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.

Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.

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.

Storage duration of transfused red blood cells is not significantly associated with postoperative adverse events in pediatric cardiac surgery patients.

The aim of this study was to evaluate the association of storage duration of transfused red blood cells with the risk of postoperative serious adverse events in pediatric cardiac surgery patients. We studied 517 patients and found that 22 patients (4.3%) had at least one serious adverse event. The maximum and mean storage duration of transfused red blood cells did not differ significantly between patients with and without serious adverse events (maximum, p = 0.89; mean, p = 0.81). In our study of pediatric cardiac surgery patients, the storage duration of transfused red blood cells was not significantly associated with the risk of serious adverse events.

Urinary Albumin Levels Predict Development of Acute Kidney Injury After Pediatric Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: Mortality and morbidity of acute kidney injury (AKI) after cardiac surgery still remain high. The authors undertook the present study to evaluate the utility of early postoperative urinary albumin (uAlb) as a diagnostic marker for predicting occurrence of AKI and its severity in pediatric patients undergoing cardiac surgery. DESIGN: A prospective observational study. SETTING: A single-institution university hospital. PARTICIPANTS: All patients<18 years of age who underwent repair of congenital heart disease with cardiopulmonary bypass between July 2010 and July 2012 were included in the study. Neonates age<1 month were excluded from the study population. INTERVENTIONS: The association between uAlb and occurrence of AKI within 3 days after admission to the intensive care unit was investigated. Criteria from pediatric-modified Risk Injury Failure Loss and End-stage kidney disease (pRIFLE) were used to determine the occurrence of AKI. The value of uAlb was measured at intensive care unit admission immediately after cardiac surgery in all participants from whom a 5-mL urine sample was obtained. MEASUREMENTS AND MAIN RESULTS: Of 376 patients, AKI assessed by pRIFLE was identified in 243 (64.6%): 172 for risk (R; 45.7%), 44 for injury (I; 11.7%), and 27 for failure (F; 7.2%). One hundred thirty-three patients (35.4%) were classified as being without AKI (normal [N]) by pRIFLE. The concentration of uAlb was significantly higher in AKI patients than in non-AKI patients (median [interquartile range]): uAlb (µg/mL): 13.5 (6.4-39.6) v 6.0 (3.4-16), p<0.001; uAlb/Cr (mg/gCr): 325 (138-760) v 121 (53-269), p< 0.001. CONCLUSIONS: The utility of uAlb for prompt diagnosis of AKI was shown. Obtaining uAlb measurements early after pediatric cardiac surgery may be useful for predicting the occurrence and severity of AKI.

Isoflurane Induces Transient Impairment of Retention of Spatial Working Memory in Rats.

Postoperative cognitive dysfunction (POCD) occurs in nearly one-third of patients after non-cardiac surgery. Many animal behavior studies have investigated the effect of general anesthesia on cognitive function. However, there have been no studies examining the effects on working memory specifically, with a focus on the retention of working memory. We demonstrate here that isoflurane anesthesia induces deficits in the retention of spatial working memory in rats, as revealed by an increase in isoflurane- induced across-phase errors in the delayed spatial win-shift (SWSh) task with a 30-min delay in an 8-arm radial arm maze on post-anesthesia days (PADs) 1,2,4, and 10. A post-hoc analysis revealed a significant increase in across-phase errors on PAD 1 and recovery on PAD 10 in the isoflurane group. In contrast, within-phase errors independent of the retention of working memory were unaffected by isoflurane. These results demonstrate that isoflurane anesthesia transiently impairs the retention of spatial working memory in rats.

[Subcutaneous continuous injection of octreotide decreased the tumor marker levels and induced cystic necrosis of the tumors in a case of pancreatic neuroendocrine tumor with multiple hepatic metastases].

For symptom alleviation, subcutaneous continuous injection of octreotide was administered to a patient with pancreatic neuroendocrine tumor (NET) accompanied by multiple hepatic metastases and ascites. The level of the tumor marker neuron-specific enolase decreased to the normal range and cystic necrosis of the tumors was confirmed. There have been some reports on the antineoplastic effects of octreotide on pancreatic NET; therefore, octreotide appears to be a valid option as a therapeutic agent in patients with highly advanced pancreatic NET, in whom administration of molecular targeted or anticancer agents is difficult because of a poor general status.

[Acoustic respiratory rate monitoring in a patient with a tracheostomy: a case report].

Acoustic respiratory rate (RRa) monitoring has been validated for patients after general anesthesia and has been shown to be a useful technique. However, its feasibility in patients with a tracheostomy has not been assessed yet. Successful monitoring of RRa in a patient with a tracheostomy is described in this case report. A 56-year-old male patient was scheduled for cranioplasty after severe subarachnoidal hemorrhage under general anesthesia. A tracheostomy tube had been placed in the patient because of airway obstruction and altered spontaneous breathing. The acoustic sensor was placed at the usual position and RRa was successfully monitored by Rad 87 (Masimo Corp., Irvine). Statistical analysis was made for comparison of respiratory rate determined by RRa monitoring with respiratory rate visually counted by intensive care nurses. There was no statistically significant difference between the two respiratory rates (P = 0.82). RRa monitoring is useful even in patients with a tracheostomy.

ALBI score predicts morphological changes in esophageal varices following direct-acting antiviral-induced sustained virological response in patients with liver cirrhosis.

BACKGROUND: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.

Accuracy of blood-glucose measurements using glucose meters and arterial blood gas analyzers in critically ill adult patients: systematic review.

INTRODUCTION: Glucose control to prevent both hyperglycemia and hypoglycemia is important in an intensive care unit. Arterial blood gas analyzers and glucose meters are commonly used to measure blood-glucose concentration in an intensive care unit; however, their accuracies are still unclear. METHODS: We performed a systematic literature search (January 1, 2001, to August 31, 2012) to find clinical studies comparing blood-glucose values measured with glucose meters and/or arterial blood gas analyzers with those simultaneously measured with a central laboratory machine in critically ill adult patients. RESULTS: We reviewed 879 articles and found 21 studies in which the accuracy of blood-glucose monitoring by arterial blood gas analyzers and/or glucometers by using central laboratory methods as references was assessed in critically ill adult patients. Of those 21 studies, 11 studies in which International Organization for Standardization criteria, error-grid method, or percentage of values within 20% of the error of a reference were used were selected for evaluation. The accuracy of blood-glucose measurements by arterial blood gas analyzers and glucose meters by using arterial blood was significantly higher than that of measurements with glucose meters by using capillary blood (odds ratios for error: 0.04, P<0.001; and 0.36, P<0.001). The accuracy of blood-glucose measurements with arterial blood gas analyzers tended to be higher than that of measurements with glucose meters by using arterial blood (P=0.20). In the hypoglycemic range (defined as <81 mg/dl), the incidence of errors using these devices was higher than that in the nonhypoglycemic range (odds ratios for error: arterial blood gas analyzers, 1.86, P=0.15; glucose meters with capillary blood, 1.84, P=0.03; glucose meters with arterial blood, 2.33, P=0.02). Unstable hemodynamics (edema and use of a vasopressor) and use of insulin were associated with increased error of blood glucose monitoring with glucose meters. CONCLUSIONS: Our literature review showed that the accuracy of blood-glucose measurements with arterial blood gas analyzers was significantly higher than that of measurements with glucose meters by using capillary blood and tended to be higher than that of measurements with glucose meters by using arterial blood. These results should be interpreted with caution because of the large variation of accuracy among devices. Because blood-glucose monitoring was less accurate within or near the hypoglycemic range, especially in patients with unstable hemodynamics or receiving insulin infusion, we should be aware that current blood glucose-monitoring technology has not reached a high enough degree of accuracy and reliability to lead to appropriate glucose control in critically ill patients.

Low serum concentrations of vitamin B6 and iron are related to panic attack and hyperventilation attack.

Patients undergoing a panic attack (PA) or a hyperventilation attack (HVA) are sometimes admitted to emergency departments (EDs). Reduced serotonin level is known as one of the causes of PA and HVA. Serotonin is synthesized from tryptophan. For the synthesis of serotonin, vitamin B6 (Vit B6) and iron play important roles as cofactors. To clarify the pathophysiology of PA and HVA, we investigated the serum levels of vitamins B2, B6, and B12 and iron in patients with PA or HVA attending an ED. We measured each parameter in 21 PA or HVA patients and compared the values with those from 20 volunteers. We found that both Vit B6 and iron levels were significantly lower in the PA/HVA group than in the volunteer group. There was no significant difference in the serum levels of vitamins B2 or B12. These results suggest that low serum concentrations of Vit B6 and iron are involved in PA and HVA. Further studies are needed to clarify the mechanisms involved in such differences.

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.

[Effect of continuous interscalene block with ropivacaine at a low concentration on postoperative pain relief after arthroscopic rotator cuff reconstruction].

BACKGROUND: The analgesic effect of continuous interscalene block with ropivacaine at a low concentration was compared with that of single-shot interscalene block after arthroscopic rotator cuff reconstruction (ARCR). METHODS: Eighty patients scheduled to undergo ARCR from January 2010 to March 2012 were assigned to a group receiving postoperative continuous interscalene block (continuous group, n=46) and a group receiving single-shot interscalne block (single group, n=34). In both groups, ultrasound-guided interscalene block was performed before induction of general anesthesia. In the Continuous group, continuous interscalene infusion with 0.1% ropivacaine was performed up to postoperative 48 hours. Pain intensity (Prince-Henry scale), additional use of analgesics, and adverse effects were recorded. Statistical analysis was performed with Mann-Whitney test, and P<0.05 was considered to be significant. RESULTS: Pain intensity in the continuous group was significantly lower than that in the single group on the night of the day of operation and the morning of the first postoperative day. The frequency of use of additional analgesic in the continuous group was approximately half of that in the single group. No complete motor block was recorded during continuous infusion of ropivacaine. CONCLUSIONS: Postoperative continuous interscalene block with 0.1% ropivacaine provided sufficient analgesia without complete motor block.

[Increase in serum vecuronium concentration following sugammadex administration in a pediatric patient after prolonged sedation].

It is known that blood concentration of rocuronium increases after administration of sugammadex, but this is not clear in the case of vecuronium. We report a pediatric case in which serum vecuronium concentration increased following sugammadex administration after prolonged sedation using vecuronium. A 19-month-old girl weighing 7.8 kg had a history of aortic valvuloplasty at 4 months of age due to truncus arteriosus. She presented again to our hospital due to aortic regurgitation. She underwent aortic valvuloplasty and then aortic valve replacement. The postoperative course was complicated with severe heart failure and acute kidney injury requiring peritoneal dialysis. For that reason she required long-term sedation including administration of a large amount of muscle relaxant due to severe low cardiac output syndrome after aortic valvuloplasty. A total of 615 mg (79 mg x kg(-1)) of vecuronium was administered over a period of 24 days. On weaning from mechanical ventilation, 125 mg (16 mg x kg(-1)) of sugammadex was given. Vecuronium concentration measured by high-performance liquid chromatography (HPLC) was 5.03 ng x ml(-1) before sugammadex administration and increase to 13.98 ng x ml(-1) after that. However, blood concentration of metabolic products of vecuronium did not exceed the lower limits of measurement in each sample. She was successfully weaned from mechanical ventilation without recurarizarion. Serum concentration of vecuronium increased after administration of sugammadex because extravascular vecuronium was redistributed to intravascular space according to the concentration gradient induced by binding and clathration of vecuronium. The measured values of vecuronium after sugammadex administration on HPLC represented the total amount of free vecuronium and vecuronium combined with sugammadex. Recurarization might occur after sugammadex reversal in patients after long-term administration of vecuronium, especially if relatively smaller doses of sugammadex were given. We experienced a pediatric case in which serum vecuronium concentration increased following sugammadex administration after prolonged sedation using vecuronium. There is a risk of recurarization after sugammadex reversal in patients after long-term administration of vecuronium.

[An autopsy of G-CSF-producing anaplastic carcinoma of the pancreas with impaired accumulation on FDG-PET after S-1 chemotherapy].

This paper presents a woman in her 70's with G-CSF producing anaplastic carcinoma of the pancreas(Stage IVb)who underwent chemotherapy by S-1 alone. On FDG-PET after the first course, accumulation of FDG was impaired remarkably. After the second course, the patient died of carcinomatous pleuritis and peritonitis on the 88th day after initiation of treatment. G-CSF producing anaplastic carcinoma of the pancreas is extremely rare and there are no reports with regard to response evaluation by FDG-PET. Thus, this case has significant clinical value.

Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts.

Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent signaling, in macrophages. Ligand-mediated receptor trafficking to lipid rafts represents an early event in signal initiation of immune cells. Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91(phox)-deficient macrophages. CO selectively inhibited ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with the inhibition of ligand-induced ROS production in macrophages. TLR3 did not translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory effect of CO on TLR-induced cytokine production was abolished in gp91(phox)-deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated LPS-induced NADPH oxidase activity in vitro, potentially by binding to gp91(phox). Thus, CO negatively controlled TLR signaling pathways by inhibiting translocation of TLR to lipid rafts through suppression of NADPH oxidase-dependent ROS generation.

Effects of pharyngeal cooling on brain temperature in primates and humans: a study for proof of principle.

BACKGROUND: Pharyngeal cooling decreases brain temperature by cooling carotid arteries. This study was designed to evaluate the principle of pharyngeal cooling in monkeys and humans. METHODS: Monkeys (n = 10) were resuscitated following 12 min of cardiac arrest. Pharyngeal cooling (n = 5), in which cold saline (5°C) was perfused into the cuff at the rate of 500 ml/min, was initiated simultaneously with the onset of resuscitation for 30 min. Patients (n = 3) who were in an intensive care unit were subjected to 30 min of pharyngeal cooling under propofol anesthesia. RESULTS: In the animal study, core brain temperature was significantly decreased compared with that in the control group by 1.9°C (SD = 0.8, P < 0.001) and 3.1°C (SD = 1.0, P < 0.001) at 10 min and 30 min after the onset of cooling, respectively. The cooling effect was more evident in an animal with low postresuscitation blood pressure. Total dose of epinephrine, number of direct current shocks, and recovery of blood pressure were not different between the two groups. The pharyngeal epithelium was microscopically intact on day 5. In the clinical study, insertion of the cuff and start of perfusion did not affect heart rate or blood pressure. Tympanic temperature was decreased by 0.6 ± 0.1°C/30 min without affecting bladder temperature. The pharynx was macroscopically intact for 3 days. CONCLUSIONS: Pharyngeal cooling rapidly and selectively decreased brain temperature in primates and tympanic temperature in humans and did not have adverse effects on return of spontaneous circulation, even when initiated during cardiac arrest in primates.

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study.

INTRODUCTION: Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness. METHODS: We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality. RESULTS: We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15, acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected]. CONCLUSIONS: In non-septic patients, high fever (≥39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00940654.

Effects of propofol on left ventricular mechanoenergetics in the excised cross-circulated canine heart.

Although propofol is commonly used for general anesthesia, its direct effects on left ventricular (LV) contractility and energetics remain unknown. Accordingly, we studied the effects of intracoronary propofol on excised cross-circulated canine hearts using the framework of the Emax (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-V(O2) (myocardial oxygen consumption per beat) relationship. We obtained 1) the V(O2)-PVA relationship of isovolumic contractions with varied LV volumes at a constant Emax, 2) the V(O2)-PVA relationship with varied LV volumes at a constant intracoronary concentration of propofol, and 3) the V(O2)-PVA relationship under increased intracoronary concentrations of either propofol or CaCl(2) at a constant LV volume to assess the cardiac mechanoenergetic effects of propofol. We found that propofol decreased Emax dose-dependently. The slope of the linear V(O2)-PVA relationship (oxygen cost of PVA) remained unchanged by propofol. The PVA-independent V(O2)-Emax relationship (oxygen cost of Emax) was the same for propofol and Ca(2+). In conclusion, propofol showed a direct negative inotropic effect on LV. At its clinical concentrations, decreases in contractility by propofol were relatively small. Propofol shows mechanoenergetic effects on the LV that are similar to those of Ca(2+) blockers or ß-antagonists-i.e., it exerts negative inotropic effects without changing the oxygen costs of Emax and PVA.

Antinociceptive effects of intrathecal landiolol injection in a rat formalin pain model.

Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive effects. Further investigation of the antinociceptive mechanism of landiolol is required.