Up-and-Down Determination of Different Crystalloid Coload Volumes on the ED 90 of Prophylactic Norepinephrine Infusion for Preventing Postspinal Anesthesia Hypotension During Cesarean Section.

Background: Fluid loading improves hemodynamic stability and reduces the incidence rate of post-spinal anesthesia hypotension when prophylactic vasopressors are administered. We investigated the impact of different crystalloid coload volumes on the 90% effective dose (ED) of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension in non-hypertensive patients undergoing cesarean section. Methods: Patients were randomly allocated to receive one of the different crystalloid coload volumes (0mL/kg [0mL/kg Group], 5mL kg [5mL/kg Group], and 10mL kg [10mL/kg Group]) in combination with prophylactic norepinephrine infusion immediately after the induction of spinal anesthesia. The prophylactic norepinephrine infusion doses were determined using the up-and-down sequential allocation methodology, with an initial dose of 0.025 µg/kg/min and a gradient of 0.005 µg/kg/min. The primary endpoint was the effective dose at which 90% (ED 90) of patients responded to prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension. Results: The estimated effective dose of norepinephrine infusion, at which 90% (ED 90) of patients responded, was found to be 0.084 (95% CI, 0.070 to 0.86), 0.074 (95% CI, 0.059 to 0.077), and 0.063 (95% CI, 0.053 to 0.064) µg/kg/min in the three groups, respectively. Conclusion: A crystalloid coload of 5 mL/kg or 10 mL/kg, as opposed to the groups receiving 0 mL/kg crystalloid coloads, resulted in a reduction of approximately 11.9% and 25.0%, respectively, in the ED90 of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension during cesarean section.

The effects of temperament type on infusion extravasation in newborns.

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation.

Effect of in-line filtration in newborns: study protocol of the Intravenous Neonatal Central Access Safety (INCAS) randomized controlled trial.

BACKGROUND: Particulate contamination due to infusion therapy (administration of parenteral nutrition and medications) carries a potential health risk for infants in neonatal intensive care units (NICUs). This particulate consists of metals, drug crystals, glass fragments, or cotton fibers and can be generated by drug packaging, incomplete reconstitution, and chemical incompatibilities. In-line filters have been shown to remove micro-organisms, endotoxin, air, and particles in critically ill adults and older infants, but its benefits in newborn remain to be demonstrated. Moreover, 50% of inflammatory episodes in the setting of NICUs are blood culture-negative. These episodes could be partly related to the presence of particles in the infusion lines. METHODS: A multicenter randomized single-blind controlled trial was designed. All infants admitted to NICUs for which prolonged infusion therapy is expected will be enrolled in the study and randomized to the Filter or Control arm. All patients will be monitored until discharge, and data will be analyzed according to a "full analysis set." The primary outcome is the frequency of patients with at least one sepsis-like event, defined by any association of suspected sepsis symptoms with a level of c-reactive protein (CRP) > 5 mg/L in a negative-culture contest. The frequency of sepsis, phlebitis, luminal obstruction, and the duration of mechanical ventilation and of catheter days will be evaluated as secondary outcomes. The sample size was calculated at 368 patients per arm. DISCUSSION: This is the first multicenter randomized control trial that compares in-line filtration of parenteral nutrition and other intravenous drugs to infusion without filters. Sepsis-like events are commonly diagnosed in clinical practice and are more frequent than sepsis in a positive culture contest. The risk of these episodes in the target population is estimated at 30-35%, but this data is not confirmed in the literature. If the use of in-line filters results in a significant decrease in sepsis-like events and/or in any other complications, the use of in-line filters in all intravenous administration systems may be recommended in NICUs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05537389, registered on 12 September 2022 ( https://classic. CLINICALTRIALS: gov/ct2/show/results/NCT05537389?view=results ).

Intravenous Lidocaine for the Management of Chronic Pain: A Narrative Review of Randomized Clinical Trials.

Background: Chronic pain remains a serious health problem with significant impact on morbidity and well-being. Available treatments have only resulted in relatively modest efficacy. Thus, novel therapeutic treatments with different mechanisms have recently generated empirical interest. Lidocaine is postulated to provide anti-inflammatory and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) and voltage gated calcium receptors. Emerging research indicates that lidocaine could be a reasonable alternative for treating chronic pain. Objective: Considering the evidence surrounding lidocaine's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of lidocaine's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of lidocaine in the treatment of chronic pain from database inception to June 2022. Results: A total of 25 studies were included in the narrative review. Findings on available studies suggest that intravenous infusion of lidocaine is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous lidocaine is currently mixed for a variety of chronic pain syndromes. Findings indicate that evidence for efficacy is limited for: CRPS, and cancer pain. However, there is good evidence supporting the efficacy of intravenous lidocaine as augmentation in chronic post-surgical pain. Conclusion: Lidocaine may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of lidocaine in attenuating pain signaling pathways.

Effects of hydromorphone-based patient-controlled intravenous analgesia on postoperative hypoxaemia: a randomised controlled non-inferiority clinical trial.

OBJECTIVE: This study aimed to compare the effects of patient-controlled intravenous analgesia (PCIA) with and without low-basal infusion on postoperative hypoxaemia. DESIGN: A randomised parallel-group non-inferiority trial. SETTING: The trial was conducted at a grade-A tertiary hospital from December 2021 to August 2022. PARTICIPANTS: 160 adults undergoing gastrointestinal tumour surgery and receiving postoperative PCIA. INTERVENTIONS: Participants randomly received a low-basal (0.1 mg/hour of hydromorphone) or no-basal infusion PCIA for postoperative 48 hours. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was area under curve (AUC) per hour for hypoxaemia, defined as pulse oxygen saturation (SpO2) <95%. Secondary outcomes included: AUC per hour at SpO2<90% and <85%, hydromorphone consumption, ambulation time and analgesic outcomes up to 48 hours after surgery. RESULTS: Among 160 randomised patients, 159 completed the trial. An intention-to-treat analysis showed that AUC per hour (SpO2<95%) was greater in the low-basal infusion group compared with the no-basal infusion group, with a median difference of 0.097 (95% CI 0.001 to 0.245). Non-inferiority (margin: ratio of means (ROM) of 1.25) was not confirmed since the ROM between the two groups was 2.146 (95% CI 2.138 to 2.155). Hydromorphone consumption was higher in the low-basal group than in the no-basal group (median: 5.2 mg versus 1.6 mg, p<0.001). Meanwhile, there were no differences in the AUC values at the other two hypoxaemia thresholds, in ambulation time, or pain scores between the groups. CONCLUSIONS: Among the patients receiving hydromorphone PCIA after gastrointestinal tumour resection, low-basal infusion was inferior to no-basal infusion PCIA for postoperative hypoxaemia at SpO2<95% up to 48 hours after surgery. TRIAL REGISTRATION NUMBER: ChiCTR2100054317.

Efficacy of intravenous acetaminophen on postoperative shivering: A meta-analysis of randomized controlled trials.

PURPOSE: Postoperative shivering (POS) is a common and vital complication after anesthesia, which may result in serious consequences and uncomfortable experiences. Acetaminophen has been used to treat fever and mild to moderate pain. However, there is not enough evidence to prove its advantage for POS. This meta-analysis aimed to explore the prophylactic use of acetaminophen as a valid agent for POS. METHODS: Two researchers independently searched PubMed, the Cochrane Library, and Embase for controlled clinical trials. The meta-analysis of randomized controlled trials (RCTs) was performed by Review Manager. RESULTS: Nine trials with 856 patients were included in our meta-analysis. Acetaminophen significantly reduced POS compared with placebo (pooled risk ratio [RR]: 0.43, 95% confidence interval [CI]: 0.35-0.52). What is more, not only 15 mg/kg but also 1000 mg intravenous acetaminophen could reduce the incidence of shivering compared with placebo. CONCLUSION: Our present meta-analysis demonstrates that the intravenous prophylactic infusion of acetaminophen may prevent POS, and the results may provide new evidence to expand the clinical value of acetaminophen in addition to its routine usage.

Effects of Low-Dose Ketamine Infusion on the Positive and Negative Domains of Hopelessness and Suicidal Thoughts.

Background: Low-dose ketamine infusion has been demonstrated to exert antisuicidal effects on patients with treatment-resistant depression (TRD) and strong suicidal ideation. Although evidence suggests an association between hopelessness and suicidality, very few studies have investigated the antihopelessness effects of ketamine.Methods: This study included 84 patients with TRD and strong suicidal ideation. The diagnosis of depression was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for major depressive disorder. They were randomly assigned to receive a single infusion of either 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. Hopelessness and suicidal symptoms were assessed at baseline, at 240 minutes postinfusion, and on Days 2, 3, 7, and 14 postinfusion. The assessments were performed using the self-report Beck Hopelessness Scale (BHS) and Positive and Negative Suicide Ideation Inventory (PANSI). The analysis focused on the positive and negative domains of the BHS and PANSI, respectively. The clinical trial was conducted between August 15, 2018, and November 30, 2021.Results: Statistical analyses performed using a generalized linear model revealed that the ketamine group had significantly higher PANSI-positive (P = .008) and lower PANSI-negative (P = .015) suicidal ideation scores on Day 2 postinfusion than did the midazolam group. At 240 minutes postinfusion, the ketamine group had significantly lower BHS-negative domain scores than did the midazolam group (P = .031). Notably, the observed ketamine-induced reduction in hopelessness at 240 minutes postinfusion was associated with its antisuicidal effect on Day 2 postinfusion.Discussion: A single infusion of low-dose ketamine resulted in a brief (∼4 hours) yet significant reduction in hopelessness. Subjective antisuicidal effects of ketamine were noted on Day 2 postinfusion. Further studies are needed to elucidate the neuromechanisms underlying the antihopelessness and antisuicidal effects of ketamine.Trial Registration: UMIN Clinical Trials Registry identifiers: UMIN000033916 and UMIN000033760.

Adjuvant 5-fluorouracil and portal vein infusion chemotherapy followed by gemcitabine for pancreatic cancer.

BACKGROUND: Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer. METHODS: 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were OS and treatment completion. RESULTS: Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1-, 3-, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1-, 3-, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively). CONCLUSION: Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer.

Intravenous fluid therapy: an audit and discussion of improvements required for prescribers and administrators.

BACKGROUND: Foundation doctors and nurses are the clinicians most closely involved in fluid assessment, intravenous (IV) fluid prescription and administration. However, both groups report challenges regarding IV fluids. At a large NHS trust in England, adherence to the National Institute for Health and Care Excellence (NICE) guideline CG174, regarding IV fluids, was largely unknown. AIMS: To assess the baseline adherence, within the hospitals, to CG174 and identify areas for improvement. METHODS: A set of 12 audit standards were developed and used to collect data across 29 clinical areas between September 2022 and May 2023, with 255 patients receiving IV fluids at any time during their inpatient stay included. FINDINGS: For two standards target adherence of 95% was achieved, with an adherence less than 50% in most. Areas of particularly poor adherence included assessing and meeting fluid and electrolyte requirements, patient reassessment and developing IV fluid management plans. CONCLUSION: Trust baseline adherence to NICE CG174 requires improvement, particularly regarding patient assessment and reassessment, and meeting electrolyte requirements.

A randomized controlled pilot study of daily intravenous ketamine over three days for treatment-resistant depression.

BACKGROUND: Studies have confirmed the rapid antidepressant action of ketamine in depressive episodes. Nevertheless, a standardized procedure for the delivery of ketamine infusion in individuals suffering from treatment-resistant depression, particularly in terms of infusion frequency and total dosage, remains undetermined. In addition, an efficacious ketamine regimen for persistent pain management involved a continuous 10-day infusion period with no notable adverse effects. Consequently, the primary objective of this study was to evaluate the antidepressant capacity of consecutive ketamine infusions spanning over three successive days, the duration of therapeutic response, and the overall safety profile of the treatment. METHODS: In this randomized controlled trial, participants aged 18-64 with treatment-resistant depression were randomized to receive either intravenous ketamine or midazolam (used as an active placebo) for 40 min daily over three consecutive days. Statistical analysis using repeated measures ANOVA was employed to assess the changes in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression-Severity from the initial assessment to 10 and 31 days post-infusion. Additionally, the duration of response and remission was evaluated using Kaplan-Meier survival analysis. RESULTS: Out of 33 randomized participants, 20 underwent the treatment as planned. By day 10th, the ketamine group had a mean reduction in MADRS score of 12.55 (95% CI = 6.70-18.09), whereas the midazolam group had a decrease of 17.22 (95% CI = 11.09-23.36). This pattern continued to day 31, with ketamine showing a mean score decrease of 13.73 (95% CI = 7.54-19.91) and midazolam a fall of 12.44 (95% CI = 5.61-19.28). Both treatments were well tolerated, with dissociative symptoms in the ketamine group being temporary and ceasing by the end of each infusion. CONCLUSION: Intravenous ketamine given for three consecutive days did not show a notable antidepressant advantage when compared to the active placebo midazolam, highlighting the need for further research into effective treatments schedules for treatment-resistant depression. TRIAL REGISTRATION: NCT05026203, ClinicalTrials.gov, registered on 24/08/2021.

Extended-Infusion ß-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Current evidence is conflicting for associations of extended-infusion ß-lactam (EI-BL) therapy with clinical outcomes. Objective: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). Design, Setting, and Participants: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion ß-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. Exposures: EI-BL (ie, ≥3-hour infusion). Main Outcomes and Measures: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the ß-lactam used to treat the index GN-BSI). Results: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). Conclusions and Relevance: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Determination of ED90s of Phenylephrine and Norepinephrine Infusion for Prevention of Spinal Anesthesia-Induced Hypotension in Patients with Preeclampsia During Cesarean Delivery.

Background: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery. Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 µg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 µg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery. Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582-0.628) and 0.054 (95% CI: 0.053-0.056) µg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576-1.226) and 0.055 (95% CI: 0.047-0.109) µg/kg/min, respectively, with an efficacy ratio of 12.1:1. Conclusion: The administration of 0.6 µg/kg/min phenylephrine and 0.05 µg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.

Effective Management of Severe Amlodipine/Atenolol Overdose with Intravenous Calcium, Hyperinsulinemic Euglycemia Therapy, and Continuous Veno-Venous Hemodialysis: A Case Report.

BACKGROUND Amlodipine, a calcium channel blocker, and atenolol, a beta blocker, are commonly used as a fixed drug combination (FDC) to treat hypertension. Intentional or non-intentional overdose of amlodipine-atenolol results in hypotension and myocardial depression with a high risk of mortality. This report describes a 64-year-old man with an overdose of amlodipine-atenolol, presenting as an emergency with hypotension, bradycardia, and severe metabolic acidosis. He was successfully treated with intravenous calcium chloride infusion, hyperinsulinemia euglycemia therapy (HIE), and continuous veno-venous hemodialysis (CVVHD). CASE REPORT A 64-year-old man was diagnosed with essential hypertension 1 week prior to the admission. He had been prescribed 1 FDC tablet of amlodipine and atenolol (5+50 mg) per day; however, he took 1 table of the FDC per day for 3 days and then took 3-4 tablets each day during the next 4 days. He was brought to the hospital with hypotension, bradycardia, and severe metabolic acidosis and was diagnosed with amlodipine-atenolol overdose. He was treated with intravenous calcium chloride infusion, HIE, and CVVHD. His hemodynamics started to improve after administering these therapies for 6 h. Inotropes were gradually tapered off and stopped. He was extubated on day 5 and recovered completely. CONCLUSIONS This report shows the serious effects amlodipine-atenolol overdose and the challenges of emergency patient management. An overdose of FDC of amlodipine and atenolol can cause cardiovascular collapse and severe metabolic acidosis. Timely and aggressive management with intravenous calcium infusion, HIE, and CVVHD is essential.