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Road to Perioperative Medicine: A Perspective From China

期刊: ANESTHESIA AND ANALGESIA, 2019; 129 (3)

With the development of anesthesiology, patient safety has been remarkably improved, but the postoperative mortality rate at 30 days is still as high as 0.56%-4%, and the morbidity is even higher. Three years ago, the Chinese Society of Anesthesiology proposed that the direction of the anesthesiology development should be changed to perioperative medicine in China. Anesthesiologists should pay more attention to the long-term outcome. In this article, we introduced what we have done, what the challenges are, and what we should do in the future with regard to the practice of perioperative medicine in China.

JIF:3.49

Grade 3 Echocardiographic Diastolic Dysfunction Is Associated With Increased Risk of Major Adverse Cardiovascular Events After Surgery: A Retrospective Cohort Study

期刊: ANESTHESIA AND ANALGESIA, 2019; 129 (3)

BACKGROUND: Diastolic dysfunction is common and may increase the risk of cardiovascular complications. This study investigated the hypothesis that, in patients with isolated left ventricular diastolic dysfunction, higher grade diastolic dysfunction was associated with greater risk of major adverse cardiovascular events (MACEs) after surgery. METHODS: This was a retrospective cohort study. Data of adult patients with isolated echocardiographic diastolic dysfunction (ejection fraction, >= 50%) who underwent noncardiac surgery from January 1, 2015 to December 31, 2015 were collected. The primary end point was the occurrence of postoperative MACEs during hospital stay, which included acute myocardial infarction, congestive heart failure, stroke, nonfatal cardiac arrest, and cardiac death. The association between the grade of diastolic dysfunction and the occurrence of MACEs was assessed with a multivariable logistic model. RESULTS: A total of 2976 patients were included in the final analysis. Of these, 297 (10.0%) developed MACEs after surgery. After correction for confounding factors, grade 3 diastolic dysfunction was associated with higher risk of postoperative MACEs (odds ratio, 1.71; 95% confidence interval, 1.28-2.27; P < .001) when compared with grades 1 and 2. Patients with grade 3 diastolic dysfunction developed more non-MACE complications when compared with grades 1 and 2 (uncorrected odds ratio, 1.44; 95% confidence interval, 1.07-1.95; P = .017). CONCLUSIONS: In patients with isolated diastolic dysfunction undergoing noncardiac surgery, 10.0% develop MACEs during hospital stay after surgery; grade 3 diastolic dysfunction is associated with greater risk of MACEs.

JIF:3.49

The GCs-SGK1-ATP Signaling Pathway in Spinal Astrocytes Underlied Presurgical Anxiety-Induced Postsurgical Hyperalgesia

期刊: ANESTHESIA AND ANALGESIA, 2019; 129 (4)

BACKGROUND: Patients undergoing surgery often feel anxious. Accumulating evidence indicated that presurgical anxiety was related to the more severe postsurgical pain. An animal model was established that exposed Sprague-Dawley rats to a single-prolonged stress (SPS) procedure to induce presurgical anxiety-like behaviors. The experiment revealed that presurgical anxiety not only aggravated but also prolonged postsurgical pain. However, the underlying mechanisms were unknown. METHODS: The rats in group C + Cort, group I + Cort, group A + Cort, and group AI + Cort were injected with corticosterone. The rats in group C + RU486, group I + RU486, group A + RU486, and group AI + RU486 were injected with mifepristone (RU486). The rats in group C + GSK650394 and group AI + GSK650394 were injected with GSK650394. The rats in group C + FC1 and group AI + FC1 were injected with fluorocitrate (FC) 30 minutes before SPS, 30 minutes before incision, and on postoperative days 1, 2, 3, 4, and 5. The rats in group C + FC2 and group AI + FC2 were injected with FC on postoperative days 7, 8, 9, 10, 11, 12, and 13. The paw withdrawal mechanical threshold was assessed 24 hours before SPS and from postoperative days 1 to 28. The level of corticosterone was determined by enzyme-linked immunosorbent assay. The expression of serum/glucocorticoid regulated kinase 1 (SGK1), interleukin-1 beta, and tumor necrosis factor-alpha was visualized by Western blot. The concentrations of adenosine triphosphate (ATP) were measured by ATP assay kit. RESULTS: This study showed SPS elevated plasma glucocorticoids and ATP release from astrocytes, which meant the mechanical pain hypersensitivity in presurgical anxiety-induced postsurgical hyperalgesia was dependent on GCs-SGK1-ATP signaling pathway. SGK1 protein level in astrocytes was increased in response to the glucocorticoid stimuli and enhanced the extracellular release of ATP. Furthermore, spinal astrocytes played a key role in the maintenance. Targeting spinal astrocytes in maintenance phase prevented the pathological progression. CONCLUSIONS: These data suggested an important signaling pathway that affected the pain sensitivity after operation caused by presurgical anxiety.

JIF:3.49

Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial

期刊: ANESTHESIA AND ANALGESIA, 2019; 129 (5)

BACKGROUND: Phenylephrine (PE) is currently the vasopressor of choice to prevent and treat spinal-induced hypotension at cesarean delivery (CD). However, its use is often associated with reflex bradycardia. Norepinephrine (NE) has been put forward as an alternative vasopressor during CD due to its ability to treat hypotension while maintaining heart rate (HR). Recent studies have focused on the role of NE used as an infusion with favorable results compared to PE. No studies have compared equipotent bolus doses of PE and NE at CD. We hypothesized that when used in equipotent doses as an intermittent bolus regimen to prevent and treat spinal-induced hypotension, NE would result in a reduction in the incidence of bradycardia compared to PE. METHODS: This was a double-blind, randomized clinical trial of women undergoing elective CD under spinal anesthesia. Women were randomized to receive either PE 100 mu g or NE 6 mu g when the systolic blood pressure (SBP) was below baseline. In addition to the randomized treatment, ephedrine was given intravenously to both groups if the SBP was below baseline and the HR <60 bpm or if the SBP was <80% of baseline for 2 consecutive readings. The primary outcome was bradycardia (HR <50 bpm) in the predelivery period. Secondary outcomes included hypotension (SBP <80% of baseline), hypertension (SBP >120% of baseline), tachycardia (HR >120% of baseline), >= 2 episodes of bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar scores. RESULTS: One hundred twelve patients were randomized. The incidence of bradycardia was lower in the NE group compared to the PE group (10.7% vs 37.5%; P < .001; difference [95% confidence interval {CI}], -26.8% [-41.8% to -11.7%]), implying an estimated 71% relative reduction (95% CI, 35%-88%). The distribution of the number of bradycardia episodes was also different between the 2 groups (P = .007). Further testing showed that the patients in the PE group had a higher risk of multiple bradycardia episodes (>= 2 episodes) compared to the NE group (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring rescue boluses of ephedrine was lower in the NE group compared to the PE group (7.2% for NE versus 21.4% for PE; P < .03; difference [95% CI], -14.3% [-27.0% to -1.6%]). No differences were observed between the 2 groups in the incidence of other secondary outcomes. CONCLUSIONS: When used as an intermittent bolus regimen to prevent and treat spinal-induced hypotension during CD, NE resulted in a significant reduction in the incidence of bradycardia as compared to an equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered by NE during CD is superior to that of PE due to less fluctuations in HR and possibly cardiac output.

JIF:3.49

Recognizing the Chinese Pioneer of Neuraxial Labor Analgesia: Dr Guang-Bo Zhang and Her Unpublished Manuscript From More Than a Half-Century Ago

期刊: ANESTHESIA AND ANALGESIA, 2019; 128 (1)

Dr Guang-Bo Zhang was the first anesthesiologist to administer and study the effects of labor epidural analgesia in China. Between September 1963 and March 1964, she conducted an observational study evaluating the effects of neuraxial analgesia for laboring women. She presented her research and prepared an article; however, due to the Great Proletarian Cultural Revolution (Cultural Revolution), which began in 1966, her work went unpublished. She successfully preserved her unpublished article, notes, and slides throughout the Cultural Revolution by hiding them in a countryside location near Beijing. These 54-year-old, previously unpublished documents represent the first known clinical trial of neuraxial labor analgesia conducted in China.

JIF:3.49

Minimum Alveolar Concentration-Awake of Sevoflurane Is Decreased in Patients With End-Stage Renal Disease

期刊: ANESTHESIA AND ANALGESIA, 2019; 128 (1)

BACKGROUND: End-stage renal disease (ESRD) has been shown to be associated with abnormal neural function. Clinically used inhaled anesthetic agents typically exert their effect through multiple target receptors in the central nervous system. Pathological changes in the brain may alter sensitivity to inhaled anesthetic agents. This study aimed to determine the minimum alveolar concentration-awake (MAC(awake)) of sevoflurane in patients with ESRD compared to patients with normal renal function. METHODS: Patients underwent inhalational induction of anesthesia and received sevoflurane at a preselected concentration according to a modified Dixon "up-and-down" method starting at 1.0% with a step size of 0.2%. The concentration of sevoflurane used for each consecutive patient was increased or decreased based on a positive or negative response to verbal command in the previous patient. Serum neuron-specific enolase, a biomarker of impaired neurons, was also measured. RESULTS: Forty-one patients were enrolled: 20 with ESRD and 21 as controls. The MAC(awake) of sevoflurane in patients with ESRD was significantly lower than that observed in the control group (0.56% [standard deviation {SD} = 0.10%] vs 0.67% [SD = 0.08%]; P = .031). Patients with ESRD exhibited higher serum neuron-specific enolase levels compared to the control group (16.4 ng/mL [SD = 5.0] vs 8.7 ng/mL [SD = 2.9]; P < .001). CONCLUSIONS: MAC(awake) of sevoflurane is somewhat lower in patients with ESRD compared to those with normal renal function. Impaired cerebral function may partly contribute to the reduction in anesthetic requirement.

JIF:3.49

Pharmacological Characterization of Levorphanol, a G-Protein Biased Opioid Analgesic

期刊: ANESTHESIA AND ANALGESIA, 2019; 128 (2)

BACKGROUND: Levorphanol is a potent analgesic that has been used for decades. Most commonly used for acute and cancer pain, it also is effective against neuropathic pain. The recent appreciation of the importance of functional bias and the uncovering of multiple mu opioid receptor splice variants may help explain the variability of patient responses to different opioid drugs. METHODS: Here, we evaluate levorphanol in a variety of traditional in vitro receptor binding and functional assays. In vivo analgesia studies using the radiant heat tail flick assay explored the receptor selectivity of the responses through the use of knockout (KO) mice, selective antagonists, and viral rescue approaches. RESULTS: Receptor binding studies revealed high levorphanol affinity for all the mu, delta, and kappa opioid receptors. In S-35-GTP gamma S binding assays, it was a full agonist at most mu receptor subtypes, with the exception of MOR-1O, but displayed little activity in beta-arrestin2 recruitment assays, indicating a preference for G-protein transduction mechanisms. A KO mouse and selective antagonists confirmed that levorphanol analgesia was mediated through classical mu receptors, but there was a contribution from 6 transmembrane targets, as illustrated by a lower response in an exon 11 KO mouse and its rescue with a virally transfected 6 transmembrane receptor splice variant. Compared to morphine, levorphanol had less respiratory depression at equianalgesic doses. CONCLUSIONS: While levorphanol shares many of the same properties as the classic opioid morphine, it displays subtle differences that may prove helpful in its clinical use. Its G-protein signaling bias is consistent with its diminished respiratory depression, while its incomplete cross tolerance with morphine suggests it may prove valuable clinically with opioid rotation.

JIF:3.49

Preoperative Salivary Cortisol am/pm Ratio Predicts Early Postoperative Cognitive Dysfunction After Noncardiac Surgery in Elderly Patients

期刊: ANESTHESIA AND ANALGESIA, 2019; 128 (2)

BACKGROUND: The diagnosis of postoperative cognitive dysfunction (POCD) requires complicated neuropsychological testing and is often delayed. Possible biomarkers for early detection or prediction are essential for the prevention and treatment of POCD. Preoperative screening of salivary cortisol levels may help to identify patients at elevated risk for POCD. METHODS: One hundred twenty patients >60 years of age and undergoing major noncardiac surgery underwent neuropsychological testing 1 day before and 1 week after surgery. Saliva samples were collected in the morning and the evening 1 day before surgery. POCD was defined as a Z-score of <=-1.96 on at least 2 different tests. The primary outcome was the presence of POCD. The primary objective of this study was to assess the relationship between the ratio of am (morning) to pm (evening) salivary cortisol levels and the presence of POCD. The secondary objective was to assess the relationship between POCD and salivary cortisol absolute values in the morning or in the evening. RESULTS: POCD was observed in 17.02% (16 of 94; 95% confidence interval [CI], 9.28%-24.76%) of patients 1 week after the operation. A higher preoperative am/pm salivary cortisol ratio predicted early POCD onset (odds ratio [OR], 1.56; 95% CI, 1.20-2.02; P = .001), even after adjusting for the Mini-Mental Sate Examination score (odds ratio, 1.55; 95% CI, 1.19-2.02; P = .001). The area under the receiver operating characteristic curve for the salivary cortisol am/pm ratio in individuals with POCD was 0.72 (95% CI, 0.56-0.88; P = .006). The optimal cutoff value was 5.69, with a sensitivity of 50% and specificity of 91%. CONCLUSIONS: The preoperative salivary cortisol am/pm ratio was significantly associated with the presence of early POCD. This biomarker may have potential utility for screening patients for an increased risk and also for further elucidating the etiology of POCD.

JIF:3.49

Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model

期刊: ANESTHESIA AND ANALGESIA, 2019; 128 (2)

BACKGROUND: It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole. METHODS: Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL center dot kg(-1). External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period. RESULTS: The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate-blood pressure product, and coronary perfusion pressure during 2-40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05). CONCLUSIONS: In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.

JIF:3.49

Effect of Remote Ischemic Preconditioning in Patients Undergoing Hepatectomy With Portal Triad Clamping: A Randomized Controlled Trial

期刊: ANESTHESIA AND ANALGESIA, 2019; 129 (6)

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce liver injury in patients undergoing hepatectomy for colorectal liver metastasis, but its role is unclear in hepatocellular carcinoma patients with portal triad clamping during hepatectomy. METHODS: In this prospective, randomized trial, 140 patients with hepatocellular carcinoma undergoing liver resection requiring portal triad clamping were randomized to a RIPC group or a control group. Patients in the RIPC group received RIPC (3 cycles of 5-minute ischemia and 5-minute reperfusion in right upper limb with cuff pressure at 30 kPa [225 mm Hg]) approximately 10 minutes after induction of anesthesia. In the control group, patients received sham RIPC (the cuff was not inflated). The primary outcome was the postoperative peak level of total bilirubin (TBIL) and was analyzed with the independent t test. Secondary outcomes were liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. RESULTS: Data from 136 patients (69 in the RIPC group and 67 in the control group) were analyzed. The RIPC group had on average a 5.9 mu mol lower peak level of TBIL than the control group; the mean difference is -5.9, and the 95% confidence interval (CI) reverses to -17.9 to 6.1. There were no significant differences between the 2 groups in liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. CONCLUSIONS: We found no evidence that RIPC can reduce postoperative liver injury after hepatectomy.

JIF:3.49

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