Development of an Evidence-Based List of Non-Antineoplastic Vesicants: 2024 Update.

Infiltration of a vesicant, called extravasation, can result in severe patient injuries. Recognition of vesicants and their relative risk of injury is essential to extravasation prevention, early recognition, and appropriate treatment. In this article, the Vesicant Task Force (VTF) updates the previously published Infusion Nurses Society (INS) vesicant list from 2017. The 2024 INS list diverges from earlier vesicant lists, such as the 2017 VTF list, by adopting a risk stratification approach based upon documented patient outcomes, in contrast to the reliance on expert consensus or only surrogate risk indicators, such as pH and osmolarity. The methodology used to create the updated list is explained, and the criteria for high- and moderate-risk vesicants and cautionary vesicants are defined.

Assessment of the effect of unfractionated heparin administered either by intravenous infusion vs. subcutaneous injection on heparin-binding protein, and plasminogen activator inhibitor-1 in critically ill septic patients: a randomized controlled trial.

OBJECTIVE: The study compared the impact of unfractionated heparin (UFH) administered via two routes (infusion and subcutaneous injection) on heparin-binding protein (HBP) and plasminogen activator inhibitor-1 (PAI-1) levels in critically ill sepsis patients. PATIENTS AND METHODS: Forty critically ill sepsis patients were randomly assigned to receive either a low-dose intravenous infusion of UFH (500 units/hour) or subcutaneous UFH (5,000 units/8 hours) for seven days. HBP and PAI-1 were measured at baseline and on days one, two, and seven. RESULTS: Intravenous administration of UFH showed a significant reduction in percentage change of HBP compared to subcutaneous administration on days one [(-35% vs. -13%, p = 0.03*) (*indicates a significant result *p < 0.05, relative to the subcutaneous group)] and seven (-62% vs. -39%, p = 0.02*). Also, the percentage change of PAI-1 was significantly reduced in the infusion group compared to the subcutaneous group on days one (-28% vs. -3%, p = 0.008*), two (-42% vs. -3%, p = 0.001*), and seven (-62% vs. 27%, p = 0.001*), respectively. Furthermore, a significant improvement in the 14-day survival was observed in the infusion group compared to the subcutaneous group (p = 0.008*). CONCLUSIONS: Intravenous infusion was the route of choice for UFH administration in critically ill septic patients, with a promising effect on HBP, PAI-1, and survival.

Steady-state trumps accuracy: target-controlled infusion as a gain switch.

Target-controlled infusion (TCI) is a mature technology that enables the delivery of intravenous anaesthetics in the concentration domain. The accuracy of the pharmacologic models used by TCI systems is imperfect, especially regarding pharmacodynamic predictions. This shortcoming of TCI devices is not critical. That TCI systems produce steady-state effect-site concentrations at or near a specified target is a more important attribute than a high level of accuracy because anaesthesiologists titrate to a stable level of drug effect whatever the actual concentration is. In this sense, TCI functions as a 'gain switch'. Achieving a steady state is more important than perfect accuracy.

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

A Monoclonal Antibody to PACAP for Migraine Prevention.

BACKGROUND: Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) is a new avenue for treating migraine. The efficacy and safety of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention are unclear. METHODS: In a phase 2, double-blind, randomized, placebo-controlled trial, we enrolled adult participants (18 to 65 years of age) with migraine for whom two to four previous preventive treatments had failed to provide a benefit. The trial included a 4-week treatment period and an 8-week follow-up period. Participants were randomly assigned in a 2:1:2 ratio to receive a single-dose baseline infusion of 750 mg of Lu AG09222, 100 mg of Lu AG09222, or placebo. The primary end point was the mean change from baseline in the number of migraine days per month, during weeks 1 through 4, in the Lu AG09222 750-mg group as compared with the placebo group. RESULTS: Of 237 participants enrolled, 97 received 750 mg of Lu AG09222, 46 received 100 mg of Lu AG09222, and 94 received placebo. The mean number of baseline migraine days per month was 16.7 in the overall population, and the mean change from baseline over weeks 1 through 4 was -6.2 days in the Lu AG09222 750-mg group, as compared with -4.2 days in the placebo group (difference, -2.0 days; 95% confidence interval, -3.8 to -0.3; P = 0.02). Adverse events with a higher incidence in the Lu AG09222 750-mg group than in the placebo group during the 12-week observation period included coronavirus disease 2019 (7% vs. 3%), nasopharyngitis (7% vs. 4%), and fatigue (5% vs. 1%). CONCLUSIONS: In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 weeks. (Funded by H. Lundbeck; HOPE ClinicalTrials.gov number, NCT05133323.).

Intravenous Magnesium for the Management of Chronic Pain:An Updated Review of the Literature.

Background: Available therapeutic options are currently limited by their modest efficacy. As a result, novel pharmacotherapeutic treatments with different mechanisms have recently attracted empirical attention. Magnesium, a divalent cation, is postulated to provide analgesic and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) receptor. Objective: Considering the evidence surrounding magnesium's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of magnesium'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 magnesium in the treatment of chronic pain from database inception to May 2022. Results: A total of 33 studies were included in the narrative review, out of which 26 were randomized controlled trials. Findings on available studies suggest that intravenous infusion of magnesium is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous magnesium is currently equivocal for a variety of chronic pain syndrome. Findings indicate that evidence for efficacy is poor or equivocal for: CRPS, neuropathic pain, chronic low back pain, and migraine prophylaxis. However, there is good evidence supporting the efficacy of intravenous magnesium for treating renal colic pain and pelvic pain related to endometriosis. Conclusion: Magnesium may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of magnesium in attenuating pain signaling pathways.

An observational study on the application of fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery.

The aim of this study was to evaluate the efficacy of fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery. The clinical data of 88 patients with rheumatic heart disease undergoing valve replacement surgery were retrospectively analyzed and grouped based on different treatment methods. Among them, 44 cases received fast-track cardiac anesthesia using target-controlled infusion of fentanyl and propofol from November 2019 to July 2021 were set as the control group, and 44 cases received fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol from August 2021 to February 2022 were set as the study group. The study group showed shorter postoperative awakening time, extubation time, and hospital stay duration, and lower dosage of dopamine and nitroglycerin consumption compared to the control group (P < .05). At T5 and T6, both groups exhibited higher ACTH, cortisol (Cor), and C3a than at T0, and the study group showed significantly lower ACTH, Cor, and C3a at T5 and T6 than the control group (P < .05). At T7, the control group showed higher ACTH, Cor, and C3a than at T0, and ACTH, Cor, and C3a were significantly lower in the study group than in the control group at T7 (P < .05). Fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery has demonstrated favorable application effects, which stabilizes hemodynamics, alleviates myocardial damage, suppresses endocrine stress responses, and does not increase adverse reactions, thereby exhibiting good safety.

Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease.

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD. METHODS: In this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg dose group), or at a dose of 3 mg per kilogram every 4 weeks (3-mg dose group). The primary end point was overall response (complete or partial response) in the first six cycles; the key secondary end point was a patient-reported decrease in chronic GVHD symptom burden, as assessed by a reduction of more than 5 points on the modified Lee Symptom Scale (range, 0 to 100, with higher scores indicating worse symptoms). The primary end point would be met if the lower bound of the 95% confidence interval exceeded 30%. RESULTS: A total of 241 patients were enrolled (80 patients in the 0.3-mg dose group, 81 in the 1-mg dose group, and 80 in the 3-mg dose group). The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the patients in the 0.3-mg dose group, 67% (95% CI, 55 to 77) of the patients in the 1-mg dose group, and 50% (95% CI, 39 to 61) of the patients in the 3-mg dose group. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60%, 69%, and 41% of the patients in the three dose groups, respectively. The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade. Adverse events leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group, 22% in the 1-mg dose group, and 18% in the 3-mg dose group. CONCLUSIONS: Targeting CSF1R-dependent monocytes and macrophages with axatilimab resulted in a high incidence of response among patients with recurrent or refractory chronic GVHD. (Funded by Syndax Pharmaceuticals and Incyte; AGAVE-201 ClinicalTrials.gov number, NCT04710576.).

Effect of systemic lidocaine infusion on optic nerve sheath diameter during laparoscopic hysterectomy: a randomized controlled study.

BACKGROUND: During laparoscopic hysterectomy (LH), the elevation of intra-abdominal and intra-thoracic pressures due to pneumoperitoneum (PP) results in an increase in intracranial pressure (ICP). The Trendelenburg position (TP) is an accentuating factor. This trial aimed to assess the effect of intravenous (IV) lidocaine infusion on optic nerve sheath diameter (ONSD), a widely accepted surrogate measure for ICP, during PP and TP. METHODS: A randomized, placebo-controlled study was conducted on 66 patients scheduled for LH, equally divided into a lidocaine group and a saline group. ONSD, the primary outcome, was recorded before induction (T1), before PP initiation in the supine position (T2), five minutes (T3), 30 minutes (T4), and 60 minutes (T5) after PP and TP, and five minutes after termination of PP in the supine position (T6). Secondary outcomes included numerical rating scale (NRS) scores at arrival to the post-anesthesia care unit (PACU), 6, 12, and 24 hours after surgery, and postoperative adverse effects. RESULTS: ONSD at T4 and T5 was significantly lower in the lidocaine group than in the saline group (T4: 4.94±0.43 mm vs. 5.27±0.37 mm; P =0.003, T5: 5.08±0.46 vs. 5.41±0.38 mm; P =0.004). The lidocaine group had significantly lower NRS values than the saline group only at PACU arrival (median [Q1-Q3]: 5 [4-6] vs. 6 [5-6.25]; P =0.016). Fewer patients in the lidocaine group experienced postoperative headache (P =0.029). CONCLUSIONS: IV lidocaine during LH can attenuate the ONSD distension, decrease pain scores at PACU arrival, and reduce the incidence of postoperative headache.

Oxaliplatin-induced peripheral neuropathy with hepatic arterial versus intravenous infusion in metastatic colorectal cancer.

BACKGROUND: Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with the intravenous (IV) route has not been specifically explored so far. METHODS: We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000-05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE, and FFCD 2000-05 trials and through a review of Gustave Roussy patients' electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grades 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. RESULTS: A total of 363 patients were included (IV, 300; HAI, 63). In total, 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN either (p = 0.23). CONCLUSION: The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not reduce the incidence, precocity, and severity of PN.

In sepsis or septic shock, prolonged vs. intermittent infusion of ß-lactam antibiotics reduces mortality at 90 d.

SOURCE CITATION: Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs intermittent infusions of ß-lactam antibiotics in adults with sepsis or septic shock: a systematic review and meta-analysis. JAMA. 12 June 2024. [Epub ahead of print.] 38864162.

In sepsis, continuous and intermittent infusion of ß-lactam antibiotics did not differ for mortality at 90 d.

SOURCE CITATION: Dulhunty JM, Brett SJ, De Waele JJ, et al; BLING III Study Investigators. Continuous vs intermittent ß-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial. JAMA. 12 June 2024. [Epub ahead of print.] 38864155.

Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

A single-centre study on abnormal antinuclear antibodies in children caused by intravenous infusion of gamma globulin.

Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children. Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group. Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results. Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies.

Physical Compatibility of Intravenous Ondansetron Hydrochloride and Nafcillin Sodium.

Information on the physical compatibility of intravenous (IV) medications is vital for patient care and safety in acute care settings. Drug information resources list ondansetron and nafcillin as IV compatible, however, bolus concentrations of ondansetron are not reported. This study investigated the in vitro physical compatibility of bolus and infusion concentrations of ondansetron hydrochloride with nafcillin sodium. Two admixtures were prepared: 1) ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL, and 2) ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL. The admixtures were prepared in triplicate using aseptic technique according to manufacturer guidance and stored at room temperature (22-23 °C) for up to 24 hours. Admixtures were examined for visual precipitation, turbidity, and pH at baseline and at 1, 5, 8, and 24 hours. Admixture 1 developed a haze immediately after mixing, which was sustained over 24 hours. There was a demonstrative change in absorbance after 1 hour, but pH remained stable until hour 24. Admixture 2 developed a haze at 5 hours, but the absorbance and pH remained stable until hour 24; a decrease in the pH was observed in all samples at hour 24. This in vitro study revealed that ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL are not physically compatible when administered through the same IV line. No demonstrative change was observed with ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL; however, concurrent administration of these medications is questionable when delivered through an IV line for periods of five hours or longer.