ECMO在脓毒症中应用的研究进展

体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)是一种心肺支持技术,临床上能够为严重、可逆性的心肺衰竭患者提供循环、呼吸支持.近年来,新生儿、儿童和成人脓毒症患者应用ECMO治疗的成功报道日渐增多,掀起了脓毒症患者应用ECMO治疗的热潮.然而,ECMO在脓毒症患者中的临床应用却一直存在争议.大量回顾性研究表明新生儿及儿童脓毒症患者中应用的成功率相对较高,成人脓毒症患者应用ECMO治疗例数较少,但仍可在其他治疗无效的前提下尽早尝试ECMO治疗.     

Plasma Concentrations of Oseltamivir and Oseltamivir Carboxylate in Critically Ill Children on Extracorporeal Membrane Oxygenation Support

Introduction

To evaluate the effect of extracorporeal membrane oxygenation (ECMO) support on pharmacokinetics of oseltamivir and oseltamivir carboxylate (OC) in children.

Methodology

Steady state 0–12 hour pharmacokinetic sampling was performed in new influenza A (H1N1) infected children treated with oseltamivir while on ECMO support. Cmax, Cmin and AUC_{0–12 h} were calculated. The age-specific oseltamivir dosage was doubled to counter expected decreased plasma drug concentrations due to increased volume of distribution on ECMO support.

Principal Findings

Three patients were enrolled aged 15, 6 and 14 years in this pharmacokinetic case series. For two children the OC plasma concentrations were higher than those found in children and adults not on ECMO. These increased plasma concentrations related to the increased oseltamivir dosage and decreased kidney function. In one patient suboptimal plasma concentrations coincided with a decreased gastric motility.

Conclusion

Oseltamivir pharmacokinetics do not appear to be significantly influenced by ECMO support. Caution is required in case of nasogastric administration and decreased gastric motility. Due to the limited number of (paediatric) patients available further multicenter studies are warranted.     

Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation

Background and Objectives

Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality.

Methods

Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality.

Results

Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI.

Conclusion

The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.     

Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support

Background

Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor.

Methods

We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb> 50 mg/dL was used as a marker of severe hemolysis.

Results

154 patients received ECMO for cardiac (n= 115) or pulmonary (n=39) indications. Patients’ mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p=0.026), lower 24-hour lactic acid (p=0.023), shorter ECMO duration (P=0.01), fewer RBC transfusions on ECMO (p=0.008) and lower level of PFHb 24-hours post ECMO implantation (p=0.029). 24-hour PFHb> 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p=0.002. A Cox proportional hazard analysis identified PFHb> 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 – 8.8, p= 0.011).

Conclusion

PFHb> 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.     

Continuous Glucose Monitoring in Patients Undergoing Extracorporeal Ventricular Assist Therapy

Background

Dysregulations of blood glucose (BG) are associated with adverse outcome in critical illness; controlling BG to target appears to improve outcome. Since BG-control is challenging in daily intensive care practice BG-control remains poor especially in patients with rapidly fluctuating BG. To improve BG-control and to avoid deleterious hypoglycemia, automated online-measurement tools are advocated. We thus evaluated the point-accuracy of the subcutaneous Sentrino^® Continuous Glucose Monitoring System (CGM, Medtronic Diabetes, Northridge, California) in patients undergoing extracorporeal cardiac life support (ECLS) for cardiogenic shock.

Methods

Management of BG was performed according to institute’s standard aiming at BG-levels between 100–145 mg/dl. CGM-values were recorded without taking measures into therapeutic account. Point-accuracy in comparison to intermittent BG-measurement by the ABL-blood-gas analyzer was determined.

Results

CGM (n = 25 patients) correlated significantly with ABL-values (r = 0.733, p<0.001). Mean error from standard was 15.0 mg/dl (11.9%). 44.2% of the readings were outside a 15% range around ABL-values. In one of 635 paired data-points, ABL revealed hypoglycemia (BG 32 mg/dl) whereas CGM did not show hypoglycemic values (132mg/dl).

Conclusions

CGM reveals minimally invasive BG-values in critically ill adults with dynamically impaired tissue perfusion. Because of potential deviations from standard, CGM-readings must be interpreted with caution in specific ICU-populations.     

A Case of Vivax Malaria Complicated by Adult Respiratory Distress Syndrome and Successful Management with Extracorporeal Membrane Oxygenation

Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.     

Vancomycin Dosing in Neutropenic Patients

Background

To compare vancomycin pharmacokinetic parameters in patients with and without neutropenia.

Methods

Patients ≥18 years admitted on general wards were included. Routinely vancomycin trough and peak plasma concentrations were measured with a fluorescence polarization immunoassay. Pharmacokinetic parameters of individual patients were determined with maximum a posterior Bayesian estimation (MW Pharm 3.60). Neutropenia was defined as neutrophils <0.5×10⁹ cells/L.

Principal Findings

A total of 171 patients were included. Patients with neutropenia (n = 56) had higher clearance of vancomycin (CLva), 67 (±26) mL/min, compared to patients without neutropenia (n = 115), CLva 50 (±22) mL/min (p<0.001). No significant difference was found in serum creatinine and vancomycin volume of distribution. Neutropenia was positively associated with CLva, independently of relevant co-variables (B: 12.122, 95%CI: 1.095 to 23.149, p = 0.031). On average patients with neutropenia needed 33% higher doses of vancomycin to attain adequate exposure, i.e. AUC₂₄≥400 mg×h/L. Furthermore, 15 initially neutropenic patients in our study group received vancomycin for a second administration period. Ten patients received the second administration period during another neutropenic period and 5 patients during a non-neutropenic phase. All 5 patients with vancomycin during both neutropenic and non-neutropenic phase had higher CLva (91 (±26) mL/min) during the neutropenic period and lower CLva (45 (±10) mL/min) during the non-neutropenic phase (p = 0.009).

Conclusion

This study shows that most patients with neutropenia have augmented CLva. In a small group of patients that received vancomycin during two episodes, the augmented CLva seems to be reversible in the non-neutropenic period. Our data indicate that it is important to increase the daily dose with one third in patients with neutropenia (from 15 mg/kg twice daily to 13 mg/kg three times daily). Frequent performance of therapeutic drug monitoring in patients with neutropenia may prevent both therapy failure due to low AUCs and overcomes toxicity due to high vancomycin trough concentrations during recovery from neutropenia.     

Plasma Concentrations of Brain-derived Neurotrophic Factor in Patients Undergoing Minor Surgery: A Randomized Controlled Trial

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631 +/- 337 (mean +/- SD) pg ml(-1) in the propofol group and were 549 +/- 512 pg ml(-1) in the thiopental-isoflurane group (P = 0.31). At 15 min, concentrations significantly decreased in the propofol group (247 +/- 219 pg ml(-1), P = 0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597 +/- 471 pg ml(-1), P = 0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24 h, concentrations significantly decreased below baseline in both groups (propofol: 232 +/- 129 pg ml(-1), P = 0.0015; thiopental-isoflurane: 253 +/- 250 pg ml(-1), P = 0.016). In the propofol group, there was a weak but statistically significant positive correlation (R2 = 0.38, P = 0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surgery.     

Alterations in Electrolyte and Trace-Element Concentrations During Simulated Extracorporeal Blood Circulation

In our studies with simulated extracorporeal blood circulation we observe damaging effects on blood cells, especially under oxygenating conditions. In order to characterize these effects we also analysed electrolyte and trace-element concentrations in plasma during and after simulated extracorporeal blood circulation. Highest resorption effects for magnesium and highest desorption effects for calcium, copper and iron are found with oxygen gas flow in the system. Membrane permeability for electrolytes seems to be induced as well. Cellular damage due only to mechanical stress within the perfusion system can be neglected.     

不同浓度的右美托咪定对老年腰椎术患者的镇静效果、氧化应激和血流动力学的影响

目的:探讨不同浓度的右美托咪定对老年腰椎术患者的镇静效果、氧化应激和血流动力学的影响。方法:选取2013年3月-2018年4月期间我院收治的老年腰椎术患者90例为研究对象。根据随机数字表法将患者分为对照组(n=30)、低浓度组(n=30)以及高浓度组(n=30)。低浓度组麻醉诱导前输注0.5μg/kg右美托咪定,高浓度组输注1μg/kg右美托咪定,对照组不输注右美托咪定。比较给药前(T0)、给药后10 min(T1)、给药后30 min(T2)、给药后60 min(T3)的听觉诱发电位指数(AAI)、改良/镇静视觉评分(OAA/S)。比较T0、T3、手术后24h(T4)的三组患者丙二醛(MDA)、超氧化物歧化酶(SOD)水平。比较T0-T3时间点三组患者的心率(HR)、平均动脉压(MAP)情况。观察三组患者术后不良反应发生情况。结果:与T0时间点比较,三组T1-T3时间点AAI、OAA/S均显著降低(P0.05);与对照组相比,低浓度组与高浓度组T1-T3时间点AAI、OAA/S均较低,且高浓度组低于低浓度组(P0.05)。与T0时间点比较,三组T3、T4时间点MDA均显著升高,T3时间点SOD显著降低(P0.05);与对照组相比,低浓度组与高浓度组T3、T4时间点MDA均降低,且高浓度组低于低浓度组(P0.05);高浓度组T3、T4时间点SOD高于低浓度组和对照组(P0.05)。与T0时间点比较,三组T2、T3时间点HR、MAP均降低(P0.05);与对照组相比,低浓度组、高浓度组T2、T3时间点HR均降低,且高浓度组低于低浓度组(P0.05);与对照组相比,低浓度组、高浓度组T2、T3时间点MAP均降低,但高浓度组高于低浓度组(P0.05)。三组患者术后不良反应总发生率比较差异无统计学意义(P0.05)。结论:1μg/kg右美托咪定对老年腰椎术患者的镇静效果较好,可有效维持血流动力学稳定,减轻氧化应激反应。     

不同吸入氧浓度联合PCV-VG模式对行腹腔镜膀胱癌根治术的老年患者氧合及肺损伤的影响

摘要 目的：探讨不同吸入氧浓度联合压力控制容量保证通气模式(PCV-VG)对行腹腔镜膀胱癌根治术的老年患者氧合及肺损伤的影响。方法：选择2022年3月至2023年3月在我院拟行全身麻醉下腹腔镜膀胱癌根治术的90例老年膀胱癌患者为研究对象,随机分为A组、B组和C组,各30例。所有患者在PCV-VG模式维持机械通气,其中A组、B组、C组的吸入氧浓度分别为40 %、50 %、60 %。检测所有患者通气前（T0）、通气后1 h、2 h和3h（T1-3）及撤管后0.5 h（T4）时心率（HR）、平均动脉压（MAP）、右心房压（RAP）、动脉血氧分压（PaO₂）,计算氧合指数（PaO₂/FiO₂）、呼吸指数（RI）,记录术后24 h临床肺部感染评分（CPIS）、PACU停留时间、术后住院时间,比较三组手术前及手术结束后血清肺表面活性蛋白A（SP-A）、Clara细胞分泌蛋白（CC16）表达水平及术后肺部并发症发生率。结果：三组在T0、T1、T2、T3和T4时HR、MAP、RAP比较无差异（P>0.05）;在T1、T2、T3和T4时,A组PaO₂、PaO₂/FiO₂均小于B组和C组,RI均大于B组和C组（P<0.05）;而B组与C组在各时间点PaO₂、PaO₂/FiO₂、RI比较无差异（P>0.05）;三组PACU停留时间比较无差异（P>0.05）;B组术后CPIS评分低于A组和C组,术后住院时间短于A组和C组（P<0.05）;C组术后血清SP-A、CC16表达水平均高于A组和B组（P<0.05）;B组术后肺部并发症发生率低于A组和C组（P<0.05）。结论：50%的吸入氧浓度联合PCV-VG模式可有效改善行腹腔镜膀胱癌根治术的老年患者的氧合功能,减轻肺损伤,对于减少术后并发症发生和促进康复具有积极作用,值得临床予以重视。     

不同浓度七氟醚联合瑞芬太尼对腹腔镜胆囊切除术患者应激反应和认知功能的影响

摘要 目的：探讨不同浓度七氟醚联合瑞芬太尼对腹腔镜胆囊切除术（LC）患者应激反应和认知功能的影响。方法：选择2022年6月至2022年12月期间在扬州大学附属医院接受LC的患者120例,按照随机数字表法将患者分为低浓度组[1.0最低肺泡有效浓度（MAC）七氟醚联合瑞芬太尼,n=60]和高浓度组（1.5MAC七氟醚联合瑞芬太尼,n=60）。对比两组血流动力学指标[心率（HR）、收缩压（SBP）、舒张压（DBP）]、苏醒质量、应激反应指标[超氧化物歧化酶（SOD）、丙二醛（MDA）、总抗氧化能力（T-AOC）]、认知功能和不良反应发生情况。结果：低浓度组插管后即刻（T1）~拔管时（T5）时间点HR、SBP、DBP高于高浓度组（P<0.05）。低浓度组的自主呼吸时间、苏醒时间、拔管时间、定向力恢复时间短于高浓度组（P<0.05）。两组术后1h SOD、T-AOC均下降,但低浓度组高于高浓度组（P<0.05）。两组术后1h MDA升高,但低浓度组低于高浓度组（P<0.05）。低浓度组术后6 h、术后12 h、术后24 h简易精神状态检查量表（MMSE）评分高于高浓度组（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。结论：与1.5MAC七氟醚相比,1.0MAC 七氟醚联合瑞芬太尼应用于LC患者的效果更好,可保持血流动力学平稳,有效控制机体的应激反应,同时还可减轻认知功能影响,提高苏醒质量。     

Characteristics of Patients Undergoing Bariatric Surgery in Canada

Objective: The increasing prevalence of obesity has led to an increased use of bariatric surgery in the treatment of severely obese individuals. The characteristics of patients undergoing bariatric procedures outside of clinical studies and on a national level have not previously been reported. Research Methods and Procedures: Acute‐care hospital discharge data from the Canadian Institute for Health Information were analyzed to determine the demographic and clinical features and in‐hospital mortality rates of individuals undergoing bariatric surgery in Canada. Data from individuals undergoing surgery in fiscal year 2002/2003 were compared with data from 1993/1994. Results: Over 1100 bariatric surgeries were performed in Canada in 2002/2003, with the vast majority being performed in middle‐aged women. Ten percent of patients had hypertension or diabetes, and only 1% or fewer had dyslipidemia or cardiovascular or cerebrovascular disease. Compared with 1993/1994, patients undergoing surgery in 2002/2003 were older, more likely to have diabetes or hypertension, and had shorter hospital stays. In‐hospital mortality rates were <1% in both years. Discussion: In the last decade, there has been a small increase in the average age and the number of patients with concomitant cardiovascular risk factors who are undergoing bariatric procedures in Canada. However, the vast majority of surgeries are being performed in middle‐aged women with little cardiovascular comorbidity, and this is likely contributing to very low in‐hospital death rates. Such individuals likely represent a highly selected sample of severely obese patients within Canada.     

Local Experience with Extracorporeal Membrane Oxygentaion in Children with Acute Fulminant Myocarditis

To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in children with acute fulminant myocarditis, we retrospectively analyzed the data of five children with acute fulminant myocarditis in the intensive care unit (ICU) at the Affiliated Children’s Hospital, Zhejiang University from February 2009 to November 2012. The study group included two boys and three girls ranging in age from 9 to 13 years (median 10 years). Body weight ranged from 25 to 33 kg (mean 29.6 kg). They underwent extracorporeal membrane oxygenation (ECMO) through a venous-arterial ECMO model with an average ECMO supporting time of 89.8 h (40–142 h). Extracorporeal circulation was established in all five children. After treatment with ECMO, the heart rate, blood pressure, and oxygen saturation were greatly improved in the four children who survived. These four children were successfully weaned from ECMO and discharged from hospital machine-free, for a survival rate of 80% (4/5). One child died still dependent on the machine. Cause of death was irrecoverable cardiac function and multiple organ failure. Complications during ECMO included three cases of suture bleeding, one case of acute hemolytic renal failure and suture bleeding, and one case of hyperglycemia. During the follow-up period of 4–50 months, the four surviving children recovered with normal cardiac function and no abnormal functions of other organs. The application of ECMO in acute fulminant myocarditis, even in local centers that experience low incidence of this disease, remains an effective approach. Larger studies to determine optimal timing of placement on ECMO to guide local centers are warranted.     

Prolactin Concentrations in Patients with Breast Cancer

Basal prolactin levels were measured before operation in 113 patients undergoing surgery for a lump in the breast. Prolactin concentrations were not significantly higher in those patients with breast cancer than in those with benign lumps. Prolactin concentrations were, however, found to be higher in premenopausal women than in postmenopausal ones, regardless of tumour histology.     

Exchangeable Potassium Study in Patients Undergoing Chronic Haemodialysis

Seven patients with chronic renal failure treated with haemodialysis for 4 to 24 months were found to have low exchangeable potassium levels. Before dialysis the plasma potassium was normal or somewhat raised (possibly owing to acidosis), though the exchangeable potassium was low. Acidosis was corrected during dialysis; plasma potassium levels fell, but clinical and electrocardiographic changes of hypokalaemia were absent. The level of 1 mEq/litre in the dialysate fluid may be too low for use in prolonged haemodialysis.     

Albumin Kinetics in Patients Undergoing Major Abdominal Surgery

Background

The drop in plasma albumin concentration following surgical trauma is well known, but the temporal pattern of the detailed mechanisms behind are less well described. The aim of this explorative study was to assess changes in albumin synthesis and transcapillary escape rate (TER) following major surgical trauma, at the time of peak elevations in two well-recognized markers of inflammation.

Methods

This was a clinical trial of radiolabeled human serum albumin for the study of TER and plasma volume. Ten patients were studied immediately preoperatively and on the 2nd postoperative day after major pancreatic surgery. Albumin synthesis rate was measured by the flooding dose technique employing incorporation of isotopically labelled phenylalanine.

Results

Fractional synthesis rate of albumin increased from 11.7 (95% CI: 8.9, 14.5) to 15.0 (11.7, 18.4) %/day (p = 0.027), whereas the corresponding absolute synthesis rate was unchanged, 175 (138, 212) versus 150 (107, 192) mg/kg/day (p = 0.21). TER was unchanged, 4.9 (3.1, 6.8) %/hour versus 5.5 (3.9, 7.2) (p = 0.63). Plasma volume was unchanged but plasma albumin decreased from 33.5 (30.9, 36.2) to 22.1 (19.8, 24.3) g/L. (p<0.001).

Conclusion

Two days after major abdominal surgery, at the time-point when two biomarkers of generalised inflammation were at their peak and the plasma albumin concentration had decreased by 33%, we were unable to show any difference in the absolute synthesis rate of albumin, TER and plasma volume as compared with values obtained immediately pre-operatively. This suggests that capillary leakage, if elevated postoperatively, had ceased at that time-point. The temporal relations between albumin kinetics, capillary leakage and generalised inflammation need to be further explored.

Trial Registration

clinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492