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End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.
Subject(s)
Humans , Anesthesia , Pain , Hospitals , Palliative Care , UniversitiesABSTRACT
Objective Although goal-directed fluid therapy (GDFT) has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator. Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications. We conducted mediation analysis using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates. Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI: 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.
Subject(s)
Humans , Blood Pressure , Goals , Postoperative Complications/epidemiology , Hemodynamics , Fluid Therapy/methodsABSTRACT
Objective To develop a risk prediction model combining pre/intraoperative risk factors and intraoperative vital signs for postoperative healthcare-associated infection(HAI)based on deep learning. Methods We carried out a retrospective study based on two randomized controlled trials(NCT02715076,ChiCTR-IPR-17011099).The patients who underwent elective radical resection of advanced digestive system tumor were included in this study.The primary outcome was HAI within 30 days after surgery.Logistic regression analysis and long short-term memory(LSTM)model based on iteratively occluding sections of the input were used for feature selection.The risk prediction model for postoperative HAI was developed based on deep learning,combining the selected pre/intraoperative risk factors and intraoperative vital signs,and was evaluated by comparison with other models.Finally,we adopted the simulated annealing algorithm to simulatively adjust the vital signs during surgery,trying to explore the adjustment system that can reduce the risk of HAI. Results A total of 839 patients were included in this study,of which 112(13.3%)developed HAI within 30 days after surgery.The selected pre/intraoperative risk factors included neoadjuvant chemotherapy,parenteral nutrition,esophagectomy,gastrectomy,colorectal resection,pancreatoduodenectomy,hepatic resection,intraoperative blood loss>500 ml,and anesthesia time>4 h.The intraoperative vital signs significantly associated with HAI were in an order of heart rate>core body temperature>systolic blood pressure>diastolic blood pressure.Compared with multivariable Logistic regression model,random forest model,and LSTM model including vital signs only,this deep learning-based prediction model performed best(ACC=0.733,F1=0.237,AUC=0.728).The simulation via simulated annealing algorithm reduced the incidence of postoperative HAI.Moreover,the incidence decreased most in the case of reducing the initial annealing temperature and choosing the last 20% of surgery procedure. Conclusions This study developed a risk prediction model for postoperative HAI based on deep learning,which combined pre/intraoperative risk factors and intraoperative basic vital signs.Using simulated annealing algorithm to adjust intraoperative vital signs could reduce the incidence of postoperative HAI to some extent.
Subject(s)
Humans , Cross Infection , Deep Learning , Delivery of Health Care , Postoperative Period , Retrospective StudiesABSTRACT
Objective To reveal the incidence,mortality,and risk factors of bleeding-related perioperative cardiac arrest(POCA). Methods We carried out a single-center retrospective case-control study which enrolled all the POCA cases reported from January 2010 to September 2020 in the patient safety incident reporting system of Peking Union Medical College Hospital.For the screening of risk factors,the patients were respectively assigned into the POCA group and the control group at a ratio of 1∶3 according to the same sex,age,American Society of Anesthesiologists(ASA)physical status,and type of surgery in the same month.Potential risk factors for POCA were first selected by univariate analysis.The significant risk factors were then checked based on the clinical experience and further included in the multivariate Logistic regression model. Results Totally 16 bleeding-related POCA cases were collected from the patient safety incident reporting system among the study period,with an overall incidence of 0.36/10 000.The blood loss volume of POCA group and control group was(7 037.50±5 477.70)ml and(375.63±675.14)ml,respectively(P<0.001),and 14(87.5%)patients suffering from bleeding-related POCA died within three days after anesthesia.According to the univariate analysis,patients' body mass index[(21.79±3.57)kg/m2 vs.(24.26±3.91)kg/m2,P=0.043],hemoglobin level[(113.44±31.08)g/L vs.(131.75±19.70)g/L,P=0.039],and alanine aminotransferase level[(17.31±7.73)U/L vs.(26.91±24.73)U/L,P=0.022]were significantly lower in the POCA group than in the control group.Further Logistic regression analysis showed that smaller body mass index and lower preoperative hemoglobin level were independently associated with the occurrence of bleeding-related POCA. Conclusions Bleeding-related POCA rarely occurred but had high mortality.Adequate precautions should be taken for the patients who are to receive surgeries with high risk of intraoperative massive bleeding.Elevating preoperative hemoglobin level might decrease the incidence of bleeding-related POCA.
Subject(s)
Humans , Case-Control Studies , Heart Arrest/etiology , Hemoglobins , Retrospective Studies , Risk FactorsABSTRACT
Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.
Subject(s)
Humans , Anesthetics, Local/therapeutic use , Double-Blind Method , Hepatectomy/adverse effects , Morphine/therapeutic use , Pain Measurement , Pain, Postoperative/etiology , Ultrasonography, InterventionalABSTRACT
Objectives To validate the reliability of the Chinese version of the Consultation and Relational Empathy (CARE) in physician-standardized patient (SP) encounter. We also tried to examine the agreement between video-based ratings and in-room ratings, as well as the agreement between the faculty ratings and SP ratings. Methods The CARE was translated into Chinese. Forty-eight anesthesia residents were recruited to make preoperative interview in SP-counter. Performance of each resident was graded by in-room raters, video raters and SP raters. Consistency between different raters was examined. Results The Chinese-CARE measure demonstrated high scale reliability with a Cronbach's alpha value of 0.95 and high consistency in the in-room ratings in intraclass correlation (coefficient=0.888,
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Objective Burnout is a triad of emotional exhaustion, depersonalization, and reduced personal accomplishment resulting from job stress. Although with distinct regional and cultural characteristics, burnout among anesthesiologists in the Tibet has not been described. This study aimed to explore the prevalence of burnout among anesthesiologists in Tibet and its associated factors. Methods A cross-sectional survey was conducted in Tibet, China, with an anonymous questionnaire. Social-demographic characteristics, work status, three dimensions of burnout assessed by the Maslach Burnout Inventory-Human Service Survey were collected and analyzed. Results A total of 133 individuals from 17 hospitals completed the survey from March to June 2018. The prevalence of moderate- to high-level of emotional exhaustion, depersonalization, and burnout in personal accomplishment was 65.4% (95%
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Objective To investigate the risk factors for patients using intraoperative vasopressor infusions during carotid body tumor(CBT)excision.Patients' mean arterial pressure(MAP)and heart rate(HR)fluctuations as well as their requirements for vasoactive agents during surgery were assessed. Methods The patients receiving CBT excision in Peking Union Medical College Hospital from May 1,2013 to July 31,2017 were included for a retrospective cohort study.The potential factors of intraoperative requirement for vasopressor infusions were investigated using univariate analysis and Logistic multivariate analysis.Furthermore,the relationships of Shamblin types of CBT with intraoperative MAP/HR fluctuations and requirements for vasoactive agents were analyzed. Results A total of 108 patients with 116 CBTs were included.Univariate analysis revealed that maximum tumor diameter >4 cm,intraoperative internal carotid artery injury,internal carotid artery reconstruction,malignant pathology,advanced Shamblin types(type Ⅱ and Ⅲ),estimated blood loss ≥400 ml,and operation duration >4 hours were associated with intraoperative requirements for vasopressor infusions.Logistic analysis showed that Shamblin type Ⅲ(OR=2.286,95% CI=1.324-14.926,P=0.016)and operation duration >4 hours(OR=3.874,95% CI=1.020-14.623,P=0.046)were risk factors for intraoperative requirements for vasopressor infusions during CBT surgery.In addition,Shamblin type Ⅲ was associated with intraoperative abnormal HR elevation and requirements for vasopressors.Conclusions Shamblin type Ⅲ and operation duration>4 hours are risk factors for intraoperative requirements of patients for using vasopressor infusions during CBT surgery.Shamblin type Ⅲ is associated with intraoperative abnormal HR elevation and requirements for vasopressors.
Subject(s)
Humans , Carotid Body Tumor , Retrospective Studies , Risk Factors , Treatment Outcome , Vascular Surgical ProceduresABSTRACT
BACKGROUND@#Whether regional anesthesia may help to prevent disease recurrence in cancer patients is still controversial. The stage of cancer at the time of diagnosis is a key factor that defines prognosis and is one of the most important sources of heterogeneity for the treatment effect. We sought to update existing systematic reviews and clarify the effect of regional anesthesia on cancer recurrence in late-stage cancer patients.@*METHODS@#Medline, Embase, and Cochrane Library were searched from inception to September 2020 to identify randomized controlled trials (RCTs) and cohort studies that assessed the effect of regional anesthesia on cancer recurrence and overall survival (OS) compared with general anesthesia. Late-stage cancer patients were primarily assessed according to the American Joint Committee on Cancer Cancer Staging Manual (eighth edition), and the combined hazard ratio (HR) from random-effects models was used to evaluate the effect of regional anesthesia.@*RESULTS@#A total of three RCTs and 34 cohort studies (including 64,691 patients) were identified through the literature search for inclusion in the analysis. The risk of bias was low in the RCTs and was moderate in the observational studies. The pooled HR for recurrence-free survival (RFS) or OS did not favor regional anesthesia when data from RCTs in patients with late-stage cancer were combined (RFS, HR = 1.12, 95% confidence interval [CI]: 0.58-2.18, P = 0.729, I2 = 76%; OS, HR = 0.86, 95% CI: 0.63-1.18, P = 0.345, I2 = 48%). Findings from observational studies showed that regional anesthesia may help to prevent disease recurrence (HR = 0.87, 95% CI: 0.78-0.96, P = 0.008, I2 = 71%) and improve OS (HR = 0.88, 95% CI: 0.79-0.98, P = 0.022, I2 = 79%).@*CONCLUSIONS@#RCTs reveal that OS and RFS were similar between regional and general anesthesia in late-stage cancers. The selection of anesthetic methods should still be based on clinical evaluation, and changes to current practice need more support from large, well-powered, and well-designed studies.
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Humans , Anesthesia, Conduction , Neoplasms , RecurrenceABSTRACT
Objective To investigate the understanding of the head and face protection of the health care workers in operating room of Peking Union Medical College Hospital during the corona virus disease-19(COVID-19) pandemic.Methods The knowledge of head and face protection of health care workers in the operating room was evaluated based on the non-registered questionnaires for protection measures collected on-line.Results The survey was conducted in two phases.In the first phase(COVID-19 outbreak),153 questionnaires were collected.In the second phase(when Beijing lowered the emergency response to level 3 and normalized the epidemic prevention and control),101 questionnaires were collected.The results showed that 98% of health care workers had used any form of protective devices during the pandemic and anesthesiologists had the highest usage rate(93.0%)of ear-loop face mask with eye shield.During the pandemic,health care workers mainly used goggles(71.2%)for protection to diagnose and treat the patients with fever and ear-loop face mask with eye shield(56.2%)for protection to diagnose and treat the non-fever patients.In the first-and second-phase survey,43% and 68% of health care workers still used protection,and they mainly used face shield(50.0% and 56.5%)and ear-loop face mask with eye shield(56.1% and 68.1%).Conclusions During the pandemic,more than 90% of the health care workers in the operating room of Peking Union Medical College Hospital were aware of head and face protection.Different healthcare workers in the operating room had different choices of head and face protection,and more than 40% of them would still keep such protection during the normalized stage of pandemic prevention and control.
Subject(s)
Humans , COVID-19 , Health Personnel , Hospitals , Operating Rooms , Pandemics , SARS-CoV-2ABSTRACT
Objective To analyze the characteristics of high-risk maternal patients and evaluate the multidisciplinary medical care system we established correspondingly. Method We collected and analyzed the medical records of high-risk maternal patients who received medical care from January 1,2017 to December 31,2020 in Peking Union Medical College Hospital. Results Ninety-eight high-risk maternal patients were included in this study,and 84.7%(83/98)of them were combined with different severe systemic diseases.Under the multidisciplinary medical care system,91 patients showed improved conditions and were discharged,and the other 7 cases had poor prognosis. Conclusions General tertiary hospitals in Beijing are receiving maternal patients with more high-risk complications.Considering the high risk and diverse diseases of maternal patients admitted to our hospital,we established a medical care system composed of a multidisciplinary panel of experts for high-risk maternal patients to improve the medical care and prognosis of the patients with high efficiency.
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Humans , Hospitalization , Hospitals, General , Prognosis , Retrospective Studies , Tertiary Care CentersABSTRACT
Hypoxemia after general anesthesia is not uncommon. For patients after thoracotomy, the differential diagnosis is usually difficult. Surgical, anesthetic, and patient-associated factors may contribute to postoperative hypoxemia. We described two patients who underwent video-assisted thoracoscopic thymectomy and developed hypoxemia immediately after extubation. Phrenic nerve injury was suspected in both patients. One case recovered spontaneously without intervention. The second case who had been demonstrated as bilateral phrenic nerve injury after the operation was continuously on ventilator after physical therapy and respiratory training for 2 months.
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A novel coronavirus that emerged in late 2019 rapidly spread around the world. Most severe cases need endotracheal intubation and mechanical ventilation, and some mild cases may need emergent surgery under general anesthesia. The novel coronavirus was reported to transmit via droplets, contact and natural aerosols from human to human. Therefore, aerosol-producing procedures such as endotracheal intubation and airway suction may put the healthcare providers at high risk of nosocomial infection. Based on recently published articles, this review provides detailed feasible recommendations for primary anesthesiologists on infection prevention in operating room during COVID-19 outbreak.
Subject(s)
Humans , Anesthesiologists , Reference Standards , Betacoronavirus , Coronavirus Infections , Epidemiology , Cross Infection , Epidemiology , Disease Outbreaks , Intubation, Intratracheal , Methods , Reference Standards , Operating Rooms , Methods , Reference Standards , Pandemics , Pneumonia, Viral , EpidemiologyABSTRACT
Objective To explore the predictive ability of the revised cardiac risk index(RCRI)in elderly patients with coronary heart disease(CHD)undergoing non-cardiac surgery. Methods We performed a retrospective study including a total of 2100 patients,aged≥65 with a history of CHD who underwent non-cardiac surgery form January 2013 to September 2019.The preoperative,intraoperative and postoperative clinical data were extracted from an electronic database.The RCRI and reconstructed-RCRI(R-RCRI)score of each patient were calculated.The primary end point was defined as an occurrence of perioperative MACE.Multivariate logistic regression analysis was performed to evaluate the risk factors of perioperative MACE.The area under the receiver operating characteristic(ROC)curve was used to compare the predictive value of RCRI,R-RCRI,and the new risk scoring system of the study for perioperative MACE. Results The incidence of perioperative MACE in elderly patients with CHD was 5.4%.Six independent risk factors of perioperative MACE for this population were identified:age≥80 years;female;history of heart failure;insulin-depended diabetes mellitus;preoperative ST segment abnormality;American Society of Anesthesiologists grade≥Ⅲ,and the risk index was 2,2,2,2,2 and 3 respectively.The area under ROC curve of RCRI,R-RCRI and risk scoring system in this study were 0.586,0.552 and 0.741. Conclusion The correlation between RCRI score and perioperative MACE was poor in elderly patients with CHD undergoing non-cardiac surgery,and a better cardiac risk assessment method should be established for this population.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Coronary Disease/complications , Logistic Models , Multivariate Analysis , Postoperative Complications/epidemiology , Retrospective Studies , Risk Assessment , Risk Factors , Surgical Procedures, OperativeABSTRACT
Objectives Transmuscular quadratus lumborum block (TQLB) may provide postoperative analgesia in patients undergoing intraperitoneal surgeries. The purpose of this study was to examine the potential efficacy of TQLB among patients undergoing retroperitoneal procedures, such as the laparoscopic partial nephrectomy (LPN). Methods This prospective, randomized, controlled study was conducted from August 2017 to November 2018 at Peking Union Medical College Hospital (Beijing, China). Patients who were scheduled for a LPN, aged 18-70 years old with an ASA physical status score of I - II were randomly assigned to receive either TQLB with 0.6 ml/kg of 0.5% ropivacaine plus general anesthesia (TQLB group) or general anesthesia alone (control group). Patient-controlled intravenous analgesia with morphine was initiated immediately upon surgery completion. The primary outcome was the cumulative consumption of morphine within 8 h after surgery. The secondary outcome included postoperative consumptions of morphine at other time points, pain score at rest and during activity, postoperative nausea and vomitting (PONV), and recovery related parameters. Results Totally 30 patients per group were recruited in the study. The 8 h consumption of morphine was lower in the TQLB group than in the control group (median, 0.023 mg/kg
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To evaluate the value of oxycodone hydrochloride for postoperative pain management in patients undergoing patient-controlled intravenous analgesia(PCIA). The medical records on postoperative pain management in our department from January 1 to June 30,2018,were retrospectively analyzed.Totally 136 patients were assigned into oxycodone,sufentanil,or morphine groups according to the opioid used in the PCIA.Patients were assessed for postoperative pain severity(scored with NRS)and adverse reactions 24,36,and 48 hours after surgery.The area under curve(AUC)was calculated. The score of pain at exercise was significantly lower in the oxycodone group(2.2±2.4)than in the sufentanil group(3.4±2.1)(=0.305,=0.0126)or the morphine group(3.4±1.7)(=0.104,=0.0277)36 hours after surgery.AUC at rest was significantly lower in the oxycodone and morphine groups than in the sufentanil group(29.00,27.00,and 40.01,respectively);in contrast,AUC at exercise was significantly lower in the oxycodone group(63.17)than in the sufentanil and morphine groups(82.00 and 80.93,respectively).The consumption of opioids was significantly higher in the sufentanil group[(37.2±16.1),(46.1±24.3),(64.4±33.4)mg]than in the oxycodone group[(20.4±14.8)(=3.571,=0.001),(24.2±16.1)(=4.63,<0.0001),(34.4±25.1)mg(=6.409,<0.0001)]or the morphine group[(16.6±11.7)(=4.233,<0.0001),(20.5±14.1)(=5.250,<0.0001),(28.8±19.0)mg(=7.354,<0.0001)]24,36,48 hours after surgery.The oxycodone group experienced less vomiting(=11.360,=0.003)and early termination of PCIA(=7.914,=0.019)compared with the other two groups. Oxycodone can be used for postoperative PCIA.It can alleviate a variety of postoperative pain,with superior analgesic efficiency and safety to sufentanil and morphine.
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To identify the possible factors that may influence the success and the complications of ultrasound-guided out-of-plane radial arterial cannulation. Multivariate Logistic regression analysis was used to analyze the clinical data of 131 patients undergoing elective surgery and ultrasound-guided out-of-plane radial artery cannulation,dynamic needle tip positioning(DNTP) technique or angular distance(AD) technique and to find out the factors associated with the one-attempt success rate,overall success rate,posterior arterial wall perforation,and local hematoma. The depth of the anterior arterial wall≥3 mm was the factor associated with posterior arterial wall perforation(=0.314,95%:0.143-0.691,=0.004) and local hematoma(=0.250,95%:0.107-0.585,=0.001).The use of DNTP method was significantly associated with posterior arterial wall perforation(=0.303,95%:0.138-0.667,=0.003). During ultrasound-guided out-of-plane radial cannulation,puncture at the arterial anterior wall sites with a depth of≥3 mm can reduce the incidence of posterior arterial wall perforation and local hematoma.Compared with AD,DNTP can lower the incidence of posterior arterial wall perforation.
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Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.
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Perioperative restrictive red blood cell(RBC)transfusion strategy,in which a trigger of hemoglobin(Hb)<7 g/dl is used,is of great benefits to save blood storage and reduce transfusion-related adverse events including infections,immunologic risks,and circulatory overload.Human body can display a series of compensatory mechanisms to acute anemia,including increased cardiac output,favored oxyhemoglobin dissociation,and lung vascular dilation.Therefore,moderate Hb decrease does not necessarily lead to hypoxemia.Patients undergoing hip surgery or suffering from septic shock and/or upper gastrointestinal bleeding can benefit from restrictive RBC transfusion;however,restrictive transfusion may be associated with adverse outcomes in patients with coronary heart disease or undergoing cardiac surgery.Restrictive RBC transfusion strategies have been included in described in many different guidelines.Most of them recommended Hb<7 g/dl to be a trigger for allogeneic RBC transfusion.For patients with an Hb of 7-10 g/dl,the application of restrictive RBC transfusion should be based on the expected blood loss,compensatory ability,and metabolic rate.
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Humans , Erythrocyte Transfusion , Hemoglobins , Perioperative Care , Practice Guidelines as Topic , Surgical Procedures, OperativeABSTRACT
Objective To investigate the effects of simvastatin on diabetic neuropathic pain and systematic inflammation in diabetic rats and explore their molecular mechanisms.Methods Totally 24 rats were equally randomized into the normal+vehicle(NV)group,diabetic+vehicle(DV)group,and diabetic+simvastatin(DS)group using the random number table.Streptozotocin(STZ)was used to establish the rat models of diabetes.Blood glucose,body mass,paw withdrawal mechanical threshold(PWMT),and paw withdrawal thermal latency(PWTL)in each group were observed on days 7,14,21,and 28 after STZ injection.On day 28 after STZ injection,rats were sacrificed,and the lumbar spinal dorsal horn and serum were collected.Western blotting was used to detect the expression of receptor for advanced glycation end products(RAGE)and the phosphorylation levels of protein kinase B(AKT),extracellular signal-regulated kinase(ERK),p38,and c-Jun N-terminal kinase(JNK)in the spinal dorsal horn of rats in each group.Enzyme-linked immunosorbent assay was performed to determine the serum concentrations of oxidized low density lipoprotein(ox-LDL)and interleukin-1β(IL-1β).Results On days 14,21 and 28 after STZ injection,the PWMT in DV group were(8.6 ± 0.8),(7.1 ± 1.6),and(7.8 ± 0.8)g respectively,which were significantly lower than (12.0 ± 0.9)(=8.482, =0.000),(11.6 ± 1.5)(=11.309, =0.000),and(11.7 ± 1.5)g(=9.801, =0.000)in NV group.The PWMT in DS group on days 21 and 28 were(9.4 ± 1.4)(=5.780, =0.000)and(9.7 ± 0.9)g(=4.775, =0.003),respectively,which were significantly improved comparing with those of DV group.On days 7,14,21,and 28,there were no significant differences in PWTL among these three groups (all <0.05).The expression of RAGE in the spinal dorsal horn of DV group was significantly higher than those of NV group(=6.299, =0.000)and DS group(=2.891, =0.025).The phosphorylation level of AKT in the spinal dorsal horn of DV group was significantly higher than those of NV group(=8.915,=0.000)and DS group(=4.103,=0.003).The phosphorylation levels of ERK( =8.313,=0.000),p38( =2.965, =0.022),and JNK(=7.459, =0.000)in the spinal dorsal horn of DV group were significantly higher than those of NV group;the phosphorylation level of JNK in the spinal dorsal horn of DS group was significant lower than that of DV group(=3.866, =0.004);however,there were no significant differences in the phosphorylation levels of ERK(=1.987,=0.122)and p38(=1.260,=0.375)in the spinal dorsal horn between DS group and DV group.The serum concentrations of ox-LDL and IL-1β in DV group were(41.86 ± 13.40)ng/ml and(108.16 ± 25.88)pg/ml,respectively,which were significantly higher than those in NV group [(24.66 ± 7.87)ng/ml(=3.606,=0.003)and(49.32 ± 28.35)pg/ml(=5.079,=0.000)] and DS group [(18.81 ± 5.62)ng/ml (=4.833, =0.000)and(32.73 ± 11.73)pg/ml(=6.510, =0.000)].Conclusions Simvastatin can relieve the mechanical allodynia of diabetic rats possibly by inhibiting the activation of RAGE/AKT and the phosphorylation of JNK in the spinal dorsal horn.Simvastatin can also decrease the serum concentrations of ox-LDL and IL-1β in diabetic rats,which may contribute to the relief of systematic inflammation.