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Objective:To analyze the clinical characteristics and outcomes of critically ill pregnant and parturient women in intensive care unit (ICU), and to provide clinical experience for the subspecialty construction of critical obstetrics.Methods:The clinical data of critically ill pregnant and parturient women admitted to the department of critical care medicine, the Second Affiliated Hospital of Kunming Medical University from January 2011 to December 2019 were collected. The main reasons for maternal transfer to ICU, the causes of maternal death, and organ support measures, etc. were summarized.Results:A total of 39 567 critically ill pregnant and parturient women were admitted to the department of obstetrics in our hospital, and 360 were transferred to ICU, with an average ICU transfer rate of 0.91%. Since 2016, the number of obstetric admissions, the number of ICU transfers and the ICU transfer rate had increased significantly. The average age of severe maternals admitted to ICU was (30.9±5.7) years old. The average acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score was 7 (4, 10). The average length of ICU stay was 1 (1, 2) day. The average ventilator duration was 9.0 (3.0, 17.5) hours. The main delivery mode of pregnant women in ICU was cesarean section (84.72%). Forty-eight patients (13.33%) underwent hysterectomy, of which 42 (87.5%) due to postpartum hemorrhage. The top 3 causes of ICU admission were severe postpartum hemorrhage [36.94% (133/360)], hypertensive disorders of pregnancy [21.67% (78/360)], pregnancy with cardiac disease [15.00% (54/360)]. The leading cause of postpartum hemorrhage in women transferred to ICU was placental abnormality [63.98% (103/161)], followed by uterine atony [28.57% (46/161)]. The average blood loss was (4 019±2 327) mL within 24 hours after delivery, and the number of women who underwent hysterectomy due to postpartum hemorrhage decreased year by year. During the study period, there were 2 maternal deaths, which were indirect obstetric deaths, 3 cases were discharged against-advice (expected death), including 1 indirect death and 2 direct obstetric death; the mortality in ICU was 1.39% (5/360).Conclusions:The most common reasons for pregnant and parturient women to be admitted to ICU were severe postpartum hemorrhage and hypertensive disorders of pregnancy. The leading cause of postpartum hemorrhage was placental problem. Indirect obstetric deaths exceeded direct obstetric deaths, mainly due to pregnancy complicated with cardiac disease and severe pneumonia. ICU has become an important battlefield for rescuing critically ill maternal and an important guarantee for reducing the maternal mortality.
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Objective:To evaluate the effect of repeated intranasal insulin on postoperative delirium (POD) in elderly patients undergoing general anesthesia.Methods:Seventy elderly patients, aged ≥65 yr, with body mass index ≤28 kg/m 2, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, undergoing elective radical gastrectomy for gastric cancer under general anesthesia, were divided into 2 groups ( n=35 each) according to the random number table method: control group (group C) and insulin group (group I). In group C, normal saline 0.5 ml was administered intranasally twice a day from 2 days before surgery until the day of surgery.In group I, insulin 20 U (0.5 ml) was administered intranasally twice a day from 2 days before surgery until the day of surgery.The regional tissue oxygen saturation (rSO 2) was measured after entering the operating room (T 0), at intubation (T 1), at 1, 2 and 3 h after the start of operation (T 2-4), at the end of surgery (T 5) and at extubation (T 6). The insulin allergic reactions, nasal irritation and hypoglycemic reactions were recorded after intranasal administration of insulin or normal saline within 2 days before operation.The blood glucose concentrations were measured at T 0, T 3 and T 5.The occurrence of POD within 3 days after operation was recorded. Results:Compared with group C, the incidence of POD was significantly decreased within 3 days after operation, and the rSO 2 was increased at T 1-6 in group I ( P<0.05). The rSO 2 was significantly higher at T 1-6 than at T 0 in two groups ( P<0.05). There were no significant changes in blood glucose concentrations at T 0, T 3 and T 5 between the two groups ( P>0.05). No insulin allergic reactions, nasal irritation and hypoglycemic reactions occurred in two groups ( P>0.05). Conclusion:Repeated intranasal administration of insulin can increase the rSO 2 during operation and decrease the occurrence of POD in elderly patients undergoing radical gastrectomy for gastric cancer.
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Pregnancy has increased susceptibility to H1N1 influenza virus infection. Maternal influenza infection is associated with increased risk of morbidity and mortality. A case of influenza A (H1N1) during late pregnancy (pregnancy 1, birth 0, pregnancy 30+2 weeks) was admitted to the Second Affiliated Hospital of Kunming Medical University on December 16th, 2018. The patient was set on mechanical ventilation with a FiO2 of 1.0, a positive end-expiratory pressure (PEEP) of 15 cmH2O (1 cmH2O = 0.098 kPa), and a tidal volume of 4-6 mL/kg (ideal body weight). However the pulse oxygen saturation (SpO2) could only be maintained at about 0.85. The disease was controlled by the treatments of anti-infection, mechanical ventilation, immune therapy, nutritional support, preventive anticoagulant treatment by heparin sodium, adequate negative fluid balance, and other organ support therapy. This article introduced the treatment process of the patient in detail, and provided experience for clinical treatment.
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Pregnancy has increased susceptibility to H1N1 influenza virus infection. Maternal influenza infection is associated with increased risk of morbidity and mortality. A case of influenza A (H1N1) during late pregnancy (pregnancy 1, birth 0, pregnancy 30+2 weeks) was admitted to the Second Affiliated Hospital of Kunming Medical University on December 16th, 2018. The patient was set on mechanical ventilation with a FiO2 of 1.0, a positive end-expiratory pressure (PEEP) of 15 cmH2O (1 cmH2O = 0.098 kPa), and a tidal volume of 4-6 mL/kg (ideal body weight). However the pulse oxygen saturation (SpO2) could only be maintained at about 0.85. The disease was controlled by the treatments of anti-infection, mechanical ventilation, immune therapy, nutritional support, preventive anticoagulant treatment by heparin sodium, adequate negative fluid balance, and other organ support therapy. This article introduced the treatment process of the patient in detail, and provided experience for clinical treatment.
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Objective To investigate high risk factors of intensive care unit-acquired weakness (ICUAW) in patients with sepsis. Methods A retrospective study was conducted. 164 patients with mechanical ventilation (MV) who were diagnosed sepsis and multiple organ dysfunction syndrome (MODS), admitted to intensive care unit (ICU) of the Second Affiliated Hospital of Kunming Medical University from January 1st, 2015 to September 30th, 2017 were enrolled. The general situation, the basic diseases (hypertension, diabetes), body mass index (BMI), protopathy diseases, the level of albumin before ICU admission, the MV time, whether to use glucocorticoid and continuous renal replacement therapy (CRRT) or not, nutrition supply (nutritional way, nutrition initiation time, amino acid/protein supply, nutritional status on ICU 3 days and 7 days), myoglobin, the length of ICU stay, the length of hospital stay, and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score were collected. The high risk factors of ICUAW in patients with sepsis complicated with MODS were analyzed further using multi-factor Logistic regression analysis. Multiple linear regression analysis was used to analyze the myoglobin related factors in sepsis patients. Results The ICUAW incidence was 25.6% (42/164). The risk factors with differences in univariate analysis were included in the multivariate Logistic regression analysis, and it was shown that the level of albumin before ICU [odds ratio (OR) = 0.232, 95% confidence interval (95%CI) = 0.061-0.885, P = 0.032], the MV time (OR = 0.380,95%CI = 0.154-0.935, P = 0.035), nutrition initiation time (OR = 2.642, 95%CI = 1.100-6.346, P = 0.030), myoglobin (OR = 4.129, 95%CI = 1.681-10.142, P =0.002) were the independent risk factors for ICUAW in sepsis patients with MODS. The linear regression showed that the level of myoglobin was positively correlated with APACHE Ⅱ score (β= 38.297, P = 0.000), negatively correlated with the length of hospital stay (β= -7.071, P = 0.048), and it had nothing to do with the MV time and the length of ICU stay. Conclusions Evaluation of muscle function should be a routine part of ICU examination. The levels of albumin,MV time, hemoglobin and nutritional start-up time were independent risk factors for ICUAW in sepsis patients with MODS. Myoglobin levels can be used as an indicator of severity.
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Objective To investigate the unmet needs of thyroid cancer patients undergoing 131Itreatment and their relationship with psychological distress and quality of life.Methods From October 2014 to March 2016,a total of 338 patients (106 males,232 females,average age (35.50±9.98) years) with thyroid cancer who were receiving 131I treatment were enrolled.The 34 items of Supportive Care Needs Survey Short Form (SNCS-SF34) were used to investigate the unmet care needs of patients.Patients' perceptions of distress and main causes of distress were measured by Distress Thermometers (DT) and issue list.The 12-item Short-Form Health Survey (SF-12) was used to measure patients' quality of life.Pearson correlation analysis was used to analyze the data.Results The degrees of patients' unmet care needs from high to low were as following:health information needs (65.38％,221/338),psychological needs (47.93％,162/338),patients' care and support needs (44.08％,149/338),physical and daily needs (36.09％,122/338) and sexual needs (34.32％,116/338).There were 47.93％(162/388) patients with DT score ＞ 4.The top three causes of patients' distress were fears,fatigue and memory deterioration.Degree of unmet needs for patients had positive correlation with the degree of psychological distress (r values:0.232-0.462,all P＜0.01).The unmet physiological and daily needs and psychological needs of patients had negative correlations with several dimensions of quality of life (r values:from-0.367 to-0.202,all P＜ 0.05).Conclusions The unmet care needs of patients with thyroid cancer have correlations with their psychological distress and quality of life.Evaluation of the unmet care needs of patients with thyroid cancer could be beneficial for providing the targeted care.
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Objective To investigate the accuracy and feasibility of brachial artery peak velocity variation (ΔVpeakbrach) and inferior vena cava variability (VIVC) as indicators of fluid responsiveness in critically ill patients. Methods A single-center prospective observation was conducted. The patients on mechanical ventilation with spontaneously breathing admitted to Department of Critical Care Medicine of the Second Affiliated Hospital of Kunming Medical University from June 2013 to August 2015 were enrolled. The patients were diagnosed as severe sepsis or sepsis shock. The peak velocity in brachial artery and diameter of the inferior vena cava at the end of inspiration and expiration was measured by bedside portable ultrasonic machine, and then ΔVpeakbrach and VIVC were calculated. The hemodynamic parameters were collected at baseline and after volume expansion (VE). The stroke volume (SV) was measured by pulse-indicated continuous cardiac output (PiCCO). Patients were classified as responders or non-responders according to the variation of SV (ΔSV) increased ≥ 15% or not after VE. Receiver operating characteristic curve (ROC) was plotted to evaluate the sensitivity and specificity of ΔVpeakbrach and VIVC in predicting volume responsiveness. Results Among 58 patients after VE, 32 patients were defined as responders and the rest 26 were defined as non-responders.There were no differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, dose of vasoactive agent, ventilator parameters and infection site. Compared with baseline hemodynamic parameters, heart rate (HR) was decreased (bpm: 95±18 vs. 103±21), and systolic blood pressure (SBP) was increased [mmHg (1 mmHg = 0.133 kPa): 92±8 vs. 80±7] after VE in responders; central venous pressure (CVP) was increased after VE in non-responders (mmHg: 11±4 vs. 8±3, all P < 0.05). The ΔVpeakbrach [(15.4±4.3)% vs. (11.2±3.5)%] and VIVC [(18.6±4.1)% vs. (14.3±3.6)%] in responders were significantly increased as compared with those of non-responders (both P < 0.05). The area under ROC curve (AUC) of ΔVpeakbrach for predicting volume responsiveness was 0.816. When the cut-off value of ΔVpeakbrach was ≥ 13.3%, the sensitivity was 71.9%, and the specificity was 80.8%. AUC of VIVC for predicting volume responsiveness was 0.733. When the cut-off value of VIVC was ≥ 19.25%, the sensitivity was 53.1%, and the specificity was 88.5%. Conclusion ΔVpeakbrach and VIVC are reliable indicators for predicting volume responsiveness in critical patients.
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Objective To assess the efficacy and safety of peginterferon ( PegIFN) α-2b in treatment of HBeAg-positive chronic hepatitis B ( CHB).Methods Thirty two patients with HBeAg-positive CHB admitted in Peking University Shenzhen Hospital during November 2013 and January 2014 were recruited in the study.Patients were center randomly assigned into two groups : 22 patients in test group were treated with 180 μg PegIFN α-2b, 1 /w for 48 wk; 10 patients in control group were treated with 180 μg PegIFN α-2a (Pegasys), 1 /w for 48wk.All patients were followed up for 24wk after treatment.Virology markers, HBV DNA levels and liver functions were monitored regularly , and adverse events were observed . Fisher’s exact test was used to compare the efficacy and safety between two groups .Results There were no statistically significant differences between the control group and test group in ALT normalization rates , HBV DNA negative rates and HBeAg serological conversion rates both at the end of treatment and at the end of 24-wk follow-up (all P >0.05).Both groups had similar adverse effect incidence rates (P >0.05), but retina disease occurred in 7 cases of test group, which was not observed in control group .Conclusion Compared with PegIFN α-2a, PegIFN α-2b has similar efficacy and safety for patients with HBeAg -positive CHB.
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Objective To compared analgesic effect of sufentanil and fentanyl in surgery patients during mechanical ventilation, and to explore the rational dosage of analgesic and sedative drugs. Methods A prospective randomized controlled trial was conducted. 600 postoperative critically ill patients underwent mechanical ventilation for 12-72 hours admitted to Department of Critical Care Medicine of the Second Affiliated Hospital of Kunming Medical University from April 2013 to March 2015 were enrolled. They were randomly divided into two groups, sufentanil and fentanyl was used for analgesia respectively, and 300 patients in each group. The initiate dosage of sufentanil and fentanil was 5 μg/h and 50 μg/h, and the dosage was adjusted. A postoperative pain score (Prince-Henry score) of 0-1, and Richmond agitation-sedation scale (RASS) score -1-0 were targeted. 1 mg/kg of propofol was used if patient could not fall in sleep or felt anxious after loading dose of sufentanil (5 μg) or fentanil (50 μg) for 5 minutes. The use of analgesic drugs, the proportion and dosage of propofol was observed in the two groups, and adverse reactions were recorded. Results The mean dose of sufentanil for analgesia was (0.07±0.02) μg·kg-1·h-1, and the mean dose of fentanyl was (0.67±0.12) μg·kg-1·h-1. The patients in the two groups received propofol 40 to 60 mg/h in night, and the use proportion of propofol in sufentanil group was slightly less than that in fentanyl group (25.7% vs. 28.3%), but the difference was not statistically significant (P > 0.05). It was found by subgroup age analysis that, the mean analgesic dose of sufentanil or fentanyl in patients over 80 years old was lower than that in 70-79 years, 60-69 years and < 60 years groups but without statistical significance. There were 11 cases (3.7%) and 21 cases (7.0%) patients suffered from respiratory depression in sufentanil group and fentanyl group, respectively, without statistical significance (P = 0.069). The hemodynamics of patients in two groups was stable during analgesia, and no accidental extubation due to restlessness was found. Conclusions A smaller dose of sufentanil for postoperative patients underwent mechanical ventilation with satisfactory analgesia was (0.07±0.02) μg·kg-1·h-1, but need to be added with 40-60 mg/h and a small dose of propofol to improve anxiety and sleep. The proportion of patients needing propofol addition was slightly lower than that of fentanyl.
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Objective To investigate the potential risk factors of organ dysfunction and mortality in the early resuscitation of severe sepsis and septic shock patients.Methods Data were retrospectively analyzed from patients with severe sepsis and septic shock receiving non-cardiac operation and admitted to Department of Critical Care Medicine of the Second Affiliated Hospital of Kunming Medical University from January 1st,2013 to December 31st,2015.The patients were divided into the senior group (≥ 65 years old) and the younger group (＜ 65 years old),the high-procalcitonin (PCT) group (PCT ＞ 100 μg/L) and the control group (PCT ≤ 100 μg/L).The stage of early resuscitation was set to the first 6 hours.The diagnostic time and the incidence of acute respiratory distress syndrome (ARDS),acute kidney injury (AKI),and cardiac insufficiency were observed,which also included the usage of continuous renal replacement therapy (CRRT).The total fluid volume and the time of vasopressor usage during the first 6 hours of early goal-directed therapy (EGDT) were also recorded,which aslo included the 28-day mortality.Results 512patients with severe sepsis and septic shock receiving non-cardiac operation were treated according to the guidelines of Surviving Sepsis Campaign:international guidelines for management of severe sepsis and septic shock:2012.EGDT was used during the early resuscitation.The incidence of ARDS,AKI,and cardiac insufficiency was 80.9％ (414/512),71.3％ (365/512),and 61.9％ (317/512) respectively.There were 205 senior patients and 307 younger,as well as 154in high-PCT group and 358 in control group.The 28-day mortality was 30.3％ (155 died).90.8％ of patients (376/414)combined with ARDS were diagnosed before EGDT.95.1％ of patients (347/365) combined with AKI were diagnosed before EGDT,among whom 14.0％ (51/365) were treated with CRRT.153 senior patients combined with cardiac insufficiency were diagnosed no longer than 12 hours after EGDT.Compared with the younger group,the incidences of ARDS and cardiac insufficiency were higher in the senior group [85.9％ (176/205) vs.77.5％ (238/307),82.9％(170/205) vs.32.9％ (147/307),both P ＜ 0.05],so were the time of vasopressor usage during EGDT (hours:5.81 ±0.28vs.5.68 ± 0.52,P ＜ 0.05) was prolonged markedly and the 28-day mortality [42.9％ (88/205) vs.21.8％ (67/307),P ＜0.05] was increased significantly.But the incidence of AKI and the total fluid volume during EGDT were not significantly different between the senior group and the younger group [incidence of AKI:74.1％ (152/205) vs.69.4％ (213/307),total fluid volume (mL):2 769 ± 1 589 vs.2 804± 1 611,both P ＞ 0.05].Compared with the control group,the incidence of ARDS was higher in the high-PCT group [86.4％ (133/154) vs.78.5％ (281/358),P ＜ 0.05].But the incidences of AKI and cardiac insufficiency were not significantly differentiated between the high-PCT group and the control group [77.9％ (120/154) vs.68.4％ (245/358),58.4％ (90/154) vs.63.4％ (227/358),both P ＞ 0.05].Multiple logistic regression analysis showed that the risk factors of increase in mortality in patients with severe sepsis and septic shock included old age [odds ratio (OR) =1.782,95％ confidence interval (95％CI) =1.173-2.708,P =0.007],ARDS (OR =1.786,95％CI =1.028-3.102,P =0.040),AKI (OR =1.878,95％CI =1.145-3.079,P =0.012),and cardiac insufficiency (OR =4.177,95％CI =2.505-6.966,P =0.000),except for gender (OR =1.112,95％CI =0.736-1.680,P =0.614).Conclusions In the senior postoperative patients with severe sepsis or septic shock,the incidence of ARDS and cardiac insufficiency,and the mortality were increased.The incidence of ARDS was correlated to the severity of infection.Old age,surgery,and EGDT could be the potential risk factors of cardiac insufficiency.
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Objective To compare the skills level before and after pediatric advanced life support course and analyze the effect of the training. Methods The pediatric advanced life support was used as the textbook. The skills were got through attending theory classes, watching demonstrations and taking part in the simulator training. The questionnaires were filled strictly and the data was analysed. Results The test scores were increased after the training (P＜0. 01). There were only 8.7% of the trainees had used the rescue equipments and 61.3% had never seen the rescue equipments before training. More than 80% of the trainees were satisfied with the training about the utility and novelty. Conclusion pediatric advanced life support course can successfully deliver a large number of healthcare providers with international unique pediatric emergency treatment skills ,and raise the participants abilities of rescuing critical children.
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BACKGROUND:The success of cell therapy will depend on the ability to monitor the fate of transplanted cells in vivo.Superparamagnetic iron oxide(SPIO)labeling is an ideal magnetic resonance contrast medium,and it offers the potential for non-invasive tracking of implanted cells.The chlormethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (CM-Dil)labeling does not have cytotoxicity,so it cannot influence cell growth.OBJECTIVE:To investigate the effects of SPIO and CM-Dil labeling and tracking on bone marrow mesenchymal stem cells(BMSCs).METHODS:Porcine BMSCs were isolated and cultured by the whole bone marrow method.BMSCs were labeled with SPIO containing 50 mg/L Ferrum and CM-Dil.The labeled BMSCs were transplanted into porcine myocardial infarction model via intracoronary infusion.The frozen sections of the cardiac tissues were obtained after 4 weeks.RESULTS AND CONCLUSION:Efficiency of SPIO and CM-Dil labeling BMSCs was nearly 100%.The SPIO and CM-Dil labeled BMSCs could be found in the cardiac muscle tissues at 4 weeks after transplantation.SPIO and CM-Dil labeling BMSCs were efficiently tracked in vivo.
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Objective To investigate the risk factors for postoperative delirium in patients undergoing noncardiac surgery. Methods From September-December 2009, 480 patients undergoing elective noncardiac surgery were included in this study. The criteria for enrolment of the patients in this study were (1) age ≥ 65 yr,(2) age ＜ 65 yr if associated with coronary artery disease, hypertension, diabetes mellitus, brain injury, cerebral hemorrhage, cerebral infarct, emphysema, chronic bronchitis; duration of operation ≥ 3 h and intraoperative blood loss was expected to exceed 20% of blood volume. The diagnosis of delirium was based on Confusion Assessment Method (CAM). Multivariate logistic regression was used to analyze the risk factors for postoperative delirium.Results Postoperative delirium developed in 79 patients during the first three postoperative days. The incidence of postoperative delirium was 16.5%. The logistic stepwise regression analysis indicated that the risk factors for delirium included advanced age, method of anesthesia, long operation, postoperative pain, emphysema and alcholic. Conclusion Age, method of anesthesia, long operation, postoperative pain, emphysema and alcholic are risk factors for postoperative delirium in patients undergoing noncardiac surgery.
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Objectives:To observe the role of nutritional support in patients after liver transplantation. Methods:Nutritional support was used in three patients after orthotopic liver transplantation(OLT).Total parenteral nutrition(TPN) was administered since the second day after the operation,the combination of enteral nutrition(EN) and parenteral nutrition(PN) was followed and then total enteral nutrition(TEN) was adopted.After that,oral intake of food was restored. Results:Postoperative patients were restored well. Conclusions:The supply of nutrition for patients after liver transplantation should be TPN→PN+EN→TEN,and then gradually increased.Once the gastroenteric functions of patients recover it is advisable to start EN as soon as possible.
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Objective To test the accuracy of American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for preoperative cardiovascular evaluation for noncardiac surgery in Chinese patients and to compare ACC/AHA guidelines with Goldman index and Lee index. Methods From January to December 2003, all patients aged ≥70 yr or patients aged 40-69 yr with a history of cardio- and cerebro-vascular disease, abnormal ECG or diabetes scheduled for noncardiovascular surgery were included in this study. A total of 1 248 patients were eligible. Their clinical data including demographic data, history of cardiovascular disease, routine physical examination and laboratory tests, the scheduled surgery and type of anesthesia were collected. The patients were then evaluated for cardiac risk and classified according to ACC/AHA guidelines (high, moderate, low and no risk), Lee index (class I -IV ) and Goldman index (class I - III ). The cardiac risk of the scheduled surgery was then stratified according to ACC/AHA guidelines. The patients were followed up until discharged from hospital. Cardiac events were defined as cardiac death, myocardial infarct, myocardial ischemia, minor myocardial cell injury, ventricular dysfunction and serious arrhythmia. Likelihood ratio of the 3 methods was calculated. Risk factors for adverse events were identified by univariate analysis and multivariate Logistic regression analysis. Results Of the 1 248 patients 694 were male and 554 female. Their age ranged from 40-102 years (mean age 65.4 yr). 44.7 % of the patients were aged ≥ 70 years. High risk operation accounted for 6.3 % and emergency operation 7.9% . One patients died of cardiac event and ten patients of other causes. Seventy-three perioperative cardiac events occurred in 53 patients. The morbidity rate was 4.2% . Goldman index and ACC/AHA cardiac risk stratification were correlated with adverse cardiac outcomes ( P
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We have used continuous epidural anaethesia for 308 cases of orthopoedis operation of poliomyelitic sequel since 1983 to 1987. The satisfactory rate of anesthesia effect is 92%. However, as the disease caused by a special change of pathology, we have also found some ineffective cases. The causes of defect are multiple. The questions met during Anesthesia in our case series were discussed.