Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

AIM: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. METHODS: A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. RESULTS: Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. CONCLUSIONS: While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.

Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease.

BACKGRUOUND: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. METHODS: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%. RESULTS: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. CONCLUSION: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

Plasma Fatty Acid Composition Is Associated with Histological Findings of Nonalcoholic Steatohepatitis.

The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 patients (134 women) with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. Multivariate analyses adjusted for age, sex, body mass index, alanine aminotransferase, hemoglobin A1c, creatinine, total cholesterol, triglyceride, and NAFLD Activity Score values showed that lower levels of arachidic, behenic, α-linolenic, eicosatetraenoic, docosapentaenoic, and docosahexaenoic acids and higher levels of mead acid were associated with fibrosis stage 3-4. Furthermore, higher lauric acid, myristic acid, and palmitic acid levels and monounsaturated fatty acids such as palmitoleic acid and oleic acid were significantly associated with high NAS in analyses adjusted for the same factors and fibrosis stage. The plasma fatty acid composition was associated with the histological evidence of NASH. Increased synthesis of fatty acids is associated with NASH; insufficient intake of n-3 essential fatty acids and reduced elongation of fatty acids are associated with fibrosis in NASH. These features may help clinicians to understand and treat advanced NASH cases.

Combined evaluation of Fibrosis-4 index and fatty liver for stratifying the risk for diabetes mellitus.

AIMS/INTRODUCTION: To investigate whether the Fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease. MATERIALS AND METHODS: Based on fatty liver disease and Fibrosis-4 index (cut-off value 1.3), we retrospectively divided 9,449 individuals, who underwent at least two annual health checkups, into four groups stratified by sex: normal; high Fibrosis-4 index without fatty liver disease; low Fibrosis-4 index with fatty liver disease; and high Fibrosis-4 index with fatty liver disease. RESULTS: Onset rates for diabetes mellitus in the normal, high Fibrosis-4 index without fatty liver disease, low Fibrosis-4 index with fatty liver disease and high Fibrosis-4 index with fatty liver disease groups were 1.6%, 4.3%, 6.8% and 10.2%, respectively, in men, and 0.6%, 0.9%, 5.3% and 7.0%, respectively, in women. Compared with the normal group, the high Fibrosis-4 index without fatty liver disease, low Fibrosis-4 index with fatty liver disease and high Fibrosis-4 index with fatty liver disease groups were at a significant risk for diabetes mellitus onset in both male and female participants. Furthermore, in both sexes, high Fibrosis-4 index with fatty liver disease remained a significant risk factor on multivariate analysis (high fibrosis-4 index with fatty liver disease group: adjusted hazard ratio 4.03, 95% confidence interval 2.19-7.42 [men] and adjusted hazard ratio 6.40, 95% confidence interval 1.77-23.14 [women]). CONCLUSIONS: Individuals with fatty liver disease and high Fibrosis-4 index had a higher risk of diabetes mellitus onset. Therefore, Fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease and identify patients requiring intervention.

Additional Effect of Luseogliflozin on Semaglutide in Nonalcoholic Steatohepatitis Complicated by Type 2 Diabetes Mellitus: An Open-Label, Randomized, Parallel-Group Study.

INTRODUCTION: Untreated nonalcoholic fatty liver may progress to nonalcoholic steatohepatitis (NASH) and cirrhosis and induce hepatocellular carcinoma and liver failure. Type 2 diabetes mellitus (T2DM), often complicated with nonalcoholic fatty liver disease (NAFLD), is a driver of NAFLD progression. Thus, efficacious treatment strategies for patients with coexisting NAFLD and T2DM are important for preventing NAFLD progression. Although previous studies have demonstrated that either sodium-glucose transporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1 RAs) benefit NASH patients with T2DM, the rate of NASH resolution has not sufficiently improved. Therefore, we developed a protocol for a randomized controlled trial to examine whether the addition of an SGLT2i to the treatment regimen of patients receving a GLP-1 RA (combination therapy), within the therapeutic dose range for T2DM, increases the rate of NASH resolution in patients with coexisting NASH and T2DM. METHODS: This open-label, randomized, parallel-group study commenced in June 2021, will conclude recruitment in May 2023, and will end by March 2025. Sixty patients with NASH complicated by T2DM are enrolled at the Ehime University Hospital in Toon, Japan. Participants will be randomized into: (1) an intervention group receiving combination therapy with the SGLT2i luseogliflozin 2.5 mg, once daily (Taisho Pharmaceutical, Tokyo, Japan) and the GLP-1 RA semaglutide 0.5 mg, once per week (Novonordisk, Copenhagen, Denmark); and (2) a control group receiving monotherapy with the GLP-1 analog semaglutide. The primary endpoints, which will be ascertained by liver biopsy, are: (1) NASH resolution rate from baseline without worsening of liver fibrosis after 52 weeks of intervention; (2) rate of improvement from baseline of at least 1 point in the NAFLD activity score without worsening of liver fibrosis after 52 weeks of intervention; and (3) rate of improvement from baseline of at least one fibrosis stage without worsening of NASH after 52 weeks of intervention. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) number: UMIN000045003. Japan Registry of Clinical Trials registration number: jRCTs061210009.

Fatty liver with metabolic disorder, such as metabolic dysfunction-associated fatty liver disease, indicates high risk for developing diabetes mellitus.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction-associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM. MATERIALS AND METHODS: We retrospectively assessed 9,459 participants who underwent two or more annual health check-ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non-overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants). RESULTS: The DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre-diabetes (P < 0.01). CONCLUSIONS: Fatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.

Relationship between body composition and the histology of non-alcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: Causes of non-alcoholic fatty liver disease and its progression include visceral fat accumulation and loss of muscle mass; however, which of the two phenomena is more critical is unclear. Therefore, we intended to examine the relationship between body composition and non-alcoholic fatty liver disease progression as indicated by fibrosis and the non-alcoholic fatty liver disease activity score. METHODS: This cross-sectional study comprised 149 patients (55 men; age, 20-76 years) treated for non-alcoholic fatty liver disease between December 2010 and January 2020. Body composition measurements, histological examinations of liver samples, and comprehensive blood chemistry tests were performed. The relationship between body composition and non-alcoholic fatty liver disease histology findings was analyzed using the logistic regression model. RESULTS: Fibrosis was significantly and inversely correlated with muscle mass and appendicular skeletal muscle mass and significantly and positively correlated with fat mass, fat mass/height squared, visceral fat area, and waist-hip ratio (P < 0.05). After adjustment for sex, blood chemistry measurements, and body composition indices, fibrosis remained associated with appendicular skeletal muscle mass, fat mass, fat mass/height squared, and visceral fat area (P < 0.05). Non-alcoholic fatty liver disease activity score ≥ 5 significantly correlated with fat mass and fat mass/height squared in a univariate but not multivariate analysis. CONCLUSIONS: Fibrosis in non-alcoholic fatty liver disease, an indicator of unfavorable long-term outcomes, is associated with more indices of fat mass than of those of muscle mass. Hence, fat mass should be controlled to prevent non-alcoholic fatty liver disease progression.

Nonalcoholic fatty liver disease is a risk factor for glucose intolerance onset in men regardless of alanine aminotransferase status.

INTRODUCTION: Fatty liver disease (FLD) is a surrogate condition for glucose intolerance development. FLD may involve normal or abnormal liver enzyme levels. Whether FLD is a risk factor for glucose intolerance, regardless of liver enzyme levels, remains unknown. We assessed relationships between the development of impaired fasting glucose (IFG) and FLD, liver enzyme abnormalities, and alcohol consumption. MATERIALS AND METHODS: We retrospectively evaluated 8,664 participants with more than two annual health check-ups. Participants were classified according to sex, alcohol consumption, alanine aminotransferase (ALT) levels, and fatty liver status. RESULTS: In univariate analyses, IFG onset among men was related to normal or high ALT levels with FLD in the nonalcoholic and alcoholic groups (P-trend < 0.01). In multivariate analyses, IFG onset among nonalcoholic men was associated with normal or high ALT levels with FLD, independent of potential confounding factors (P-trend < 0.01). However, IFG onset was non-independently associated with any condition among alcoholic men. In univariate analyses, IFG onset among women was related to normal or high ALT levels with FLD in the nonalcoholic group (P-trend < 0.01) and high ALT levels with FLD in the alcoholic group (P-trend < 0.05). In multivariate analyses, IFG onset was independently associated with only normal ALT levels in nonalcoholic FLD women. CONCLUSIONS: Among nonalcoholic men and women, FLD was a risk factor for IFG onset, including normal ALT concentrations. Care is needed for individuals with nonalcoholic FLD, regardless of liver injury, possibly helping reduce glucose intolerance risk.

Insulin-like growth factor-1 is inversely associated with liver fibrotic markers in patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Insulin-like growth factor-1 (IGF-1) regulates mitochondrial function, oxidative stress, inflammation, stellate cells and insulin sensitivity in the liver, and it might be associated with liver fibrosis from non-alcoholic steatohepatitis. In contrast, type 2 diabetes mellitus is closely associated with the progression from non-alcoholic fatty liver to non-alcoholic steatohepatitis and cirrhosis, so careful evaluation of liver fibrosis is required for patients with type 2 diabetes mellitus. Therefore, we examined the relationship between IGF-1 and liver fibrosis markers in type 2 diabetes patients without obvious alcoholic consumption and determined whether IGF-1 is associated with fibrosis of non-alcoholic fatty liver disease. MATERIALS AND METHODS: We selected 415 patients with type 2 diabetes without obvious alcohol consumption, who were admitted to Uwajima City Hospital between May 2013 and December 2016. We collected and analyzed clinical data to determine correlations between IGF-1 or IGF-1 standard deviation score and fibrosis-4 index or 7S domain of type IV collagen. RESULTS: Multiple linear regression analysis showed that the fibrosis-4 index was inversely correlated with IGF-1 and IGF-1 standard deviation score. Furthermore, the 7S domain of type IV collagen was also inversely correlated with IGF-1 and IGF-1 standard deviation score. CONCLUSIONS: IGF-1 was inversely correlated with liver fibrosis markers in type 2 diabetes mellitus patients without obvious alcoholic consumption. Measuring serum IGF-1 levels might help clinicians to identify type 2 diabetes mellitus patients with advanced non-alcoholic steatohepatitis.

Free testosterone concentration is inversely associated with markers of liver fibrosis in men with type 2 diabetes mellitus.

The association between serum testosterone level and liver fibrosis in patients with non-alcoholic fatty liver disease is unclear. To clarify this association, we investigated the relationship between serum free testosterone concentration and markers of liver fibrosis in men with type 2 diabetes mellitus but no obvious features of alcohol consumption. This retrospective observational cross-sectional study enrolled 248 men with type 2 diabetes mellitus. The FIB-4 index was measured as a marker of liver fibrosis, and multiple linear regression analysis was performed to examine its association with serum free testosterone concentration. In addition, the 7S domain of type IV collagen (IV-7S) was examined in 140 of the 248 patients. The mean free testosterone concentration was 10.6 ± 6.8 pg/mL and the means of the FIB-4 index and IV-7S were 1.64 ± 1.19 and 4.02 ± 1.11 ng/mL, respectively. After adjusting for all relevant variables, serum free testosterone concentrations were inversely associated with both the FIB-4 index and IV-7S (ß; -0.28, P < 0.0001, and ß; -0.28, P = 0.002, respectively). Measuring serum free testosterone concentrations in men with type 2 diabetes mellitus may help to predict progression to advanced liver disease. Identifying patients at risk may help to prevent the development of cirrhosis and hepatocellular carcinoma.

Optimal fentanyl dosage for attenuating systemic hemodynamic changes, hormone release and cardiac output changes during the induction of anesthesia in patients with and without hypertension: a prospective, randomized, double-blinded study.

PURPOSE: The purpose of this study was to compare the dose-related effects of fentanyl on systemic hemodynamics, hormone release and cardiac output in response to endotracheal intubation in patients with and without hypertension. METHODS: Forty-five patients without hypertension and 45 patients with hypertension (total 90 patients) undergoing elective general surgical, urological or gynecological procedures under general anesthesia were studied. The patients were randomly divided into three groups to receive either saline (control), 2.0 µg/kg fentanyl or 4.0 µg/kg fentanyl before tracheal intubation. Anesthesia was induced via intravenous target controlled infusion of propofol (plasma concentration, 4.0 µg/mL) followed by administration of the three drugs. Heart rate, blood pressure, and cardiac output were continuously monitored using Flo Trac/Vigileo system™ and Bispectral index from before anesthetic induction until 10 min after tracheal intubation. RESULTS: In patients without hypertension, there was a significant difference in mean arterial pressure (MAP) among the three groups 2 min after intubation. Cardiac index (CI) in all three groups decreased before intubation compared with that in the awake period, returning to awake values after intubation in all three groups. There was a significant difference in CI between the 4 µg/kg fentanyl group and the other two groups immediately and 1 min after intubation. In patients with hypertension, a differential time course of MAP changes was observed among the three groups after intubation. CI in the three groups decreased after the induction of anesthesia and increased after intubation in control and 2 µg/kg fentanyl groups compared with that in the awake period. CONCLUSIONS: The present study shows that it is preferable to administer 2 µg/kg fentanyl in patients without hypertension and 4 µg/kg fentanyl in patients with hypertension in order to minimize the changes in heart rate, systolic blood pressure and cardiac output associated with tracheal intubation.

Effects of landiolol on left ventricular function during electroconvulsive therapy: a transthoracic echocardiographic study.

The purpose of this study was to examine the effects of landiolol on left ventricular (LV) systolic function, using transthoracic echocardiography, during electroconvulsive therapy (ECT). Fourteen patients undergoing ECT were studied. Bilateral ECT was performed after administration of thiopentone (2 mg/kg), succinylcholine (1 mg/kg), and initiation of assisted mask ventilation with 100% oxygen. Patients received a bolus injection of landiolol (0.125 mg/kg) or saline immediately after anesthetic induction and prior to electrical shock. LV systolic function was examined by transthoracic echocardiography prior to anesthetic induction, throughout the ECT procedure, and for 10 min after the seizure. Electrical shock resulted in a significant decrease in fractional area change (FAC) when compared with the awake condition in the control group [FAC when awake: 48 +/- 3%; 1 min after ECT: 38 +/- 4%*; 2 min after ECT: 36 +/- 4%*; 3 min after ECT: 40 +/- 3%*; mean +/- standard deviation, *p < 0.05 compared with awake]. Landiolol infusion stabilized systemic hemodynamics and LV systolic function. The study demonstrated that landiolol is a suitable agent to minimize hemodynamic changes and transthoracic echocardiographic variability after ECT.

Effects of landiolol, a short-acting beta-1 blocker, on hemodynamic variables during emergence from anesthesia and tracheal extubation in elderly patients with and without hypertension.

PURPOSE: Tracheal extubation and emergence procedures induce abrupt changes in hemodynamics and humoral responses. We conducted a prospective randomized study to examine the effects of the short-acting beta-1 blocker, landiolol, on hemodynamics during emergence from anesthesia in elderly patients with and without hypertension. METHODS: Thirty-one hypertensive and 32 normotensive elderly patients were randomly divided into two groups: a control (placebo group) and a landiolol infusion group. Landiolol was dissolved in 20 ml of saline and administered as an infusion at the rate of 0.125 mg kg(-1) min(-1) for 1 min and then decreased to 0.04 mg kg(-1) min(-1) until extubation. Control patients received an equal volume of saline. Heart rate and blood pressure were recorded every minute from immediately before the administration of landiolol up to the discontinuation of landiolol, and every 5 min from the discontinuation of landiolol to 30 min after termination of the infusion. RESULTS: Systolic blood pressure in the control group patients with hypertension increased during anesthesia emergence and tracheal extubation, as did the heart rate. Landiolol infusion in the elderly patients with hypertension partially prevented the increase in systolic blood pressure and completely prevented the increase in heart rate associated with emergence from anesthesia. Landiolol infusion in the elderly patients without hypertension brought about a decrease in heart rate during emergence and tracheal extubation. CONCLUSION: This study indicates that the use of a landiolol infusion for preventing hemodynamic instability in elderly patients during the emergence period would be dependent on the presence or absence of hypertension in these patients.

Comparative effects of propofol, landiolol, and nicardipine on hemodynamic and bispectral index responses to endotracheal intubation: a prospective, randomized, double-blinded study.

STUDY OBJECTIVES: To examine the comparative effects of propofol, landiolol, and nicardipine on hemodynamic responses and bispectral index (BIS) changes to endotracheal intubation. SETTING: Operating room of a university-affiliated general hospital. PATIENTS: 27 ASA physical status I and II patients who were scheduled to undergo elective general surgical, urological, or gynecological procedures with general anesthesia. STUDY DESIGN: Prospective, randomized, double-blinded study. INTERVENTIONS: Patients were divided into three groups as follows: Group 1 received propofol, 1 mg/kg; Group 2 received landiolol, 0.1 mg/kg; and Group 3 received nicardipine, 1 mg. After baseline measurements were recorded, anesthesia was induced with propofol, fentanyl, and vecuronium. Patients' lungs were ventilated with 100% oxygen for 120 seconds, at which time one of one of the study drugs was administered. Laryngoscopy and tracheal intubation were performed 4 minutes after anesthetic induction. MEASUREMENTS: Cardiac index (CI) and stroke volume index (SVI) were monitored continuously. Bispectral index was also monitored continuously from 5 minutes after tracheal intubation. MAIN RESULTS: Heart rate values in Group 3 increased 30 seconds after intubation; this increase lasted for 1 minute after intubation. Systolic blood pressure in all three groups decreased after induction of anesthesia and before tracheal intubation, and values returned closer to baseline values 30 seconds after intubation. In the propofol group, CI and SVI decreased after administration of additional propofol, lasting for 30 seconds after intubation. The BIS values rapidly decreased after induction of anesthesia, with no intergroup differences noted in BIS values (propofol group, 39+/-7; landiolol group, 44+/-14; nicardipine group, 41+/-9). However, BIS was significantly lower in the propofol group than in the other two groups from 30 seconds to 5 minutes after intubation. CONCLUSIONS: Landiolol, 0.1 mg/kg, before intubation provides effective hemodynamic stability in the postintubation period.