Prospective Double-blind Randomized Study Research Articles

The value of lung ultrasound score in neonatal respiratory distress syndrome: a prospective diagnostic cohort study.

The accurate diagnosis of critically ill patients with respiratory failure can be achieved through lung ultrasound (LUS) score. Considering its characteristics, it is speculated that this technique might also be useful for patients with neonatal respiratory distress syndrome (NRDS). Thus, there is a need for precise imaging tools to monitor such patients. This double-blind randomized cohort study aims to investigate the impact of LUS and related scores on the severity of NRDS patients. This study was conducted as a prospective double-blind randomized study. Bivariate correlation analysis was conducted to investigate the relationship between LUS score and Oxygenation Index (OI), Respiratory Index (RI), and Sequential Organ Failure Assessment (SOFA) score. Spearman's correlation coefficient was used to generate correlation heat maps, elucidating the associations between LUS and respective parameters in different cohorts. Receiver Operating Characteristic (ROC) curves were employed to calculate the predictive values, sensitivity, and specificity of different scores in determining the severity of NRDS. This study ultimately included 134 patients admitted to the intensive care unit (ICU) between December 2020 and June 2022. Among these patients, 72 were included in the NRDS cohort, while 62 were included in the Non-NRDS (N-NRDS) cohort. There were significant differences in the mean LUS scores between NRDS and N-NRDS patients (p < 0.01). The LUS score was significantly negatively correlated with the OI (p < 0.01), while it was significantly positively correlated with the RI and SOFA scores (p < 0.01). The correlation heatmap revealed the highest positive correlation coefficient between LUS and RI (0.82), while the highest negative correlation coefficient was observed between LUS and OI (-0.8). ROC curves for different scores demonstrated that LUS score had the highest area under the curve (0.91, 95% CI: 0.84-0.98) in predicting the severity of patients' conditions. The combination of LUS and other scores can more accurately predict the severity of NRDS patients, with the highest AUC value of 0.93, significantly higher than using a single indicator alone (p < 0.01). Our double-blind randomized cohort study demonstrates that LUS, RI, OI, and SOFA scores can effectively monitor the lung ventilation and function in NRDS. Moreover, these parameters and their combination have significant predictive value in evaluating the severity and prognosis of NRDS patients. Therefore, these results provide crucial insights for future research endeavors.

Comparative study between rocuronium and magnesium sulfate as adjuvants to local anesthetics for peribulbar block

Background &amp; Objective: Peribulbar anesthesia is frequently used in cataract surgeries. Compared to retrobulbar anesthesia, this approach is associated with less significant consequences. However, the prolonged onset of orbital akinesia and the frequent need for block replenishment are considered drawbacks. We aimed to investigate the impact of adding rocuronium and magnesium sulfate to a commonly used local anesthetic combination on the onset of corneal anesthesia and the degree of lid and globe akinesia during peribulbar block in ocular surgeries.&#x0D; Patients and Methods: This prospective double-blinded randomized study was conducted in the ophthalmic surgery operating theater, Ain Shams University Hospital from January 2019 to April 2020. We enrolled 75 patients from both sexes, with American Society of Anesthesiology (ASA) physical status I–III, ages 40-80 y, and an axial globe length less than or equal to 26 mm planned for cataract surgery under peribulbar block in the study following institutional ethical board approval and written informed patient consents. Patients were randomly divided into three groups, 25 patients per group, based on the drugs they received: Group O (control group): received local anesthetic + 0.9% normal saline (1 ml). Group M: received local anesthetic + magnesium sulphate 50 mg in normal saline. Group R: received local anesthetic + rocuronium at a dose of 0.06 mg/kg (maximum 5 mg) in normal saline.&#x0D; Results: Our study found statistically significant more rapid onset of action (mean time to start surgery) in rocuronium group (7.00 ± 1.22 min) than control group and magnesium sulfate group (9.00 ± 1.47 and 9.00 ± 1.15 min) respectively, (P &lt; 0.001); Moreover, no significant difference was noted between control group and magnesium sulfate group. In addition, no relevant difference was reported regarding duration of surgery between the groups.&#x0D; Conclusion: During cataract surgery, the addition of rocuronium to the local anesthetic mixture in the peribulbar nerve block has been found to enhance ocular akinesia and corneal anesthesia. Furthermore, the use of rocuronium demonstrated a significantly faster onset and shorter time needed to achieve the appropriate conditions to initiate the surgical procedure compared to the use of magnesium sulfate. Addition of magnesium sulfate showed good results regarding akinesia, corneal anesthesia and need for supplementary injections but it did not significantly fasten the onset of block and hence the time to start surgery.&#x0D; Key words: Cataract; Magnesium Sulfate; Peribulbar Block; Rocuronium&#x0D; Citation: Nagy M, Abo El-Ella S, El-Shafey MA, Helal AM, Zekry MR. Comparative study between rocuronium and magnesium sulfate as adjuvants to local anesthetics for peribulbar block. Anaesth. pain intensive care 2024;28(1):55−61; DOI: 10.35975/apic.v28i1.2157&#x0D; Received: February 18, 2023; Reviewed: July 30, 2023; Accepted: December 23, 2023

Efficacy of Magnesium Sulfate and Dexmedetomidine as Adjuvants to Ropivacaine in Supraclavicular Brachial Plexus Block: A Randomised Clinical Study

Introduction: Peripheral nerve blocks have recently proven to be extremely promising in terms of patient satisfaction. In upper limb procedures, rapid and deep anaesthesia can be achieved with supraclavicular ultrasound-guided access to the brachial plexus. To improve the quality of local anaesthesia, adjuvants such as magnesium sulfate and dexmedetomidine have been added to the local anaesthetic. Aim: To evaluate the efficacy of magnesium sulfate and dexmedetomidine as adjuvants to ropivacaine in supraclavicular Brachial Plexus Blockade (BPB). Materials and Methods: A prospective randomised doubleblind study was conducted in the Department of Anaesthesiology from June 2016 to November 2017 ( 1 year and 6 months) at King George's Medical University, Lucknow, Uttar Pradesh, India. A total of 60 patients were divided into two groups using a computer-generated random number for upper limb surgeries (below the mid-humerus) under supraclavicular brachial plexus block. Group A (n=30) received ropivacaine 0.5% (30 mL) plus dexmedetomidine 50 µg for the supraclavicular block, and Group B received ropivacaine 0.5% (30 mL) plus magnesium sulfate 150 mg in 1 mL Normal Saline (NS) 0.9% for the same block. A comparison of these two groups was conducted for the time of onset, duration of sensory and motor block, haemodynamic stability, postoperative analgesia, and complications. Statistical analyses such as Student’s t-test, Chi-square test, and MannWhitney U-test were used. Results: The mean age of Group A was 28.03±5.86 years and Group B was 31.07±7.06 years. The sensory block and motor block onset were significantly faster among patients of Group A (6.47±1.43 min and 8.50±1.46 min) compared to Group B (9.57±1.22 min and 11.77±1.19 min). The mean duration of analgesia was significantly longer (p&lt;0.001) in Group A (1034.10±61.07 min) compared to Group B (460.00±35.82 min). The duration of sensory block and motor block was also significantly higher (p&lt;0.001) in Group A compared to Group B. Both groups were haemodynamically stable, but sedation was significantly higher in Group A. Conclusion: Dexmedetomidine 50 µg is a superior adjuvant compared to magnesium sulfate 150 mg with ropivacaine 0.5% in supraclavicular brachial plexus block as it significantly hastens onset time and prolongs the duration of sensory and motor blocks and the duration of analgesia.

Epidural nalbuphine versus dexmedetomidine as adjuvants to bupivacaine in lower limb orthopedic surgeries for postoperative analgesia: a randomized controlled trial

BackgroundAdministration of adjuvant drugs epidurally in combination with local anesthetics offers new dimensions in the management of postoperative pain. This study aimed to compare the addition of either nalbuphine or dexmedetomidine to epidural bupivacaine for postoperative analgesia in lower limb orthopedic surgeries under combined spinal-epidural anesthesia.MethodsThis prospective randomized double-blind study included 69 patients scheduled for lower limb orthopedic surgeries. Anesthesia was started with 15 mg hyperbaric bupivacaine 0.5% intrathecally, and then an epidural bolus dose of 12 ml (10 ml 0.25% bupivacaine with 2 ml normal saline in group C, 2 ml (10 mg) nalbuphine in group N or dexmedetomidine 2 ml (100 µg) in group D was administered when sensory regression to T10. Postoperatively, when visual analogue scale (VAS) was ≥ 3, an epidural top-up dose of 8 ml (6 ml 0.25% bupivacaine plus 2 ml normal saline in group C, 2 ml (2 mg) nalbuphine in group N or 20 µg dexmedetomidine (2 ml) in group D was given. The primary outcome was to evaluate the duration of postoperative analgesia and secondary outcomes were any side effects and patient satisfaction.ResultsThe onset of epidural analgesia was 17.83 ± 2.53 versus 13.39 ± 1.27 versus 12.17 ± 1.27 min in groups C, N and D, respectively (p value < 0.001). The mean duration of analgesia was 241.3 ± 14.24 versus 318.38 ± 22.54 versus 365.87 ± 18.01 min in groups C, N and D, respectively (p value < 0.001). The mean sedation score was less in group C than group N and D (P < 0.001). The patient satisfaction score showed the lowest degree of satisfaction in group C (p value < 0.001). Top-up doses consumed and total analgesic requirements were lower in groups N and D than in group C. There was a statistically significant difference between the studied groups regarding VAS over time (p value < 0.001), intraoperative bradycardia (p value 0.029), and shivering (p value 0.029).ConclusionThe addition of either nalbuphine or dexmedetomidine to epidural bupivacaine was effective for postoperative analgesia in terms of onset, duration, and patient satisfaction with the superiority of dexmedetomidine over nalbuphine.Trial registrationApproval from the research ethics committee of the Faculty of Medicine, Zagazig University was obtained with the reference number (ZU-IRB#:7045-15-8-2021) and it was registered under clinicaltrials.gov (NCT05041270) on registration date 13/09/2021.

Analgesic Sparing Effect of Dexamethasone with Levobupivacaine in Quadratus Lumborum Block in Patients Undergoing Unilateral Inguinal Hernia Repair

Abstract Background The QLB is an effective analgesic technique for various abdominal wall incisinos. The QLB covers T7 to L2 dermatomes. Levobupivacaine is a long-acting LA agent, commonly used for peripheral nerve block due to its better safety profile than that of bupivacaine. Dexamethasone as an adjuvant to LA has been shown to prolong the duration of pain-free period, less requirement for rescue opioids consumption, more patient satisfaction and lesser incidence of nausea and vomiting. Objective To assess the analgesic sparing effect of adding dexamethasone to levobupivacaine in quadratus lumborum block in patients undergoing unilateral inguinal hernia repair under general anesthesia. Patients and Methods After approval of the anesthesiology department and scientific and ethical committees, this prospective double blind randomized clinical trial study was conducted in Ain Shams University Hospitals. Sixty patients scheduled for elective ingunial surgeries under general anesthesia were included in this study. Results Our study did not have any complications associated with the use of dexamethasone with levobupivacaine in QLB. Type 1 QLB failed to provide postoperative analgesia in surgeries involving dissection in the retroperitoneal area as there were high chances of damaging the thoracolumbar fascia. Conclusion The addition of dexamethasone to levobupivacaine in QLB in unilateral inguinal hernia repair surgery provides a prolonged duration of postoperative analgesia, with reduced analgesic requirements, a better quality of analgesia in terms of NRS compared to levobupivacaine alone group.

Ultrasound Guided Fascia Iliaca Compartment Block versus Three in One Block for Post Operative Analgesia in Patients Undergoing Hip and Knee Replacement Surgeries

Abstract Background Patients undergoing total hip and knee arthroplasty experience substantial and sustained postoperative pain. Inadequate analgesia may impede physical therapy and rehabilitative efforts and delay hospital dismissal. Peripheral nerve blockade of the lumbosacral plexus has emerged as an analgesic approach. In several studies, unilateral peripheral block provided quality of analgesia and functional outcomes similar to those of continuous epidural analgesia and superior to those of systemic analgesia, but with fewer side effects because of their opioid-sparing properties. Peripheral nerve block techniques may be the optimal analgesic method following total joint arthroplasty. Aim of the Work To compare postoperative analgesia between ultrasound-guided FICB and three in one nerve block. Study design a prospective randomized double-blinded study. Patients and Methods The study was conducted on 80 randomly chosen patients from 21 to 65 years old in Ain Shams University Hospitals after approval of the medical ethical committee. Patients were divided randomly into two groups, each group consisted of 40 patients group I and group II. After preoperative assessment and obtaining baseline vital data, all patients received spinal anesthesia. Patients in the group I received FICB (35-40 ml of 0.25% bupivacaine). Patients in group II received three in one bock (35-40 mL of bupivacaine 0.25%). Results Both FICB and three in one block provided good quality of postoperative analgesia and patient satisfaction as evidenced by low VAS and low postoperative rescue analgesic requirements. Both techniques provided equal sensory blockage of femoral nerve, obturator nerve, and genitofemoral nerve, but sensory blockage of LFC nerve was demonstrated in 92.5% patients in FICB and 62.5% of patients in three in one block, which was significantly lower (p-value &amp;lt;0.001 HS). VAS at 12 hours after surgery during movement of 3.68 ± 2.77 in the FICB group and 4.90 ±0.18 in the 3 in 1 group were statistically significant (P value = 0.007). Conclusion The FICB provides a high degree of sensory blockade of the LFC nerve and improves analgesia when continuous passive motion is initiated in the early postoperative period; also, it is easy to perform, reliable and does not threaten any vital organ. Thus, FICB can be recommended as an alternative to three in one block for the treatment of pain after hip and knee arthroplasty.

A prospective double-blinded randomized study on drug-eluting stent implantation into nitrate-induced maximally dilated vessels in patients with coronary artery disease

BackgroundPercutaneous coronary intervention (PCI) has been developed using drug-eluting stents (DES); however, stent implantation is associated with concerns of stent thrombosis and target vessel revascularization (TVR). The stent diameter is a critical factor in TVR and clinical events. The nitrate administration in coronary angiography can dilate the reference vessel diameter, enabling accurate vessel size measurement and optimal stent implantation support. This study was designed to evaluate the effect of stent implantation in the maximally dilated coronary artery in patients with coronary artery disease (CAD).MethodsThis prospective double-blinded randomized (1:1) study is designed to compare the efficacy and safety between DES implantation into the nitrate-induced maximally dilated vessels and conventional DES implantation in patients with CAD. A total of 400 patients who underwent PCI with a sirolimus-eluting stent will be enrolled. The primary endpoint is the mean diameter of the deployed stents. Secondary endpoints include cardiac death, myocardial infarction, stent thrombosis, or ischemia-driven TVR 1 year after the procedure.DiscussionThis study will be the first randomized controlled trial to evaluate the effect of DES implantation on nitrate-induced maximally dilated vessels in patients with CAD.Trial registrationThe trial was registered on 18 June 2021 as Effect of Ultimaster Stents Treated to the Most Dilated Coronary Vessels (ClinicalTrials.gov Identifier: NCT04931784).

Comparative Evaluation of Intranasal Dexmedetomidine Spray Versus Intranasal Normal Saline Spray in Patients Undergoing Transalveolar Extractions for Anxiety Reduction: A Randomized Control Study.

Dexmedetomidine has dose-dependent selectivity for alpha 2 adrenoceptors. It is a good sedative with analgesic characteristics and good haemodynamic stability. Intranasal sedation is a non-invasive medication delivery method that is both safe and well accepted by both children and adults. One of the most common procedures in maxillofacial surgery is transalveolar extraction. In minor oral surgery, a painless transalveolar extraction with little post-operative pain would be ideal. To examine the effectiveness of intranasal dexmedetomidine spray against intranasal normal saline spray in patients undergoing transalveolar extractions for anxiety relief. We compared sedation effect by Ramsay sedation scale, analgesia by visual analogue scale, monitored BP and pulse rate for anxiety, and spo2 levels for any complication in this prospective double-blinded randomized control study for two groups, A group with intranasal dexmedetomidine spray and the B group of intranasal NS spray for placebo effect at 0min, 15min, 30min, and 45min until transalveolar extraction. As a result of the intranasal spray of dexmedetomidine, there were no related problems such as respiratory depression. There was a substantial difference in sedation and analgesia between group A and the placebo group, as well as a significant decrease in pulse rate and hypotension in the dexmedetomidine group to reduce anxiety. Intranasal injection of atomized dexmedetomidine (1.5mcg/kg) for patient sedation having transalveolar extractions or other minor surgical operations in oral and maxillofacial surgery is clinically effective, convenient, lowers anxiety, and safe.Clinical Trial Registration: No. CTRI/2021/07/035181.

The effect of different pressures of pneumoperitoneum on the optic nerve sheath diameter – A prospective study

Abstract Background and Aims: Increased intra-abdominal pressure (IAP) and carbon dioxide gas during pneumoperitoneum leads to various systemic changes involving cardiovascular, respiratory, and cerebral physiology. In our study, we aimed to investigate the effect of standard (13–15 mmHg) and low (6–8 mmHg) pressure pneumoperitoneum on optic nerve sheath diameter (ONSD) using ultrasound, which is a reflection of intracranial pressure (ICP). Patient hemodynamics, surgery duration and surgeons’ comfort, and ease of performing surgery at low-pressure pneumoperitoneum were studied as secondary objectives. Materials and Methods: In this prospective double-blind randomized study, 75 patients of the American Society of Anesthesiologists physical status grades I and II, of both genders undergoing elective laparoscopic surgery, were allocated into two groups – S (standard IAP 13–15 mmHg) and L (low IAP 6–8 mmHg). ONSD acquired at different time points: before induction of anesthesia (T1), 5 min after intubation (T2), 5 min after the creation of pneumoperitoneum (T3), 5 min before desufflation (T4), and 5 min before extubation (T5). ONSD of 5 mm is taken as the cutoff value to correlate raised ICP. Continuous variables were analyzed by the Student’s t-test, and categorical data were assessed by the Chi-square test. Results: There was a significant increase in ONSD with insufflation in both the groups; however, T3 is higher than the cutoff value (&gt;5 mm) in Group S. The ONSD values at T1 (baseline) and at T2 (after intubation) were comparable between the groups, with P = 0.1855 and P = 0.8988, respectively. With pneumoperitoneum, the increase in ONSD (T3) is significantly higher in Group S than in Group L with P = 0.0022, attributing to the high IAP in Group S. Conclusion: Laparoscopic surgery with low-pressure pneumoperitoneum can be a safe approach, particularly in individuals at risk of raised ICP.

Comparison of two different doses of magnesium sulfate as an adjuvant to intrathecal bupivacaine in patients with pre-eclampsia undergoing elective cesarean section: A prospective double-blind randomized study

Background: Intrathecal magnesium sulfate is now emerging as a safe and effective adjuvant for spinal anesthesia (SA). The aim of the present study was to compare the efficacy of two doses of intrathecal magnesium in parturients with pre-eclampsia. Methods: This prospective randomized double-blind study was conducted on 105 parturients undergoing elective cesarean section (CS) who were randomized into three groups of 35 each: Group C, M50, and M75. Group M50 and group M75 received 50 mg of 50% (0.1 ml) and 75 mg of 50% (0.15 ml) magnesium sulfate, respectively. All of the groups received 10 mg of 0.5% heavy bupivacaine with normal saline accordingly to make a total volume of 2.2 ml. The sensory and motor block characteristics, visual analogue scale (VAS) score, post-operative analgesic requirements, hemodynamic parameters, and adverse effects were compared. Results: The sensory and motor block characteristics were significantly delayed in group M75 compared to group M50 and the control group (P < 0.05). VAS scores were significantly high in the control group up to 6 h as compared to group M50 and group M75 (P < 0.05). The time to first rescue analgesia was significantly extended in group M75 (222.86 ± 12.502 min) as compared to group M50 (221.14 ± 13.671 min) and the control group (127.43 ± 11.464 min) (P < 0.05) Conclusion: Intrathecal magnesium sulfate at doses of 50 mg and 75 mg in pre-eclamptic parturients undergoing elective CS results in prolonged duration of analgesia, decreased VAS scores and also delays the first rescue analgesic requirement with a favorable adverse effect profile in terms of decreased incidence of nausea and shivering.

Evaluation of analgesic efficacy of magnesium sulfate as an adjuvant to caudal bupivacaine in pediatric infraumbilical surgeries – A prospective randomized double-blind study

Evaluation of analgesic efficacy of magnesium sulfate as an adjuvant to caudal bupivacaine in pediatric infraumbilical surgeries – A prospective randomized double-blind study

Outcome of perioperative 24-hour infusion of intravenous lignocaine on pain and QoR-15 scores after breast cancer surgery-A randomised controlled trial.

Despite many analgesic modalities available, postoperative pain management after breast cancer surgery remains a challenge, which translates into poor quality of recovery, if untreated. Intravenous lignocaine with its anti-inflammatory, antihyperalgesic, and analgesic properties could provide a good option for these patients. The aim of this study was to evaluate the effect of intravenous lignocaine on postoperative pain relief and quality of recovery in patients undergoing surgery for breast cancer. In this prospective double-blind placebo-controlled randomised study, sixty-six patients undergoing breast cancer surgery were assigned 1:1 to placebo or intravenous lignocaine (Group L). Group L received an intravenous 1.5 mg/kg of lignocaine bolus at induction, followed by an intravenous infusion of 1 mg/kg/h for 24 hours intravenously, while the control group was given equal volume of normal saline. Pain scores, opioid utilisation, and quality of recovery (QoR-15) at 24 hours and on the day of suture removal were compared. Statistically significant reduction was observed in both static (P = 0.01, 6 hours) and dynamic postoperative pain (P = 0.030, 24 hours), with consequential delay in the need for the first dose of opioid (P = 0.014) as well as decreased 24-hour postoperative opioid consumption (P < 0.001) and decreased post-operative nausea and vomiting (PONV) (P < 0.05) in the lignocaine group. Global QoR-15 was significantly better at 24 -hours in group L on postoperative day 1 (P < 0.001), albeit there was no significant difference at suture removal. No lignocaine related side effects were observed. Intravenous lignocaine can be safely used as an alternative perioperative non-opioid analgesic for early postoperative pain and recovery.

Efficacy of fentanyl versus clonidine as an adjuvant to ropivacaine compared to ropivacaine for postoperative analgesia in caudal block for infraumblical pediatric surgeries: A prospective double-blinded randomized control study

Efficacy of fentanyl versus clonidine as an adjuvant to ropivacaine compared to ropivacaine for postoperative analgesia in caudal block for infraumblical pediatric surgeries: A prospective double-blinded randomized control study

Study of Two Different Volumes of 0.75% Ropivacaine for Ultrasound Guided Supraclavicular Brachial Plexus Block on Successful Blockade and Diaphragmatic Motility

Background &#x0D; Use of ultrasound guidance during supraclavicular brachial plexus block allows the usage of a lower anesthetics dose and minimizing unwanted effects of the anesthesia.&#x0D; Objective To compare the success of sensory blockade and the incidence of hemidiaphragmatic dysfunction in patients receiving two different volume of 0.75% Ropivacaine for ultrasound guided supraclavicular brachial plexus block.&#x0D; Method A prospective randomized double-blinded comparative study was conducted. Group A patients (n=30) received 20 ml and Group B (n=30) received 25 ml of 0.75% Ropivacaine for ultrasound guided supraclavicular brachial plexus block. Hemodynamic parameters, oxygen saturation, diaphragmatic excursion, onset of sensory blockade and time for completion of blockade were measured. Independent t-test, Chi-square test and Mann-Whitney U test were used to analyze the data at p value of less than 0.05 using Statistical Package for Social sciences (version 11.5).&#x0D; Result At 30 minutes, 29 (96.67%) patients in group B and 27 (90.0%) patients in group A had no sensation in median, radial, ulnar, musculocutaneous and medial cutaneous nerves territories; however, it was not significant statistically (p value &gt; 0.05). At 30 minutes in Group A, 25 (83.33%) patients had no diaphragmatic hemiparesis and five (16.67%) patients had partial diaphragmatic hemiparesis. However, three (10%) patients had no diaphragmatic hemiparesis in Group B, 25 (83.33%) patients had partial and two (6.67%) patients had complete diaphragmatic hemiparesis and it was statistically significant (p &lt; 0.05). Age and sex had no effect on diaphragmatic hemiparesis in both groups (p value &gt; 0.05).&#x0D; Conclusion The patients receiving lower volume of Ropivacaine had less incidence of hemidiaphragmatic dysfunction with similar sensory blockade as compared to the patients receiving higher volume of Ropivacaine.

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial

BackgroundAlfaxalone is a fast acting intravenous anaesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid allopregnanolone responsible for maintenance of cognition and neuroprotection by activation of brain pregnane X receptors and consequent increased production of mature brain-derived neurotrophic factor (m-BDNF). Two studies are reported here: an in vitro study investigated whether alfaxalone activates human pregnane X receptors (h-PXR) as effectively as allopregnanolone; and a clinical study that measured postoperative changes in serum m-BDNF and cognition in patients after alfaxalone anaesthesia compared with propofol and sevoflurane.MethodsIn vitro Activation of h-PXR by allopregnanolone and alfaxalone solutions (206 - 50,000 nM) was measured using human embryonic kidney cells expressing h-PXR hybridised and linked to the firefly luciferase gene. Light emission by luciferase stimulated by each ligand binding with h-PXR was measured.Clinical A double blind prospective randomised study of patients undergoing hip arthroplasty anaesthetised with alfaxalone TIVA (n = 8) or propofol TIVA (n = 3) or propofol plus sevoflurane inhalational anaesthesia (n = 4). The doses of anaesthetics were titrated to the same depth of anaesthesia (BIS 40-60). Subjects’ cognitive performance was assessed using the Grooved Pegboard Test, Digit Symbol Substitution Test (DSST) and Mini Mental State examination (MMSE) for 7 days postoperatively. Serum m-BDNF concentrations were measured for 7 postoperative days.ResultsIn vitro Allopregnanolone and alfaxalone both activated h-PXR, alfaxalone being more efficacious than allopregnanolone: 50,000 nM, p = 0.0019; 16,700 nM, p = 0.0472; 5600 nM, p = 0.0031.Clinical Alfaxalone treated subjects scored better than propofol and sevoflurane anaesthetised patients in the cognition tests: (MMSE p = 0.0251; Grooved Pegboard test dominant hand pre v post anaesthesia scores p = 0.8438 for alfaxalone and p = 0.0156 for propofol and propofol/sevoflurane combined). The higher cognition scores were accompanied by higher serum m-BDNF levels in the alfaxalone anaesthetised patients (p < 0.0001).ConclusionsThese results suggest that sedation and anaesthesia induced by the synthetic neuroactive steroid alfaxalone may be accompanied by effects normally caused by physiological actions of allopregnanolone at PXR, namely, increased secretion of m-BDNF and consequent neuroprotection and preservation of cognition.Trial registrationThe clinical trial was registered on 17/01/2018 with the Australian New Zealand Clinical Trials Registry: registration number ACTRN12618000064202 [Universal Trial Number U1111-1198-0412].

Outcomes of near confluent laser versus combined less dense laser and bevacizumab treatment of prethreshold ROP Type 1 Zone 2: a randomized controlled trial

BackgroundTo evaluate the results of near confluent laser therapy versus combined less dense laser and intra vitreal bevacizumab in treatment of infants with type 1 retinopathy of prematurity (ROP) in zone II.MethodsThis is a prospective double-blinded randomized clinical trial study. Infants with Type 1 ROP in Zone 2 were randomized into case and control groups. Conventional laser therapy was executed for control group and combination of IVB and laser treatment was employed for the case group.ResultsEighty-six eyes from 43 infants were analyzed in this trial. The first group included 42 eyes from 21 infants receiving a combination of laser ablation and IVB. The second group contained 44 eyes from 22 infants who received only conventional laser therapy. The combined IVB and laser ablation group demonstrated the neovascularization regression (20 out of 21 infants) one week after the procedure. In the conventional laser therapy group, this regression was found in (12 out of 22 infants) within one week after laser therapy (P = 0.001). Plus disease regression was observed in 20 (20/21) of combined treatment group and 7 infants (7/22) of conventional laser treatment group after one week.ConclusionCombined less dense laser and bevacizumab treatment resulted in more rapid regression in comparison with the conventional laser treatment.Trial registrationIRCT20201120049450N1, 27/12/2021.

Immunological Efficacy and Safety of a New Pneumococcal Polysaccharide Conjugated Thirteen-Valent Vaccine in the Immunization of Adults and Children (Results of Clinical Studies in the Russian Federation)

Relevance. The need to create a domestic pneumococcal polyvalent vaccine is one of the main directions of the «Strategy for the development of vaccine prevention of infectious diseases for the period up to 2035».Aim. To evaluate the immunological efficacy and safety of the pneumococcal polysaccharide conjugate adsorbed thirteen-valent (PCV13) vaccine in the immunization of adults and children in theRussian Federation.Materials and methods. The immunological efficacy and safety of the pneumococcal polysaccharide conjugated adsorbed thirteen-valent vaccine were studied in a prospective comparative randomized double-blind study in parallel groups in adult volunteers aged 18 to 65 years and a multicenter open comparative study in parallel groups in young children. In a clinical study of adults, 60 volunteers were randomized into two groups according to the 1:1 scheme (groupI, n = 30; group II, n = 30). A clinical study in children included 119 volunteers aged 15 months who were divided according to the 1:1:1 scheme (group I, n = 39; group II, n = 40; group III, n = 40). The reference vaccine in both studies is Prevenar® 13 (Pfizer Inc., USA).Results. A clinical study in adults showed no statistically significant difference between the study groups according to the results of primary (the proportion of volunteers whose concentration of serotype-specific IgG to each of the 13 pneumococcal serotypes is equal to or exceeds the level of 0.35 mcg/ml (p &gt; 0.039) before vaccination and 4 weeks after vaccination) and secondary criteria for evaluating effectiveness. Thus, the results obtained indicate a comparable level of immunogenicity of PCV13 with the comparison drug Prevenar®13 with a single intramuscular injection to healthy volunteers aged 18–65 years. Safety in both groups was comparable, 15 local reactions were registered, including 7 in group I volunteers who received the test drug, and 8 in comparison group volunteers. There were no statistically significant differences in the frequency of registered adverse events between the groups. Similar results were obtained with the immunization of children. For all 13 serotypes of the new PCV13 in relation to the reference drug, both primary and secondary criteria for assessing immunogenicity during immunization of children have been achieved (Difference ≤ 10% and GMC and GMT Ratio ≥ 0.5, respectively), which proves no less effectiveness of the pneumococcal polysaccharide conjugated adsorbed thirteen-valent vaccine compared with the reference vaccine Prevenar® 13. During the clinical study, a total of 27 adverse events were registered in children, which were associated with the introduction of vaccines and were represented by local and systemic reactions (5 AEs in study participants from group I (5/39) 12.80%, 18 AEs in study participants from group II (18/40) 45.0% and 4 AEs in study participants from group III (4/40) 10%). No SAEs were registered in this study.Conclusion. The obtained results of the researches in children and adults allow us to recommend the preparation pneumococcal polysaccharide conjugate adsorbed thirteen-valent vaccine for immunization in order to prevent pneumococcal infection, both adults and children according to the 2+1 scheme within the National vaccination schedule and the calendar of preventive vaccinations according to epidemic indications of the Russian Federation.

Effect of Combined Epidural Morphine and Midazolam on Postoperative Pain in Patients Undergoing Major Abdominal Cancer Surgery.

The objective was to compare analgesic effect of combined epidural morphine-midazolam with either drug alone on postoperative pain in patients undergoing major abdominal cancer surgery. Eighty-four patients were allocated in prospective randomized double-blind study to receive epidural analgesia. Patients received 5mg morphine in morphine (Mor) group, 5mg midazolam in midazolam (Mid) group, 5mg morphine + 5mg midazolam in morphine-midazolam (MM) group, 0.25% bupivacaine was added to injected solution with same volume in all groups. All groups were compared with time of first analgesic request, total analgesic consumption, number of epidural doses, postoperative Visual Analog Scale score, and adverse events. Time of first analgesic request was 4 to 8 hours in Mid versus 12 to 23 and 14 to 24 hours in Mor and MM groups, respectively, with significant difference between Mid versus Mor ( P <0.001), Mid versus MM ( P <0.001), and Mor versus MM groups ( P <0.031). Analgesic consumption was more in Mid than Mor and MM groups, with significant difference between Mid versus Mor ( P <0.008), Mid versus MM ( P <0.001), with no significant difference between Mor and MM groups ( P <0.6). The number of epidural doses in Mid was 1 to 3 versus 1 to 3, and 1 to 2 in Mor and MM groups, respectively, with significant difference between Mid versus Mor ( P <0.025), Mid versus MM ( P <0.004), with no significant difference between Mor and MM groups ( P =1.0). Addition of midazolam to epidural morphine prolonged time of first analgesic request and decreased total analgesic consumption.

A Comparative Study to Evaluate the Efficacy of Dexmedetomidine and Clonidine to Accentuate the Perioperative Analgesia of Caudal 0.25% Isobaric Levobupivacaine in Pediatric Infraumbilical Surgeries

BackgroundCaudal block is an efficient way to offer perioperative analgesia for painful sub-umbilical interventions. It enables early ambulation and periprocedural hemodynamic stability. These are important advantages over general anesthesia, notably in preterm babies and in children with cardiopulmonary comorbidities. In this study, we aimed to compare the effect of dexmedetomidine and clonidine to accentuate the perioperative analgesia of 0.25% isobaric levobupivacaine in pediatric caudal anesthesia.MethodologyA prospective double-blind randomized control study was conducted on 60 patients with the American Society of Anesthesiologists (ASA) physical status I, between the ages of one to six undergoing infraumbilical abdominal surgery under caudal anesthesia in the Department of Anaesthesia, Sardar Patel Medical College, Bikaner. Patients were randomly allocated to the following three groups of 20 each: group L, 1 mL/kg of levobupivacaine 0.25%; group LD, 1 mL/kg of levobupivacaine 0.25% with 0.5 µg/kg of dexmedetomidine; and group LC, 1 mL/kg of levobupivacaine 0.25% with 0.5 µg/kg of clonidine. Intraoperative and postoperative hemodynamic parameters were recorded for 24 hours. Patients’ pain scores, sedation scores, and Bromage scores were recorded. In our study, the main observation was the duration of analgesia and the total analgesic requirement for 24 hours.ResultsThere was a significant difference in the duration of analgesia among the three groups (p < 0.001). Group LC had the highest duration of analgesia of 492.00 (50.01) minutes, followed by group LD 486.00 (54.71) minutes, and the lowest in group L 291.00 (40.25) minutes. There was a significant difference between the three groups in terms of the total dose of analgesics in 24 hours (p < 0.001), with the median total dose of analgesics being the highest in Group L. Three groups differed significantly in terms of motor block, which was limited to up to 180 minutes in groups LC and LD with no residual motor block.ConclusionsThe addition of α2 agonists such as clonidine or dexmedetomidine at a dose of 0.5 µg/kg as an adjuvant to caudal levobupivacaine (0.25%) at 1 mL/kg significantly prolongs the duration of opioid-free analgesia in children undergoing infraumbilical abdominal surgeries without prolonging the motor blockade and any side effects. Moreover, dexmedetomidine does not offer a significant advantage over clonidine regarding the analgesia duration.

Efficacy of intravenous dexmedetomidine versus intraperitoneal dexmedetomidine in laparoscopic cholecystectomy – A prospective randomized double-blinded study

Background: Dexmedetomidine now has become one of the frequently used drugs as part of a multimodal analgesic regimen to provide improved pain control at all perioperative stages for laparoscopic surgeries. Aims and Objectives: In this prospective, double-blind, randomized, and control trial, we compared the postoperative analgesic efficacy of intravenous (IV) dexmedetomidine and intraperitoneal (IP) dexmedetomidine in laparoscopic cholecystectomy. Materials and Methods: Sixty patients of the American Society of Anesthesiologists Grade I and II undergoing laparoscopic cholecystectomy were allocated into two groups. The patients in Group-IV had received 30 ml of 0.5 μg/kg Dexmedetomidine infusion intravenously plus 40 ml of Ropivacaine (30 mL of 0.5% Ropivacaine and 10 ml NS) intraperitoneally and in Group-IP received 30 ml NS intravenously and 40 ml of Ropivacaine plus Dexmedetomidine (30 mL of 0.5% Ropivacaine and 0.5 μg/kg Dexmedetomidine diluted in 10 ml NS) intraperitoneally after removal of the gallbladder. Patients were assessed during the first 24 h postoperatively for time to the first requirement of analgesia, total analgesic consumption, sedation, hemodynamics, side effects, and patient satisfaction. Results: Time to first request of analgesia (min) was longer (216.46±42.19 vs. 108.03±48.77) and total analgesic consumption (mg) was lower (92.50±32.26 vs 115.0±38.056) in Group-IV than in Group-IP. A significant difference was observed in visual analogue score in Group-IV at 1 h, 2 h, 4 h postoperatively and in the patient satisfaction score (P=0.024) in comparison to Group-IP. Conclusion: The postoperative analgesic effects and patient satisfaction, of low dose IV Dexmedetomidine plus IP instillation of Ropivacaine, are superior to low dose IP Dexmedetomidine added to Ropivacaine.