Safety Of Continuous Intravenous Infusion Research Articles

#2564 Terlipressin given by continuous infusion versus boluses in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Abstract Background and Aims Hepatorenal syndrome (HRS) is one of the complications among patients with cirrhosis. Available guidelines recommended terlipressin with albumin as part of HRS management. To date there is no consensus on whether terlipressin should be given via bolus or continuous intravenous infusion. This study aims to compare the effectiveness and safety of continuous intravenous infusion versus intravenous boluses of terlipressin in the treatment of patients with HRS and cirrhosis. Method A comprehensive search for databases of randomized controlled trials (RCTs) comparing continuous intravenous infusion versus intravenous boluses of terlipressin among adult patients with hepatorenal syndrome was done. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched using relevant terms including hepatorenal syndrome, acute kidney injury, cirrhosis, terlipressin, bolus, and continuous infusion until December 2023. Response to therapy defined as decrease in serum creatinine or regression of acute kidney injury was the primary outcome of interest, while safety in terms of drug-related events, mortality, and transplant-free survival were the secondary outcomes. Data extraction was performed using a standardized data form. The reviewers independently screened the studies and assessed the methodological quality using the Cochrane Risk of Bias tool and any discrepancies were resolved by consensus among the authors. Random-effects meta-analysis was done using Review Manager 5.4. Results A total of three studies, one high quality and two moderate quality RCTs, were included in the review, involving a total of 240 patients. Pooled analysis showed that continuous infusion was as effective or better than bolus infusion in achieving the primary outcome (RR 1.12, 95% CI 0.95-1.32, I2 = 0%). In one study, 28- and 90-day mortality were not significantly different, while 90-day transplant-free survival was not significantly different between continuous and bolus groups from another trial (53% vs 69% p = 0.26). Higher incidence of adverse events were also reported in the bolus group, RR 0.37, 95% CI 0.13-1.04 (p = 0.06). Conclusion There is limited evidence to suggest that continuous infusion of terlipressin may demonstrate resolution of acute kidney injury more frequently than bolus infusion, and that continuous infusion is associated with decreased adverse events. Larger randomized controlled trials with higher quality are needed to ascertain the effects on mortality, need for renal replacement therapy, and transplant-free survival.

A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial).

Ketamine has been used to control refractory cancer pain as an adjuvant to opioids. We conducted a prospective phase II study to investigate the efficacy and safety of 5-day continuous intravenous infusion (CIVI) of Ketamine in terminally ill cancer patients with refractory cancer pain. Hospitalized terminally ill cancer patients with refractory cancer pain were enrolled. Refractory cancer pain was indicated by requirements for 4 or more rescue opioids or pain intensity using numerical rating scale > personalized pain goal (PPG) despite of intravenous morphine equivalent daily dose (IV MEDD) ≥ 120mg/day. The CIVI of ketamine was increased from .05mg/kg/hour to .5mg/kg/hour by .05 every 8 hours if pain intensity exceeded PPG or if number of rescue opioids ≥2 during prior 8 hours was required. The primary end-point was overall pain response rate, which indicates complete response (both rescue opioid ≤3/day and pain intensity ≤ PPG) plus partial response (rescue opioid ≤3/day), without unacceptable toxicities. Among 21 eligible patients enrolled between September 2019 and January 2023, 20 were analyzed. Most pain mechanisms were mixed type (n = 15, 75%), with neuropathic component (n = 17, 85%). The baseline background opioids were IV MEDD 186mg/24hour (range, 124-592), number of rescue opioids was 6 (IQR, 5-9), and median PPG was 4 (IQR, 3-4). The overall pain response rate was 50% (n = 10) including 40% (n = 8) for complete pain response and 10% (n = 2) for partial pain response. This study showed efficacy of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. CIVI of ketamine could be a useful tool in these patients considering the limited treatment options. (NCT03362073, Initial Release: November 15, 2017).

The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer

BackgroundPlatinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present.AimThis study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed.MethodsThis prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs).ResultsThe mPFS was 6.5 months (95% confidence interval (CI): 3.8–9.1 m) while the mOS was 12.3 months (95% CI: 7.6–18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS.ConclusionsThe incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients.ClinicalTrials.govNCT05574998.

THE TREATMENT OF HEPATORENAL SYNDROME WITH TERLIPRESSIN: CONTINUOUS INTRAVENOUS INFUSION VS INTRAVENOUS BOLUSES A RANDOMISED CONTROLLED STUDY ON SYNDROME

Objective: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis, with terlipressin and albumin being the most common treatment. The study aimed to compare the effectiveness and safety of continuous intravenous infusion vs. intravenous boluses of terlipressin in treating type 1 h.
 Methods: A randomized controlled trial was conducted on cirrhosis patients with type 1 h. Patients were allocated to receive terlipressin via continuous infusion (TERLI-INF group) or intravenous boluses (TERLI-BOL group). Demographic, clinical, and laboratory data were collected, and treatment details were recorded. The primary endpoint was the frequency of drug-related adverse events. Secondary endpoints included therapy responsiveness and 90-day transplant-free survival.
 Results: Both groups exhibited similar baseline characteristics. While treatment length and cumulative albumin doses were comparable, TERLI-INF patients received lower terlipressin doses. Severe treatment-related adverse events differed between groups. Univariate analysis identified several baseline parameters significantly associated with response to terlipressin. The study supports continuous terlipressin infusion's superiority in treating type 1 h, with lower adverse event rates and improved patient response.
 Conclusion: The study concludes that continuous intravenous terlipressin infusion is safer and more effective in treating type 1 h in decompensated cirrhosis patients compared to intravenous boluses. Lower terlipressin dosages were effective in continuous infusion, indicating improved safety. The MELD score was an independent predictor of response, and therapy responsiveness was associated with improved 90 d survival.

Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer.

BACKGROUNDLung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of primary lung cancer. However, efficacy and safety of the current regimens for NSCLC is unsatisfactory. Therefore, there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIMTo investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin (Rh-endostain) using an infusion pump in retreated advanced NSCLC.METHODSPatients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited. These patients received continuous intravenous infusion of Rh-endostain using an infusion pump. Objective response rate (ORR), clinical benefit rate (CBR), median progression-free survival (mPFS), and incidences of adverse events (AEs) were analyzed after treatment.RESULTSA total of 45 patients with retreated advanced NSCLC were included, and all of them were evaluated. In these patients, ORR was 22.2%, CBR was 84.4%, and mPFS was 5.3 mo. The following AEs were observed, decreased hemoglobin (34 cases, 75.6%), nausea/vomiting (32 cases, 71.1%), elevated transaminase (24 cases, 53.3%), leukopenia (16 cases, 35.6%), thrombocytopenia (14 cases, 31.1%), and constipation (1 case, 3.4%). None of the patients had leukopenia, nausea /vomiting, and constipation of grade III and above.CONCLUSIONThe patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump. Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

Continuous cyclosporine a infusion in patients with severe Kawasaki disease.

The efficacy and safety of continuous intravenous infusion of cyclosporine A (CICsA) in patients with intravenous immunoglobulin-resistant Kawasaki disease are unclear. Between 2010 and 2020, 83 patients with Kawasaki disease that was not responsive to intravenous immunoglobulin (total dose ≥ 4 g/kg) were enrolled. All patients were started on CICsA (3 mg/kg/day) and switched to oral cyclosporine A (CsA) (4-6 mg/kg/day). Treatment efficacy, occurrence of coronary artery lesions (CALs), and laboratory parameters were evaluated. Patients were divided into two groups according to CICsA response: the responder group (afebrile ≤24 h after CICsA without additional treatment) and the weak responder group (afebrile >24 h after CICsA requiring additional treatment). Fifty-five patients became afebrile within 24 and 74 h became afebrile in less than 72 h. Adverse events included hypertension in four and hyperkalemia in two patients. Thirty-nine patients were defined as responders and 44 patients as weak responders. There were no significant differences in CAL between the two groups. In weak responders, white blood cells, neutrophils, and C-reactive protein levels were higher, and albumin, immunoglobulin G, and CsA concentration were lower than in responders, indicating that weak responders had more severe inflammatory findings. However, there were no significant differences in CAL. Logistic regression analysis revealed that the response to treatment for CICsA was associated with immunoglobulin G levels at baseline and CsA concentrations the day after CICsA. Although CICsA required additional treatments in about half of the cases, a favorable clinical course was observed by using this strategy, especially for reducing CAL.

CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

A Single Center Phase II Study of Continuous Infusion of Low-dose 5- fluorouracil for Heavily Pretreated Patients With Metastatic Colorectal Cancer

Objective: Many patients with metastatic colorectal cancer (MCRC) cannot afford the targeted therapy in China. There is no standard treatment when these patients whose tumors relapsed following the first- and second- line chemotherapy. The goal of the present study is to evaluate the efficacy and safety of continuous intravenous infusion (CIV) of low-dose 5-fluorouracil5-FUfor heavily pretreated patients with MCRC. Methods: Twenty-three heavily pretreated patients with MCRC received 5-FU 200 mg/m2 per day as CIV for more than 30 days. Efficacy and safety was evaluated after one cycle of chemotherapy. Results: No patient achieved complete response (CR), 2 patients partial response (PR), 8 patients stable disease (SD), and 13 patients progression disease (PD). Response rate (RR) was 8.7%, disease control rateCR+PR+SD was 43.5%Toxicity was mild. Conclusion: This study showed that continuous venous infusion of low-dose 5-fluorouracil was moderately active and well tolerated in heavily pretreated patients with MCRC. Keywords: Low-dose 5-fluorouracil, continuous intravenous infusion, metastatic colorectal cancer.

A Pilot Study of Efficacy and Safety of Continuous Intravenous Infusion of Pantoprazole in the Treatment of Severe Erosive Esophagitis

Reflux esophagitis is a common disease. Erosive reflux esophagitis is a more advanced stage of reflux esophagitis. Although death from reflux disease is uncommon, significant morbidity and mortality from complications, such as esophageal ulcer, stricture, and cancer, are not uncommon. Proton pump inhibitors are the popular medication for reflux esophagitis. The objective of this study was to determine the efficacy and safety of continuous intravenous infusion of pantoprazole in the treatment of severe erosive esophagitis. From February 2005 to November 2006, all patients with grade 4 erosive reflux esophagitis were screened for the study. Eligible patients were randomized into two groups. Each patient in the study group received intravenous pantoprazole 80 mg loading dose over 5 min, followed by 8 mg/h intravenous infusion for 72 h, then 40 mg orally once a day for 4 days. Each patient in the control group received 40 mg pantoprazole intravenously once a day for 72 h, then orally once a day for 4 days. A second endoscopic gastrointestinal examination (EGD) was performed on treatment days 6-8 (+/-1 day if day 7 was on a weekend) to document any healing of esophagitis in either the study or the control group. In the study group, severe erosive esophagitis healed completely in three patients and significantly in the other three by the time of the second endoscopy. In the control group, severe erosive esophagitis healed partially in five patients, and no improvement was seen at all in one patient by the time of second endoscopy. The difference in the intervention between those two groups was statistically different (P = 0.015). There were no significant complications in either group. Severe erosive esophagitis can be completely healed in a few days if pantoprazole is given intravenously and continuously for 72 h. It is safe to give pantoprazole intravenously and continuously for treatment of severe erosive esophagitis.

Efficacy and Safety of a Furosemide Continuous Infusion Following Cardiac Surgery

To review the literature regarding the efficacy and safety of continuous intravenous infusion of loop diuretics following cardiac surgery. Articles were identified through a MEDLINE search (1966-March 2006) using the key words furosemide, bumetanide, torsemide, ethacrynic acid, loop diuretics, continuous infusions, intravenous infusions, surgery, cardiac surgery, cardiovascular surgery, and thoracic surgery. Search results were limited to studies in human subjects published in English. Additional references were identified through review of the bibliographies of the articles cited. All clinical trials and observational reports identified that evaluated or described the efficacy and/or safety of a continuous infusion of a loop diuretic in adult or pediatric patients who had undergone cardiac surgery were included in this review. Loop diuretics are often used to promote diuresis following cardiac surgery. Studies in patients who have undergone cardiac surgery have demonstrated that a more consistent and sustained diuresis is produced by a continuous infusion of furosemide compared with intermittent bolus doses of furosemide. However, there does not appear to be a significant difference in total urine output or change in serum electrolyte levels when furosemide is administered as a continuous infusion compared with intermittent bolus doses. A continuous infusion of furosemide is an effective and safe method of diuresis in patients undergoing cardiac surgery.

Efficacy and safety of continuous intravenous infusion of remifentanil in preterm infants undergoing laser therapy in retinopathy of prematurity: clinical experience.

Preterm infants often require surgery. As experimental evidence suggests that premature infants may experience pain and this could even result in fatal complications, the anaesthesiologist must face problems related to lowbirth weight, high risk of hypothermia, concomitant pulmonary disease and metabolic and receptor immaturity. Recently remifentanil has been considered an optimal analgesic drug in a preterm infant undergoing mechanical ventilation and frequent surgical manoeuvres, but no clinical studies have been reported in the literature. The aim of our study was to evaluate the efficacy of a continuous intravenous infusion of remifentanil in premature infants undergoing laser therapy for retinopathy of prematurity (ROP). Six premature infants with ROP were scheduled for laser therapy. The procedure was performed in the neonatal intensive care unit. Transcutaneous carbon dioxide, pulse oximetry, respiratory rate, ECG and noninvasive blood pressure were continuously monitored. Infusion of remifentanil started with a dose of 0.75-1 microg x kg-1x min-1, 1 h before surgery. A midazolam bolus dose (0.20 mg x kg-1) was administered and the remifentanil infusion was increased to 3-5 microg x kg-1x min-1 taking into account haemodynamic and respiratory changes or spontaneous movements. Increased dosage was necessary only for 10 min during the procedure. No changes in temperature and ventilatory settings were observed and after 2 h from the surgical procedure the preterm infants were back to their preoperative status. A continuous infusion of remifentanil allowed optimal control of surgical stress and a return to preoperative status and ventilatory settings without side-effects.