Role of Novel Glucagon-like Peptide-1 Receptor Analogue Polyethylene Glycol Loxenatide in Type 2 Diabetes: A Systematic Review and Meta-analysis.

Background: Polyethylene glycol loxenatide (peg-loxenatide) is a novel glucagon-like peptide-1 receptor agonist developed and available for clinical use in China. This meta-analysis was performed as no meta-analysis has analysed the efficacy and safety of peg-loxenatide in type 2 diabetes (T2DM). Methods: Electronic databases were systematically reviewed for RCTs having patients living with T2DM receiving peg-loxenatide in treatment arm and placebo/any other diabetes medicine in control arm. The primary outcome was to evaluate changes in glycated haemoglobin. The secondary outcomes were to evaluate alterations in weight, blood pressure, fasting glucose, prandial glucose, lipids, and adverse events. Results: Data from four trials (718 patients) were analysed. Over 12-24 weeks of clinical use, HbA1c was significantly lower in patients receiving standard-dose peg-loxenatide (100 mcg/week) {MD -0.95% [95% confidence interval (CI): -1.19 to -0.71]; P < 0.01; I2 = 76%} and high-dose peg-loxenatide (200 mcg/week) [MD -1.15% (95% CI: -1.47 to -0.82); P < 0.01; I2 = 90%], as compared to placebo. Standard-dose peg-loxenatide was not associated with increased occurrence of nausea [RR 2.87 (95% CI: 0.56 to 14.72); P = 0.21; I2 = 10%], vomiting [RR 4.73 (95% CI: 0.53 to 41.88); P = 0.16; I2 = 0%], and anorexia [RR 0.78 (95% CI: 0.18 to 3.28); P = 0.73; I2 = 0%]. Occurrence of nausea [RR 16.85 (95% CI: 3.89 to 72.92); P < 0.01; I2 = 10%], vomiting [RR 15.90 (95% CI: 2.99 to 84.55); P < 0.01; I2 = 0%], and anorexia [RR 3.85 (95% CI: 1.24 to 11.88); P = 0.02; I2 = 0%] was significantly higher with high-dose peg-loxenatide, as compared to placebo. Conclusion: Peg-loxenatide (100 mcg/week) is the most appropriate dose for clinical use as it is associated with good glycaemic efficacy with minimal gastro-intestinal side effects.

Challenges in Anesthesia in Wilson's Disease: A Systematic Review of the Existing Literature.

Wilson's disease (WD) is a disorder of copper metabolism presenting with a wide variety of organ dysfunctions affecting predominantly the neurological, hepatic, and hematological systems. Due to its multi-systemic nature, administering anesthesia to a patient with WD is challenging and requires an in-depth knowledge of the disease pathophysiology. A systematic search for literature pertaining to the anesthetic management of patients with WD yielded 19 case reports, which we have included in this review to explore and summarize peri-operative concerns and the safe anesthesia practices in this condition.

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed the safety and efficacy of lobeglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving type-2 diabetes patients receiving lobeglitazone in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids and adverse events. RESULTS: From initially screened 65 articles, data from 4 RCTs (828 patients) which fulfilled all criteria was analysed. Over 24 weeks, when compared to sitagliptin 100 mg/d and half maximal pioglitazone dose (15 mg/d), lobeglitazone 0.5 mg/day had comparable impact on HbA1c [MD 0.03% (95%CI: 0.11-0.17); P = 0.65; I2 = 0%], fasting glucose [MD 1.47 mg/dl (95%CI: 4.66-7.60); P = 0.64; I2 = 0%], triglycerides [MD-9.96 mg/dl (95%CI: 43.55-23.62); P = 0.56; I2 = 81%], LDL-cholesterol [MD0.74 mg/dl (95%CI: 4.60-6.09); P = 0.79; I2 = 0%] and HDL-cholesterol [MD1.55 mg/dl (95%CI: 3.72-6.82); P = 0.56]. Occurrence of treatment-emergent adverse events (AEs) [RR 1.07 (95% CI:0.78-1.47); P = 0.67; I2 = 0%] and severe AEs [RR 1.05(95%CI: 0.42-2.65); P = 0.91; I2 = 0%] were similar. Edema and weight gain were significantly higher with lobeglitazone compared to controls [RR 2.58 (95%CI: 1.08-6.17); P = 0.03; I2 = 0%]. Lobeglitazone 0.5 mg/d compared to half-maximal pioglitazone (15 mg/d), had similar edema and weight gain [RR 1.65 95% CI: 0.78-1.47)]. BMD percent changes at neck of femur was comparable in both groups [MD 0.07% (95%CI: 0.19-0.33); P = 0.60; I2 = 91%]. Low dose lobeglitazone (0.25 mg/d) was inferior to high dose lobeglitazone (0.5 mg/d) with regards to glycaemic efficacy with advantage of lower weight gain and edema. CONCLUSION: The current evidence makes lobeglitazone unlikely to replace pioglitazone as the preferred thiazolidinedione in T2DM.

Medical and Surgical Care of Critical Burn Patients: A Comprehensive Review of Current Evidence and Practice.

Critically ill burn patients pose several unique challenges to care providers. The concepts of fluid resuscitation, nutritional management, organ support and wound care are rapidly evolving. There is a pressing need to review emerging evidence and incorporate these into practice for the effective management of burn patients. We have searched the PubMed and Google Scholar databases to review the current evidence on the acute care management of adult as well as paediatric burn patients. The rationales for current practices have been integrated into the review. The management of critically ill burn patients requires an in-depth knowledge of the pathophysiology of burn injury, a tailored approach for timely resuscitation, timely diagnosis of organ specific problems, and comprehensive wound care. This review will help the doctors and healthcare providers involved in the management of critical burn patients in their day-to-day practice.

Trendelenburg in Acute Respiratory Distress Syndrome: Should We Do More than Proning?

How to cite this article: Datta PK, Kundu R. Trendelenburg in Acute Respiratory Distress Syndrome: Should We Do More than Proning? Indian J Crit Care Med 2022;26(8):976-977.

Looking for a Silver Lining to the Dark Cloud: A Google Trends Analysis of Contraceptive Interest in the United States Post Roe vs. Wade Verdict.

Background In the wake of the recent Roe vs. Wade judgment, we performed a Google Trends analysis to identify the impact of this decision on the interests regarding contraceptive choices in the United States. Methods A Google Trends search between April 6 and July 5, 2022, with the United States as the area of interest, was performed using the five most popular contraception choices. In addition, a second trend search was performed using oral and injectable hormonal birth control measures. Results Trends showed a spike in interest regarding various contraceptive methods immediately following the verdict. The highest increase in interest was noted for "vasectomy," followed by "tubal ligation." With respect to oral and injectable birth control measures, "morning after pill" showed a marked spike in interest. Conclusion This verdict has triggered increased interest in contraceptive practices, which can be translated into better reproductive health with proper public health initiatives.

Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial.

Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve -25.6 (95% confidence intervals -31.4 to -15.9) /minute; P <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e' ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.

Sevoflurane Consumption During Inhalational Induction in Children: A Randomized Comparison of Minute Ventilation-Based Techniques With Standard Fixed Fresh Gas Flow Technique.

This study was done to ascertain the optimum fresh gas flow (FGF) offering the best balance between rapid induction and minimal waste in pediatric patients. Forty-five children (weighing 10-20 kg) undergoing elective procedures under general anesthesia were randomly assigned into 3 groups: 0.5 minute ventilation (MV), MV, and S (FGF = 6 L/min). After priming the pediatric closed circuit, anesthesia was induced using a face mask with 8% sevoflurane in 100% oxygen (Draeger Primus Vista 120 anesthesia machine) at FGF-determined MV per group allocation. After loss of eyelash reflex (time 1 [T1]), intravenous cannulation (T2) and laryngeal mask airway (LMA) placement (T3) were done. Total sevoflurane consumed during induction (measured using logbook function) was the primary outcome. The cost of sevoflurane, any reflex movement, tachycardia (heart rate change > 20%), or additional propofol boluses required were also recorded. Sevoflurane consumption (3.8 vs 5.8 vs 9.2 mL) and cost of sevoflurane (104.2 vs 199.4 vs 312.8 rupees) were lowest in group 0.5 MV (P < .001). There was no difference in hemodynamic parameters, movement on cannulation/LMA insertion, and rescue propofol boluses required. For pediatric sevoflurane induction, half the MV-based FGF provided similar anesthetic conditions for LMA insertion with minimum sevoflurane consumption.

Anesthesia maintenance with 'induction dose only' sevoflurane during pediatric ophthalmic examination: comparison with standard low-flow technique through a randomized controlled trial.

BACKGROUND: Sevoflurane is preferred for pediatric day care procedures. However, financial and environmental costs remain major limitations. Induction dose of sevoflurane could itself be sufficient for maintaining anesthesia with low fresh gas flow during short noninvasive procedures. METHODS: Fifty children, aged 1-5 years, scheduled for ophthalmic examination under anesthesia, were randomized into two groups. All children were induced with 8% sevoflurane in O2 : N2 O (40 : 60). In the Group S, anesthesia was maintained with 2% sevoflurane at 1 l·min-1 fresh gas flow [O2 : N2 O = 50 : 50]. In Group L, the sevoflurane vaporizer was turned off and fresh gas flow was reduced to 0.5 l·min-1 [O2 : N2 O = 50 : 50]. HR, BP, MAC, BIS, total sevoflurane consumption, ocular deviation, body movement, time to laryngeal mask airway removal (TWO ), and airway complications were compared between the groups. Rescue propofol bolus was used, if needed. RESULTS: Median duration of examination was 14 min (IQR = 9-17) in Group S and 15 min (IQR = 10-17) in Group L. Sevoflurane consumption was lower in the Group L (7 ml) compared to Group S (9 ml) [median difference = 2 ml, P < 0.001, 95% CI = 0.96-3.04]. TWO was lower in Group L (86 s) compared to Group S (131 s) [median difference = 45 s, P = 0.002, 95% CI = 19.85-70.15]. There was no difference in hemodynamic parameters, incidence of ocular deviation, movement or airway complications, and need for rescue propofol. CONCLUSION: Induction dose of sevoflurane is, in itself, adequate for maintaining anesthesia for short noninvasive ophthalmic examinations lasting approximately 15 min. This method significantly reduces sevoflurane consumption and cost.

Magnesium sulfate or diltiazem as adjuvants to total intravenous anesthesia to reduce blood loss in functional endoscopic sinus surgery.

STUDY OBJECTIVE: This study was designed to know whether addition of magnesium sulfate (MgSO4) or diltiazem to total intravenous anesthesia (TIVA) (propofol) aided reduction in blood loss during functional endoscopic sinus surgery (FESS). The secondary outcomes measured were surgeon's assessment of the surgical field and hemodynamics. DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING: Operating room. PATIENTS: Forty-five American Society of Anesthesiologists I and II adult patients (18-60years) undergoing FESS. INTERVENTIONS: All groups received propofol-fentanyl TIVA. Patients were randomly allocated to 1 of the 3 groups (MgSO4 group, n=15; diltiazem group, n=15; saline group, n=15). MEASUREMENTS: Intraoperative bleeding was quantified, and quality of surgical field was graded. Hemodynamic parameters were recorded. MAIN RESULTS: Addition of both MgSO4 and diltiazem significantly reduced blood loss (240 and 350mL) in comparison to control group (415mL) (P=.003). The surgical field was significantly better in the MgSO4 group compared with the diltiazem (P=.028) and saline groups (P=.0001). CONCLUSION: It was concluded that the addition of both MgSO4 and diltiazem to TIVA propofol results in significant reduction in blood loss and significant improvement in the quality of surgical field during FESS without causing any adverse effects on the hemodynamics or on the recovery from anesthesia. The surgical field in the MgSO4 group was significantly better than that in the diltiazem group (P=.04).

Dextrose-containing intraoperative fluid in neonates: a randomized controlled trial.

BACKGROUND: Glucose requirement in neonates during surgery and the impact of glucose supplementation on neonatal metabolism remain unclear. AIM: This study was designed to identify an appropriate perioperative fluid regimen in neonates which maintains carbohydrate and lipid homeostasis. METHODS: Forty-five neonates undergoing primary repair of a trachea-esophageal fistula were randomly allocated into three groups. During surgery, the neonates received either 1% dextrose in Ringer lactate (RL) (group D1) at 10 ml·kg(-1) ·h(-1) , or 2% dextrose in RL (group D2) at 10 ml·kg(-1) ·h(-1) , or 10% dextrose in N/5 saline at 4 ml·kg(-1) ·h(-1) and replacement fluid with 6 ml·kg(-1) ·h(-1) of RL (group D4). Glucose homeostasis, electrolyte balance, acid-base status, and endocrine and metabolic parameters were compared among the groups during the perioperative period. RESULTS: Blood glucose increased in all the three groups at the end of surgery, with no significant difference in blood glucose and incidence of hyperglycemia (BG > 150 mg·dl(-1) ) among them. At 24 h after surgery, blood glucose and incidence of hyperglycemia was significantly higher in Group D1 compared to Group D4. Base excess, bicarbonate, lactate, and pH showed a significant fall in Group D1. There was no significant difference in serum-free fatty acids, serum beta-hydroxy butyrate, and serum cortisol in three groups. At the end of surgery, serum insulin was significantly lower and glucagon : insulin (G : I) ratio was higher in Group D1 compared to Group D4. CONCLUSIONS: All three solutions, when infused at 10 ml·kg(-1) ·h(-1) , are equally effective in maintaining glucose homeostasis, but 1% dextrose-containing fluid promotes catabolism, insulin resistance, rebound hyperglycemia, and acidosis. Therefore, 2-4% dextrose-containing fluids is more suitable compared to 1% dextrose-containing fluids for use during major neonatal surgeries requiring average fluid infusion rate of 10 ml·kg(-1) ·h(-1) .