Contribution of prophylactic administration of flurbiprofen for mesenteric traction syndrome to postoperative leakage or bleeding in gastrointestinal surgery: a retrospective observational study.

PURPOSE: Mesenteric traction syndrome (MTS) sometimes occurs during abdominal surgery. Prophylactic administration of flurbiprofen, a non-steroidal anti-inflammatory drug, prevents the development of MTS. However, administration of non-steroidal anti-inflammatory drugs for postoperative pain increases the incidence of postoperative bleeding. Our aim was to examine the effect of prophylactic flurbiprofen administration on postoperative leakage or bleeding after gastrointestinal surgery. METHODS: A retrospective observational study on patients who underwent open or laparoscopic abdominal surgery was conducted. Perioperative, anesthesia and medical records were reviewed. Patients who did (Flurbio-Group) or did not receive (Control-Group) prophylactic flurbiprofen administration were compared. Then, the Flurbio-Group and Control-Group were each divided into two groups according to whether the patients did or did not develop MTS (Flurbio-MTS-Group and Flurbio-no-MTS-Group, respectively, Control-MTS-Group and Control-no-MTS-Group, respectively). RESULTS: This study included 188 patients (Flurbio-MTS-Group, 1 patient; Flurbio-no-MTS-Group, 31 patients; Control-MTS-Group, 59 patients; Control-no-MTS-Group, 97 patients). Seventeen patients developed postoperative leakage or bleeding. Eleven Flurbio-MTS-Group patients (18.6%), 4 Flurbio-no-MTS-Group patients (12.9%, 4/31), and only 2 Control-no-MTS-Group patients (2%, 2/97) developed postoperative leakage or bleeding. Multivariate logistic regression analysis demonstrated that there was a qualitative interaction effect between prophylactic administration of flurbiprofen and the development of MTS on postoperative leakage or bleeding. CONCLUSION: Prophylactic flurbiprofen administration increased the risk of postoperative leakage or bleeding among patients who did not develop MTS.

Lower blood return temperature than core temperature as a causal factor of decreased cardiac output assessed by transpulmonary thermodilution during blood purification.

We aimed to evaluate whether cardiac output assessed by transpulmonary thermodilution during blood purification is affected by the difference between the blood return temperature and core temperature. We applied different blood return temperatures using a thermostat bath during blood purification in four pigs. After the blood return temperature stabilized and blood purification process stopped, the cardiac output assessed by transpulmonary thermodilution was measured. The thermostat bath was set at 35°C, 40°C, 45°C, and 50°C, with the order changed at random; four measurements were made at each temperature. Cardiac function was evaluated by echocardiography when ice-cold saline was administered in a pig. A decrease in the blood return temperature resulted in decreased cardiac output assessed by transpulmonary thermodilution, whereas an increase resulted in increased cardiac output assessed by transpulmonary thermodilution. Echocardiography revealed that the change in the blood return temperature did not affect the left ventricular ejection fraction.

In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters.

INTRODUCTION: Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane. OBJECTIVE: The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem). METHODS: We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters. RESULTS: The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group. CONCLUSIONS: Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability.

Retrospective study of predictive factors for postoperative complications of hepatectomies lasting 12 or more hours.

OBJECTIVES: Hepatectomy is used to treat several liver diseases, although perioperative mortality and postoperative complication rates remain high. Given the lack of relevant studies to date, the present study aimed to investigate potential predictive factors for postoperative complications in patients undergoing hepatectomies lasting 12 or more hours (termed "extremely long hepatectomies"). METHODS: Adult patients undergoing treatment in the intensive care unit (ICU) after extremely long hepatectomies at Fujita Health University Hospital between 2014 and 2017 were enrolled in the study. Postoperative complications were classified as "major complications" and "non-major complications" according to the Clavien-Dindo Classification grading system. We also divided our study population into "simple hepatectomy" and "non-simple hepatectomy" subgroups for further analysis. Statistical analyses were performed using the Mann-Whitney U test, chi-squared test, and multiple logistic regression analysis. RESULTS: In total, 114 patients (Major Complications Group, n=44; Non-Major Complications Group, n=70) were enrolled. In the Simple Hepatectomy Group, there were no significant variables. In the Non-Simple Hepatectomy Group, female sex (odds ratio [OR], 13.4; 95% confidence interval [CI], 1.00-1.81×102; p=0.04) and lactate levels at ICU admission (OR, 1.6; 95% CI, 0.99-2.59; p=0.05) were independent factors associated with major postoperative complications. CONCLUSIONS: In the Simple Hepatectomy Group, there were no significant variables. In the Non-Simple Hepatectomy Group, female sex and lactate levels at ICU admission of patients who underwent extremely long hepatectomies may be independent factors associated with major postoperative complications.

Increased intrapharyngeal pressure with combined use of high-flow nasal cannula and a surgical face mask: a preliminary study.

OBJECTIVES: Nasal high-flow (NHF) therapy provides continuous positive airway pressure (CPAP), flushes the anatomical dead space, and improves mucociliary clearance. CPAP is usually applied at a flow rate at or above an established threshold value with the mouth closed because it is hard to maintain it with an open mouth. We conducted a prospective study to validate our hypothesis that CPAP can be applied with the mouth open through a surgical face mask. METHODS: We inserted 12-Fr nasogastric tubes through the noses of 18 healthy individuals and fixed each tube within the pharynx to monitor the intrapharyngeal pressure. We monitored the pressure during the following two conditions: NHF oxygen with the mouth open (condition O) and NHF oxygen with the mouth open and wearing a surgical face mask (condition OM). We set the NHF rate at 40 L/min and the oxygen concentration at 21%, under all conditions. We measured the intrapharyngeal pressure five times during each inspiration and expiration, and calculated mean values. RESULTS: The mean expiratory intrapharyngeal pressure (median [interquartile range]) increased significantly from the baseline during conditions O (2.08 [1.58-4.02] cm H2O) and OM (3.35 [2.72-3.79] cm H2O). In addition, there was a significant difference in pressure between conditions O and OM (p=0.0263, Wilcoxon signed-rank test). CONCLUSIONS: In our healthy volunteers, the intrapharyngeal pressures increased during expiration with an open mouth while wearing a surgical face mask.

Evidence and Perspectives on the Use of Polymyxin B-Immobilized Fiber Column Hemoperfusion among Critically Ill Patients.

BACKGROUND: Sepsis frequently leads to multiple organ failure due to the uncontrolled amplification and spread of inflammation, even if the infectious source is controlled. Lipopolysaccharide (LPS), a typical pathogen-associated molecular pattern (PAMP), is adsorbed by the polymyxin B-immobilized fiber column (PMX). PMX has been used for decades in Europe. Results of a North American randomized controlled trial (RCT) on PMX have recently been announced in a press release; results of large-scale observational studies and meta-analyses have also been reported in the last several years. SUMMARY: To date, 3 multicenter RCTs on PMX hemoperfusion have been conducted outside of Japan. All of them enrolled postoperative patients with sepsis or septic shock secondary to intra-abdominal infection. However, confidence in the level of evidence provided by these RCTs is very low. Results from recent propensity-matched analyses and meta-analyses indicate that PMX hemoperfusion may improve survival outcomes among patients with sepsis. LPS is an important causative PAMP in sepsis; it triggers the immune response. PMX adsorbs LPS by using a polymyxin B-immobilized fiber that has high affinity for LPS. Moreover, PMX has other mechanisms of action, such as endogenous cannabinoid and activated neutrophil and monocyte adsorption, monocyte surface antigen alteration, and regulation of apoptosis in renal tubular cells. Furthermore, clinical research shows that PMX hemoperfusion can improve patients' hemodynamic status and pulmonary oxygenation and can sustain its endotoxin adsorption capability beyond 2 h. Improved pulmonary oxygenation among patients with sepsis-associated acute respiratory distress syndrome is linked to the effectiveness of PMX hemoperfusion in treating acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). Key Messages: Meta-analysis indicates that PMX hemoperfusion may improve the survival outcomes of patients with sepsis; LPS adsorption is an important treatment modality in sepsis. Many novel findings on the mechanisms of action of PMX, beyond endotoxin adsorption, have been reported. Additionally, a prolonged duration of PMX hemoperfusion has been shown to be efficacious, and beneficial effects on AE-IPF have been demonstrated. The use of PMX hemoperfusion for the correct duration and at the right time in appropriate patients may lead to favorable therapeutic outcomes.

A devised strategy for tracheal extubation for predicted difficult airway in a child with unilateral vocal cord paralysis: a case report.

BACKGROUND: Extubation is a more challenging medical practice than intubation, and countermeasures against it are similar to those described in the Difficult Intubation Guidelines, but problems cannot be overcome by completely the same methods. We predicted difficult extubation in a pediatric patient with left recurrent laryngeal nerve paralysis and devised an extubation method. CASE PRESENTATION: The patient was a 2-year-and-8-month-old boy scheduled for cleft palate repair. Concomitant cardiac anomaly and first and second branchial arch syndrome-associated facial malformations, such as mandibular micrognathia and auricular malformation, were observed. He had a past medical history of difficult intubation and respiratory arrest on a catheter test under intravenous sedation at 4 months old. Left recurrent laryngeal nerve paralysis was discovered on preoperative examination of the cleft palate, based on which difficulty in postoperative extubation was predicted. A catheter for tracheal tube exchange proposed by the extubation guidelines of the Difficult Airway Society (DAS) was placed, endoscopic examination was performed while inducing spontaneous breathing and swallowing reflex by an otolaryngologist, and the tube was removed while movement of the tissue around the glottis was visually evaluated. The patient was managed in an ICU after extubation, and both the systemic and respiratory conditions were favorable. CONCLUSIONS: Extubation and airway management could be safely performed by devising extubation while conforming to the DAS guidelines.

Spontaneous intracranial hypotension manifesting as a unilateral subdural hematoma with a marked midline shift.

Spontaneous intracranial hypotension (SIH) is a syndrome in which hypovolemia of the cerebrospinal fluid (CSF) results in various symptoms. Although its prognosis is usually benign, cases with a rapid neurologic deterioration resulting in an altered mental status have been reported. One of the characteristic radiographic findings in such cases is the presence of bilateral accumulation of subdural fluid (hematoma/hygroma). When SIH-related subdural hematoma is present only unilaterally with a concomitant midline shift, making an accurate diagnosis may be challenging, and inadvertent hematoma evacuation may result in further neurologic deterioration. We report a 58-year-old woman with an altered mental status who had visited a local hospital and in whom a brain CT showed a unilateral subdural hematoma with a marked midline shift. She was referred to our department because of her neurologic deterioration after hematoma evacuation. A CT myelography revealed a massive CSF leakage in the entire thoracic epidural space. She made a full neurologic recovery following blood patch therapy. Our case is unique and educational because the suspicion for SIH as an underlying cause of subdural hematoma is warranted in nongeriatric patients not only with bilateral but also unilateral lesions. An immediate search for CSF leakage may be important in cases with failed hematoma evacuation surgery.

[Acute normovolemic hemodilution to reduce allogenic blood transfusion in patients undergoing radical cystectomy].

BACKGROUND: Allogenic blood transfusion is associated with a number of well-recognized risks and complications. We report here acute normovolemic hemodilution (ANH) to reduce allogenic blood transfusion during radical cystectomy. METHODS: Forty five patients (hematocrit > 35%, ASA status I-II) undergoing elective open radical cystectomy were investigated retrospectively by dividing into two groups, namely ANH group (group H; n=25), and control group (group C; n=20). After induction of general anesthesia combined with epidural anesthesia, autologous whole blood (800-1600ml) is collected in a series of collection bags (group H). When hemoglobin level dropped below the trigger (hemoglobin 7-8 g x dl(-1)) during surgery, allogenic blood transfusion (group C) and/or autologous blood transfusion (group H) were given. RESULTS: No differences in intraoperative blood loss and urine volume between the two groups were observed. Nine patients in group C made use of allogenic blood transfusion (mean 570 ml). In contrast, no patients were given allogenic blood in group H. Two weeks after the operation, there was no difference in hemoglobin concentrations between the two groups and no serious complications occurred in all the patients studied. CONCLUSIONS: ANH may be effective in reducing the necessity of allogenic blood transfusion during radical cystectomy with a relatively large surgical blood loss.

[Effects of percutaneous lidocaine administration and xenon-ray irradiation on post-herpetic neuralgia in liver transplant recipients: a report of three cases].

We report three cases of liver transplant recipients (LTRs) with postherpetic neuralgia (PHN). They were referred to our department because of poor pain control. Repeated percutaneous lidocaine (2%, 15 ml) administration to the site of the pain via an iontophoresis system and xenon-ray irradiation were effective for the three patients. Visual analogue scale for pain decreased significantly and requirements of analgesics diminished considerably during the therapy without serious side effects. PHN is relatively common in LTRs, but treatment options are restricted because of immunosuppressive therapy and hepatic and/or renal dysfunction. However noninvasive frequent iontophoretic administration of lidocaine and xenon-ray irradiation produced satisfactory pain relief for PHN in LTRs.

[Case of myotonic dystrophy with pulmonary atelectasis and torsade de pointes in the perioperative period].

A 42-year-old woman with myotonic dystrophy (MD) was scheduled for total hysterectomy and left ovariectomy. The patient received intravenous induction of anesthesia with propofol 60 mg and vecuronium 4 mg. Anesthesia was maintained with a minimum dose of propofol, air, oxygen and epidural anesthesia with the catheter at the T12-L1 level. Surgery and anesthesia were uneventful except for transient decreased Sp(O2) during anesthesia induction due to a septum in the left main bronchus. Chest radiographs at the end of surgery showed atelectasis of the whole left lung. Therefore, the patient was kept intubated, sedated with propofol, and mechanically ventilated in the intensive care unit. During the course of its treatment, torsade de pointes (TdP) ventricular tachycardia suddenly occurred but resolved spontaneously within 45 sec. without any medications. Prolonged QT interval by hypokalemia was suspected as the main factor. With the patient of MD, we have to pay attention to weakening of reserve capacity of pulmonary function and lethal arrhythmia in the perioperative period.

[Cost benefit analysis of portable disposable patient-controlled epidural analgesia pump under the diagnosis procedure combination based payment system].

BACKGROUND: The aim of this study was to assess how portable disposable patient-controlled epidural analgesia (PCEA) pumps (P group) affect the total costs of postoperative pain management compared with ordinary continuous epidural analgesia pumps without patient-controlled analgesia(C group). METHODS: The hospital income, material costs and costs of drugs for postoperative analgesia were analyzed in 446 surgical patients (C group) between April 2005 and November 2005 and in 417 surgical patients (P group) between April 2006 and November 2006, respectively. RESULTS: Considerable cost savings were achieved when PCEA pumps was used (C group--1300 yen/per patient; P group + 1950 yen/per patient). CONCLUSIONS: PCEA pumps itself work out as designated insured medical materials and additional drugs for postoperative analgesia in the ward is cleared under the diagnosis procedure combination (DPC)-based payment system. Clearance of PCEA pumps under the DPC-based payment system and cost savings of additional drugs for postoperative analgesia in the ward contributed to increases in the profit of the hospital. The DPC-based payment system may offer an economic incentive to introduction of PCEA.

[Effects of postoperative continuous epidural analgesia after laparoscopy-assisted colectomy].

BACKGROUND: This study was conducted to evaluate the effects of continuous epidural analgesia on the postoperative pain and the early recovery after laparoscopy-assisted colectomy (LAC). METHODS: A total of 50 patients undergoing elective LAC were investigated for postoperative pain score and other variables retrospectively. RESULTS: Thirty patients who had received epidural analgesia (E group) showed significantly lower pain scores for 2 and 24 hours after surgery, compared with twenty patients who had received analgesics intramuscularly or transrectally (C group). The patients in the E group needed significantly less supplemental analgesics than those in C group for 12 to 24 hours after the operation. The incidence of postoperative complications and the early recovery were not significantly different between the two groups. CONCLUSIONS: These results show that postoperative continuous epidural analgesia is effective for postoperative pain relief in patients after laparoscopy-assisted colectomy.

[The effects of postoperative continuous epidural analgesia after laparoscopy-assisted distal gastrectomy].

BACKGROUND: This study was conducted to evaluate the effects of continuous epidural analgesia on the postoperative pain and the early recovery after laparoscopy-assisted gastrectomy (LAG). METHODS: A total of 66 patients undergoing elective LAG were investigated for postoperative pain score and other variables retrospectively. RESULTS: Forty-four patients who had received epidural analgesia (E group) showed significantly lower pain scores for 2, 12 and 48 hours after surgery, compared with 22 patients who had received analgesics intramuscularly or transrectally (C group). The patients in the E group needed significantly less supplemental analgesics than those in C group for 2 and 12 hours after the operation. The early recovery and the incidence of postoperative complications were not significantly different between the two groups. CONCLUSIONS: These results show that postoperative continuous epidural analgesia is effective for postoperative pain relief in patients after laparoscopy-assisted gastrectomy.

Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin.

OBJECTIVE: Overexpression of erythropoietin (Epo) in mice (Epo-tg6) leads to an increase in hematocrit and blood volume, and strongly reduces endurance upon exercise. It was the aim of this study to characterize the mechanisms underlying the reduced cardiac performance. METHODS: Left (LV) and right (RV) ventricular function was measured with and without norepinephrine (NE) stimulation in 12 anaesthetized Epo-tg6 and in 13 wild-type (WT) control mice. RESULTS: There were no differences in heart function under baseline resting conditions. Stimulation with NE (10 microl bolus injections of 1-100 ng per mouse) in WT mice led to a dose-dependent increase in heart rate (HR), LV developed pressure (LVDP) and rate of rise in LV pressure (LV dP/dt(max)), while LV end-diastolic pressure (LVEDP) was unchanged. Except for HR, these parameters increased to a lesser extent in EPO-tg6 mice. Strikingly, LVEDP strongly increased in Epo-tg6 mice after NE (up to >20 mmHg). Eleven out of 13 Epo-tg6, but none of the WT mice died or required resuscitation after high-doses of NE. In these cases severe diastolic dysfunction became overt since the relative myocardial relaxation time was significantly prolonged and the duration of diastole was shortened. Moreover, the ECG showed a marked ST segment depression as well as deep negative T-waves. The NE-induced reduction in myocardial adenosin-triphosphate (ATP) content was more pronounced in Epo-tg6 mice after 10 min of continuous NE infusion (50 ng/min per mouse). CONCLUSION: NE-induced stress in Epo-tg6 mice led to acute heart failure associated with diastolic dysfunction and myocardial ischemia.

Altered pulmonary vascular reactivity in mice with excessive erythrocytosis.

Pulmonary vascular remodeling during chronic hypoxia may be the result of either oxygen deprivation or erythrocytosis. To separate experimentally the effects of hypoxia and erythrocytosis, we analyzed transgenic mice that constitutively overexpress the human erythropoietin gene in an oxygen-independent manner. These mice are characterized by polycythemia but have normal blood pressure, heart rate, and cardiac output. In transgenic mice, pulmonary artery pressure (PAP) was increased in vivo but was reduced in blood-free perfused lungs. The thromboxane receptor agonist U46619 caused a smaller rise in PAP in isolated transgenic lungs than in lungs from wild-type mice. The transgenic pulmonary vasculature was characterized by elevated prostacyclin production, stronger endothelial nitric oxide synthase expression, and reduced pulmonary vascular smooth muscle thickness. The fact that transgenic polycythemic mice have marked pulmonary hypertension in vivo but not in vitro suggests that their pulmonary hypertension is due to the increased blood viscosity, thus supporting an independent role of polycythemia in the development of pulmonary hypertension. In addition, our findings indicate that the lungs of transgenic animals adapt to the high PAP by elevated synthesis of vasodilators and reduced vascular smooth muscle thickness that tend to reduce vascular tone and vascular responsiveness.

Targeted disruption of the mouse PAS domain serine/threonine kinase PASKIN.

PASKIN is a novel mammalian serine/threonine kinase containing two PAS (Per-Arnt-Sim) domains. PASKIN is related to the Rhizobium oxygen sensor protein FixL and to AMP-regulated kinases. Like FixL, the sensory PAS domain of PASKIN controls the kinase activity by autophosphorylation in a (unknown) ligand-dependent manner. In Saccharomyces cerevisiae, the two PASKIN orthologues PSK1 and PSK2 phosphorylate three translation factors and two enzymes involved in glycogen synthesis, thereby coordinately regulating protein synthesis and glycolytic flux. To elucidate the function of mammalian PASKIN, we inactivated the mouse Paskin gene by homologous recombination in embryonic stem cells. Paskin(-/-) mice showed normal development, growth, and reproduction. The targeted integration of a lacZ reporter gene allowed the identification of the cell types expressing mouse PASKIN. Surprisingly, PASKIN expression is strongly upregulated in postmeiotic germ cells during spermatogenesis. However, fertility and sperm production and motility were not affected by the PASKIN knockout. The Ppp1r7 gene encoding Sds22, a regulatory subunit of protein phosphatase 1, shares the promoter region with the Paskin gene, pointing towards a common transcriptional regulation. Indeed, Sds22 colocalized with the cell types expressing PASKIN in vivo, suggesting a functional role of protein phosphatase-1 in the regulation of PASKIN autophosphorylation.

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis.

We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs at any age. Thus, we investigated the mechanisms preventing thrombembolism in this mouse model. Blood analysis revealed an age-dependent elevation of reticulocyte numbers and a marked thrombocytopenia that matched the reduced megakaryocyte numbers in the bone marrow. However, platelet counts were not different from wild-type controls, when calculations were based on the distribution (eg, plasma) volume, thereby explaining why thrombopoietin levels did not increase in transgenic mice. Nevertheless, bleeding time was significantly increased in transgenic animals. A longitudinal investigation using computerized thromboelastography revealed that thrombus formation was reduced with increasing age from 1 to 8 months in transgenic animals. We observed that increasing erythrocyte concentrations inhibited profoundly and reversibly thrombus formation and prolonged the time of clot development, most likely due to mechanical interference of red blood cells with clot-forming platelets. Transgenic animals showed increased nitric oxide levels in the blood that could inhibit vasoconstriction and platelet activation. Finally, we observed that plasmatic coagulation activity in transgenic animals was significantly decreased. Taken together, our findings suggest that prevention of thrombembolic disease in these erythrocytotic transgenic mice was due to functional consequences inherent to increased erythrocyte concentrations and a reduction of plasmatic coagulation activity, the cause of which remains to be elucidated.