analgesic therapies or novel single molecules possessing multiple analgesic targets is becoming increasingly attractive. In previous experiments we showed that a substance P antagonist injected intrathecally potentiated the antinociceptive effects of potent opioid receptor agonist, biphalin. Based on examination of the biphalin structure–activity relationship, we designed and synthesized a novel chimeric peptide, termed AA501 (N′(Tyr-D-Ala-Gly-Phe), Nʺ(Z-Trp) hydrazide, Z=benzyloxycarbonyl). AA501 consists of an opioid receptor agonist pharmacophore related to biphalin and a substance P receptor antagonist pharmacophore, both linked by a hydrazide bridge. The present study evaluates the ability of a novel chimeric peptide, AA501, to bind to opioid and substance P receptors and to produce antinociception in tail-flick and formalin tests, and in a neuropathic pain model when administered intrathecally to rats.

Living liver donors for adult liver transplant recipients undergo extensive liver resection. Partial donor hepatectomies may alter postoperative drug metabolism and hemostasis; thus, the risks and the benefits of pain management for this unique patient population may need to be reassessed. The safety and efficacy of combined epidural analgesia and field infiltration in our initial living liver donor group are presented. A thoracic epidural catheter was placed before general anesthesia in 2 female and 6 male donors (44.2 +/- 11.3 years old, mean +/- standard deviation [SD], range 26-56). At the end of surgery, incisions were infiltrated (bupivacaine 0.25%), and an epidural infusion was used (bupivacaine 0.1% + hydromorphone hydrochloride 0.02%). Clinical outcomes were followed for 5 days. The time sequence of pain intensity on a 0-10 visual analog scale clustered into 3 phases, the intensity of which differed significantly from each other (2.2 +/- 0.6, 0.69 +/- 0.2, and 2.37 +/- 0.3 respectively, P = 0.028). Right shoulder pain was observed in 75% of the donors. Sedation, pruritus, and nausea were minimal. Consistently maximal international normalized ratio elevation occurred at 17.6 +/- 7 hours postoperatively, then slowly declined. Platelet counts were lowest on day 3. No neurologic injury or local anesthetic toxicity was observed. This 2-site approach provided effective, safe, postoperative analgesia for our donors. Universally, coagulopathy ensued, indicating a potentially increased risk for epidural hemorrhage at epidural catheter removal and mandating close postoperative neurologic and laboratory monitoring. Research is needed to advance the understanding of postoperative coagulopathy and hepatic dysfunction in these donors to further optimize their perioperative management, including that of analgesia.

BACKGROUND Reports of perioperative serum sodium increase in liver transplant (LT) recipients are mostly restricted to unintentional rapid serum sodium overcorrection with subsequent development of central pontine myelinolysis. We examined intraoperative serum sodium changes and their effect on short-term outcomes after LT. METHODS We retrospectively analyzed data of all LT recipients over a period of 3.5 years. Collected information included preoperative and postoperative serum sodium (Napre and Napost), delta sodium (ΔNa), intraoperative serum sodium peak and trough with corresponding maximum ΔNa, intraoperative peak blood glucose, history of hepatic encephalopathy, perioperative diuretics, intraoperative administration of vasopressin, dopaminergic agents, alkalizing drugs (sodium bicarbonate [NaHCO3], tromethamine), crystalloids, colloids, fresh frozen plasma (FFP), and packed red blood cells (PRBC). The delta of serum osmolality (ΔOsm) was calculated from Napre and Napost, blood urea nitrogen, and blood glucose values, and the correlation between ΔNa and ΔOsm was examined. Outcomes analyzed included intubation for ≥2 days, postanesthesia care unit/surgical intensive care unit (PACU/SICU) length of stay (LOS) for ≥2 days, need of SICU admission, hospital LOS, postoperative neurological complications, and mortality. Univariate and multivariate analyses were performed to test associations between ΔNa and outcomes. A P value

SummaryBackground A test dose is used to detect intravascular injection during neuraxial block in pediatrics. Accidental intravascular epidural local anesthetic injection might be unrecognized in anesthetized children leading to potential life-threatening complications. In children, sevoflurane anesthesia blunts the hemodynamic response when intravascular cathecolamines are administered. No studies have explored the hemodynamics and the criteria for a positive test dose result following phenylephrine in sevoflurane anesthetized children. Methods Healthy children undergoing minor procedures were randomly assigned to receive intravenous placebo, or 5 μg∙kg−1 phenylephrine (n = 11/group) during sevoflurane anesthesia. Hemodynamic response was assessed using electrocardiography, pulse oxymetry and non-invasive blood pressure monitoring for 5 min following drug administration in anesthetized patients. Results All patients receiving phenylephrine showed a decreased heart rate (HR) but not all of them met the positive criterion for test dose response. Overall, at 1 min, patients receiving phenylephrine showed a 25% decrease in HR from the baseline while an increase in blood pressure was noticed in 54% of patients receiving phenylephrine. Discussion Phenylephrine might be a future indicator of positive intravascular test dose. Further investigation is needed to find out the phenylephrine dose that elicits a reliable hemodynamic response and whether phenylephrine needs to be dose age-adjusted in order to appreciate relevant hemodynamic changes in children receiving neuraxial blocks undergoing general anesthesia.

According to the American Academy of Pain Medicine and the Institute of Medicine, pain affects more Americans than cancer, diabetes, and cardiac disease combined. Current analgesics only provide modest relief, frequently carry black box warnings, and are susceptible to abuse. The ability of current medical science to treat pain effectively is limited by an incomplete understanding of the mechanisms of pain signaling in diverse individuals across different circumstances and the high prevalence of side effects after systemic or regional administration of available analgesics. Despite increasing interest in developing new analgesic molecules by translating preclinical research on mechanisms of pain processing and harnessing innovative methods of drug delivery, the majority of new analgesic drug launches from 1990 to 2010 were reformulations of existing pharmaceuticals within well-established drug categories such as opioids and NSAIDs.

Background: Anesthetic and fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may influence 30-day postoperative outcomes. We investigated intraoperative management differences and their relation to outcomes in all consecutive patients undergoing HIPEC and CRS following the first 2 years after initiation of this surgical oncology program in a single center. Methods: Following IRB approval we retrospectively recorded demographics, intraoperative anesthetic and fluid management and 30-day postoperative cardiopulmonary, renal, infectious, neurologic, and surgical complications, mortality and length-of-stay in patients undergoing CRS and HIPEC. The Chi-square, Fisher’s exact and Wilcoxon two-sample tests were used for statistics. A p < 0.05 was significant. Results: We identified 34 patients with a mean age of 53.9 ± 11.5 years. Postoperative complications occurred in 14 patients (41%), twelve of whom (35%) had pulmonary adverse events. Patients with complications were significantly older (p=0.04) and were significantly longer hospitalized (p=0.00). Neither primary malignancy type nor intraoperative fluid replacement differed between groups. Patients with complications had mild preoperative anemia (p=0.052).

Titration of volatile anesthetics to anesthetic effect monitoring using the bispectral index (BIS) has been shown to decrease anesthetic requirements and facilitate recovery from anesthesia unrelated to liver transplantation (OLT). To determine whether availability of such monitoring influences its utilization pattern and affect anesthetic care and outcomes in OLT, we conducted a retrospective analysis in recipients with and without such monitoring. We evaluated annual BIS utilization over a period of 7 years, and compared 41 BIS-monitored patients to 42 controls. All received an isoflurane/air/oxygen and opioid-based anesthetic with planned postoperative ventilation. Data collection included age, body mass index (BMI), gender, Model for End-stage Liver Disease (MELD) score, and time to extubation (TtE). Mean preanhepatic, anhepatic, and postanhepatic end-tidal isoflurane concentrations were compared, as well as BIS values for each phase of OLT using the Kruskal-Wallis and Wilcoxon signed-rank tests, respectively. The use of anesthetic effect monitoring when available increased steadily from 15% of cases in the first year to almost 93% by year 7. There was no significant difference in age, gender, BMI, MELD, or TtE between groups. The BIS group received less inhalational anesthetic during each phase of OLT compared to the control group. However, this difference was statistically significant only during the anhepatic phase (P = .026), and was clinically not impressive. Within the BIS group, the mean BIS value was 38.74 ± 5.25 (mean ± standard deviation), and there was no difference for the BIS value between different transplant phases. Availability of anesthetic effect monitoring as an optional monitoring tool during OLT results in its increasing utilization by anesthesia care teams over time. However, unless integrated into an intraoperative algorithm and an early extubation protocol for fast tracking of OLT recipients, this utilization does not appear to provide a clinical benefit but instead drives cost.

Introduction: The purpose of this study was to determine the correlation between body mass index (BMI) and upper and lower arm as well as lower leg circumferences and the frequency of correct blood pressure (BP) cuff fit. We explored recommendations for the most likely BP cuff size and location for the three BMI categories. Materials and Methods: Following IRB approval we retrospectively analyzed a research database of bariatric surgical patients with a BMI of ≥40 kg/m 2 . Data included patients′ characteristics, upper and lower arm as well as lower leg circumferences. Patients were divided into three groups based on BMI (kg/m 2 , Group I: 55). Appropriate cuff fit using a standard or large adult BP cuff (CRITIKON ® , GE Healthcare, Waukesha, Wisconsin, USA) on the upper and lower arm, and lower leg was determined. We analyzed the percent proportion of proper cuff fit for cuff sizes and locations between groups using appropriate nonparametric testing. Results: Limb circumference correlated significantly with BMI (P = 0.01), and the upper arm correlated most closely (r = 0.76). A standard adult BP cuff on the lower arm fit properly in >90% and >80% and in Groups I and II, respectively. A large cuff on the lower arm was appropriate in 87% of Group III. In two participants, a large cuff fit properly on the lower leg. Discussion: Limb circumference significantly correlated with BMI. Recommendations for proper cuff fit in different BMI categories can be made.

Increasingly, pain is being recognized as a major medical problem. Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”1. Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life1. Pain is widely underestimated and undertreated. In Western countries, 10% of population have acute or chronic pain, and up to 30% of those with disabilities suffer from chronic pain2. The most common types of chronic noncancer pain are arthritis, low back pain, other musculoskeletal pain or stiffness, and fibromyalgia. Chronic pain, defined by the IASP as “pain that persists beyond the normal time of healing... ”3, is a significant problem associated with many long-term diseases, including musculoskeletal disorders, various neurological conditions such as diabetic, HIV-related, or postherpetic neuropathies, and cancer. Most patients find oral medications effective. However, some patients with chronic pain have inadequate pain relief, intolerable side effects, progressive lack of efficacy (tolerance) or allergy associated with oral medications4.

Corrigendum to ‘‘Corticotropin-releasing hormone (CRH) produces analgesia in a thermal injury model independent of its effect on systemic beta-endorphin and corticosterone’’ [Regul. Pept. 118 (2004) 39–43] M. Soledad Cepeda, Iwona Bonney*, Jocelyn M. Weiss, Jairo Moyano, Daniel B. Carr Department of Anesthesia, San Ignacio Hospital, Javeriana University School of Medicine, Bogota, Colombia Departments of Anesthesia and Medicine, Tufts-New England Medical Center, Box #298, 750 Washington Street, Boston, MA 02111, USA