Restrictive blood transfusion and 1-year mortality in patients undergoing open abdominal surgery: A retrospective propensity score-matched cohort study.

BACKGROUND: The importance of patient blood management is increasingly recognized in surgery patients. This study aimed to examine the effect of perioperative restrictive blood transfusion on 1-year mortality and blood transfusion rate in open abdominal surgery. METHODS: We retrospectively studied 452 consecutive patients who underwent open abdominal surgery before (liberal group: 233 patients) and after (restrictive group: 219 patients) implementing intraoperative restrictive transfusion of red blood cell. The trigger levels of hemoglobin were less than 9-10 g/dL in the liberal group and less than 7-8 g/dL in the restrictive group. All-cause mortality at 1-year as the primary outcome and the transfusion rate of any allogeneic blood products as secondary outcome were compared between the liberal group and the restrictive group by the propensity-score matching. RESULTS: Among a total of 452 patients (69 ± 11 yr., 70.5 % men), overall mortality at 1 year was 8.4 % and the proportion of patients who received any allogeneic blood products was 19.6 %. Compared with 155 propensity-score matched patients of the liberal group, 155 matched patients of the restrictive group had significantly lower 1-year mortality (4 [2.5 %] versus 18 [11.6 %], p = 0.003, percent absolute risk reduction [%ARR]; 9.0, 95 % confidential interval [CI], 3.1-14.7) and had significantly lower proportion of patients who received any allogeneic blood products (21 [13.5 %] versus 41 [26.4 %], p = 0.006, %ARR; 12.9, 95 % CI, 3.9-21.5). CONCLUSIONS: The results of this study indicate that intraoperative restrictive blood transfusion reduces 1-year mortality and the transfusion rate of allogeneic blood products.

Heterologous functional expression of ascidian Nav1 channels and close relationship with the evolutionary ancestor of vertebrate Nav channels.

Voltage-gated sodium channels (Nav1s) are responsible for the initiation and propagation of action potentials in neurons, muscle, and endocrine cells. Many clinically used drugs such as local anesthetics and antiarrhythmics inhibit Nav1s, and a variety of inherited human disorders are caused by mutations in Nav1 genes. Nav1s consist of the main α subunit and several auxiliary ß subunits. Detailed information on the structure-function relationships of Nav1 subunits has been obtained through heterologous expression experiments and analyses of protein structures. The basic properties of Nav1s, including their gating and ion permeation, were classically described in the squid giant axon and other invertebrates. However, heterologous functional expression of Nav1s from marine invertebrates has been unsuccessful. Ascidians belong to the Urochordata, a sister group of vertebrates, and the larval central nervous system of ascidians shows a similar plan to that of vertebrates. Here, we report the biophysical properties of ascidian Ciona Nav1 (CiNav1a) heterologously expressed in Xenopus oocytes. CiNav1a exhibited tetrodotoxin-insensitive sodium currents with rapid gating kinetics of activation and inactivation. Furthermore, consistent with the fact that the Ciona genome lacks orthologous genes to vertebrate ß subunits, the human ß1 subunit did not influence the gating properties when coexpressed with CiNav1a. Interestingly, CiNav1a contains an ankyrin-binding motif in the II-III linker, which can be targeted to the axon initial segment of mammalian cortical neurons. Our findings provide a platform to gain insight into the evolutionary and biophysical properties of Nav1s, which are important for the development of targeted therapeutics.

Clinical Simulation Model of Fibrinogen Decline During Hemorrhage in Major Noncardiac Surgery.

BACKGROUND: Monitoring of decrease in fibrinogen levels with surgical blood loss is crucial for timely transfusion of fresh frozen plasma (FFP) to avoid coagulopathic bleeding. Here, we validated a simulation model to predict hemorrhagic reductions in fibrinogen levels during major noncardiac surgery. METHODS: We retrospectively performed exponential regression analysis of intraoperative blood loss and fibrinogen levels to develop a simulation model in the initial 50 patients and applied the model to another 59 patients to compare the measured and simulated fibrinogen levels. We examined the relationship between FFP transfusion and the measured fibrinogen levels or blood loss. The fibrinogen trigger level of FFP transfusion was below 130 mg/dL, although the decision of a perioperative blood transfusion was at the discretion of the anesthesiologists and surgeons. RESULTS: Application of the simulation model based on the initial 50 patients to another 59 patients showed no difference between the measured and estimated fibrinogen levels (189 ± 61 versus 186 ± 62, P = 0.60, mean difference: -2.28, limits of agreement: -69.42 to 64.84). The estimated fibrinogen level (mg/dL) = preoperative fibrinogen × exp (-1.90 × [blood loss/estimated circulation volume]), in which the estimated circulation volume = (70 [mL/kg] × body weight [kg]). FFP transfusion was significantly related to the measured fibrinogen level (cutoff: 145; 95% confidence intervals: 124-168; P = 0.0003) but not blood loss (P = 0.12). CONCLUSIONS: Fibrinogen level simulation predicted a hemorrhagic fibrinogen decline, thereby guiding FFP transfusion during active surgical bleeding. Further studies on the usefulness of fibrinogen level simulation are warranted.

An α7-related nicotinic acetylcholine receptor mediates the ciliary arrest response in pharyngeal gill slits of Ciona.

Ciliary movement is a fundamental process to support animal life, and the movement pattern may be altered in response to external stimuli under the control of nervous systems. Juvenile and adult ascidians have ciliary arrays around their pharyngeal gill slits (stigmata), and continuous beating is interrupted for seconds by mechanical stimuli on other parts of the body. Although it has been suggested that neural transmission to evoke ciliary arrest is cholinergic, its molecular basis has not yet been elucidated in detail. Here, we attempted to clarify the molecular mechanisms underlying this neurociliary transmission in the model ascidian Ciona Acetylcholinesterase histochemical staining showed strong signals on the laterodistal ciliated cells of stigmata, hereafter referred to as trapezial cells. The direct administration of acetylcholine (ACh) and other agonists of nicotinic ACh receptors (nAChRs) onto ciliated cells reliably evoked ciliary arrest that persisted for seconds in a dose-dependent manner. While the Ciona genome encodes ten nAChRs, only one of these called nAChR-A7/8-1, a relative of vertebrate α7 nAChRs, was found to be expressed by trapezial cells. Exogenously expressed nAChR-A7/8-1 on Xenopus oocytes responded to ACh and other agonists with consistent pharmacological traits to those observed in vivo Further efforts to examine signaling downstream of this receptor revealed that an inhibitor of phospholipase C (PLC) hampered ACh-induced ciliary arrest. We propose that homomeric α7-related nAChR-A7/8-1 mediates neurociliary transmission in Ciona stigmata to elicit persistent ciliary arrest by recruiting intracellular Ca2+ signaling.

Allergic Acute Coronary Artery Stent Thrombosis After the Administration of Sugammadex in a Patient Undergoing General Anesthesia: A Case Report.

In addition to cutaneous, gastrointestinal, hemodynamic, and respiratory symptoms, allergic reactions can induce an acute coronary syndrome in normal or atheromatous coronary arteries and can cause coronary stent thrombosis. Here, we report a case of coronary stent thrombosis due to allergic acute coronary syndrome during anaphylaxis induced by sugammadex in a female patient undergoing general anesthesia. She was emergently treated with percutaneous transluminal coronary balloon angioplasty with catecholamine, vasodilator, and intraaortic balloon support. Knowledge of perioperative allergy-triggered acute coronary syndrome is crucial for prompt and appropriate treatment.

Effect of Furosemide under Hyperchloremic Acidosis on Intraoperative Oliguria and Acute Kidney Injury in Patients with Normal Renal Function.

BACKGROUND: Renal function tends to deteriorate in a hyperchloremic acidifying environment, which is reflected by a decrease in the difference between sodium and chloride. OBJECTIVES: To examine the effect of furosemide administered under hyperchloremic acidosis on intraoperative oliguria and acute kidney injury in patients with preoperatively normal renal function. METHODS: In patients undergoing abdominal or orthopedic surgeries (April 2010-November 2018), we retrospectively identified patients who preoperatively had a normal renal function but experienced intraoperative oliguria under hyperchloremic acidosis (a sodium-chloride difference < 30 mEq/L) without dehydration. We compared the perioperative urine output and the incidence of postoperative acute kidney injury between patients who intraoperatively received an initial dose of 5 mg of furosemide (the furosemide group) and patients who did not intraoperatively receive furosemide (the control group). RESULTS: We identified 62 patients in the furosemide group and 48 patients in the control group. The furosemide group intraoperatively received 0.11 ± 0.06 mg/kg of furosemide (range 0.06-0.39 mg/kg). Compared to the control group, the furosemide group had greater urine output (mL/kg/h) in the operating room (1.1 ± 0.7 vs. 0.3 ± 0.1, p < 0.01) and on postoperative day 1 (1.2 ± 0.5 vs. 1.1 ± 0.4, p = 0.02). The incidence of postoperative acute kidney injury was lesser in the furosemide group than that in the control group (8.0 vs. 27.0%, p < 0.01; multivariate OR 0.18; 95% CI 0.05-0.61; p < 0.01). CONCLUSIONS: In surgery patients under hyperchloremic acidosis, furosemide (0.1 mg/kg) resolved intraoperative oliguria and reduced the incidence of postoperative acute kidney injury.

[Assessment of Fibrinogen Replacement Therapy by the Combined Simulation of the Fibrinogen Concentration and Fibrin Polymerization].

BACKGROUND: Fibrinogen replacement therapy is effective for attaining perioperative hemostasis in critical bleeding due to acquired hypofibrinogenemia. By simulating the fibrinogen level and fibrin polymerization, we compared the effect of fibrinogen replacement therapy using cryoprecipitate or fibrinogen concentrate versus the effect of fresh frozen plasma. METHODS: We simulated the plasma concentration of fibrinogen during fibrinogen replacement therapy in a model of cardiopulmonary bypass (CPB) and intensive care unit (ICU). We estimated fibrin polymerization (FIBTEM A10, thromboelastometry) by the simulated fibrinogen level, and compared this value with the fibrinogen level and FIBTEM in clinical patients. RESULTS: In the simulation model of CPB and ICU, cryoprecipitate and fibrinogen concentrate both effectively restored the fibrinogen level and FIBTEM, compared to fresh frozen plasma. In clinical patients, the simulated values of the fibrinogen level and FIBTEM after administering the fibrinogen concentrate were similar to the measured values. CONCLUSIONS: In the simulation model, which combines the fibrinogen level and fibrin polymerization, cryoprecipitate and fibrinogen concentrate effectively normalize the fibrinogen level and fibrin polymerization, compared to fresh frozen plasma. The fibrinogen concentrate also demonstrated efficacy in treating hypofibrinogenemia in clinical patients. The combined simulation model is useful in assessing the efficacy of fibrinogen replacement therapy by cryoprecipitate or by fibrinogen concentrate.

[Vocal cord paralysis associated with tracheal intubation: incidence, risk analysis, and classification of severity].

Vocal cord paralysis after tracheal intubation is rare. It causes severe hoarseness and aspiration, and delays recovery and discharge. Arytenoid cartilage dislocation and recurrent nerve paralysis are main causes of vocal cord paralysis. Physical stimulation of the tracheal tube as well as patient and surgical characteristics also contribute. Vocal cord paralysis occurs in 1 (0.07%) of 1,500 general surgery patients and on the left side in 70% of cases. It is associated with surgery/anesthesia time (two-fold, 3-6 hours; 15-fold, over 6 hours), age (three-fold, over 50 years), and diabetes mellitus or hypertension (two-fold). Symptoms resolve in 2-3 months. In adult cardiovascular surgery, vocal cord paralysis occurs in 1 (0.7-2%) of 50-100 cardiac surgery patients and 1 (8.6-32%) of 3-10 thoracic aortic surgery patients. In pediatric cardiac surgery, vocal cord paralysis occurs in 1 (0.1-0.5%) of 200-1,000 patients. We classified the severity of vocal cord paralysis as I, severe hoarseness; II, aspiration or dysphagia; and III, bilateral vocal cord paralysis, aspiration pneumonia, or the need for tracheal re-intubation or tracheotomy. We discuss the importance of informed consent for the patient and family.

[Fetal anesthesia in cesarean section for patients with congenital diaphragmatic hernia].

We experienced two cases of anesthesia for cesarean section in patients with prenatally diagnosed congenital diaphragmatic hernia (CDH). Fentanyl/midazolam anesthesia was selected for fetal sedation at birth. The blood samples were obtained from the maternal vein, umbilical vein and umbilical artery for measuring blood drug concentrations during anesthesia. Midazolam concentrations in umbilical vein were 137 and 256 ng.ml-1. Spontaneous breathing and movement of the newborns were restrained in both cases and these sedations facilitated preoperative general management for newborns with CDH.