Evaluation of coagulation status using clot waveform analysis in general ward patients with COVID-19.

Coronavirus disease (COVID-19)-related systemic cytokine response induces the production of procoagulant factors, which predisposes patients to a prothrombotic state. Viscoelastic testing can identify the degree of hypercoagulability, which is related to outcomes. We aimed to study the changes in clot waveform analysis (CWA) parameters in COVID-19 patients on hospital admission compared to those in a group of healthy individuals. We conducted a retrospective study of COVID-19 patients admitted to general wards and evaluated demographic and clinical parameters as well as laboratory parameters, including coagulation parameters. CWA data from patients (n = 62) with COVID-19 prior to the initiation of anticoagulation therapy were compared with those from healthy controls (n = 67). The measured CWA parameters were min1, min2, max2, and delta change. CWA, fibrinogen, and D-dimer values were higher in COVID-19 patients than in healthy controls (p < 0.001). CWA profiles were consistent with hypercoagulability and characterized by an increase in density, velocity, and acceleration of clot formation. Activated partial thromboplastin time, fibrinogen, D-dimer, and C-reactive protein (CRP) values were higher in patients in whom all CWA parameters were raised than in patients with just a few elevated CWA parameters, while Sequential Organ Failure Assessment scores, prothrombin time, fibrin degradation product levels and platelet counts did not differ between the two groups. CWA variables showed hypercoagulopathy on admission in COVID-19 patients who were hospitalized in the general ward, and this pattern was more pronounced in critically ill patients with elevated fibrinogen, D-dimer, and CRP levels. Our results may help identify patients at high risk of thromboembolism.

Effects of Hemodilution on Clot Waveform Analysis Parameters, Clotting Factors, and Thrombin Generation Assays in a Dilutional Model Based on Analysis of 11 Healthy Male Blood Donors.

BACKGROUND Clot wave analysis (CWA) during activated partial thromboplastin time (aPTT) measures the speed and extent of fibrin polymerization in the plasma. This study aimed to evaluate the effects of hemodilution on CWA parameter, clotting factors, and thrombin generation assays in a dilutional model. MATERIAL AND METHODS Platelet-poor plasma obtained from 11 healthy male volunteers was diluted with 0.9% sodium chloride by 10-80% to analyze coagulation profiles, CWA, clotting factors, and thrombin generation assays. CWA includes 5 parameters: the time-dependent variable (aPTT), rate/acceleration (min1, min2, and max2), and magnitude of signal change (delta). RESULTS Critically low activities of 30% for clotting factors and 100 mg/dl of fibrinogen were determined at dilutions of 70% and 60%, respectively. Peak thrombin and endogenous thrombin potential were significantly lower compared with baseline after 50% and 80% dilution, respectively. aPTT did not correlate with the decrease in the clotting factors up to dilutions of 50% and subsequently became abnormal values. As the change in rate/acceleration parameters parallels the time course of clotting factor activity in a dilution-dependent linear manner, these parameters indicate an intervention threshold at critically low activities of clotting factors. The strongest correlations were observed between clotting factors and aPTT, clotting factors and min2, delta and peak thrombin (r=0.95), and delta and fibrinogen (r=0.98). CONCLUSIONS aPTT was significantly correlated with clotting factors, while the rate/acceleration parameters and delta changed with variation in thrombin and fibrinogen generation. These findings may help in evaluating coagulability.

Storage-Related Changes in Autologous Whole Blood and Irradiated Allogeneic Red Blood Cells and Their Ex Vivo Effects on Deformability, Indices, and Density of Circulating Erythrocytes in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Blood-processing techniques and preservation conditions cause storage lesions, possibly leading to adverse outcomes after transfusion. The authors investigated the metabolic changes and deformability of red blood cells (RBCs) during storage and determined the effect of storage lesions on circulating RBCs during cardiac surgery. DESIGN: Prospective study. SETTING: Tertiary care center affiliated with a university hospital. PARTICIPANTS: Adults who underwent elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: The authors collected aliquots of autologous and irradiated allogeneic RBCs and blood samples from seven patients who received autologous whole blood and nine patients who received irradiated allogeneic RBCs before incision (baseline), at the start and end of cardiopulmonary bypass, and at completion of surgery. MEASUREMENTS AND MAIN RESULTS: The authors analyzed RBC deformability, erythrocyte indices, and density distribution to evaluate blood banking-induced alterations of autologous and allogeneic RBCs and changes in circulating RBCs in recipients, after blood transfusion. Time-dependent biochemical changes and significant decreases in deformability during storage occurred in both groups; however, homologous RBCs had significantly lower deformability than autologous RBCs. Trends in mean corpuscular volume and mean corpuscular hemoglobin concentration differed in both groups. In the homologous transfusion group, during cardiac surgery, RBC deformability, mean corpuscular volume, and mean corpuscular hemoglobin concentration showed significant changes compared with baseline values, and a greater number of denser subpopulations was observed at surgery completion. CONCLUSIONS: Blood-processing techniques contribute to storage lesions, suggesting that transfusion of autologous whole blood, rather than allogeneic RBCs, could maintain the ability of circulating RBCs to deform and lead to potentially better transfusion outcomes.

Thromboelastometry and a hemostasis management system are most beneficial for guiding hemostatic therapy in cardiac surgery patients with a EuroSCORE II of ≥1.83%: a randomized controlled two-step trial.

PURPOSE: We evaluated the efficacy of hemostatic therapy based on point-of-care (POC) testing in patients undergoing cardiac surgery. METHODS: This was a single-institution, prospective, randomized, double-blinded study. In step 1, 90 patients scheduled for elective cardiac surgery underwent complete blood count and fibrinogen measurements at baseline, after cardiopulmonary bypass (CPB) initiation (CPB start), just after CPB end, and in the intensive care unit (ICU). In step 2, 72 patients scheduled for elective cardiac surgery underwent conventional laboratory coagulation tests (control group) or POC coagulation tests (POC group). Transfusions were prepared using the fibrinogen and platelet values at mainly "CPB start" for the control group, and using the ROTEM values at mainly "CPB end" for the POC group. Consequently, the step 2 patients were divided into high- and low-risk subgroups based on the EuroSCORE II by logistic regression analysis; transfusion data and bleeding volumes were compared between the control and POC groups within the high- and low-risk subgroups. RESULTS: In step 1, all blood components were significantly decreased at CPB start compared with baseline, and platelet and fibrinogen levels remained almost constant from CPB start to end. In step 2, the transfusion rates and perioperative bleeding volumes did not significantly differ between the control and POC groups. Subgroup analysis suggested that only the high-risk subgroup significantly differed regarding perioperative red blood cell transfusion and total bleeding volume in the ICU. CONCLUSIONS: POC testing is beneficial for cardiac surgery patients with a EuroSCORE II of ≥1.83%.

Dose-dependent effect of stored-blood transfusions on recipient red blood cell indices, deformability and density.

We prospectively studied the dose-dependent effect of transfused stored red blood cells (RBCs) on recipient RBC indices, deformability and cell density in 10 patients administered stored RBCs for blood transfusion during general surgery. There were dose-dependent decreases in mean corpuscular volume and increases in mean corpuscular haemoglobin concentration after completion of 4- and 6-unit stored RBC transfusions. The amount of dense populations increased proportionately with the amount of stored RBCs transfused. The maximal deformability index value was significantly and dose-dependently decreased, suggesting that hemodynamic blood flow, especially the microcirculation may be impaired in patients who receive large amounts of stored RBCs.

Changes in Erythrocyte Morphology at Initiation of Cardiopulmonary Bypass Without Blood Transfusion Were Not Associated With Less Deformability During Cardiac Surgery.

OBJECTIVES: During cardiac surgery, circulating red blood cells (RBCs) are at risk of exposure to environmental factors during extracorporeal circulation and transfusion of stored RBCs. For this study, the authors observed morphological differences, deformability, density distribution, and erythrocyte indices of RBCs during cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTING: Tertiary care center affiliated with a university hospital. PARTICIPANTS: Adults who underwent elective cardiac surgery requiring CPB. INTERVENTIONS: Blood samples were obtained from 13 patients before incision (baseline), at initiation of CPB, after separation from CPB, and at completion of surgery. MEASUREMENTS AND MAIN RESULTS: The morphological index (MI) in RBCs using light microscopy and the maximum deformability index (DImax) using an ektacytometer were evaluated. In addition, the fractionation of RBCs and erythrocyte indices were measured. The MI at initiation of CPB was significantly higher without blood transfusion compared with baseline, although the DImax did not significantly decrease simultaneously. The DImax after separation from CPB and at completion of surgery were significantly lower than that at baseline. This lowered DImax was accompanied by a significantly reduced mean corpuscular volume and elevated mean corpuscular hemoglobin concentration compared with baseline. Dense RBC subpopulations increased after initiating CPB. The MI after separation from CPB and at completion of surgery partially recovered. Administered stored RBCs showed a high MI and the lowest DImax. CONCLUSIONS: Morphological changes at initiation of CPB are considered potentially reversible transformations without loss of the membrane surface area and do not have a significant effect on the DImax. A decrease in deformability likely is due to transfusion of stored RBCs.

Effects of crystalloids and colloids on microcirculation, central venous oxygen saturation, and central venous-to-arterial carbon dioxide gap in a rabbit model of hemorrhagic shock.

OBJECTIVE: The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids. METHODS: An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20 mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 22 rabbits (control) were intravenously given 40 mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200 mL, administered under the same conditions as HES. RESULTS: After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group. CONCLUSION: Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.

Association Between Platelet Count and Postoperative Blood Loss in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass and Fresh Frozen Plasma Administration Guided by Thromboelastometry.

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple factors, including reduced coagulation factors and a low platelet count.Methods and Results:In this study, we undertook a post hoc analysis to identify factors associated with increased postoperative blood loss in 97 patients undergoing cardiac surgery with CPB, with fresh frozen plasma administered according to a ROTEM-guided algorithm. We identified 24 patients for the top quartile of postoperative blood loss, >528 mL and defined as having excessive blood loss. Using Spearman's rank correlation test and multivariable linear regression, we reanalyzed the participants' demographic, surgical and anesthetic variables, laboratory test results, blood loss, and transfusion data. Univariate analysis indicated that patients who experienced higher postoperative blood loss received a significantly higher heparin dose, had a higher requirement for fresh frozen plasma transfusion during surgery, and had a significantly lower hematocrit and platelet count at the end of surgery compared with patients without excessive blood loss. Multivariate analysis showed that platelet count at the end of surgery (odds ratio 0.780, 95% confidence interval 0.629-0.967; P=0.024) was an independent factor for excessive blood loss. CONCLUSIONS: Low platelet count at the end of surgery was associated with excessive postoperative bleeding during cardiac surgery with CPB.

Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

INTRODUCTION: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. METHODS: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. RESULTS: The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. CONCLUSION: It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

In vitro and in vivo effects of hemodilution on kaolin-based activated clotting time predicted heparin requirement using a heparin dose-response technique.

PURPOSE: The heparin dose-response (HDR) technique is based on activated clotting time (ACT) response to a fixed-dose heparin bolus, which varies substantially among patients. It is unclear, however, whether hemodilution-associated reductions in coagulation and anticoagulation factors affect the HDR slope. METHODS: For in vitro hemodilution, aliquots of whole blood from healthy volunteers were diluted 9:1 and 8:2 v/v with normal saline. For in vivo hemodilution, a prospective observational study was performed on 46 patients who underwent elective cardiovascular surgery with or without cardiopulmonary bypass. HDR slope, antithrombin (AT) activity, complete blood count, and other coagulation parameters were compared after induction of anesthesia and after hemodilution with 500 ml of intravenous fluid. RESULTS: In vitro 10 and 20 % hemodilution significantly increased the HDR slope relative to baseline, reducing the heparin requirement. Hemodilution of heparinized samples significantly prolonged ACT, whereas there was no significant change in non-heparinized blood. The percent changes in fibrinogen and AT activity were significantly greater at 20 % than those of the other coagulation variables. In vivo, hemodilution significantly increased the HDR slope and reduced heparin requirement. The percent change in fibrinogen due to hemodilution was significantly greater than the change in AT activity. Target ACTs of 300 and 450 s were not achieved in 83.3 and 53.8 % of patients, respectively. CONCLUSION: In vitro and in vivo hemodilution significantly increased the HDR slope and reduced the requirement for heparin. In vitro, the HDR slope did not change in parallel but became steeper, depending on the degree of hemodilution.

[The Use of Thromboelastometry and Tranexamic Acid Reduces Blood Loss and Transfusion Requirements in Cardiac Surgery under Cardiopulmonary Bypass].

BACKGROUND: We evaluated whether using thromboelastometry and tranexamic acid influenced blood loss and transfusion requirements in cardiac surgery requiring cardiopulmonary bypass. METHODS: We perfomed a retrospective analysis examining perioperative coagulation results, and the transfusion requirements of concentrated red cells (CRCs), fresh frozen plasma (FFP) and platelet administration between 12 months before and 10 months after thromboelastometry and tranexamic acid had been introduced in our institution. We also recorded patients' demographic details, the surgery performed and patient outcomes. RESULTS: After the introduction of thromboelastometry and tranexamic acid, fewer units of CRC were transfused during surgery, and fewer patients required postoperative CRC transfusion. Intra- and postoperative FFP requirements were also reduced. Intraoperative blood loss, blood loss in the first 24 hr after surgery, and length of hospital stay were also reduced. CONCLUSIONS: The use of ROTEM and tranexamic acid can potentially reduce blood loss and transfusion requirements in cardiac surgery.

Reappearance of circulating heparin in whole blood heparin concentration-based management does not correlate with postoperative bleeding after cardiac surgery.

OBJECTIVE: The Hepcon Heparin Management System (HMS) facilitates administration of higher heparin and lower protamine doses, which may affect bleeding potential due to heparin rebound. The present study evaluated heparin rebound in patients for whom the Hepcon HMS was used to determine whether point-of-care tests detect residual heparin and residual heparin is associated with postoperative blood loss. DESIGN: Prospective study. SETTING: Tertiary care center affiliated with a university hospital. PARTICIPANTS: Adults undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: In blood samples obtained at baseline, at 2 minutes, and at 1, 2, 4, 6, and 24 hours after heparin neutralization, heparin concentrations were measured using an automated chromogenic assay. Activated coagulation time (ACT), activated partial thromboplastin time (APTT), and thromboelastometry 2 hours after heparin neutralization also were examined in the last 22 study patients enrolled. MEASUREMENTS AND MAIN RESULTS: All 31 patients had measurable heparin levels 2 hours after protamine administration; 22 patients exhibited a primary failure to reverse heparin after protamine administration, and 9 patients had measureable heparin levels 2 hours after complete heparin reversal (ie, heparin rebound). The thromboelastometric variable, INTEM-CT:HEPTEM-CT ratio, correlated with heparin concentration (r=0.72), but ACT (r=-0.12), APTT (r=0.36), and whole blood heparin concentration, determined using the Hepcon HMS, did not. Peak heparin concentration (0.18±0.07 U/mL) at 4 hours was not correlated with mediastinal blood loss. CONCLUSION: Circulating heparin detected by the chromogenic assay was too low to be clinically significant based on postoperative bleeding, although all 31 patients had residual heparin or heparin rebound at 2 hours after protamine administration with use of the Hepcon HMS.

Current problems and working status of female anesthesiologists in Japan.

The rapid growth of the elderly population and the progress in surgical techniques in Japan have led to increased numbers of patients who undergo surgery. Anesthetics are essential for surgery. A survey conducted by the Japanese Society of Anesthesiologists showed that, during the past 10 years, the proportion of females among all the members has increased from 27 to 35 %, and the proportion of female councilors has risen from 3.9 to 6.7 %. However, the conditions of full-time employment remain inadequate for female physicians. Therefore, many female physicians in their 30s or older do not work as anesthesiologists. To support female anesthesiologists and their vital roles in surgical diagnosis and treatment, return-to-work assistance programs have been developed. It is also necessary to improve the working conditions for female anesthesiologists to allow them to continue their work, and to provide education for young female physicians to enhance their professional pride.

[A patient with congenital antithrombin III deficiency who underwent laparoscopic renal resection].

A 66-year-old man with congenital antithrombin III (ATIII) deficiency was scheduled to undergo laparoscopic renal resection. On admission the plasma ATIII activity was as low as 56%. After giving ATIII intravenously, the plasma ATIII activity increased to 103% on the day of surgery. It is usually difficult to monitor ATIII during surgery. Instead, we measured activated clotting times (ACTs). The ACT before operation was 178 seconds. During the operation, the ACT dropped to 81 seconds. We administered 3,000 units of heparin, and the ACT increased to 182 seconds. After surgery, the plasma ATIII activity was 68%. We managed the ACT activity to a target value of 100% postoperatively, until the patient was switched from heparin to oral warfarin. He was discharged without complications 10 days after surgery. In this patient, the ACT decreased during the operation, as did the ATIII activity. Although the half-life of the ATIII preparation was 3 days, it appeared that the ATIII activity, which was high preoperatively, decreased during the operation. Coagulation abnormalities could be managed quickly by measuring ACT. Our results suggest that the measurement of ACT is an effective technique for the intraoperative monitoring of patients with congenital ATIII deficiency.

The fentanyl concentration required for immobility under propofol anesthesia is reduced by pre-treatment with flurbiprofen axetil.

PURPOSE: We hypothesized that nonsteroidal anti-inflammatory drugs decrease the plasma fentanyl concentration required to produce immobility in 50% of patients in response to skin incision (Cp50incision) compared with placebo under target-controlled infusion (TCI) propofol anesthesia. METHODS: Sixty-two unpremedicated patients scheduled to undergo gynecologic laparoscopy were randomly assigned to receive placebo (control group) or flurbiprofen axetil 1 mg·kg(-1) (flurbiprofen group) preoperatively. General anesthesia was induced with fentanyl and propofol, and intubation was performed after succinylcholine 1 mg·kg(-1). Propofol was administered via a target-controlled infusion (TCI) system (Diprifusor™) set at an effect-site concentration of 5 µg·mL(-1). Fentanyl was given by a TCI system using the STANPUMP software (Schafer model). The concentration for the first patient was set at 3 ng·mL(-1) and modified in each group according to the up-down method. Skin incision was performed after more than ten minutes equilibration time. Serum fentanyl concentration, bispectral index (BIS), and hemodynamic parameters were measured two minutes before and after skin incision. The Cp50incision of fentanyl was derived from the mean of the crossovers (i.e., the serum fentanyl concentrations of successive participants who responded and those who did not or vice versa). RESULTS: Ten and 11 independent crossover pairs were collected in the control and flurbiprofen groups, respectively, representing 42 of 62 enrolled patients. The mean (SD) fentanyl Cp50incision was less in the flurbiprofen group [0.84 (0.63) ng·mL(-1)] than in the control group [1.65 (1.15) ng·mL(-1)]; P = 0.007; however, there were no differences in BIS, blood pressure, or heart rate, between groups. CONCLUSION: Preoperative flurbiprofen axetil decreased the Cp50incision of fentanyl by 49% during propofol anesthesia without changing the BIS or hemodynamic variables.

[A case of postoperative convulsive seizure following tranexamic acid infusion during aortic valve replacement].

We present a case of postoperative convulsive seizure in an 84-year-old man who underwent an aortic valve replacement. The patient had hypertension associated with hyperaldosteronism and chronic interstitial nephritis. The duration of cardiopulmonary bypass was 74 min. A generalized seizure lasting approximately 1 minute occurred at 1 hour after the patient's arrival in the intensive care unit. A total of 9 generalized seizures, which were aborted by the intravenous administration of diazepam (5 mg), occurred every 30 min. For seizure control, the continuous administration of midazolam (2 mg x hr(-1)) was initiated. On the day after the discontinuation of the midazolam, a generalized seizure recurred and an infusion of sodium thiopental was started. No further seizures were observed. On the sixth postoperative day, the patient was extubated and discharged without any neurological abnormalities. Imaging showed old small areas of cerebral infarction in the basal ganglia, which were not thought to have contributed to the seizures. The blood sugar, sodium, and calcium levels were within the normal limits. The seizures were likely due to a total dose of 8 g of tranexamic acid (TXA) administered intraoperatively. Possible mechanisms of TXA-induced seizures include blockage of inhibitory cortical y -aminobutyric acid-A receptors.

Hemostatic capability of ultrafiltrated fresh frozen plasma compared to cryoprecipitate.

This in vitro study evaluated the potential hemostatic effect of fresh frozen plasma (FFP) ultrafiltration on clotting factors, coagulation parameters, and plasma properties. ABO-specific units of FFP (n = 40) were prepared for the concentrated FFP and cryoprecipitate. Plasma water was removed from FFP by ultrafiltration using a dialyzer with a pump running at a 300 mL/min. The aliquot of each concentrated FFP after 50, 100, 200, and 250 mL of fluid removal were measured the standard coagulation assay, clotting activity, and plasma properties to compare those parameters of cryoprecipitate. Concentrated FFP contained 36.5% of fibrinogen in FFP with a mean concentration of 7.2 g/L, lower than the cryoprecipitate level. The levels of factor VIII (FVIII), von Willebrand factor (VWF):antigen (Ag), and VWF:ristocetin cofactor (RCo) were also lower in concentrated FFP, whereas the levels of factor V, factor IX, factor XIII, antithrombin and albumin was higher in concentrated FFP. Maximum clot firmness (MCF) in thromboelastometry was approximately one-half of that in cryoprecipitate. Although the levels of VWF:Ag, VWF:RCo, and FVIII differed depending on the ABO blood types, fibrinogen levels, and MCF were not significantly different among the ABO blood groups in FFP and concentrated FFP.

Auditory evoked potential index does not correlate with observer assessment of alertness and sedation score during 0.5% bupivacaine spinal anesthesia with nitrous oxide sedation alone.

PURPOSE: The aim of this study was to evaluate the auditory evoked potential (AEP) index as a hypnosis monitor during nitrous oxide (N(2)O) sedation added to spinal analgesia. METHODS: Forty-five patients scheduled to undergo surgery under spinal anesthesia were recruited after giving informed consent. Adequate anesthesia levels were confirmed, and a disposable AEP index sensor (aepEX, Medical Device Management) was placed. A tight facemask was fitted, and a fresh gas flow of 100% oxygen 10 L/min was provided. AEP index monitoring was then initiated, and measurements and observer assessment of alertness/sedation (OAA/S) scores were recorded manually. N(2)O was administered in stepwise increases in the end-tidal concentration of 33%, 50%, and 67%. Paired AEP index and OAA/S scores were obtained immediately before each change in N(2)O concentration. RESULTS: Sixteen patients were excluded from final analysis because of nausea, vomiting, or abnormal excitatory behaviors. The increases in N(2)O concentration induced significant decreases in OAA/S scores and no substantial AEP index changes. Although OAA/S scores of 1 and 2 were observed in only two and five patients, respectively, a reduction in the OAA/S score from 5 to 1 was associated with a significant decrease in AEP index to the level indicative of moderate sedation. CONCLUSION: The AEP index might not be a suitable indicator of light hypnosis as defined by an OAA/S score of ≥3 during sedation with N(2)O alone.

[The correlation of middle ear pressure variations with mastoid pneumatization during nitrous oxide administration].

BACKGROUND: The present study evaluated the relationship between the middle ear (ME) pressure increase rate (PIR) and the mastoid size as well as the effect of mastoid size on the incidence of nausea and vomiting during nitrous oxide (N2O) anesthesia. METHODS: Twelve healthy male volunteers were recruited. The extent of mastoid pneumatization was measured planimetrically using a mastoid X-ray (Schuller's view). The ears were then divided into a small or large mastoid group according to the median value. The ME pressure was compared just before each increase to 33%, 50%, and 67% N2O. Using the ME pressure curve, the PIR for the first peak of the curve steepness was calculated. RESULTS: Increasing the end-tidal N2O concentration to 50% and 67% in the large mastoid group and to 33%, 50%, and 67% in the small mastoid group significantly increased the ME pressure. The PIR in the ears in the large mastoid group was significantly lower and the incidence of nausea was 33% in the small mastoid group during 33% N2O anesthesia. CONCLUSIONS: A higher PIR in the ears and a higher incidence of nausea were observed in the small mastoid group, compared with the large mastoid group.