Effects of fentanyl administration in mechanically ventilated patients in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Fentanyl is selected to manage pain in critical care patients on mechanical ventilation in the intensive care unit (ICU). However, the usefulness of fentanyl compared with other opioids is unknown. This study examined the evidence for using fentanyl to improve the clinical outcomes of ICU patients, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. METHODS: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases in June 2021. Two independent assessors reviewed studies to identify randomized, controlled trials (RCTs) that compared the intravenous administration of fentanyl and other opioids in mechanically ventilated patients in the ICU. The study quality was assessed using the GRADE system and Cochrane methodology. The primary outcome was mortality. The secondary outcomes were the duration of mechanical ventilation, duration of the ICU stay, incidence of severe adverse events, and incidence of delirium. We integrated outcome data using a random-effects model and showed absolute values and certainty of evidence in the GRADE evidence profile. RESULTS: Seven RCTs met the study inclusion criteria with 534 patients (251 were treated with fentanyl and 283 with other opioids, including 242 with remifentanil and 41 with morphine). Among 191 participants from 2 RCTs, fentanyl was not associated with mortality (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.24 to 2.60; low-quality evidence). Regarding the secondary outcomes, fentanyl did not shorten the duration of mechanical ventilation (mean difference, 0.49 h; 95% CI, - 0.90 to 1.88; moderate-quality evidence) or the duration of the ICU stay (mean difference, 7.04 h; 95% CI, - 3.27 to 17.35; moderate-quality evidence) compared with other opioids. Fentanyl did not increase the incidence of severe adverse events (RR, 0.98; 95% CI, 0.50 to 1.90; low-quality evidence) or delirium (RR, 1.27; 95% CI, 0.79 to 2.04; low-quality evidence). CONCLUSIONS: Although fentanyl is a frequently administered opioid in the ICU, patients' outcomes are not different between fentanyl use and use of other opioids. However, the GRADE evaluation provides little certainty to support the results of this systematic review. Therefore, further large RCTs are required to confirm our conclusions. TRIAL REGISTRATION: PROSPERO, CRD42019130648 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130648 ).

Effects of preoperative plasma exchange therapy with albumin replacement fluid on blood coagulation in patients undergoing ABO-incompatible living-donor kidney transplantation using rotational thromboelastometry.

BACKGROUND: ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®). METHODS: Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n = 13) and non-PEX group (ABO compatible without PEX, n = 15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCEplatelet, which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM. RESULTS: The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p < 0.01). Maximum clot firmness (MCF) of EXTEM (MCFEXTEM), MCFFIBTEM, and MCEplatelet was significantly lower in the PEX than non-PEX group (p < 0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCFEXTEM and MCEplatelet, and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCFEXTEM and MCEplatelet. CONCLUSIONS: These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®. TRIAL REGISTRATION: UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.

Swallowing action immediately before intravenous fentanyl at induction of anesthesia prevents fentanyl-induced coughing: a randomized controlled study.

PURPOSE: Fentanyl is a strong µ-opioid analgesic which attenuates the stimulation of surgical invasion and tracheal intubation. However, intravenous fentanyl often induces coughing [fentanyl-induced coughing (FIC)] during induction of anesthesia. We found that the swallowing action, when requested at induction of anesthesia, attenuated FIC. In the current study, we investigated the relationship between the occurrence of FIC and the swallowing action. METHODS: The study included American Society of Anesthesiologists physical status I or II patients, aged 20-64 years, who were undergoing elective surgery. They were divided into two groups-one group was urged to perform the swallowing action immediately before intravenous fentanyl (S group), and the other group performed no swallowing action (non-S group). The patients first received intravenous fentanyl and were observed for 90 s. Each patient's background, dose of fentanyl and occurrence of coughing were investigated from their records and a motion picture recording. The incidence of FIC was evaluated by chi-squared test, and severity was tested by Wilcoxon rank-sum test. P < 0.05 was considered statistically significant. RESULTS: The incidence of FIC in the S group and non-S group was 14.0 and 40.4%, respectively. The risk of FIC was reduced in the S group by 75%; risk ratio (95% confidence interval) was 0.35 (0.20, 0.60). The number of coughs in the S group were less than in the non-S group (P < 0.001). CONCLUSION: The swallowing action immediately before intravenous fentanyl may be a simple and clinically feasible method for preventing FIC effectively. Clinical trial number: UMIN000012086 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=Rn000014126&language=J ).

[A Randomized Control Study Comparing the Effects of Tracheal Intubation Performed either via the McGRATH® MAC or the Macintosh Laryngoscope].

BACKGROUND: The McGRATH® MAC (McGRATH) laryngoscope is a newly developed video device, which enables us to perform tracheal intubation minimally invasive. The aim of this study is to evaluate and com- pare the hemodynamic changes triggered by intuba- tion using either the McGRATH or the Macintosh laryngoscope. METHODS: Thirty-seven patients, between 20 and 42 years of age with ASA status I or II, were randomly assigned to two groups : the McGRATH (n=19) or the Macintosh laryngoscope (n=18). Anesthesia was induced with fentanyl 2 µg · kg⁻¹, propofol 2 mg · kg⁻¹, sevoflurane 2%, and rocuronium 0.6 mg · kg⁻¹. We recoded the hemodynamic changes (blood pressure, heart rate) every minute up to 5 minute after intuba- tion. We also recoded the time needed to complete the tracheal intubation. In all cases, the same certified anesthesiologist performed tracheal intubation. Data were presented as mean ± SD. Statistical analyses were performed using the t-test for comparisons of the patients' demographic data, blood pressure, and heart rate between groups. RESULTS: There were no significant differences in two groups regarding age, weight, height, and sex. Comparing the average time needed to complete the tracheal intubation, the McGRATH group took longer than Macintosh group (40.5 ± 15.3 seconds vs. 29.4? 4.73 seconds, P=0.01). There was no significant differ- ence in blood pressure and heart rate just before tra- cheal intubation. The McGRATH laryngoscope had a significantly lower value than the Macintosh laryngo- scope in systolic pressure (101.2?7.9 vs. 111 ?16.8 mmHg, P=0.03) and heart rate (71.5?9.9 vs. 79.7? 12.3 mmHg, P=0.02) at one minute after tracheal intu- bation. CONCLUSIONS: The McGRATH laryngoscope is less invasive for hemodynamic parameters than the Macin- tosh laryngoscope. These findings suggest that the McGRATH laryngoscope may enable us to perform tracheal intubation less invasively.

Comparison of Changes in Chest Wall Mechanics and Respiratory Timing Between Patient-Controlled Epidural Analgesia and Intravenous Patient-Controlled Analgesia After Laparoscopic Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Upper abdominal surgery is associated with postoperative diaphragmatic dysfunction. Whether patient-controlled epidural analgesia (PCEA) is superior to intravenous patient-controlled analgesia (IV-PCA) in preventing postoperative diaphragmatic dysfunction is still unclear in laparoscopic gastric surgery. METHODS: Sixteen patients undergoing laparoscopic gastrectomy randomly received either PCEA or IV-PCA. The primary outcomes were the change in chest wall mechanics and respiratory timing, measured by respiratory inductive plethysmography (Respitrace; Ambulatory Monitoring Inc., Ardsley, New York, United States) before and after surgery, and analyzed by a data acquisition system (PowerLab; ADInstruments, Dunedin, New Zealand). Inspiratory time (Ti), expiratory time (Te), total respiratory cycle time (Ttot), proportion of inspiratory time over total respiratory cycle time (Ti/Ttot), respiratory rate (RR), and abdominal contribution to tidal volume (AB/VT [%]) were calculated from the stored data. AB/VT, relative volume contribution of diaphragm to tidal breathing, represents an index of diaphragmatic function. Because the diaphragm is the main contributor to tidal volume, decreases in AB/VT indicate diaphragm dysfunction. Changes in outcomes over time between the two groups were analyzed using a linear mixed model, and two-sided p values < 0.05 were considered statistically significant. The secondary outcomes were postoperative pain score (visual analog scale (VAS)), bowel function recovery, and hospital stay duration. RESULTS: Postoperative AB/VT in the IV-PCA group was significantly decreased compared to preoperative levels. AB/VT in the PCEA group was significantly higher than the IV-PCA group on postoperative day (POD) 1. Change in AB/VT over time between the PCEA group and the IV-PCA group differed significantly (p = 0.01). A decrease of AB/VT during POD 1 to 3 was observed in the IV-PCA group but not in the PCEA group. As for respiratory timing, there were significant increases in RR with a reduction of Te and Ttot compared to preoperative levels on POD 1 in the PCEA group. There were significant decreases in RR and Ti/Ttot with an increase of Te and Ttot compared to preoperative levels on POD 1 in the IV-PCA group. There was a significant difference in the change of the Ttot over time between the two groups (p = 0.046). There were no significant differences in the changes of Te, Ti/Ttot, Ti, and RR over time between the two groups. There was no significant difference in VAS over time at rest and mobilization, recovery of bowel function, and hospital stay between the two groups. CONCLUSIONS: Continuous ropivacaine infusion with PCEA partially attenuated diaphragmatic dysfunction after laparoscopic gastrectomy, while pain relief by continuous intravenous administration of fentanyl could not attenuate diaphragmatic dysfunction. This suggests that PCEA might ameliorate postoperative diaphragmatic dysfunction after laparoscopic gastrectomy.

A case of spinal nerve neurotoxicity with ropivacaine after combined spinal and epidural anesthesia.

BACKGROUND: Neurotoxicity caused by a local anesthetic after regional anesthesia is a rare but serious problem for anesthesiologists. It is difficult to diagnose neurotoxicity from anesthetics because of the large number of possible diagnoses. In this case report, careful monitoring by neurological examinations helped to diagnose local neurotoxicity caused after epidural anesthesia. CASE DESCRIPTION: A 41-year-old pregnant woman who underwent emergency cesarean delivery under combined spinal-epidural anesthesia suffered left leg paralysis after surgery. Multiple neurological examinations (e.g., electromyography, nerve conduction study) revealed that the paralysis was induced by the neurotoxicity of ropivacaine. The neurological examinations were also useful to monitor the recovery process. CONCLUSIONS: This is the first clinical case report that describes the diagnosis of and recovery from local anesthesia-induced neurotoxicity monitored by electromyography and nerve conduction study. Neurological disorders caused by regional anesthetics should be carefully examined and diagnosed using these neurological examinations.

Retrolaminar versus epidural block for postoperative analgesia after minor video-assisted thoracic surgery: a retrospective, matched, non-inferiority study.

BACKGROUND: The role of thoracic epidural analgesia (TEA) for postoperative analgesia after video-assisted thoracic surgery (VATS) is still controversial. Some studies have reported the efficacy of ultrasound-guided retrolaminar block (RLB) for the postoperative management of pain after chest wall surgery. The purpose of this study was to compare the postoperative analgesic efficacy and adverse effects of ultrasound-guided RLB with those of TEA in patients undergoing minor VATS procedures. METHODS: A total of 192 relevant records of patients were enrolled in this study. We reviewed electronic medical records of patients undergoing minor VATS procedures under general anesthesia. The primary outcome was the median differences in the numerical rating scale (NRS) scores during rest between the groups at the morning of postoperative day 1 (POD 1m). A propensity-matched analysis incorporating preoperative variables was used to compare the efficacy of postoperative analgesia in two groups. RESULTS: Overall, 94 patients were identified for analysis. Propensity score matching resulted in 47 patients in each group. There were no significant differences in the NRS scores between the two groups. The median differences in NRS scores during rest between the two groups at POD 1m were under 1, which indicates non-inferiority of RLB. There were no significant differences in the incidence of adverse effects and rescue dose of analgesic consumption between the two groups. CONCLUSIONS: The analgesic effects of continuous ultrasound-guided RLB were non inferior to those of TEA for minor VATS procedures.

Costal and crural diaphragm function during sustained hypoxia in awake canines.

In humans and other mammals, isocapnic hypoxia sustained for 20-60 min exhibits a biphasic ventilation pattern: initial increase followed by a significant ventilatory decline ("roll-off") to a lesser intermediate plateau. During sustained hypoxia, the mechanical action and activity of the diaphragm have not been studied; thus we assessed diaphragm function in response to hypoxic breathing. Thirteen spontaneously breathing awake canines were exposed to moderate levels of sustained isocapnic hypoxia lasting 20-25 min (80 ± 2% pulse oximeter oxygen saturation). Breathing pattern and changes in muscle length and electromyogram (EMG) activity of the costal and crural diaphragm were continuously recorded. Mean tidal shortening and EMG activity of the costal and crural diaphragm exhibited an overall biphasic pattern, with initial brisk increase followed by a significant decline (P < 0.01). Although costal and crural shortening did not differ significantly with sustained hypoxia, this equivalence in segmental shortening occurred despite distinct and differing EMG activities of the costal and crural segments. Specifically, initial hypoxia elicited a greater costal EMG activity compared with crural (P < 0.05), whereas sustained hypoxia resulted in a lesser crural EMG decline/attenuation than costal (P < 0.05). We conclude that sustained isocapnic hypoxia elicits a biphasic response in both ventilation and diaphragmatic function and there is clear differential activation and contribution of the two diaphragmatic segments. This different diaphragm segmental action is consistent with greater neural activation of costal diaphragm during initial hypoxia, then preferential sparing of crural activation as hypoxia is sustained. NEW & NOTEWORTHY In humans and other mammals, during isocapnic hypoxia sustained for 20-60 min ventilation exhibits a biphasic pattern: initial increase followed by significant ventilatory decline ("roll-off"). During sustained hypoxia, the function of the diaphragm is unknown. This study demonstrates that the diaphragm reveals a biphasic action during the time-dependent hypoxic "roll-off" in ventilation. These results also highlight that the two diaphragm segments, costal and crural, show differing, distinctive contributions to diaphragm function during sustained hypoxia.

Effect of pentoxifylline on diaphragmatic contractility in septic rats.

We investigated the effects of pentoxifylline (PTX) on endotoxin-induced diaphragmatic dysfunction in vitro. Seventy-two rats were divided into 3 groups: a group in which endotoxin (20 mg/kg) was injected intraperitoneally (endotoxin-group), a group in which PTX (100 mg/kg) was injected intraperitoneally 30 min before injection of endotoxin (endotoxin-PTX group), and a group in which only saline was given (sham group). Left hemidiaphragms were removed 4 h after injection of endotoxin. We evaluated the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. We measured serum TNF-alpha concentrations, diaphragm malondialdehyde (MDA) levels (an index of oxygen-derived free radical-mediated lipid peroxidation), and diaphragm cAMP concentrations. Diaphragmatic force generation capacity was signifi cantly reduced after injection of endotoxin. Serum TNF-alpha concentrations and diaphragmatic MDA levels were significantly elevated after injection of endotoxin. PTX administration significantly improved diaphragmatic contractility and prevented the elevation in TNF-alpha concentrations and MDA levels after injection of endotoxin. There were no significant changes in the diaphragm cAMP concentrations among the 3 groups. These results demonstrated that PTX administration prevented endotoxin-induced diaphragmatic dysfunction without changing diaphragm muscle cAMP concentrations. The protective effects of PTX against endotoxininduced diaphragmatic contractile deterioration might be caused by attenuating TNF-alpha-mediated oxygen-derived free radical production.

Medullar impairment resolves hiccups.

BACKGROUND: In a previous article we reported the time that hiccups stop as the instant when CO2 levels in both expiratory gas (EtCO2) and inspiratory gas (InspCO2) reach approximately 50 mmHg. To support our findings, in this article we aim to clarify the precise values of the CO2 level in arterial blood (PaCO2) and venous blood (PvCO2) during plastic bag rebreathing. METHODS: A healthy male volunteer was asked to perform a rebreathing experiment using a 20 L air-filled plastic bag. During the experiment, his blood oxygen saturation level (SpO2), EtCO2 and InspCO2 were measured until the volunteer gave up. PaCO2 and PvCO2 were measured at the following four points: P0, when the rebreathing started; P1, when both EtCO2 and InspCO2 indicated the same value; P2, when both reached 50 mmHg; and P3, when SpO2 dropped to 90%. RESULTS: InspCO2 increased from the beginning and showed the same value as EtCO2 at P1. PaCO2 at P1 was almost the same value as both InspCO2 and EtCO2. After P1, InspCO2, EtCO2 and PaCO2 increased at the same rate, and at P2, they reached the level of PvCO2. After P2, all four markers continued to show the same value as they gradually increased. CONCLUSIONS: Creating conditions inside the body in which PaCO2 increases to the same level as PvCO2 will stop hiccups consistently. Although other physiological pathways to stop hiccups may exist, for a successful outcome it is important that the balance of power between the cerebellum and the medulla is drastically altered.

Effectiveness of arginine vasopressin for the management of refractory hemorrhagic shock in a patient with autonomic dysreflexia caused by spinal cord injury.

BACKGROUND: Arginine vasopressin has been used for the management of refractory vasodilatory shock. However, it is still unclear whether arginine vasopressin is useful for hypotension in patients with spinal cord injury. CASE DESCRIPTION: A 78-year-old man with autonomic dysreflexia and paralysis below the level corresponding to Th2 due to spinal cord injury previously underwent cholecystectomy. During the surgery, accidental hemorrhage led him to refractory hemorrhagic shock unresponsive to fluid resuscitation and catecholamine. Lasting hypotension was improved with arginine vasopressin. CONCLUSION: We described a rare case report on the use of arginine vasopressin for management of refractory hemorrhagic shock in a patient with autonomic dysreflexia.

CO2 retention: The key to stopping hiccups.

BACKGROUND: While investigating the mechanisms behind hiccups, our team discovered what could be the sufficient physiological conditions for terminating even persistent cases. METHODS: To investigate the role of CO2 retention, a healthy male volunteer was asked to perform three kinds of rebreathing experiments using different materials: (I) a 20 L air-filled plastic bag, (II) a 20 L air-filled plastic bag with a 1.5 × 1.5 cm hole and (III) a 20 L oxygen-filled plastic bag. During each experiment, CO2 level upon expiration (EtCO2 ) and inspiration (InspCO2 ) were measured until the volunteer gave up. Once the safety of this manoeuvre was demonstrated with the volunteer, we performed the technique using the materials from experiment (I) on two actual patients with persistent hiccups. RESULTS: In experiments (I) and (III), InspCO2 increased from the beginning and reached almost the same level as EtCO2 after 90 seconds. Both levels continued simultaneously increasing, finally reaching 56 mm Hg in (I) and 79 mm Hg in (III), respectively. In (II), both increased; however, after 120 seconds, EtCO2 plateaued at 47 mm Hg and InspCO2 at 37 mm Hg. In the actual patients, both CO2 levels reached the same value of 35.9 mm Hg at 60 seconds and 37.0 mm Hg at 90 seconds, and hiccups stopped at 195 seconds and at 359 seconds when EtCO2 reached 50 mm Hg and 53 mm Hg, respectively. CONCLUSION: The study determined that to successfully obstruct the mechanisms causing hiccups, it is necessary that the level of InspCO2 not only increases at the same level as EtCO2 , but also reaches approximately 50 mm Hg.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

BACKGROUND AND PURPOSE: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. METHODS: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. RESULTS: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. CONCLUSIONS: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

Background and Purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Direct inotropic effect of the beta-2 receptor agonist terbutaline on impaired diaphragmatic contractility in septic rats.

The purpose of this study was to determine which beta-adrenoceptor agonist (1 or 2) is responsible for the direct inotropic effects on diaphragmatic contractility during sepsis. Rats were divided into two groups: a cecal ligation and perforation (CLP) group and a sham group. The hemidiaphragm was removed at 16 hours after the operation. Dobutamine (a beta-1 agonist) or terbutaline (a beta-2 agonist) was administered to an organ bath containing diaphragmatic tissues, and muscle contractility was assessed. Muscle contractility was diminished in the CLP group. Terbutaline increased peak twitch tension, caused an upward shift in the force-frequency curves, and improved contractility of the fatigued diaphragm in the CLP group. Dobutamine did not have any effect on these parameters in the CLP group. We conclude that activation of beta-2 adrenoceptors might be responsible for the direct inotropic effects on the diaphragm in an intra-abdominal septic model.

A selective beta2-adrenergic agonist, terbutaline, improves sepsis-induced diaphragmatic dysfunction in the rat.

BACKGROUND: Sepsis causes diaphragmatic dysfunction, which can lead to the development of respiratory failure. We previously reported that isoproterenol, non-selective beta-adrenergic agonist, improved contractility of the diaphragm in a septic rat model. Since beta(2)-adrenoceptor agonists are widely used in the treatment of chronic respiratory disease, we investigated the effect of terbutaline, a selective beta(2)-adrenergic agonist, on contractility of the septic rat diaphragm and the contribution of intracellular Ca(2+) to the effect of terbutaline in vitro. METHODS: Forty-eight rats were divided into a sham group (in which sham laparotomy was performed) and a CLP group (in which peritonitis was induced by cecal ligation and perforation). The left hemidiaphragm was removed at 16 h after the operation. The effect of terbutaline (10(-)(6) M) on contractility of the diaphragm was assessed by twitch characteristics (twitch tension, contraction time and contraction velocity) and force-frequency relationship. In addition, to investigate the role of calcium ions in the effect of terbutaline on contractility of the diaphragm, contractility of the diaphragm was assessed after the pre-incubation of the diaphragm with methoxy-verapamil (10(-)(5) M), Ca(2+)-free Krebs-Ringer's solution buffered with 2 mM of ethylene glycol tetra-acetic acid (EGTA), and ryanodine (10(-)(6) M). RESULTS: Terbutaline significantly improved twitch characteristics and force-frequency relationship of the diaphragm in the CLP group (P<0.01). Incubation with methoxy-verapamil or calcium-free solution with EGTA did not show any changes in the inotropic effect of terbutaline in the CLP group. However, incubation with ryanodine completely abolished the inotropic effect of terbutaline in the CLP group. CONCLUSIONS: The present study demonstrated that terbutaline increased contractility of the diaphragm in the septic rats. Since this inotropic effect was abolished by ryanodine administration, calcium release from the sarcoplasmic reticulum may contribute to the terbutaline-induced improvement in dysfunction of the septic diaphragm.

Effects of ulinastatin on pulmonary artery pressure during abdominal aortic aneurysmectomy.

STUDY OBJECTIVE: Abdominal aortic aneurysmectomy (AAAectomy) results in a general ischemia-reperfusion syndrome accompanied by an acute rise in pulmonary artery pressure (PAP). We examined whether ulinastatin, a urinary trypsin inhibitor, prevents ischemia-reperfusion injury and increase in PAP after aortic unclamping (XU) during AAAectomy. DESIGN: Prospective study. SETTING: Public, university-affiliated hospital. PATIENTS: Sixteen patients (11 males and 5 females) scheduled for AAAectomy. INTERVENTIONS AND MEASUREMENTS: The patients received 300000 IU of ulinastatin intravenously before XU (n = 8) or no additional treatment (n = 8) (control). Heart rate, central venous pressure, PAP, pulmonary arterial wedge pressure, arterial pressure, mixed venous oxygen saturation (Sv(O2)), and cardiac output were monitored. Arterial and mixed venous blood samples were analyzed for pH, Pa(CO2), Pa(O2), hemoglobin, and oxygen saturation, and the physiological shunt function (Qs/Qt) were calculated. Plasma concentrations of malondialdehyde, myeloperoxidase, granulocyte elastase, alpha1-antitrypsine, and thromboxane B2 and the stable hydrolysis products of thromboxane A2 were measured. Measurements were conducted before aortic crossclamping (XC) (baseline) and at 10, 30, and 60 minutes after XU. MAIN RESULTS: A significant increase in PAP was observed 10 minutes after XU in the control group but not in the ulinastatin group. At 60 minutes after XU, Qs/Qt values had increased in the control group but had decreased in the ulinastatin group. There were no significant changes in malondialdehyde, thromboxane B2, granulocyte elastase, and alpha1-antitrypsine levels after XU in either group. A significant decrease in the plasma level of myeloperoxidase after XU was found in both groups. CONCLUSIONS: The present study demonstrated that ulinastatin prevents increase in PAP and shunting after XU during AAAectomy.

Ventilation and diaphragm activity during sustained hypoxia in awake canines.

In humans, isocapnic hypoxia sustained for 20-30 min elicits a biphasic ventilatory response with an initial increased peak followed by a roll-off to a lesser, intermediate plateau. However, it is uncertain if this hypoxic roll-off is common for all mammals, as canines have been a notable exception. We examined the effect of moderate isocapnic hypoxia (SpO2 80%) sustained for 20 min in 13 adult, awake, intact canines. The ventilatory response to sustained isocapnic hypoxia in these canines was not maintained: after an initial brisk response, ventilation declined significantly to an intermediate plateau. The hypoxic ventilatory decline occurred via a decrease in tidal volume, without change in breathing frequency. Distinct from airflow, costal diaphragm EMG showed a concurrent decline during sustained isocapnic hypoxia. However, the change in ventilation during sustained hypoxia in canines was very different from the response in humans. Although some decline in ventilation during sustained hypoxia may be common to all mammals, there are notable differences among species.

NMDA receptor-mediated mechanism of ketamine-induced facilitation of glutamatergic excitatory synaptic transmission.

The effect of ketamine on CA1-field EPSPs (fEPSPs) in rat hippocampal slices was investigated. Ketamine (100 microM) facilitated fEPSPs at 0.05 Hz. The fEPSP facilitation was suppressed completely by AP-5 and partially by propranolol, and also by an increase in stimulation frequency. These results indicate that ketamine facilitates excitatory synaptic transmission by activating NMDA receptors via beta-adrenoceptors under conditions in which NMDA receptor channel block is slight.