Antinociceptive and analgesic effect of continuous intravenous infusion of maropitant, lidocaine and ketamine alone or in combination in cats undergoing ovariohysterectomy

Background Multimodal analgesia consists of the combination of analgesic drugs at low doses to act in different places along the path of pain. Studies with continuous infusion of analgesic drugs in cats are not common. This study aimed to evaluate the analgesic effect of maropitant, lidocaine and ketamine alone or in combination (intravenous bolus + subsequent continuous intravenous infusion) in the management of acute postoperative pain in cats undergoing ovariohysterectomy. Seventy healthy cats undergoing an ovariohysterectomy received a standard anesthetic protocol consisting of acepromazine and morphine, propofol (anesthesia induction), and isoflurane (anesthesia maintenance). The animals were stratified into seven groups (n = 10 in each group): control (CG), maropitant (MG), lidocaine (LG), ketamine (KG), maropitant + lidocaine (LMG), maropitant + ketamine (KMG), and maropitant + lidocaine + ketamine (LKMG). All drugs were injected first as an intravenous bolus and then by continuous intravenous infusion. During surgery, esophageal temperature, respiratory rate, heart rate, oxygen saturation, expired isoflurane concentration, and partial pressure of carbon dioxide at the end of expiration were evaluated at 7 time points. Postoperative pain was evaluated for 6 h after extubation using the visual analogue scale and the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats. Results Adverse effects related to maropitant, lidocaine and ketamine infusion were not observed. Pain scores were lower in the MG, KG and LG groups when compared to the CG group using both scales. Although pain scores were also lower in all combination groups than CG, more animals in these groups required rescue analgesia compared to MG. This indicates that the postoperative analgesic effect of all drugs, either alone or in combination, confers analgesia, although the combinations did not promote greater analgesia. Conclusions Continuous intravenous infusion of maropitant, lidocaine, and ketamine alone induces postoperative analgesic effect in cats undergoing ovariohysterectomy, but combinations of these drugs did not increase the analgesic effect. No adverse effect was observed with any drug or their combination.

Chlorpromazine Efficiently Treats the Crisis of Pheochromocytoma: Four Case Reports and Literature Review

Pheochromocytoma multisystem crisis (PMC) is a potentially lethal emergency due to catecholamine secretion. The condition manifests as severe hypertension to intractable cardiogenic shock and has a high mortality rate. This study explored the efficacy and safety of applying chlorpromazine on PMC patients. The study included seven patients (median age, 42 years; range, 14–57 years) diagnosed with pheochromocytoma. Four consecutive PMC patients were admitted to our critical care unit between 2016 and 2020 due to abdominal or waist pain, nausea, and vomiting. Their blood pressure (BP) fluctuated between 200–330/120–200 and 40–70/30–50 mmHg. Chlorpromazine (25 or 50 mg) was injected intramuscularly, followed by continuous intravenous infusion (2–8 mg/h). The patients' BP decreased to 100–150/60–100 mmHg within 1–3 h and stabilized within 3–5 days. Two weeks later, surgical tumor resection was successfully performed in all four patients. Similar clinical outcomes were also obtained in three patients with sporadic PMC reported in the literature who received chlorpromazine treatment, which reduced their BP readings from >200/100 mmHg to 120/70 mmHg. Our observations, combined with sporadic reports, showed that chlorpromazine efficiently controlled PMC. Thus, future studies on the use of chlorpromazine are warranted.

Determination of the Median Effective Dose of Dexmedetomidine for the Prevention of Emergence Agitation in Geriatric Patients Undergoing Major Open Surgery With General Anesthesia: A Prospective, Double-Blinded, Dose-Response Trial

Dexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia. A total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5 μg·kg−1·h−1 continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by .05 depending on the response of the previous patient, according to the Dixon up-and-down method. An “effective” or “ineffective” response was determined based on the Riker sedation-agitation score (RSAS), we defined “effective” as RSAS<5, and “ineffective” as RSAS≥5. The ED50 of dexmedetomidine in prevention of EA was .30 μg·kg−1·h−1 (95% CI, .27–.33) and the predicted ED95 was .42 μg·kg−1·h−1 (95% CI, .38–.51). The incidence of bradycardia was significantly increased in the group without EA compared to the group with EA (57.1% vs 13.6%, P = .002). The ED50 of dexmedetomidine in prevention of EA was .30 μg·kg−1·h−1 (95% CI, .27–.33) and the predicted ED95 was .42 μg·kg−1·h−1 (95% CI, .38–.51). Bradycardia was the main complication.

Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies

BackgroundFull application of cytokines as oncoimmunotherapeutics requires identification of optimal regimens. Our initial effort with intravenous bolus recombinant human interleukin-15 (rhIL-15) was limited by postinfusional reactions. Subcutaneous injection and continuous intravenous infusion for 10 days (CIV-10) provided rhIL-15 with less toxicity with CIV-10 giving the best increases in CD8+ lymphocytes and natural killer (NK) cells. To ease rhIL-15 administration, we shortened time of infusion. Treatment with rhIL-15 at a dose of 3–5 µg/kg as a 5-day continuous intravenous infusion (CIV-5) had no dose-limiting toxicities while effector cell stimulation was comparable to the CIV-10 regimen.MethodsEleven patients with metastatic cancers were treated with rhIL-15 CIV-5, 3 µg (n=4), 4 µg (n=3), and 5 µg/kg/day (n=4) in a phase I dose-escalation study (April 6, 2012).ResultsImpressive expansions of NK cells were seen at all dose levels (mean 34-fold), including CD56bright NK cells (mean 144-fold for 4 µg/kg), as well as an increase in CD8+ T cells (mean 3.38-fold). At 5 µg/kg/day, there were no dose-limiting toxicities but pulmonary capillary leak and slower patient recovery. This led to our choice of the 4 µg/kg as CIV-5 dose for further testing. Cytolytic capacity of CD56bright and CD56dim NK cells was increased by interleukin-15 assayed by antibody-dependent cellular cytotoxicity (ADCC), natural cytotoxicity and natural killer group 2D-mediated cytotoxicity. The best response was stable disease.ConclusionsIL-15 administered as CIV-5 substantially expanded NK cells with increased cytotoxic functions. Tumor-targeting monoclonal antibodies dependent on ADCC as their mechanism of action including alemtuzumab, obinutuzumab, avelumab, and mogamulizumab could benefit from those NK cell expansions and provide a promising therapeutic strategy.Trial registration numbersNCT01572493, NCT03759184, NCT03905135, NCT04185220 and NCT02689453.

Continuous Intravenous Infusion of Bumetanide to Achieve Diuresis in Patients with Congestive Heart Failure and Chronic Kidney Disease: A Rapid Review

Bumetanide falls in the class of loop diuretics like furosemide. The effects of both have been extensively researched and are well documented. In medical practice furosemide is more widely used in patients both orally and through intravenous administration.

Development and evaluation of a heparin gel for transdermal delivery via laser-generated micropores

Aim: Our study investigated the feasibility of transdermal delivery of heparin, an anticoagulant used against venous thromboembolism, as an alternative to intravenous administration. Materials & methods: Skin was pretreated using ablative laser (Precise Laser Epidermal System [P.L.E.A.S.E.®] technology) for enhanced delivery of heparin. In vitro permeation studies using static Franz diffusion cells provided a comparison between delivery from 0.3% w/v heparin-loaded poloxamer gel and solution across untreated and laser-treated dermatomed porcine ear skin. Results: No passive delivery of heparin was observed. Laser-assisted delivery from solution (26.07 ± 1.82 μg/cm2) was higher (p < 0.05) than delivery from heparin gel (11.28 ± 5.32 μg/cm2). However, gel is likely to sustain the delivery over prolonged periods like a maintenance dose via continuous intravenous infusion. Conclusion: Thus, ablative laser pretreatment successfully delivered heparin, establishing the feasibility of delivering hydrophilic macromolecules using the transdermal route.