Oral midodrine for prophylaxis against post-spinal anesthesia hypotension during hip arthroplasty in elderly population: a randomized controlled trial.

BACKGROUND: We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. METHODS: This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP < 80% baseline) was treated with 10 mg ephedrine. The primary outcome was intraoperative ephedrine consumption. Secondary outcomes were the incidence of post-spinal hypotension, bradycardia, and hypertension (MAP increased by > 20% of the baseline reading). RESULTS: We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. CONCLUSION: The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. CLINICAL TRIAL REGISTRATION: This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05548985 .

Pioglitazone Enhances ß-Arrestin2 Signaling and Ameliorates Insulin Resistance in Classical Insulin Target Tissues.

INTRODUCTION: Pioglitazone is a thiazolidinedione oral antidiabetic agent. This study aimed to investigate the effects of pioglitazone as insulin sensitizer on ß-arrestin2 signaling in classical insulin target tissues. METHODS: Experiments involved three groups of mice; the first one involved mice fed standard chow diet for 16 weeks; the second one involved mice fed high-fructose, high-fat diet (HFrHFD) for 16 weeks; and the third one involved mice fed HFrHFD for 16 weeks and received pioglitazone (30 mg/kg/day, orally) in the last four weeks of feeding HFrHFD. RESULTS: The results showed significant improvement in the insulin sensitivity of pioglitazone-treated mice as manifested by significant reduction in the insulin resistance index. This improvement in insulin sensitivity was associated with significant increases in the ß-arrestin2 levels in the adipose tissue, liver, and skeletal muscle. Moreover, pioglitazone significantly increased ß-arrestin2 signaling in all the examined tissues as estimated from significant increases in phosphatidylinositol 4,5 bisphosphate and phosphorylation of Akt at serine 473 and significant decrease in diacylglycerol level. CONCLUSION: To the best of our knowledge, our work reports a new mechanism of action for pioglitazone through which it can enhance the insulin sensitivity. Pioglitazone increases ß-arrestin2 signaling in the adipose tissue, liver, and skeletal muscle of HFrHFD-fed mice.

The Use of Topical Nitroglycerin to Facilitate Radial Arterial Catheter Insertion in Children: A Randomized Controlled Trial.

OBJECTIVES: To determine whether the use of topical nitroglycerin patch increases radial artery diameter and facilitate cannulation in children. DESIGN: Randomized controlled trial. SETTING: Cairo University Hospital. PARTICIPANTS: Children aged 2 to 8 years old scheduled for cardiac surgery. INTERVENTION: In the nitroglycerin group (n = 20), a gauze-covered, half-sized nitroglycerin patch (5 mg) was applied at the site of radial pulsation 1 hour before induction of anesthesia. In the control group (n = 20), a gauze pad was applied to the bare skin at the site of radial pulsation with no intervention. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the diameter of the radial artery in both limbs using ultrasonography. Other outcomes included the degree of arterial palpability, number of arterial punctures, and incidence of successful first puncture cannulation. The radial artery diameter increased after 30 minutes and 60 minutes compared with the baseline value in the nitroglycerin group in both limbs, whereas no change was reported in the radial artery diameter in the control group. The nitroglycerin group showed a greater incidence of successful first cannulation trial, a fewer number of trials, and a shorter cannulation time compared with the control group. There were no significant hypotensive episodes in any patient. CONCLUSION: Local application of a half-sized, 5 mg nitroglycerin patch for 60 minutes in children increased the radial artery diameter bilaterally, increased the rate of first trial success, and decreased the time needed for arterial cannulation without significant hypotensive episodes.

Oleic acid acutely impairs glucose homeostasis in standard chow diet but not high-fructose, high-fat diet-fed mice by acting on free fatty acid receptor 1

Abstract This study aimed to investigate the acute effects of oleic acid (OA) on glucose homeostasis in mice fed a standard chow diet (SCD) and a high-fructose, high-fat diet (HFrHFD); moreover, the role of free fatty acid receptor 1 (FFAR1) was evaluated. The mice in the two groups were further divided into three subgroups as follows: control, OA (40 mg/kg), and OA + GW1100 (0.4 mg/kg, selective FFAR1 blocker). After a 16-week feeding period, the mice received the drugs via intraperitoneal (i.p.) injection followed by an i.p. glucose tolerance test (IPGTT) 30 min later. After 3 days, the mice received the same drugs to examine the effects of the drugs on the hepatic levels of phosphatidylinositol-4,5-bisphosphate (PIP2) and diacylglycerol (DAG). OA in the SCD-fed mice significantly increased the blood glucose level (48%, P < 0.001) after 30 min of glucose load compared to that in the control group, but did not affect the levels of PIP2 and DAG. Pre-injection with GW1100 significantly decreased the area under the curve of the IPGTT (28%, P < 0.05) in the SCD group compared to that in the SCD + OA group. OA reduced the blood glucose level (35%, P < 0.001) after 120 min of glucose load in the HFrHFD-fed mice; in addition, it increased hepatic PIP2 (160%, P < 0.01) and decreased hepatic DAG (60%, P < 0.001) levels. Pre-injection with GW1100 blocked the effects of OA on hepatic PIP2 and DAG without affecting the glucose tolerance. In conclusion, OA acutely impaired the glucose tolerance in the SCD-fed mice by acting on FFAR1 but did not improve it in the HFrHFD-fed mice.