Fixing the anesthesia research crisis in Japan.

To explore the current status of anesthesia research activity in Japan, we analyzed the number of abstracts presented at the Japanese Society of Anesthesiologists (JSA) annual meetings by several factors including gender, society branches, and subspecialty categories. The number of abstracts at JSA annual meetings has declined sharply since 2016 with no gender gap. A decrease in the neurological field predated the overall decline, but other subspecialty categories showed a similar decline. Although the Tokyo, Tokai-Hokuriku, and Kyushu branches were responsible for more than half of the reduction, the trend was similar among all branches. In a survey regarding academic activities of university hospital residents and faculty, Ph.D. aspirants' rate was only 20-30%. Residents had never presented an abstract at scientific conferences and never published any papers at nearly 40% and 30% of the university hospitals, respectively. Our survey suggests that junior anesthetists are losing interest in research. Senior faculty and mentors must redouble efforts to embed and encourage research in departments and by anesthetists in training. If a revival of anesthesia research in Japan does not occur then a service only specialty awaits.

Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial.

PURPOSE: This trial was conducted to confirm the non-inferiority of remimazolam versus propofol in the induction and maintenance of general anesthesia in surgical patients. METHODS: Surgical patients (n = 375) were randomized to remimazolam started at 6 or 12 mg/kg/h by continuous intravenous (IV) infusion until the loss of consciousness (LoC), followed by 1 mg/kg/h to be adjusted as appropriate until the end of surgery or IV propofol administered as a slow bolus of 2.0-2.5 mg/kg until LoC followed by 4-10 mg/kg/h until the end of surgery. Efficacy was measured via the combined primary endpoint of no intraoperative awakening/recall, no need for rescue sedatives, and no body movements. Adverse events and adverse drug reactions (ADRs) were monitored for safety. RESULTS: Efficacy rates were 100% in all treatment groups, and the non-inferiority of remimazolam was demonstrated [95% confidence interval (- 0.0487; 0.0250)]. The time to LoC was longer in the remimazolam 6 (p < 0.0001) and 12 mg/kg/h (p = 0.0149) groups versus propofol. The time to extubation was longer in both remimazolam groups versus the propofol group (p ≤ 0.0001). The incidence of ADRs was similar in the remimazolam groups (39.3% and 42.7%, respectively) compared with the propofol group (61.3%). Decreased blood pressure occurred in 20.0% and 24.0% of patients treated with 6 and 12 mg/kg/h remimazolam, respectively, compared with 49.3% of patients receiving propofol. Injection site pain was reported in 18.7% of propofol patients but not in those receiving remimazolam. CONCLUSIONS: This trial demonstrated that remimazolam was well tolerated and non-inferior to propofol with regard to efficacy as a sedative hypnotics for general anesthesia. CLINICAL TRIAL REGISTRATION: This trial is registered with the Japan Pharmaceutical Information Center - Clinical Trials Information (JapicCTI). JapicCTI number: 121973.

Combination therapy of 15-epi-lipoxin A4 with antibiotics protects mice from Escherichia coli-induced sepsis*.

OBJECTIVES: Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 µg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli. MEASUREMENTS AND MAIN RESULTS: Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli. CONCLUSIONS: 15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

A general anaesthetic propofol inhibits aquaporin-4 in the presence of Zn²âº.

AQP4 (aquaporin-4), a water channel protein that is predominantly expressed in astrocyte end-feet, plays an important role in the brain oedema formation, and is thereby considered to be a potential therapeutic target. Using a stopped-flow analysis, we showed that propofol (2,6-diisopropylphenol), a general anaesthetic drug, profoundly inhibited the osmotic water permeability of AQP4 proteoliposomes in the presence of Zn²âº. This propofol inhibition was not observed in AQP1, suggesting the specificity for AQP4. In addition, the inhibitory effects of propofol could be reversed by the removal of Zn²âº. Other lipid membrane fluidizers also similarly inhibited AQP4, suggesting that the modulation of protein-lipid interactions plays an essential role in the propofol-induced inhibition of AQP4. Accordingly, we used Blue native PAGE and showed that the profound inhibition caused by propofol in the presence of Zn²âº is coupled with the reversible clustering of AQP4 tetramers. Site-directed mutagenesis identified that Cys²5³, located at the membrane interface connecting to the C-terminal tail, is responsible for Zn²âº-mediated propofol inhibition. Overall, we discovered that propofol specifically and reversibly inhibits AQP4 through the interaction between Zn²âº and Cys²5³. The findings provide new insight into the functional regulation of AQP4 and may facilitate the identification of novel AQP4-specific inhibitors.

Safety and efficacy of dexmedetomidine for long-term sedation in critically ill patients.

PURPOSE: We evaluated the safety and efficacy of long-term administration of dexmedetomidine in patients in the intensive care unit (ICU). Primary endpoint was the incidence of hypotension, hypertension, and bradycardia. Secondary endpoints were withdrawal symptoms, rebound effects, the duration of sedation with Richmond Agitation-Sedation Scale (RASS) ≤ 0 relative to the total infusion time of dexmedetomidine, and the dose of additional sedatives or analgesics. METHODS: Dexmedetomidine 0.2-0.7 µg/kg/h was continuously infused for maintaining RASS ≤ 0 in patients requiring sedation in the ICU. Safety and efficacy of short-term (≤ 24 h) and long-term (>24 h) dexmedetomidine administration were compared. RESULTS: Seventy-five surgical and medical ICU patients were administered dexmedetomidine. The incidence of hypotension, hypertension, and bradycardia that occurred after 24 h (long-term) was not significantly different from that occurring within 24 h (short-term) (P = 0.546, 0.513, and 0.486, respectively). Regarding withdrawal symptoms, one event each of hypertension and headache occurred after the end of infusion, but both were mild in severity. Increases of mean arterial blood pressure and heart rate after terminating the infusion of dexmedetomidine were not associated with the increasing duration of its infusion. The ratio of duration with RASS ≤ 0 was ≥ 85 % until day 20, except day 9 (70 %) and day 10 (75 %). There was no increase in the dose of additional sedatives or analgesics after the first 24-h treatment period. CONCLUSIONS: Long-term safety of dexmedetomidine compared to its use for 24 h was confirmed. Dexmedetomidine was useful to maintain an adequate sedation level (RASS ≤ 0) during long-term infusion.

Symptoms overlooked in hospitalized cancer patients: Impact of concurrent symptoms on oversight [corrected] by nurses.

OBJECTIVE: Physical and psychological symptoms in cancer patients are frequently overlooked by medical staff. However, little is known regarding the potential impacts of concurrent physical and psychological symptoms on the overlooking of other symptoms. The aim of this study was to examine the impact of concurrent symptoms on the overlooking of other symptoms in cancer inpatients. METHOD: A total of 255 cancer inpatients in the general wards of one university hospital, who were referred to the palliative care team, were included. On the day of referral, nurses and patients were independently assessed for the presence of the following eight symptoms: pain, fatigue, nausea and vomiting, shortness of breath, lack of appetite, dry mouth, sleep problems, and distressed feelings. The presence of delirium was also separately assessed by nurses and psychiatrists on the team. A total of nine symptoms detected by nurses and those reported by patients or psychiatrists were compared, and logistic regression analysis was performed to identify the variables associated with the overlooking of these symptoms. RESULTS: The most frequently reported symptom was pain (76.5%), followed by distressed feelings (49.8%), sleep problems (34.1%), and delirium (25.1%). The proportion of those overlooked was more than one quarter (25.0-63.6%) for all symptoms except pain (12.8%). Significant associations were found between the overlooking of shortness of breath and concurrent delirium (odds ratio [OR] = 110.9); the overlooking of sleep problems and concurrent lack of appetite (OR = 9.1); and the overlooking of distressed feelings and concurrent dry mouth (OR = 27.7). No patient demographic characteristic was associated with the overlooking of any other symptoms. SIGNIFICANCE OF RESULTS: The presence of some specific concurrent symptoms is likely to lead to the overlooking of other symptoms in cancer inpatients by nurses. Comprehensive assessments of physical and psychological symptoms in daily clinical practice are needed.

Questionnaire survey on current status of home care and support for patients with hematological diseases.

In order to survey the current status of home care and support for patients with hematological diseases, questionnaires were sent to 3,591 hospitals and home care facilities in Tokyo and surrounding prefectures. The first survey showed that 81.7% of medical staff members at hospitals reported that they had experience with home care and support, but only 24.9% of home care facility staff members had such experience. The second questionnaire, surveying 1,202 personnel, identified four factors hampering successful establishment of home care and support networks for hematological diseases. These included insufficient familial support for patients, difficulty making end of life decisions by family members and patients, limited access to transfusion support, and financial problems.

[Anesthetic management of a neonate with congenital cystic adenomatoid malformation].

We report the anesthetic management of a female neonate with congenital cyst adenoid malformation (CCAM) type III of the lung who underwent the lower right lobe resection 22 days after birth. General anesthesia was induced with propofol and rocuronium. The trachea was intubated with a 3.0 standard tube. Anesthesia was maintained with sevoflurane in an air/oxygen mixture and fentanyl. Intraoperative anesthetic course was uneventful except transient desaturation during lung compression. Immediately, the saturation was restored by interruption of lung compression. One lung ventilation was not necessary in this operation. Postoperative course was uneventful. Patient was discharged home on the 28th postoperative day.

[Efficacy and safety of sugammadex (Org 25969) in reversing moderate neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 98 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional doses of rocuronium or vecuronium for maintenance of moderate block. At T2 reappearance sugammadex 0-4.0 mg . kg-1 was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 82.1 min in the placebo group to 1.8 min in the 4.0 mg . kg-1 sugammadex group. For the vecuronium-induced neuromuscular block, it decreased from 83.2 min in the placebo group to 2.1 min in the sugammadex 4.0 mg . kg-1 group. Plasma concentrations of sugammadex were approximately dose proportional over the dose range of 0.5 to 4.0 mg . kg-1 and independent of the neuromuscular blocking agents used. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients.

[Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.

BACKGROUND: In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-induced neuromuscular blockade, this advantage has not been confirmed in clinical settings when no neuromuscular monitoring is used. In this multicenter observational study, we sought to determine whether sugammadex reduces the incidence of postoperative residual weakness compared with neostigmine when the administration of rocuronium and its antagonists is not guided by neuromuscular monitoring. METHODS: This study was conducted in two 5-month periods that preceded and followed the introduction of sugammadex into clinical practice in Japan. Five university-affiliated teaching hospitals participated in this study. Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase. The timing and doses of rocuronium, neostigmine, and sugammadex were determined by the attending anesthesiologists without the use of neuromuscular function monitoring devices. To ascertain the incidence of postoperative residual neuromuscular weakness, the train-of-four ratio (TOFR) was determined acceleromyographically after tracheal extubation. Since our practice also does not usually involve calibration and normalization of accelerographic responses, both TOFR <0.9 and TOFR <1.0 were used as the criteria for defining postoperative residual weakness. RESULTS: In the first phase, 109 patients received neostigmine (average dose 33 µg/kg) and 23 patients were considered (by clinical criteria) to have adequate recovery and did not receive neostigmine (spontaneous recovery group). In the second phase, 117 patients received sugammadex (average dose 2.7 mg/kg) for antagonism of rocuronium-induced blockade. The incidence (95% confidence interval) of TOFR <0.9 under spontaneous recovery, after neostigmine, and after sugammadex, was 13.0% (2.8%-33.6%), 23.9% (16.2%-33.0%), and 4.3% (1.7%-9.4%), respectively. The incidence (95% confidence interval) of TOFR <1.0 in these groups was 69.6% (47.1%-86.6%), 67.0% (57.3%-75.7%), and 46.2% (36.9%-55.6%), respectively. The use of sevoflurane in the neostigmine group and the short interval between the administration of the last doses of rocuronium and sugammadex were associated with a higher incidence of postoperative residual weakness. CONCLUSIONS: This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.

Atrial natriuretic peptide reduces hepatic ischemia-reperfusion injury in rabbits.

PURPOSE: Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model. METHODS: With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 µg/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated. RESULTS: Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion. CONCLUSIONS: ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.

A prospective randomized multicenter comparative study of BLM-240 (desflurane) versus sevoflurane in Japanese patients.

The present study was conducted to evaluate the efficacy and safety of BLM-240 (desflurane) in comparison to sevoflurane in Japanese patients. A total of 216 patients were enrolled in this randomized comparative study at 15 medical institutions. The patients received either BLM-240 with 50-70 % N2O in O2 (n = 111), BLM-240 with 30 % O2 in air (n = 55), or sevoflurane with 50-70 % N2O in O2 (n = 50). Efficacy was evaluated by an efficacy rate based on an efficacy evaluation criteria and recovery time to extubation from the discontinuation of the anesthetics. Safety was evaluated by incidence of adverse drug reactions (ADR) and other clinical indicators. The efficacy rate of BLM-240 was 98.8 % (164/166 patients), indicating that BLM-240 is effective as an anesthetic. Time from discontinuation of anesthetic delivery to extubation was 9.7 ± 0.6 min in the BLM-240/N2O group and 14.3 ± 0.9 min in the sevoflurane/N2O group, meeting the pre-defined non-inferiority criteria of BLM-240 to sevoflurane. There was no statistically significant difference in the incidence of total ADR between the BLM-240 group (62.0 %) and sevoflurane group (48.0 %). The results indicate that BLM-240 is an effective and safe inhalation anesthetic in Japanese patients.

[Anesthetic management of a patient with severe aortic stenosis undergoing spine surgery].

An 87-year-old man with severe aortic stenosis (AS), refusing aortic valve surgery, was scheduled to undergo posterior spinal fusion. According to American College of Cardiology/American Heart Association (ACC/AHA) 2008 Guideline, aortic valve surgery is recommended before non-cardiac surgery in a patient with severe AS. Several reports have noted that non-cardiac surgery could be performed safely with careful anesthetic management by adjusting left ventricular preload and systemic arterial pressure, and avoiding tachycardia. We used pulmonary artery catheter to estimate left ventricular preload, which is an especially essential factor for maintaining cardiac output. Transesophageal echocardiography has been proved to be superior to pulmonary artery catheter for evaluating left ventricular preload. However, it is difficult to perform in the prone position. Although pulmonary artery wedge pressure (PAWP) is influenced in prone position due to the chest compression, PAWP combined with cardiac index and their responsiveness to fluid administration is valuable in hemodynamic management in a patient with severe AS.

[Perioperative anticoagulant therapy in a patient with congenital antithrombin III deficiency undergoing posterior spinal fusion].

A 22-year-old female was scheduled to undergo posterior thoracolumbar spinal fusion. She had been diagnosed with congenital antithrombin III (AT-III) deficiency by the onset of pulmonary embolism and deep vein thrombosis after the first operation at the age of 18. Thereafter she had taken warfarin, 5 mg daily, until 4 days before the surgery. Preoperatively, we administered AT-III products to regulate AT-III activity. The posterior spinal fusion was performed successfully without surgical complications. Postoperatively, we continued administration of AT-III products to maintain AT-III activity above 75%. We also used low dose unfractionated heparin with AT-III by continuous intravenous infusion. Heparin was administered with dose adjustment to achieve a target activated partial thromboplastin time of 45 to 60 seconds. After the activated partial thromboplastin time was stabilized in the target range, we started warfarin therapy (target international normalized ratio, 1.5 to 2.5) on postoperative day 16 and stopped administration of heparin on postoperative day 19. There was no thrombosis complications during the perioperative period. Good anticoagulant management was achieved in a patient with congenital AT-III deficiency undergoing posterior spinal fusion.

The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury.

Whereas pneumonia is the most common cause of death and disability worldwide, most cases of pneumonia spontaneously resolve. Mechanisms that promote pneumonia resolution remain to be determined. Resolvin E1 (RvE1) is an endogenous mediator that displays proresolving actions in sterile inflammation. In this study, we developed a new model of aspiration pneumonia to evaluate the effect of RvE1 on acute lung injury caused by acid aspiration and subsequent bacterial challenge. Mice received hydrochloric acid into the left lung followed by the enteric pathogen Escherichia coli. I.v. administration of RvE1 (approximately 0.005 mg/kg) prior to acid injury selectively decreased lung neutrophil accumulation by 55% and enhanced clearance of E. coli. RvE1 significantly decreased lung tissue levels of several proinflammatory chemokines and cytokines, including IL-1beta, IL-6, HMGB-1, MIP-1alpha, MIP-1beta, keratinocyte-derived chemokine, and MCP-1, in a manner independent of the anti-inflammatory mediators IL-10 and lipoxin A4. In addition, animals treated with RvE1 had a marked improvement in survival. These findings in experimental aspiration pneumonia have uncovered protective roles for RvE1 in pathogen-mediated inflammation that are both anti-inflammatory for neutrophils and protective for host defense, suggesting that RvE1 represents the first candidate for a novel therapeutic strategy for acute lung injury and pneumonia that harnesses natural resolution mechanisms.

Multicenter study verifying a method of noninvasive continuous cardiac output measurement using pulse wave transit time: a comparison with intermittent bolus thermodilution cardiac output.

BACKGROUND: Many technologies have been developed for minimally invasive monitoring of cardiac output. Estimated continuous cardiac output (esCCO) measurement using pulse wave transit time is one noninvasive method. Because it does not require any additional sensors other than those for conducting 3 basic forms of monitoring (electrocardiogram, pulse oximeter wave, and noninvasive (or invasive) arterial blood pressure measurement), esCCO measurement is potentially useful in routine clinical circulatory monitoring for any patient including low-risk patients. We evaluated the efficacy of noninvasive esCCO using pulse wave transit time in this multicenter study. METHODS: We compared esCCO and intermittent bolus thermodilution cardiac output (TDCO) in 213 patients, 139 intensive care units (ICUs), and 74 operating rooms (ORs), at 7 participating institutions. We performed electrocardiogram, pulse oximetry, TDCO, and arterial blood pressure measurements in patients in ICUs and ORs; a single calibration was performed to measure esCCO continuously. TDCO measurement was performed once daily for ICU patients and every hour for OR patients, and just before the removal of the pulmonary arterial catheter from patients in both the ICU and OR. We evaluated esCCO against TDCO with correlation analysis and Bland and Altman analysis and also assessed the change of bias over time. Furthermore, we inspected the impact of change in systemic vascular resistance (SVR) on change in bias because abnormal SVR was assumed to be a factor contributing to the change of the bias. RESULTS: From among 588 esCCO and TDCO datasets (excluding calibration points), 587 datasets were analyzed for 213 patients. The analysis results show a correlation coefficient of 0.79 (P < 0.0001, 95% confidence limits of 0.756-0.819), a bias (mean difference between esCCO and TDCO) of 0.13 L/min (95% confidence interval of bias 0.04-0.22 L/min), and a precision (1 SD) of 1.15 L/min (95% prediction interval was -2.13 to 2.39 L/min). There were no significant differences among 3 defined time intervals over 48 hours after calibration (repeated-measures analysis of variance P = 0.781) in the ICU. The influence of SVR on esCCO analysis showed a correlation coefficient between SVR and an error of 0.37 (P < 0.0001, 95% confidence interval 0.298-0.438). CONCLUSION: The efficacy of noninvasive esCCO technology was compared with TDCO in 213 cases. Five hundred eighty-seven datasets comparing esCCO and TDCO showed close correlation and small bias and precision, which were comparable to current arterial waveform analysis technologies.

The ability of a new continuous cardiac output monitor to measure trends in cardiac output following implementation of a patient information calibration and an automated exclusion algorithm.

A new non-invasive continuous cardiac output (esCCO) monitoring system solely utilizing a routine cardiovascular monitor was developed, even though a reference cardiac output (CO) is consistently required. Subsequently, a non-invasive patient information CO calibration together with a new automated exclusion algorithm was implemented in the esCCO system. We evaluated the accuracy and trending ability of the new esCCO system. Either operative or postoperative data of a multicenter study in Japan for evaluation of the accuracy of the original version of esCCO system were used to develop the new esCCO system. A total of 207 patients, mostly cardiac surgical patients, were enrolled in the study. Data were manually reviewed to formulate a new automated exclusion algorithm with enhanced accuracy. Then, a new esCCO system based on a patient information calibration together with the automated exclusion algorithm was developed. CO measured with a new esCCO system was compared with the corresponding intermittent bolus thermodilution CO (ICO) utilizing statistical methods including polar plots analysis. A total of 465 sets of CO data obtained using the new esCCO system were evaluated. The difference in the CO value between the new esCCO and ICO was 0.34 ± 1.50 (SD) L/min (95 % confidence limits of -2.60 to 3.28 L/min). The percentage error was 69.6 %. Polar plots analysis showed that the mean polar angle was -1.6° and radial limits of agreement were ±53.3°. This study demonstrates that the patient information calibration is clinically useful as ICO, but trending ability of the new esCCO system is not clinically acceptable as judged by percentage error and polar plots analysis, even though it's trending ability is comparable with currently available arterial waveform analysis methods.

Retrospective evaluation of intravenous fentanyl patient-controlled analgesia during labor.

PURPOSE: Because the safety of intravenous fentanyl patient-controlled analgesia (iv-PCA) administered during labor remains unclear, we retrospectively examined the labor records from January 2005 to December 2007 in our institution, with a focus on both maternal and neonatal outcomes, as compared to no analgesia. METHODS: Parturients over 35 weeks of gestational age who received fentanyl iv-PCA (iv-PCA group) or no analgesia (control group) during labor were enrolled. The former group received iv-PCA through a pump programmed to give a loading dose of 0.05 mg fentanyl, followed by bolus injection of 0.02 mg fentanyl, with a lock-out interval of 5 min. This analgesia was initiated at the parturient's request and was discontinued before the second stage of labor, to ensure neonatal safety. During labor, both maternal and fetal heart rates, maternal pulse oximeter oxygen saturation (SpO(2)), respiratory rate, and sedation and nausea scores were continuously monitored, and the neonatal outcomes including umbilical arterial pH, Apgar scores, and other parameters were recorded. RESULTS: The data of 129 of the 143 parturients who received fentanyl iv-PCA were analyzed, while 697 parturients delivered without any analgesia during the 3-year study period. While iv-PCA prolonged the duration of labor and increased oxytocin use, no obvious maternal or neonatal complications of fentanyl use were recorded. Except for the significantly lower rate of emergency cesarean section in the iv-PCA group, both the maternal and neonatal outcomes were comparable between the groups. CONCLUSIONS: As compared to no analgesia, fentanyl iv-PCA appears to be safe and clinically acceptable as analgesia during labor, particularly in nulliparous women.

[Comparison of continuous cardiac output measurement methods: non-invasive estimated CCO using pulse wave transit time and CCO using thermodilution].

BACKGROUND: esCCO (estimated continuous cardiac output, Nihon Kohden, esCCO) is a new cardiac output measurement system which uses pulse wave transit time to calculate cardiac output continuously and non-invasively. One of the most commonly used methods to monitor cardiac output is continuous cardiac output CCO (Edwards Lifesciences) which has an accuracy equivalent to that of thermodilution method. METHODS: We compared esCCO to CCO in 67 operating room patients and 128 intensive care unit patients. CCO and esCCO were measured simultaneously in patients with a pulmonary artery catheter inserted after admission to the operating room or intensive care unit. RESULTS: CCO and esCCO showed a high correlation with a correlation coefficient of 0.84 in 496 total data points, and 95% limits of agreement between these two methods were -2.49 to 2.35 l x min(-1). CONCLUSIONS: This result suggests that esCCO could be used to measure cardiac output accurately and non-invasively in different cases.