Detection Algorithms for Gastrointestinal Perforation Cases in the Medical Information Database Network (MID-NET®) in Japan.

BACKGROUND: The Medical Information Database Network (MID-NET®) in Japan is a vast repository providing an essential pharmacovigilance tool. Gastrointestinal perforation (GIP) is a critical adverse drug event, yet no well-established GIP identification algorithm exists in MID-NET®. METHODS: This study evaluated 12 identification algorithms by combining ICD-10 codes with GIP therapeutic procedures. Two sites contributed 200 inpatients with GIP-suggestive ICD-10 codes (100 inpatients each), while a third site contributed 165 inpatients with GIP-suggestive ICD-10 codes and antimicrobial prescriptions. The positive predictive values (PPVs) of the algorithms were determined, and the relative sensitivity (rSn) among the 165 inpatients at the third institution was evaluated. RESULTS: A trade-off between PPV and rSn was observed. For instance, ICD-10 code-based definitions yielded PPVs of 59.5%, whereas ICD-10 codes with CT scan and antimicrobial information gave PPVs of 56.0% and an rSn of 97.0%, and ICD-10 codes with CT scan and antimicrobial information as well as three types of operation codes produced PPVs of 84.2% and an rSn of 24.2%. The same algorithms produced statistically significant differences in PPVs among the three institutions. Combining diagnostic and procedure codes improved the PPVs. The algorithm combining ICD-10 codes with CT scan and antimicrobial information and 80 different operation codes offered the optimal balance (PPV: 61.6%, rSn: 92.4%). CONCLUSION: This study developed valuable GIP identification algorithms for MID-NET®, revealing the trade-offs between accuracy and sensitivity. The algorithm with the most reasonable balance was determined. These findings enhance pharmacovigilance efforts and facilitate further research to optimize adverse event detection algorithms.

Anesthetic management of pheochromocytoma and paraganglioma for patients with Fontan circulation: a case series.

BACKGROUND: Anesthetic management of pheochromocytoma and paraganglioma with Fontan circulation is challenging for physicians, with attention to cardiovascular physiology. CASE PRESENTATION: We performed anesthetic management for pheochromocytoma and paraganglioma in three patients with Fontan circulation. We maintained intraoperative central venous pressure at preoperative level under fluid infusion and administrating nitric oxide to decrease pulmonary arterial resistance. We administered noradrenaline or vasopressin if low blood pressure was present despite adequate central venous pressure. Although noradrenaline is prevalent for the case of noradrenaline-secreting tumor especially after resection, we could maintain blood pressure to administrate vasopressin without increasing central venous pressure. Retroperitoneal laparoscopic approach which could avoid intra-abdominal adhesions might be selectable as case 3. CONCLUSIONS: Sophisticated management is required for pheochromocytoma and paraganglioma with Fontan circulation.

Anesthetic management of hepatectomy for the patient with Fontan circulation: a case series.

BACKGROUND: Hepatectomy for patients with Fontan circulation consists of high central venous pressure and low pulmonary vascular resistance, and is challenging for physicians. CASE PRESENTATION: We performed anesthetic management for hepatectomy in three patients with Fontan circulation. Massive bleeding and transfusion as well as careful management were needed. Open abdominal surgery had to be conducted instead of laparoscopic surgery for controlling bleeding in one case. We successfully performed general anesthesia using nitric oxide and inotropes while monitoring arterial pressure and central venous pressure in all the cases. CONCLUSIONS: To maintain Fontan circulation during hepatectomy, it is important to manage central venous pressure and ensure appropriate circulatory volume.

Complete atrio-ventricular block with coronary artery spasm due to direct laryngoscopy in a pediatric patient with laryngeal papillomatosis: a case report.

BACKGROUND: Coronary artery spasm has rarely been reported in pediatric patients. Previous studies have reported comorbidities and risk factors for coronary artery spasms. We present the case of a complete atrio-ventricular (AV) block that occurred in the absence of other risk factors immediately after direct laryngoscopy. CASE PRESENTATION: A 2-year-old girl developed severe coronary artery spasm after direct laryngoscopy for elective laryngeal papillomatosis resection. Immediately after the initiation of laryngoscopy, complete AV block and ST elevation on lead II of the electrocardiogram were observed. These findings indicated that the complete AV block was caused by a right coronary artery spasm. CONCLUSION: Coronary artery spasm resulting in lethal arrhythmia rarely occurs in healthy pediatric patients. To the best of our knowledge, this is the first pediatric case of a severe coronary artery spasm resulting in a complete AV block due to direct laryngoscopy in a healthy patient.

Anesthetic management of laparoscopy-assisted total proctocolectomy in a cardiac sarcoidosis patient with a cardiac resynchronization therapy-defibrillator: a case report.

BACKGROUND: Cardiac sarcoidosis (CS) causes severe conduction abnormalities and arrhythmias. CS patients are increasingly being treated with cardiac resynchronization therapy-defibrillators (CRT-Ds). For the first time, we report the anesthetic management of a CS patient with a CRT-D. CASE PRESENTATION: A 65-year-old male with an implanted CRT-D due to CS was scheduled for a laparoscopy-assisted total proctocolectomy for his transverse colon cancer. His left ventricular ejection fraction was 32.0%, and his physical status was a New York Heart Association class III. General and epidural anesthesia were performed while using standard monitors and a FloTracTM system. The dual-chamber pacing (DDD) modality of the CRT-D was unchanged, and its defibrillation function was deactivated before surgery. The surgery was successfully performed, and the patient was discharged without worsening of his cardiac condition. CONCLUSIONS: A detailed understanding of this patient's condition, as well as sarcoidosis, helped to facilitate successful anesthetic management of this patient.

The Development of an Electronic Phenotyping Algorithm for Identifying Rhabdomyolysis Patients in the MID-NET Database.

We aimed to develop rhabdomyolysis (RB) phenotyping algorithms using machine learning techniques and to create subphenotyping algorithms to identify RB patients who lack RB diagnosis. Two pattern algorithms, one with a focus on improving predictive value and one focused on improving sensitivity, were finally created and had a high area under the curve value of 0.846. Although we were unable to create subphenotyping algorithms, an attempt to detect unknown RB patients is important for epidemiological studies.

Resting pupil size is a predictor of hypotension after induction of general anesthesia.

PURPOSE: Arterial hypotension is a major adverse effect of general anesthesia. Patients with pre-existing autonomic dysfunction are at greater risk of hypotension. This study was performed to examine whether objective measurement of the pupillary light reflex is predictive of intraoperative hypotension. METHODS: We studied 79 patients who underwent scheduled surgery under general anesthesia. Patients with severe cardiovascular disease or receiving antihypertensive agents were excluded. The light reflex was measured preoperatively using a portable infrared pupillometer, and the hemodynamic parameters were obtained from the anesthesia records. The patients were divided into two groups according to the development of hypotension: the hypotension and normotension groups. Multivariate logistic regression analysis was performed to determine the pupil parameters predictive of hypotension. RESULTS: Patients in the hypotension group were older and had a greater pupil size or constriction velocity than those in the normotension group. Logistic regression analysis showed that post-induction hypotension was significantly associated with maximum pupil size or constriction velocity after adjustment for age and other clinical variables. Latency of the light reflex and the percent reduction of pupil size were not associated with hypotension. Age was a relatively strong predictor of hypotension; other confounding factors were not associated with hypotension. CONCLUSION: Measurement of maximum pupil size is useful to identify patients at risk for intraoperative hypotension. The influence of age must be considered during measurement of the pupil response. CLINICAL TRIAL NUMBER: UMIN000023729 REGISTRY URL: https://www.umin.ac.jp.

Esophageal Submucosal Hematoma Possibly Caused by Gastric Tube Insertion Under General Anesthesia.

We present a case of an esophageal submucosal hematoma that developed after endovascular treatment for coil embolization for an unruptured cerebral aneurysm. The patient had received antiplatelet therapy before surgery and anticoagulation therapy during surgery. The orogastric tube was removed at case end with sustained negative pressure. After surgery, the patient reported chest and back pain and was diagnosed with an esophageal submucosal hematoma. The hematoma might have been related to the gastric tube insertion or removal. Providers should keep in mind the possibility of this complication when a patient who was given antithrombotic therapy reports chest or back pain after surgery.

[A case of persistent left superior vena cava with absent right superior vena cava found on the insertion of central venous catheter].

A 77-year-old man was scheduled to undergo the resection of hepatoma. After the induction of general anesthesia, a central venous (CV) catheter was inserted from the right internal jugular vein under the echographic observation. Then, we noticed that the size of the vein was smaller than usual, which caused a little difficulty in the insertion. The post-insertion chest X-ray showed unusual placement of the catheter's tip toward the left side of the trachea. Re-evaluation of preoperative CT revealed the persistent left superior vena cava (PLSVC) with absent right superior vena cava. Post-operative examination with echography of the neck showed that the left internal jugular vein was much greater than the right. When noticing a small right internal jugular vein in pre-procedure echography, existence of PLSVC should be considered, and meticulous CV catheterization is necessary for safety.

[Anesthetic management of a patient with Klippel-Trenaunay syndrome undergoing caesarean section].

Klippel-Trenaunay syndrome (KTS) is characterized by capillary and venous malformation and hypertrophy of bone and soft tissues. A 29-year-old primigravida, who had been diagnosed of KTS by her hemangiomas and varicosities in the right leg, pubic area, rectum, vagina and lower abdominal area, was scheduled to receive caesarean section at 37 weeks gestation because vaginal delivery might cause hemorrhagic complications and extension of the venous lesions. Regional anesthesia was avoided because of the possible injuries of unknown venous malformations or varicose veins in the epidural or spinal space. The cesarean section was performed under general anesthesia uneventfully and an infant was delivered normally. There were no complications such as massive hemorrhage, disseminated intravascular coagulation and deep venous thrombosis in the perioperative period. Careful anesthetic considerations for the prevention of hemorrhagic and thrombotic complications are necessary for cesarean section in a patient with KTS.

[Anesthetic management of a cervicoisthmic pregnancy patient undergoing cesarean section].

Cervicoisthmic pregnancy is a rare obstetric condition that is potentially dangerous for the pregnant woman due to a high risk of abortion or preterm delivery. We here present a 29-year-old woman with cervicoisthmic pregnancy undergoing cesarean section at full-term. Under combined epidural and spinal anesthesia, an infant was delivered alive, and the placenta was preserved without any forces to detach from the uterus. The surgery was completed without massive bleeding. The retained placenta was treated with methotrexate infusion into the uterus from the 6th day as well as uterine artery embolization at the 51th day postpartum. She subsequently required manual removal of the retained placenta under combined epidural and spinal anesthesia with only small bleeding. She was discharged from our hospital uneventfully. Meticulous preparation for massive bleeding and long-term treatment of the retained placenta are important in the perioperative management for cesarean section of a full-term patient with cervicoisthmic pregnancy.

Accuracy of arterial pressure waveform analysis for cardiac output measurement in comparison with thermodilution methods in patients undergoing living donor liver transplantation.

PURPOSE: The aim of this study was to assess the accuracy of the first and third versions of arterial pressure waveform cardiac output (APCO(v.1.0) and APCO(v.3.0)) measurements in comparison with thermodilution methods in patients undergoing living donor liver transplantation. METHODS: Twenty patients were anesthetized and mechanically ventilated. A radial arterial line was connected to a dedicated transducer for the APCO evaluation (FloTrac™). A pulmonary artery catheter was placed and connected to a computer system (Vigilance™) to measure intermittent thermodilution cardiac output (CO(TD)) and continuous cardiac output (CCO). RESULTS: A total of 138 measurements were analyzed. Bland-Altman analysis showed that the mean biases for CO(TD)-APCO(v.3.0), CO(TD)-APCO(v.1.0), and CO(TD)-CCO were 0.89, 1.73, and -0.79 L/min, and the adjusted percentage errors were 37.5, 30.3, and 43%, respectively. While the variance for CO(TD)-APCO(v3.0) was greater, the accuracy (bias) improved by 0.8 L/min as compared with CO(TD)-APCO(v1.0). The difference CO(TD)-APCO(v.3.0) became apparent when systemic vascular resistance was lower than 1000 dyne × s/cm(5), especially below 700 dyne × s/cm(5). CONCLUSION: These data suggest that the accuracy of APCO(v.3.0) has improved compared to APCO(v.1.0) due to the updated algorithm, but additional improvements should be evaluated, especially in patients undergoing living donor liver transplantation with low systemic vascular resistance.

Evaluation of finger and forehead pulse oximeters during mild hypothermic cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to examine and compare the four combination of pulse oximeters (POs) and monitoring sites, the Nihon Kohden BSS-9800 (N), the Masimo SET Radical (M), the Nellcor N550 D-25 (N-D) and the Nellcor N550 Max-Fast (N-MF) in patients with peripheral hypoperfusion. METHODS: About 20 adult patients undergoing cardiac surgery using mild hypothermic cardiopulmonary bypass (CPB) were studied prospectively. PO sensors were applied on fingers in N, M and N-D, while on the forehead in N-MF. RESULTS: PO failure was defined as failure to show no SpO2 value or incorrect SpO2 values. PO failure occurred in 12 patients with N, ten patients with M, four patients with N-D and ten patients with N-MF, respectively (p < 0.05 N-D vs. N, M, N-MF). The duration of PO failure was 19 +/- 30% of aortic cross-clamping with N, 29 +/- 33% with M, 10 +/- 26% with N-D and 43 +/- 57% with N-MF, respectively (p < 0.05 N-D vs. M and N-MF). CONCLUSIONS: The results suggested that N-D is most useful among four combinations of POs and monitoring sites tested in this study for monitoring SpO2 during hypoperfusion. The superiority of N-MF during hypoperfusion was not evident in the present study.

Combination therapy with cerivastatin and nifedipine improves endothelial dysfunction after balloon injury in porcine coronary arteries.

HMG-CoA reductase inhibitors and calcium channel blockers have antiatherogenic effects; however, their mechanisms remain to be elucidated. This study examined the effect of cerivastatin and/or nifedipine on the endothelial dysfunction in porcine balloon-injured coronary arteries. Normal male pigs were randomly divided into the following four groups: control, cerivastatin (1 mg/kg/d PO), nifedipine (4 mg/kg/d PO), and their combination (n = 10 each). We started the treatments 3 days before balloon injury in the proximal left coronary arteries and continued for 4 weeks after the procedure. Then, we examined endothelial vasodilator functions ex vivo in organ chambers and in vitro by Western blotting for eNOS expression. Endothelium-dependent relaxations to serotonin, but not those to bradykinin or the calcium ionophore A23187 or endothelium-independent relaxations to sodium nitroprusside, were significantly impaired by balloon injury. The monotherapy with cerivastatin or nifedipine partially improved, and their combination supernormalized the relaxations to serotonin without affecting those to bradykinin or A23187 or endothelium-independent relaxations to sodium nitroprusside. The expression of eNOS was significantly reduced by balloon injury and normalized by the combination therapy. These results indicate that the combination therapy improves endothelial dysfunction after balloon injury, in which the up-regulation of eNOS may be involved.

Inflammatory stimuli upregulate Rho-kinase in human coronary vascular smooth muscle cells.

Recent studies have demonstrated that upregulated Rho-kinase plays an important role in the pathogenesis of arteriosclerosis and vasospasm in both animals and humans. However, little is known about the molecular mechanism(s) involved in the Rho-kinase upregulation. Since inflammatory mechanisms have been implicated in the pathogenesis of arteriosclerosis and vasospasm, we examined whether inflammatory stimuli upregulate Rho-kinase in vitro and in vivo. In cultured human coronary vascular smooth muscle cells (hcVSMC), inflammatory stimuli, such as angiotensin II and interleukin-1beta, increased Rho-kinase expression (at both mRNA and protein levels) and function (as evaluated by the extent of the phosphorylation of the ERM (the ezrin/radixin/moesin) family, substrates of Rho-kinase) in a time- and concentration-dependent manner. The expression of Rho-kinase was inhibited by blockades of protein kinase C (PKC) (by either GF109253 or prolonged treatment with phorbol myristate acetate for 24 h) and an adenovirus-mediated gene transfer of dominant-active Ikappa-B, suggesting an involvement of PKC and NF-kappaB in the intracellular signal transduction pathway for the Rho-kinase expression. Furthermore, coronary vascular lesion formation (characterized by medial thickening and perivascular fibrosis) induced by a long-term administration of angiotensin II was markedly suppressed in NF-kappaB(-/-) mice with reduced expression and activity of Rho-kinase in vivo. These results indicate that the expression and function of Rho-kinase are upregulated by inflammatory stimuli (e.g. angiotensin II and IL-1beta) in hcVSMC with an involvement of PKC and NF-kappaB both in vitro and in vivo.

[Changes in serum Na+ and blood hemoglobin levels during three types of transurethral procedures for the treatment of benign prostatic hypertrophy].

BACKGROUND: Transurethral holmium YAG laser resection of the prostate (HoLR-P) and transurethral electrovaporization of the prostate (TUV-P) have recently received increasing attention as an effective minimally invasive approach for the treatment of prostatic hypertrophy. However, less information is available regarding the intraoperative changes in the serum Na+ and blood hemoglobin levels during either HoLR-P or TUV-P. METHODS: Intraoperative changes in serum Na+ and blood hemoglobin levels were investigated in 17 patients undergoing transurethral resection of the prostate (TUR-P, n = 7), HoLR-P (n = 7) or TUV-P (n = 3). The 3% D-sorbitol solution was used as the irrigating fluid in all the patients. RESULTS: In three patients, severe hyponatremia (118-123 mEq x l(-1)) developed abruptly (< or = 15 min) at various time points during TUR-P with (n = 1) or without (n = 2) cystostomy. However, no clinical symptoms were observed after development of the hyponatremia in those awake patients. No large (> 10 mEq x l(-1)) decreases in the Na+ level were observed in any of the patients undergoing HoLR-P or TUV-P. In patients undergoing TUR-P and HoLR-P, percent changes in serum Na+ level significantly correlated with those in blood hemoglobin level, but not with the resection time; the slopes were significantly larger than unity. CONCLUSIONS: The TUR syndrome is less likely to occur during HoLR-P or TUV-P. During TUR-P, the onset of severe hyponatremia appears to be unpredictable, and may not necessarily be accompanied by clinical symptoms. Frequent measurements of the serum Na+ level appear essential for early detection of severe hyponatremia.

Changes in body temperature during profound hypothermic cardiopulmonary bypass in adult patients undergoing aortic arch reconstruction.

PURPOSE: Our aim was to characterize changes in body temperatures during profound hypothermic cardiopulmonary bypass (CPB) conducted with the sternum opened. METHODS: In ten adult patients who underwent profound hypothermic (< 20 degrees C) CPB for aortic arch reconstruction, pulmonary arterial temperature (PAT), nasopharyngeal temperature (NPT), forehead deep-tissue temperature (FHT), and urinary bladder temperature (UBT) were recorded every 1 min throughout the surgery. In addition, the CPB venous line temperature (CPBT), a reasonable indicator of mixed venous blood temperature during CPB and believed to best reflect core temperature during stabilized hypothermia on CPB, was recorded during the period of total CPB. RESULTS: PAT began to change immediately after the start of cooling or rewarming, closely matching the CPBT ( r = 0.98). During either situation, the other four temperatures lagged behind PAT ( P < 0.05); however, NPT followed PAT more closely than the other three temperatures ( P < 0.05). During stabilized hypothermia, PAT, NPT, and FHT, but not UBT, closely matched the CPBT, with gradients of less than 0.5 degrees C. CONCLUSION: During induction of profound hypothermia and its reversal on total CPB with the heart in situ, a PA catheter thermistor, presumably because of its placement immediately behind the superior vena cava, would provide a reliable measure of the mixed venous blood temperature. During stabilized profound hypothermia, PAT, NPT, and FHT, but not UBT, serve as a reliable index of core temperature.

Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm.

OBJECTIVE: We have recently demonstrated that protein kinase C (PKC) and Rho-kinase play important roles in coronary vasospasm in a porcine model. However, it remains to be examined whether there is an interaction between the two molecules to cause the spasm. METHODS AND RESULTS: A segment of left porcine coronary artery was chronically treated with IL-1beta-bound microbeads in vivo. Two weeks after the operation, phorbol ester caused coronary spasm in vivo and coronary hypercontractions in vitro at the IL-1beta-treated segment; both were significantly inhibited by hydroxyfasudil, a specific Rho-kinase inhibitor. Guanosine 5'-[gamma-thio]triphosphate (GTPgammaS), which activates Rho with a resultant activation of Rho-kinase, enhanced Ca2+ sensitization of permeabilized vascular smooth muscle cells, which were resistant to the blockade of PKC by calphostin C. The GTPgammaS-induced Ca2+ sensitization was greater in the spastic segment than in the control segment. Western blot analysis revealed that only PKCdelta isoform was activated during the hypercontraction. CONCLUSIONS: These results demonstrate that PKC and Rho-kinase coexist on the same intracellular signaling pathway, with PKC located upstream on Rho-kinase, and that among the PKC isoforms, only PKCdelta may be involved. Thus, the strategy to inhibit Rho-kinase rather than PKC may be a more specific and useful treatment for coronary spasm.

Propagermanium suppresses macrophage-mediated formation of coronary arteriosclerotic lesions in pigs in vivo.

Although the importance of monocytes/macrophages in the pathogenesis of arteriosclerosis is widely accepted, effective and safe treatment to inhibit those inflammatory cells remains to be developed. It was recently found that propagermanium, which is clinically used for the treatment of chronic hepatitis type B in Japan, markedly suppresses monocyte chemotaxis in response to macrophage chemoattractant protein-1 (MCP-1) through inhibition of its receptor, C-C chemokine receptor 2, in vitro. This prompted examination of whether propagermanium suppresses the macrophage-mediated formation of coronary arteriosclerotic lesions in our porcine model in vivo. It was first confirmed that propagermanium inhibited the migration of porcine monocytes in response to MCP-1 at therapeutic concentrations in vitro. Pigs were randomly divided into two groups; one group was orally treated with propagermanium (1 mg/kg, three times/day) and another group served as a control (n = 6 each). Porcine coronary segment was treated from the adventitia with MCP-1 and oxidized low-density lipoprotein for 2 weeks. In the control group, this treatment resulted in the development of stenotic coronary lesions with hyperconstrictive responses to serotonin where arteriosclerotic lesions (neointimal formation and constrictive remodeling) were developed. Immunohistochemical analysis demonstrated the macrophage accumulation in the adventitia and the media. By contrast, in the propagermanium group, angiographic coronary stenosis, hyperconstrictive responses, histologic changes, and macrophage accumulation were all significantly suppressed. These results indicate that propagermanium suppresses macrophage-mediated formation of coronary arteriosclerotic lesions in vivo, suggesting its potential usefulness for the treatment of arteriosclerotic vascular diseases.

[Changes in acid-base balance and blood lactate levels during radio frequency ablation conducted for the treatment of hepatocellular carcinomata in patients with liver cirrhosis].

BACKGROUND: Radio frequency ablation (RFA) has recently received increasing attention as an effective minimally invasive approach for the treatment of hepatocellular carcinomata (HCCs). However, we experienced a patient with liver cirrhosis (LC, Child-Pugh class B) in whom severe lactic acidosis developed during RFA conducted for the treatment of a HCC (-4.5 cm in diameter). This case prompted us to reevaluate possible injurious effects of RFA on non-tumorous liver tissues in the vicinity of its target in LC patients. METHODS: Intraoperative changes in acid-base balance and blood lactate levels, and postoperative changes in serum transaminases were investigated in LC (Child-Pugh class A) patients undergoing either laparotomic RFA (for the treatment of HCCs [diameter < 3 cm]) or partial hepatectomy (with the aid of the Pringle's manuever), and non-LC patients undergoing pancreatectomy. RESULTS: During the intraoperative period, significant lactic acidosis developed only in the patients undergoing hepatectomy. Core temperature significantly increased following the RFA. Postoperative increases in the transaminases observed in the patients undergoing hepatectomy were far larger than those observed in the patients undergoing either RAF or pancreatectomy. CONCLUSION: RFA, conducted for the treatment of smaller HCCs, appears to be minimally invasive even in the presence of LC (Child-Pugh class A).