Adrenomedullin (AM) is a potent vasodilator peptide that was first identified in extracts of huma... more Adrenomedullin (AM) is a potent vasodilator peptide that was first identified in extracts of human pheochromocytoma [1]. To date, it is known to be synthesised in several organs and tissues, including the heart, lungs, kidneys, adipose tissue, and vascular endothelium [2]. AM affects the physiological functions of the cardiovascular system, kidneys, and central nervous system. It regulates blood pressure and vascular tone, increases cardiac output, and promotes diuresis and natriuresis [1-5]. Kitamura et al. [6, 7] were the first to report that two major molecular forms of AM circulate in the human blood, namely the biologically active mature AM (mature AM) form with an amidated C-terminus, and an inactive intermediate AM with a non-amidated
Journal of Clinical and Translational Research, 2021
Background and Aim: Adrenomedullin (AM), a vasodilatory peptide, is known for its pleiotropic act... more Background and Aim: Adrenomedullin (AM), a vasodilatory peptide, is known for its pleiotropic actions. AM levels are increased under inflammatory conditions such as sepsis and can be useful as a prognostic biomarker. However, there are only a few reports on the physiological actions of AM in the perioperative period. The aim of this single-center, prospective, and observational study was to investigate the changes in the plasma levels of mature AM (mAM) and total AM (tAM) observed during the perioperative period. In addition, we aimed to determine the association between each AM level and immune-inflammatory parameters to explore the usefulness of AM as a biomarker of the magnitude of surgical stress responses. Methods: The levels of both mAM and tAM, in addition to the levels of presepsin, interleukin-6, procalcitonin, white blood cell, and C-reactive protein, were measured in blood samples obtained during the perioperative period. Other laboratory data, including sequential organ ...
Background Cryoprecipitate, which contains fibrinogen and factor VIII in large quantities, is con... more Background Cryoprecipitate, which contains fibrinogen and factor VIII in large quantities, is concentrated from fresh frozen plasma, and it has hemostatic effects in severe bleeding. We retrospectively examined the effects of cryoprecipitate on the increase in fibrinogen levels in patients with excessive intraoperative blood loss. Methods Ninety-seven patients who were administered cryoprecipitate during surgery between June 2014 and May 2019 were enrolled in our study and categorized according to the volume of intraoperative blood loss as follows: group A, 2000–5000 mL; group B, 5000–10,000 mL; group C, > 10,000 mL. Data were extracted from electronic medical records and electronic anesthesia records. The primary endpoint was an increase in the fibrinogen level after the administration of cryoprecipitate. Results Nine patients with no fibrinogen data and four patients with a bleeding volume of less than 2000 mL were excluded; thus, 84 patients (A: n = 36, B: n = 37, C: n = 11) w...
Masui. The Japanese journal of anesthesiology, 2004
BACKGROUND We investigated retrospectively the relationship between the intrathecal dose of 0.5% ... more BACKGROUND We investigated retrospectively the relationship between the intrathecal dose of 0.5% hyperbaric bupivacaine and the use of 2% mepivacaine through an epidural catheter. METHODS Forty-nine patients undergoing cesarean section with combined spinal and epidural anesthesia (CSEA) were analyzed. They were divided into two groups; with (CSEA group) and without additional epidural injection group (spinal group). RESULTS In the CSEA group (24 patients received 1.2 +/- 0.4 ml of 0.5% hyperbaric bupivacaine), 5-10 ml of 2% mepivacaine were required to achieve the adequate surgical anesthesia. In the spinal group (25 patients received 1.6 +/- 0.3 ml of 0.5% hyperbaric bupivacaine), cesarean section was performed without additional mepivacaine before delivery. The analgesic level and the amount of fluid infusion were similar in the two groups. However, 20% of patients in the spinal group showed hypotension (systolic blood pressure below 80 mmHg), although no patients in the CSEA grou...
Abstract The aim of this study was to assess the efficacy of combined opioids by comparing four r... more Abstract The aim of this study was to assess the efficacy of combined opioids by comparing four regimens of patient-controlled epidural analgesia (PCEA) after cesarean section. Parturient patients who underwent elective or emergent cesarean section under combined spinal and epidural anesthesia from April 2013 to March 2016 were retrospectively analyzed. Based on PCEA, they were assigned to one of 4 groups: local anesthetic alone (LA), epidural single morphine administration during surgery followed by local anesthetic alone (M), local anesthetic combined with fentanyl 10 μg/h (F10), or local anesthetic combined with fentanyl 20 μg/h (F20). The primary outcome was the number of PCEA boluses used. Secondary outcomes included the use of rescue analgesia, postoperative nausea and vomiting, and postoperative pruritus. A total of 250 parturients were analyzed. Whereas the number of PCEA boluses in the LA group was significantly higher than in the other combined opioid groups on the day of surgery and postoperative day 1 (LA: 3 [1–6] and 7 [4–9] vs M: 2 [0–4] and 4 [0–7] vs F10: 1 [0–4] and 3 [0–6] vs F20: 1 [0–3] and 2 [0–8], P = .012 and 0.010, respectively), within the combined opioid groups, the number was not significantly different. Significantly fewer patients in the F20 group required rescue analgesia on postoperative day 1 and 2 (25 and 55%) than those in the M (66 and 81%) and F10 (62 and 66%) groups (P < .001 and P = .007, respectively). Postoperative nausea and vomiting and pruritus were significantly higher in the M group (P < .008 and P = .024, respectively). The results of the present study suggest that local anesthetic alone after a single administration of morphine, or local anesthetic combined with fentanyl 10 μg/h would generally be adequate for PCEA, whereas local anesthetic combined with fentanyl 20 μg/h would be suitable for conventional epidural analgesia.
Background Sepsis-3, the recent sepsis definitions, was modified based on a scoring system focuse... more Background Sepsis-3, the recent sepsis definitions, was modified based on a scoring system focused on organ failure; however, it would remain a time-consuming process to detect septic patients using these definitions. Adrenomedullin (AM) is a biomarker for diagnosing sepsis and septic shock, monitoring treatment efficacy, and prognosis. We conducted a study to assess the accuracy of AM for diagnosing and prognosing sepsis and septic shock based on the Sepsis-3 definitions.Methods This is a prospective observational single-center study. Patients admitted to the intensive care unit (ICU) were retrospectively categorized as non-sepsis, sepsis, or septic shock by Sepsis-3 definitions. Total AM (tAM) and mature AM (mAM) were measured upon ICU admission. Receiver operating characteristics (ROC) analyses were performed by calculating the area under the curve (AUC) for diagnosis and prognosis of sepsis and septic shock.ResultsA total of 98 patients were enrolled in the final analysis. Among...
Oxaliplatin is the first-line chemotherapy for metastatic colorectal cancer. Unlike other platinu... more Oxaliplatin is the first-line chemotherapy for metastatic colorectal cancer. Unlike other platinum anticancer agents, oxaliplatin does not result in significant renal impairment and ototoxicity. Oxaliplatin, however, has been associated with acute and chronic peripheral neuropathies. Despite the awareness of these side-effects, the underlying mechanisms are yet to be clearly established. Therefore, in this study, we aimed to understand the factors involved in the generation of chronic neuropathy elicited by oxaliplatin treatment. We established a rat model of oxaliplatin-induced neuropathic pain (4 mg kg-1 intraperitoneally). The paw withdrawal thresholds were assessed at different time-points after the treatment, and a significant decrease was observed 3 and 4 weeks after oxaliplatin treatment as compared to the vehicle treatment (4.4 ± 1.0 vs. 16.0 ± 4.1 g; P < 0.05 and 4.4 ± 0.7 vs. 14.8 ± 3.1 g; P < 0.05, respectively). We further evaluated the role of different mitogen-activated protein kinases (MAPKs) pathways in the pathophysiology of neuropathic pain. Although the levels of total extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglia (DRG) were not different between oxaliplatin and vehicle treatment groups, phosphorylated ERK (p-ERK) 1/2 was up-regulated up to 4.5-fold in the oxaliplatin group. Administration of ERK inhibitor PD98059 (6 μg day-1 intrathecally) inhibited oxaliplatin-induced ERK phosphorylation and neuropathic pain. Therefore, upregulation of pERK by oxaliplatin in rat DRG and inhibition of mechanical allodynia by an ERK inhibitor in the present study may provide a better understanding of intracellular molecular alterations associated with oxaliplatin-induced neuropathic pain and help in the development of potential therapeutics.
Objective: Acetaminophen is an analgesic that shows efficacy in postoperative pain relief in chil... more Objective: Acetaminophen is an analgesic that shows efficacy in postoperative pain relief in children. Many drugs such as opioids, non-steroidal anti-inflammatory drugs, and/or acetaminophen have been used in paediatric skin laser irradiation surgery for postoperative pain relief. However, acetaminophen has some advantages over opioids, and opioids are being used less often. We aimed to demonstrate the effectiveness of intravenous (IV) acetaminophen during surgery for postoperative pain in paediatric skin laser irradiation. Methods: The present study is a small, prospective, double-blinded, randomized controlled trial. Paediatric patients (1-12 years old with an American Society of Anesthesiologists physical Status I and II), scheduled for skin laser irradiation for a nevus or haemangioma between October 2014 and April 2016 were randomized into the acetaminophen (n=9) and placebo (saline, n=8) groups. The observational face scale (FS) and the Behavioural Observational Pain Scale (BOPS) scores were recorded on emergence from anaesthesia, and 1, 2, and 4 hr post-surgery. Results: Patient characteristics were not significantly different except with regard to the irradiation area and surgery time. The observational FS and BOPS scores of the acetaminophen group were lower than those of the placebo group; median (minimum-maximum) at each recording time
Background: Remifentanil is an effective drug for protecting against adverse haemodynamic respons... more Background: Remifentanil is an effective drug for protecting against adverse haemodynamic responses to tracheal intubation. We compared the haemodynamic responses during anaesthesia induction between continuous intravenous (IV) infusion and two bolus injections of remifentanil. Methods: This prospective, randomised, open-label, single-centre study included patients with American Society of Anesthesiologists physical status I-II, scheduled to undergo elective surgery under general anaesthesia. Patients were randomised into two groups based on remifentanil administration type: the continuous IV infusion group (Group C) receiving a 0.3-μg/kg/min remifentanil infusion for 5 min followed by a 0.1-μg/kg/min remifentanil infusion, and the IV bolus group (Group B) receiving a combination of two bolus injections of remifentanil (first bolus of 0.4 μg/kg and second bolus of 0.6 μg/kg after 3 min) and 0.1 μg/kg/min remifentanil. General anaesthesia was induced with 1 mg/kg propofol and 0.6 mg/kg rocuronium 3 min after remifentanil infusion (Group C) or immediately after the first bolus of remifentanil (Group B). Tracheal intubation was performed 4 min after the injection of propofol and rocuronium. Heart rate and non-invasive blood pressure were recorded at 1-min intervals from baseline (i.e., before induction) to 5 min after tracheal intubation. Results: A total of 107 patients were enrolled (Group C, 55; Group B, 52). Normotensive patients with no history of antihypertensive medication use were assigned to the normotensive subgroup (41 each in both groups), while those with hypertension but without a history of antihypertensive medication use were assigned to the untreated hypertensive subgroup (Group C vs. B, n = 7 vs. 4). Finally, patients with a history of antihypertensive medication use were assigned to the treated hypertensive subgroup (7 each in both Groups C and B). No differences in heart rate and blood pressure were observed between Groups C and B within each subgroup. Conclusions: Haemodynamic responses during anaesthesia induction were similar between continuous infusion and two bolus injections of remifentanil within both normotensive and hypertensive patients with or without medication. Trial registration: The trial was retrospectively registered with Japanese Clinical Trial Registry "UMIN-CTR" on 20 October 2016 and was given a trial ID number UMIN000024495.
Adrenomedullin (AM) is a potent vasodilator peptide that was first identified in extracts of huma... more Adrenomedullin (AM) is a potent vasodilator peptide that was first identified in extracts of human pheochromocytoma [1]. To date, it is known to be synthesised in several organs and tissues, including the heart, lungs, kidneys, adipose tissue, and vascular endothelium [2]. AM affects the physiological functions of the cardiovascular system, kidneys, and central nervous system. It regulates blood pressure and vascular tone, increases cardiac output, and promotes diuresis and natriuresis [1-5]. Kitamura et al. [6, 7] were the first to report that two major molecular forms of AM circulate in the human blood, namely the biologically active mature AM (mature AM) form with an amidated C-terminus, and an inactive intermediate AM with a non-amidated
Journal of Clinical and Translational Research, 2021
Background and Aim: Adrenomedullin (AM), a vasodilatory peptide, is known for its pleiotropic act... more Background and Aim: Adrenomedullin (AM), a vasodilatory peptide, is known for its pleiotropic actions. AM levels are increased under inflammatory conditions such as sepsis and can be useful as a prognostic biomarker. However, there are only a few reports on the physiological actions of AM in the perioperative period. The aim of this single-center, prospective, and observational study was to investigate the changes in the plasma levels of mature AM (mAM) and total AM (tAM) observed during the perioperative period. In addition, we aimed to determine the association between each AM level and immune-inflammatory parameters to explore the usefulness of AM as a biomarker of the magnitude of surgical stress responses. Methods: The levels of both mAM and tAM, in addition to the levels of presepsin, interleukin-6, procalcitonin, white blood cell, and C-reactive protein, were measured in blood samples obtained during the perioperative period. Other laboratory data, including sequential organ ...
Background Cryoprecipitate, which contains fibrinogen and factor VIII in large quantities, is con... more Background Cryoprecipitate, which contains fibrinogen and factor VIII in large quantities, is concentrated from fresh frozen plasma, and it has hemostatic effects in severe bleeding. We retrospectively examined the effects of cryoprecipitate on the increase in fibrinogen levels in patients with excessive intraoperative blood loss. Methods Ninety-seven patients who were administered cryoprecipitate during surgery between June 2014 and May 2019 were enrolled in our study and categorized according to the volume of intraoperative blood loss as follows: group A, 2000–5000 mL; group B, 5000–10,000 mL; group C, > 10,000 mL. Data were extracted from electronic medical records and electronic anesthesia records. The primary endpoint was an increase in the fibrinogen level after the administration of cryoprecipitate. Results Nine patients with no fibrinogen data and four patients with a bleeding volume of less than 2000 mL were excluded; thus, 84 patients (A: n = 36, B: n = 37, C: n = 11) w...
Masui. The Japanese journal of anesthesiology, 2004
BACKGROUND We investigated retrospectively the relationship between the intrathecal dose of 0.5% ... more BACKGROUND We investigated retrospectively the relationship between the intrathecal dose of 0.5% hyperbaric bupivacaine and the use of 2% mepivacaine through an epidural catheter. METHODS Forty-nine patients undergoing cesarean section with combined spinal and epidural anesthesia (CSEA) were analyzed. They were divided into two groups; with (CSEA group) and without additional epidural injection group (spinal group). RESULTS In the CSEA group (24 patients received 1.2 +/- 0.4 ml of 0.5% hyperbaric bupivacaine), 5-10 ml of 2% mepivacaine were required to achieve the adequate surgical anesthesia. In the spinal group (25 patients received 1.6 +/- 0.3 ml of 0.5% hyperbaric bupivacaine), cesarean section was performed without additional mepivacaine before delivery. The analgesic level and the amount of fluid infusion were similar in the two groups. However, 20% of patients in the spinal group showed hypotension (systolic blood pressure below 80 mmHg), although no patients in the CSEA grou...
Abstract The aim of this study was to assess the efficacy of combined opioids by comparing four r... more Abstract The aim of this study was to assess the efficacy of combined opioids by comparing four regimens of patient-controlled epidural analgesia (PCEA) after cesarean section. Parturient patients who underwent elective or emergent cesarean section under combined spinal and epidural anesthesia from April 2013 to March 2016 were retrospectively analyzed. Based on PCEA, they were assigned to one of 4 groups: local anesthetic alone (LA), epidural single morphine administration during surgery followed by local anesthetic alone (M), local anesthetic combined with fentanyl 10 μg/h (F10), or local anesthetic combined with fentanyl 20 μg/h (F20). The primary outcome was the number of PCEA boluses used. Secondary outcomes included the use of rescue analgesia, postoperative nausea and vomiting, and postoperative pruritus. A total of 250 parturients were analyzed. Whereas the number of PCEA boluses in the LA group was significantly higher than in the other combined opioid groups on the day of surgery and postoperative day 1 (LA: 3 [1–6] and 7 [4–9] vs M: 2 [0–4] and 4 [0–7] vs F10: 1 [0–4] and 3 [0–6] vs F20: 1 [0–3] and 2 [0–8], P = .012 and 0.010, respectively), within the combined opioid groups, the number was not significantly different. Significantly fewer patients in the F20 group required rescue analgesia on postoperative day 1 and 2 (25 and 55%) than those in the M (66 and 81%) and F10 (62 and 66%) groups (P < .001 and P = .007, respectively). Postoperative nausea and vomiting and pruritus were significantly higher in the M group (P < .008 and P = .024, respectively). The results of the present study suggest that local anesthetic alone after a single administration of morphine, or local anesthetic combined with fentanyl 10 μg/h would generally be adequate for PCEA, whereas local anesthetic combined with fentanyl 20 μg/h would be suitable for conventional epidural analgesia.
Background Sepsis-3, the recent sepsis definitions, was modified based on a scoring system focuse... more Background Sepsis-3, the recent sepsis definitions, was modified based on a scoring system focused on organ failure; however, it would remain a time-consuming process to detect septic patients using these definitions. Adrenomedullin (AM) is a biomarker for diagnosing sepsis and septic shock, monitoring treatment efficacy, and prognosis. We conducted a study to assess the accuracy of AM for diagnosing and prognosing sepsis and septic shock based on the Sepsis-3 definitions.Methods This is a prospective observational single-center study. Patients admitted to the intensive care unit (ICU) were retrospectively categorized as non-sepsis, sepsis, or septic shock by Sepsis-3 definitions. Total AM (tAM) and mature AM (mAM) were measured upon ICU admission. Receiver operating characteristics (ROC) analyses were performed by calculating the area under the curve (AUC) for diagnosis and prognosis of sepsis and septic shock.ResultsA total of 98 patients were enrolled in the final analysis. Among...
Oxaliplatin is the first-line chemotherapy for metastatic colorectal cancer. Unlike other platinu... more Oxaliplatin is the first-line chemotherapy for metastatic colorectal cancer. Unlike other platinum anticancer agents, oxaliplatin does not result in significant renal impairment and ototoxicity. Oxaliplatin, however, has been associated with acute and chronic peripheral neuropathies. Despite the awareness of these side-effects, the underlying mechanisms are yet to be clearly established. Therefore, in this study, we aimed to understand the factors involved in the generation of chronic neuropathy elicited by oxaliplatin treatment. We established a rat model of oxaliplatin-induced neuropathic pain (4 mg kg-1 intraperitoneally). The paw withdrawal thresholds were assessed at different time-points after the treatment, and a significant decrease was observed 3 and 4 weeks after oxaliplatin treatment as compared to the vehicle treatment (4.4 ± 1.0 vs. 16.0 ± 4.1 g; P < 0.05 and 4.4 ± 0.7 vs. 14.8 ± 3.1 g; P < 0.05, respectively). We further evaluated the role of different mitogen-activated protein kinases (MAPKs) pathways in the pathophysiology of neuropathic pain. Although the levels of total extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglia (DRG) were not different between oxaliplatin and vehicle treatment groups, phosphorylated ERK (p-ERK) 1/2 was up-regulated up to 4.5-fold in the oxaliplatin group. Administration of ERK inhibitor PD98059 (6 μg day-1 intrathecally) inhibited oxaliplatin-induced ERK phosphorylation and neuropathic pain. Therefore, upregulation of pERK by oxaliplatin in rat DRG and inhibition of mechanical allodynia by an ERK inhibitor in the present study may provide a better understanding of intracellular molecular alterations associated with oxaliplatin-induced neuropathic pain and help in the development of potential therapeutics.
Objective: Acetaminophen is an analgesic that shows efficacy in postoperative pain relief in chil... more Objective: Acetaminophen is an analgesic that shows efficacy in postoperative pain relief in children. Many drugs such as opioids, non-steroidal anti-inflammatory drugs, and/or acetaminophen have been used in paediatric skin laser irradiation surgery for postoperative pain relief. However, acetaminophen has some advantages over opioids, and opioids are being used less often. We aimed to demonstrate the effectiveness of intravenous (IV) acetaminophen during surgery for postoperative pain in paediatric skin laser irradiation. Methods: The present study is a small, prospective, double-blinded, randomized controlled trial. Paediatric patients (1-12 years old with an American Society of Anesthesiologists physical Status I and II), scheduled for skin laser irradiation for a nevus or haemangioma between October 2014 and April 2016 were randomized into the acetaminophen (n=9) and placebo (saline, n=8) groups. The observational face scale (FS) and the Behavioural Observational Pain Scale (BOPS) scores were recorded on emergence from anaesthesia, and 1, 2, and 4 hr post-surgery. Results: Patient characteristics were not significantly different except with regard to the irradiation area and surgery time. The observational FS and BOPS scores of the acetaminophen group were lower than those of the placebo group; median (minimum-maximum) at each recording time
Background: Remifentanil is an effective drug for protecting against adverse haemodynamic respons... more Background: Remifentanil is an effective drug for protecting against adverse haemodynamic responses to tracheal intubation. We compared the haemodynamic responses during anaesthesia induction between continuous intravenous (IV) infusion and two bolus injections of remifentanil. Methods: This prospective, randomised, open-label, single-centre study included patients with American Society of Anesthesiologists physical status I-II, scheduled to undergo elective surgery under general anaesthesia. Patients were randomised into two groups based on remifentanil administration type: the continuous IV infusion group (Group C) receiving a 0.3-μg/kg/min remifentanil infusion for 5 min followed by a 0.1-μg/kg/min remifentanil infusion, and the IV bolus group (Group B) receiving a combination of two bolus injections of remifentanil (first bolus of 0.4 μg/kg and second bolus of 0.6 μg/kg after 3 min) and 0.1 μg/kg/min remifentanil. General anaesthesia was induced with 1 mg/kg propofol and 0.6 mg/kg rocuronium 3 min after remifentanil infusion (Group C) or immediately after the first bolus of remifentanil (Group B). Tracheal intubation was performed 4 min after the injection of propofol and rocuronium. Heart rate and non-invasive blood pressure were recorded at 1-min intervals from baseline (i.e., before induction) to 5 min after tracheal intubation. Results: A total of 107 patients were enrolled (Group C, 55; Group B, 52). Normotensive patients with no history of antihypertensive medication use were assigned to the normotensive subgroup (41 each in both groups), while those with hypertension but without a history of antihypertensive medication use were assigned to the untreated hypertensive subgroup (Group C vs. B, n = 7 vs. 4). Finally, patients with a history of antihypertensive medication use were assigned to the treated hypertensive subgroup (7 each in both Groups C and B). No differences in heart rate and blood pressure were observed between Groups C and B within each subgroup. Conclusions: Haemodynamic responses during anaesthesia induction were similar between continuous infusion and two bolus injections of remifentanil within both normotensive and hypertensive patients with or without medication. Trial registration: The trial was retrospectively registered with Japanese Clinical Trial Registry "UMIN-CTR" on 20 October 2016 and was given a trial ID number UMIN000024495.
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Papers by Toyoaki Maruta