JournalTOCs

Anesthesiology
Journal Prestige (SJR): 2.123

Citation Impact (citeScore): 3
Number of Followers: 237

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0003-3022 - ISSN (Online) 1528-1175
Published by LWW Wolters Kluwer

[301 journals]

Instructions for Obtaining A nesthesiology Continuing Medical Education
(CME) Credit
- PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003675
  Issue No: Vol. 134, No. 2 (2021)
Bursting the Liposomal Bubble: Sustained-release vs. Plain Bupivacaine
- Authors: Wanderer JP; Rathmell JP.
  Abstract: Complex Information for Anesthesiologists Presented Quickly and Clearly
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003677
  Issue No: Vol. 134, No. 2 (2021)
Science, Medicine, and the Anesthesiologist
- Abstract: Key Papers from the Most Recent Literature Relevant to Anesthesiologists
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003676
  Issue No: Vol. 134, No. 2 (2021)
This Month in Anesthesiology
- PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003672
  Issue No: Vol. 134, No. 2 (2021)
Anesthesiology
- PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003674
  Issue No: Vol. 134, No. 2 (2021)
Anesthesiology
- PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003690
  Issue No: Vol. 134, No. 2 (2021)
Liposomal Bupivacaine Effective, Cost-effective, or (Just) Costly'
- Authors: McCann M.
  Pages: 139 - 142
  Abstract: “…liposomal bupivacaine was found to be superior to comparators in 46% of…conflicted [pharma-sponsored] trials but was found to be superior in only 11% of the nonconflicted trials.”
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003658
  Issue No: Vol. 134, No. 2 (2021)
Optimal Tranexamic Acid Dosing Regimen in Cardiac Surgery: What Are the
Missing Pieces'
- Authors: Faraoni D; Levy JH.
  Pages: 143 - 146
  Abstract: “…low-dose tranexamic acid (total dose of 20 mg/kg of actual body weight) provides the best balance between reduction in postoperative blood loss and red blood cell transfusion and the risk of clinical seizure.”
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003637
  Issue No: Vol. 134, No. 2 (2021)
Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal
Bupivacaine for Peripheral Nerve Block Analgesia A Systematic Review and
Meta-analysis
- Authors: Hussain N; Brull R, Sheehy B, et al.
  Pages: 147 - 164
  Abstract: BackgroundLiposomal bupivacaine is purported to extend analgesia of peripheral nerve blocks when administered perineurally. However, evidence of the clinical effectiveness of perineural liposomal bupivacaine is mixed. This meta-analysis seeks to evaluate the effectiveness of perineural liposomal bupivacaine in improving peripheral nerve block analgesia as compared with nonliposomal local anesthetics.MethodsThe authors identified randomized trials evaluating the effectiveness of peripheral nerve block analgesic that compared liposomal bupivacaine with nonliposomal local anesthetics. The primary outcome was the difference in area under the receiver operating characteristics curve (AUC) of the pooled 24- to 72-h rest pain severity scores. Secondary outcomes included postoperative analgesic consumption, time to first analgesic request, incidence of opioid-related side effects, patient satisfaction, length of hospital stay, liposomal bupivacaine side effects, and functional recovery. AUC pain scores were interpreted in light of a minimal clinically important difference of 2.0 cm · h.ResultsNine trials (619 patients) were analyzed. When all trials were pooled, AUC pain scores ± SD at 24 to 72 h were 7.6 ± 4.9 cm · h and 6.6 ± 4.6 cm · h for nonliposomal and liposomal bupivacaine, respectively. As such, perineural liposomal bupivacaine provided a clinically unimportant benefit by improving the AUC (95% CI) of 24- to 72-h pain scores by 1.0 cm · h (0.5 to 1.6; P = 0.003) compared with nonliposomal bupivacaine. Excluding an industry-sponsored trial rendered the difference between the groups nonsignificant (0.7 cm · h [−0.1 to 1.5]; P = 0.100). Secondary outcome analysis did not uncover any additional benefits to liposomal bupivacaine in pain severity at individual timepoints up to 72 h, analgesic consumption, time to first analgesic request, opioid-related side effects, patient satisfaction, length of hospital stay, and functional recovery. No liposomal bupivacaine side effects were reported.ConclusionsPerineural liposomal bupivacaine provided a statistically significant but clinically unimportant improvement in the AUC of postoperative pain scores compared with plain local anesthetic. Furthermore, this benefit was rendered nonsignificant after excluding an industry-sponsored trial, and liposomal bupivacaine was found to be not different from plain local anesthetics for postoperative pain and all other analgesic and functional outcomes. High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks.Editor’s PerspectiveWhat We Already Know about This TopicLiposomal bupivacaine was developed in an effort to extend the duration of local analgesiaDespite the availability of many studies, it remains unclear whether and when liposomal bupivacaine offers significant advantages over the standard formulationWhat This Article Tells Us That Is NewNine trials were included in a meta-analysis examining the difference in 24- to 72-h rest pain severity scores for liposomal and nonliposomal bupivacaineThe area under the curve pain scores for the 24- to 72-h period were statistically but probably not clinically significantSecondary outcome analysis likewise failed to uncover benefits for liposomal bupivacaine regarding analgesic consumption, length of stay, and functional recovery
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003651
  Issue No: Vol. 134, No. 2 (2021)
Exposure–Response Relationship of Tranexamic Acid in Cardiac Surgery A
Model-based Meta-analysis
- Authors: Zufferey P; Lanoiselée J, Graouch B, et al.
  Pages: 165 - 178
  Abstract: BackgroundIt is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid–associated seizure may be dose-related. The authors’ aim was to characterize the exposure–response relationship of this drug.MethodsDatabases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery. Observational studies were added for seizure assessment. Tranexamic acid concentrations were predicted in each arm of each study using a population pharmacokinetic model. The exposure–response relationship was evaluated by performing a model-based meta-analysis using nonlinear mixed-effect models.ResultsSixty-four randomized controlled trials and 18 observational studies (49,817 patients) were included. Seventy-three different regimens of tranexamic acid were identified, with the total dose administered ranging from 5.5 mg/kg to 20 g. The maximum effect of tranexamic acid for postoperative blood loss reduction was 40% (95% credible interval, 34 to 47%), and the EC50 was 5.6 mg/l (95% credible interval, 0.7 to 11 mg/l). Exposure values with low-dose regimens approached the 80% effective concentration, whereas with high-dose regimens, they exceeded the 90% effective concentration. The predicted cumulative blood loss up to 48 h postsurgery differed by 58 ml between the two regimens, and the absolute difference in erythrocyte transfusion rate was 2%. Compared to no tranexamic acid, low-dose and high-dose regimens increased the risk of seizure by 1.2-fold and 2-fold, respectively. However, the absolute risk increase was only clinically meaningful in the context of prolonged open-chamber surgery.ConclusionsIn cardiopulmonary bypass surgery, low-dose tranexamic acid seems to be an appropriate regimen for reducing bleeding outcomes. This meta-analysis has to be interpreted with caution because the results are observational and dependent on the lack of bias of the predicted tranexamic acid exposures and the quality of the included studies.Editor’s PerspectiveWhat We Already Know about This TopicTranexamic acid is an antifibrinolytic agent that reduces postoperative blood loss and rates of erythrocyte transfusion and rethoracotomy in cardiopulmonary bypass surgeryThere appears to be a dose–response relationship between tranexamic acid and the risk of postoperative seizureModel-based meta-analysis is an extension of traditional meta-analysis that includes parametric models to describe the effect of doseWhat This Article Tells Us That Is NewThis model-based meta-analysis found that low-dose tranexamic acid (total dose, approximately 20 mg/kg) was sufficient to reduce postoperative blood loss and erythrocyte transfusion in cardiopulmonary bypass surgeryAlthough higher tranexamic acid doses were found to achieve a marginal gain in effectiveness, they increased the risk of postoperative seizure, particularly in procedures involving a high risk of bleeding
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003633
  Issue No: Vol. 134, No. 2 (2021)
Intraoperative Blood Pressure Monitoring in Obese Patients Arterial
Catheter, Finger Cuff, and Oscillometry
- Authors: Schumann R; Meidert AS, Bonney I, et al.
  Pages: 179 - 188
  Abstract: BackgroundThe 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.MethodsThis 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).ResultsThe 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.ConclusionsThe 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 PerspectiveWhat We Already Know about This TopicOptimal blood pressure monitoring in obese surgical patients remains unknown because multiple invasive and noninvasive monitoring methods are available with little understanding of agreement between different methods.What This Article Tells Us That Is NewIn a study of 90 obese patients having bariatric surgery, the agreement between finger cuff and intraarterial measurements was better than the agreement between oscillometric and intraarterial measurements for mean arterial and diastolic blood pressure, but not systolic blood pressure. Forearm oscillometry demonstrated better measurement performance than upper arm or lower leg oscillometry.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003636
  Issue No: Vol. 134, No. 2 (2021)
Intraoperative Oxygen Concentration and Neurocognition after Cardiac
Surgery A Randomized Clinical Trial
- Authors: Shaefi S; Shankar P, Mueller AL, et al.
  Pages: 189 - 201
  Abstract: BackgroundDespite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery.MethodsA randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay.ResultsThe median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups.ConclusionsIn this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery.Editor’s PerspectiveWhat We Already Know about This TopicHigh intraoperative inspired oxygen concentration may promote inflammation and consequent neurocognitive injury.What This Article Tells Us That Is NewA total of 100 cardiac surgical patients were randomly assigned to 35 or 100% inspired oxygen before and after cardiopulmonary bypass.Neurocognitive function 2 days, 1 month, 3 months, and 6 months after surgery was similar in each group.Supplemental intraoperative oxygen does not worsen postoperative neurocognitive function. Inspired oxygen fraction should be chosen on the basis of other considerations.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003650
  Issue No: Vol. 134, No. 2 (2021)
An Electroencephalogram Metric of Temporal Complexity Tracks Psychometric
Impairment Caused by Low-dose Nitrous Oxide
- Authors: Vrijdag XE; van Waart H, Mitchell SJ, et al.
  Pages: 202 - 218
  Abstract: BackgroundNitrous oxide produces non–γ-aminobutyric acid sedation and psychometric impairment and can be used as scientific model for understanding mechanisms of progressive cognitive disturbances. Temporal complexity of the electroencephalogram may be a sensitive indicator of these effects. This study measured psychometric performance and the temporal complexity of the electroencephalogram in participants breathing low-dose nitrous oxide.MethodsIn random order, 20, 30, and 40% end-tidal nitrous oxide was administered to 12 participants while recording 32-channel electroencephalogram and psychometric function. A novel metric quantifying the spatial distribution of temporal electroencephalogram complexity, comprised of (1) absolute cross-correlation calculated between consecutive 0.25-s time samples; 2) binarizing these cross-correlation matrices using the median of all channels as threshold; (3) using quantitative recurrence analysis, the complexity in temporal changes calculated by the Shannon entropy of the probability distribution of the diagonal line lengths; and (4) overall spatial extent and intensity of brain complexity, was quantified by calculating median temporal complexity of channels whose complexities were above 1 at baseline. This region approximately overlay the brain’s default mode network, so this summary statistic was termed “default-mode-network complexity.”ResultsNitrous oxide concentration correlated with psychometric impairment (r = 0.50, P < 0.001). Baseline regional electroencephalogram complexity at midline was greater than in lateral temporal channels (1.33 ± 0.14 bits vs. 0.81 ± 0.12 bits, P < 0.001). A dose of 40% N2O decreased midline (mean difference [95% CI], 0.20 bits [0.09 to 0.31], P = 0.002) and prefrontal electroencephalogram complexity (mean difference [95% CI], 0.17 bits [0.08 to 0.27], P = 0.002). The lateral temporal region did not change significantly (mean difference [95% CI], 0.14 bits [−0.03 to 0.30], P = 0.100). Default-mode-network complexity correlated with N2O concentration (r = −0.55, P < 0.001). A default-mode-network complexity mixed-effects model correlated with psychometric impairment (r2 = 0.67; receiver operating characteristic area [95% CI], 0.72 [0.59 to 0.85], P < 0.001).ConclusionsTemporal complexity decreased most markedly in medial cortical regions during low-dose nitrous oxide exposures, and this change tracked psychometric impairment.Editor’s PerspectiveWhat We Already Know about This TopicLow-dose nitrous oxide is known to increase reaction time and error rate in psychometric tests, but no electrophysiologic measurement has been capable of measuring this effectWhat This Article Tells Us That Is NewA quantitative electroencephalogram analysis can identify associations between treatment with low-dose nitrous oxide and performance on psychometric testsTemporal complexity decreases in the medial cortical regions during nitrous oxide administration and is correlated with psychometric performance
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003628
  Issue No: Vol. 134, No. 2 (2021)
Life from Death: The Tragedy and Heroism of Dr. Paluel J. Flagg
- Pages: 218 - 218
  Abstract: As a young physician in New York City, Paluel J. Flagg, M.D. (1886 to 1970, right), lost his daughter to neonatal asphyxia in 1912. His wife also died that year. Grief-stricken, Dr. Flagg found solace in easing human suffering, and began treating leprosy patients in Haiti. In 1912, he also committed his life to the prevention and treatment of asphyxia. What better profession to accomplish this than anesthesiology' In his landmark textbook The Art of Anesthesia (1916), Flagg presaged the modern intensive care unit by calling anesthesiologists pneumatologists—respiratory experts who should extend their practice beyond the operating room. Naturally, Flagg took to refining devices for airway management. He introduced his two-piece metal endotracheal tube (left) in 1928. Spiral wires made the outer catheter flexible, and a rigid inner stylet prevented kinking during insertion. Later, Flagg would develop the first laryngoscope with batteries in the handle. As founder of the National Resuscitation Society and the Society for the Prevention of Asphyxial Death, the heroic physician taught resuscitation maneuvers to countless doctors and paramedics. A good friend of aviator Charles Lindbergh, Flagg, when his soul flew to the heavens, left behind a legacy of patient safety and abundant living progeny—8 sons, 4 daughters, 56 grandchildren, and 3 great-grandchildren. (Copyright © the American Society of Anesthesiologists’ Wood Library-Museum of Anesthesiology, Schaumburg, Illinois.)
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003678
  Issue No: Vol. 134, No. 2 (2021)
Fast-spiking Interneurons Contribute to Propofol-induced Facilitation of
Firing Synchrony in Pyramidal Neurons of the Rat Insular Cortex
- Authors: Koyanagi Y; Oi Y, Kobayashi M.
  Pages: 219 - 233
  Abstract: BackgroundThe general anesthetic propofol induces frontal alpha rhythm in the cerebral cortex at a dose sufficient to induce loss of consciousness. The authors hypothesized that propofol-induced facilitation of unitary inhibitory postsynaptic currents would result in firing synchrony among postsynaptic pyramidal neurons that receive inhibition from the same presynaptic inhibitory fast-spiking neurons.MethodsMultiple whole cell patch clamp recordings were performed from one fast-spiking neuron and two or three pyramidal neurons with at least two inhibitory connections in rat insular cortical slices. The authors examined how inhibitory inputs from a presynaptic fast-spiking neuron modulate the timing of spontaneous repetitive spike firing among pyramidal neurons before and during 10 μM propofol application.ResultsResponding to activation of a fast-spiking neuron with 150-ms intervals, pyramidal cell pairs that received common inhibitory inputs from the presynaptic fast-spiking neuron showed propofol-dependent decreases in average distance from the line of identity, which evaluates the coefficient of variation in spike timing among pyramidal neurons: average distance from the line of identity just after the first activation of fast-spiking neuron was 29.2 ± 24.1 (mean ± SD, absolute value) in control and 19.7 ± 19.2 during propofol application (P < 0.001). Propofol did not change average distance from the line of identity without activating fast-spiking neurons and in pyramidal neuron pairs without common inhibitory inputs from presynaptic fast-spiking neurons. The synchronization index, which reflects the degree of spike synchronization among pyramidal neurons, was increased by propofol from 1.4 ± 0.5 to 2.3 ± 1.5 (absolute value, P = 0.004) and from 1.5 ± 0.5 to 2.2 ± 1.0 (P = 0.030) when a presynaptic fast-spiking neuron was activated at 6.7 and 10 Hz, respectively, but not at 1, 4, and 13.3 Hz.ConclusionsThese results suggest that propofol facilitates pyramidal neuron firing synchrony by enhancing inhibitory inputs from fast-spiking neurons. This synchrony of pyramidal neurons may contribute to the alpha rhythm associated with propofol-induced loss of consciousness.Editor’s PerspectiveWhat We Already Know about This TopicPropofol-induced loss of consciousness correlates with the appearance of a synchronized alpha rhythm on the frontal cortical electroencephalogramWell-coordinated thalamocortical alpha oscillation induced by propofol exposure is the prevailing mechanistic view to explain this phenomenonThe role of local cortical circuits in propofol-induced synchronized neuronal activity is incompletely understoodWhat This Article Tells Us That Is NewMultiple whole cell patch clamp recordings in rat cortical slices reveal that propofol facilitates firing synchrony among pyramidal neuronsPropofol-induced activation of presynaptic fast-spiking interneurons was necessary to achieve firing synchrony of postsynaptic pyramidal neuronsThese observations suggest that propofol facilitates pyramidal neuron firing synchrony in the cerebral cortex by enhancing inhibitory inputs from fast-spiking interneurons
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003653
  Issue No: Vol. 134, No. 2 (2021)
Molecular Modification of Transient Receptor Potential Canonical 6
Channels Modulates Calcium Dyshomeostasis in a Mouse Model Relevant to
Malignant Hyperthermia
- Authors: Lopez J; Uryash A, Adams J, et al.
  Pages: 234 - 247
  Abstract: BackgroundPharmacologic modulation has previously shown that transient receptor potential canonical (TRPC) channels play an important role in the pathogenesis of malignant hyperthermia. This study tested the hypothesis that genetically suppressing the function of TRPC6 can partially ameliorate muscle cation dyshomeostasis and the response to halothane in a mouse model relevant to malignant hyperthermia.MethodsThis study examined the effect of overexpressing a muscle-specific nonconducting dominant-negative TRPC6 channel in 20 RYR1-p.R163C and 20 wild-type mice and an equal number of nonexpressing controls, using calcium- and sodium-selective microelectrodes and Western blots.ResultsRYR1-p.R163C mouse muscles have chronically elevated intracellular calcium and sodium levels compared to wild-type muscles. Transgenic expression of the nonconducting TRPC6 channel reduced intracellular calcium from 331 ± 34 nM (mean ± SD) to 190 ± 27 nM (P < 0.0001) and sodium from 15 ± 1 mM to 11 ± 1 mM (P < 0.0001). Its expression lowered the increase in intracellular Ca2+ of the TRPC6-specific activator hyperforin in RYR1-p.R163C muscle fibers from 52% (348 ± 37 nM to 537 ± 70 nM) to 14% (185 ± 11 nM to 210 ± 44 nM). Western blot analysis of TRPC3 and TRPC6 expression showed the expected increase in TRPC6 caused by overexpression of its dominant-negative transgene and a compensatory increase in expression of TRPC3. Although expression of the muscle-specific dominant-negative TRPC6 was able to modulate the increase in intracellular calcium during halothane exposure and prolonged life (35 ± 5 min vs. 15 ± 3 min; P < 0.0001), a slow, steady increase in calcium began after 20 min of halothane exposure, which eventually led to death.ConclusionsThese data support previous findings that TRPC channels play an important role in causing the intracellular calcium and sodium dyshomeostasis associated with RYR1 variants that are pathogenic for malignant hyperthermia. However, they also show that modulating TRPC channels alone is not sufficient to prevent the lethal effect of exposure to volatile anesthetic malignant hyperthermia–triggering agents.Editor’s PerspectiveWhat We Already Know about This TopicThe type 1 ryanodine receptor (RYR1) gene encoding the skeletal muscle sarcoplasmic reticulum Ca2+ release channel is the primary locus for malignant hyperthermia susceptibilitySecondary loci have been identified in other proteins involved with RyR1 in excitation–contraction coupling that are thought to sensitize the RyR1 channelTransient receptor potential canonical channels constitute a large and functionally versatile superfamily of cation channel proteins expressed in many cell types that control influxes of Ca2+ and other cations to regulate diverse cellular processesWhat This Article Tells Us That Is NewMuscle-specific overexpression of the nonconducting transient receptor potential canonical 6 channel both reduced intracellular Ca2+ concentration in RYR1-p.R163C mice at rest and reduced the absolute maximum levels of intracellular Ca2+ concentration reached during exposure to halothaneDespite this, its overexpression did not restore intracellular Ca2+ concentration to wild-type levels, and although its overexpression increased the length of survival after halothane exposure, it was unable to rescue the lethal phenotype
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003635
  Issue No: Vol. 134, No. 2 (2021)
Using Left Ventricular Assist Device Doppler Assessment to Understand
Pump–Patient Interactions during a Venous Arterial–Extracorporeal
Membrane Oxygenation Weaning Trial
- Authors: De Ridder SP; Jacobs S, Dauwe DF.
  Pages: 248 - 249
  Abstract: Supplemental Digital Content is available in the text.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003615
  Issue No: Vol. 134, No. 2 (2021)
Perioperative Blood Pressure Management
- Authors: Saugel B; Sessler DI.
  Pages: 250 - 261
  Abstract: Intraoperative hypotension is common during noncardiac surgery and associated with myocardial injury, acute kidney injury, and death. Postoperative hypotension is also common and associated with myocardial injury and death, and largely missed by conventional monitoring.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003610
  Issue No: Vol. 134, No. 2 (2021)
A “Soothing” Syrup' How “Father” Wiley Saved Infants from
“Mother” Winslow’s Morphine Elixir
- Pages: 261 - 261
  Abstract: From the early nineteenth to the early twentieth century, Mrs. Winslow’s Soothing Syrup (top) was marketed in the United States as a panacea for ailments that plagued infants: teething, diarrhea, colic, etc. To ensure happy or sleeping children like those depicted above (lower left), Charlotte “Mother” Winslow and her legacy firms spiked her Soothing Syrup with morphine and alcohol. Over the course of a century, sales of millions of bottles worldwide caused thousands of infant deaths. Fortunately, Dr. Harvey Washington Wiley (lower right), Chief Chemist at the U.S. Department of Agriculture and future “Father of the Food and Drug Administration,” intervened by facilitating passage of the Pure Food and Drug Act (1906). Several amendments further limited the sale of opioids, leading to the removal of morphine from a syrup that was more sinister than soothing. (Copyright © the American Society of Anesthesiologists’ Wood Library-Museum of Anesthesiology, Schaumburg, Illinois.)
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003679
  Issue No: Vol. 134, No. 2 (2021)
“Silent” Presentation of Hypoxemia and Cardiorespiratory
Compensation in COVID-19
- Authors: Bickler PE; Feiner JR, Lipnick MS, et al.
  Pages: 262 - 269
  Abstract: Severe hypoxemia presents variably, and sometimes silently, without subjective complaints of dyspnea. The adequacy of cardiovascular compensation for oxygen delivery to tissues should be a focus in all hypoxemic patients.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003578
  Issue No: Vol. 134, No. 2 (2021)
Acute Respiratory Distress Syndrome Contemporary Management and Novel
Approaches during COVID-19
- Authors: Williams GW; Berg NK, Reskallah A, et al.
  Pages: 270 - 282
  Abstract: Acute respiratory distress syndrome remains a condition that carries a high mortality. Evidence-based clinical management and emerging concepts for new therapies for COVID-19 are reviewed.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003571
  Issue No: Vol. 134, No. 2 (2021)
Clinical Effectiveness of Liposomal Bupivacaine Administered by
Infiltration or Peripheral Nerve Block to Treat Postoperative Pain A
Narrative Review
- Authors: Ilfeld BM; Eisenach JC, Gabriel RA.
  Pages: 283 - 344
  Abstract: The authors provide a comprehensive summary of all randomized, controlled trials (n = 76) involving the clinical administration of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, USA) to control postoperative pain that are currently published. When infiltrated surgically and compared with unencapsulated bupivacaine or ropivacaine, only 11% of trials (4 of 36) reported a clinically relevant and statistically significant improvement in the primary outcome favoring liposomal bupivacaine. Ninety-two percent of trials (11 of 12) suggested a peripheral nerve block with unencapsulated bupivacaine provides superior analgesia to infiltrated liposomal bupivacaine. Results were mixed for the 16 trials comparing liposomal and unencapsulated bupivacaine, both within peripheral nerve blocks. Overall, of the trials deemed at high risk for bias, 84% (16 of 19) reported statistically significant differences for their primary outcome measure(s) compared with only 14% (4 of 28) of those with a low risk of bias. The preponderance of evidence fails to support the routine use of liposomal bupivacaine over standard local anesthetics.
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003630
  Issue No: Vol. 134, No. 2 (2021)
Dying Alone
- Authors: Goff KL.
  Pages: 345 - 345
  Abstract: I sit next to your bed in the filtered light of this hospital room—
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003490
  Issue No: Vol. 134, No. 2 (2021)
Behind the Mask
- Authors: Holman AE; Gauger VT.
  Pages: 346 - 348
  Abstract: N95 masks. Surgical masks. Homemade masks. Two months ago, if someone was wearing a mask, we would wonder “why”; these days, we wonder “why” if someone is not wearing one. In response to the coronavirus disease 2019 (COVID-19) pandemic, the wearing of masks has become globally commonplace, from airports and grocery stores to homes and neighborhoods. Many hospital systems have instituted mandatory 24/7 mask-wearing policies for all employees, visitors, and patients who walk through their doors, with the goal of protecting patients and healthcare workers alike and with the hope of decreasing the spread of a disease actively wreaking medical, financial, and emotional havoc across the globe.1
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003623
  Issue No: Vol. 134, No. 2 (2021)
Perioperative Management of Glucose-lowering Drugs: Comment
- Authors: Gregory S.
  Pages: 349 - 349
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003625
  Issue No: Vol. 134, No. 2 (2021)
Perioperative Management of Glucose-lowering Drugs: Comment
- Authors: Thiruvenkatarajan V; Jesudason D, Nanjappa N, et al.
  Pages: 349 - 350
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003626
  Issue No: Vol. 134, No. 2 (2021)
Perioperative Management of Glucose-lowering Drugs: Reply
- Authors: Preiser J; Cnop M.
  Pages: 350 - 351
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003627
  Issue No: Vol. 134, No. 2 (2021)
Burst-suppression and Postoperative Delirium: Comment
- Authors: Grocott HP.
  Pages: 351 - 352
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003631
  Issue No: Vol. 134, No. 2 (2021)
Burst-suppression and Postoperative Delirium: Reply
- Authors: Pedemonte JC; Locascio JJ, Houle T, et al.
  Pages: 352 - 353
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003632
  Issue No: Vol. 134, No. 2 (2021)
Balanced Crystalloid versus 0.9% Sodium Chloride: What We Overlook in Our
Research
- Authors: Kasatkin A; Urakov A, Nigmatullina A, et al.
  Pages: 353 - 354
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003614
  Issue No: Vol. 134, No. 2 (2021)
A Contemporary Reading List
- Authors: Schwartz A.
  Pages: 354 - 355
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003616
  Issue No: Vol. 134, No. 2 (2021)
Podcasts from Anesthesiology Promoting Medical English Learning in
Non–English-speaking Countries
- Authors: Liang C; Zhang X, Fang F, et al.
  Pages: 355 - 356
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003621
  Issue No: Vol. 134, No. 2 (2021)
Pectoralis-II Myofascial Block and Analgesia: Comment: Erratum
- Pages: 357 - 357
  Abstract: In the letter beginning on page 1602 in the June 2020 issue, the author’s name “Steve Melton” is incorrect. The correct name is “M. Stephen Melton.”
  PubDate: Mon, 01 Feb 2021 00:00:00 GMT
  DOI: 10.1097/ALN.0000000000003634
  Issue No: Vol. 134, No. 2 (2021)