Continuous IV Research Articles

Continuous versus intermittent tacrolimus for graft-versus-host disease prophylaxis in pediatric hematopoietic stem cell transplantation patients (Tic Tac).

Tacrolimus is administered via a continuous or intermittent IV infusion to prevent acute graft versus host disease (aGvHD) in pediatric hematopoietic stem cell transplant (HSCT) recipients. Limited comparison data is available. The primary objective was to compare the proportion of therapeutic tacrolimus trough levels in the first 30 days post-stem cell infusion. Secondary outcomes were prevalence of aGvHD, intra-patient variability (IPV) and safety. This was a retrospective cohort study that included pediatric HSCT recipients between March 1, 2015 and October 31,2021 at BC Childrens Hospital. Adverse events were assessed using the Naranjo scoring tool. Overall, 60 transplants in 59 patients were included; n = 36 intermittent IV and n = 24 continuous IV. Median proportion of blood levels (intermittent and continuous) within 8-12 ug/L was 38% and 56%, respectively (p = 0.04). IPV was 33% and 31% and aGvHD was 39% and 38% in intermittent and continuous respectively. There was a higher proportion of adverse effects in the intermittent group with the exception of hypomagnesemia. Continuous IV tacrolimus provided a higher proportion of levels within therapeutic range. Neither achieved therapeutic trough levels in more than 56% of transplants. However, there was large intra-patient variability in both groups.

Glycemic Management in Patients with COVID-19 Admitted to the Intensive Care Unit: Evaluation of Glycemic Control and Drug Therapy.

Emerging evidence describes the high incidence and strong impact of hyperglycemia on the outcomes of critically ill patients with a diagnosis of COVID-19. Given resource limitations during the COVID-19 pandemic, clinicians moved away from using continuous IV infusions of insulin to manage hyperglycemia. To evaluate glycemic control in critically ill patients receiving various medication regimens to manage their hyperglycemia. This retrospective cohort study involved 120 mechanically ventilated adult patients (> 18 years) with COVID-19 who were admitted to the intensive care unit (ICU) between February 2020 and December 2021. The following data were collected for the first 14 days of the ICU admission: blood glucose values (up to 4 times daily), hypoglycemia events, and antihyperglycemic medication regimens. The use of IV insulin infusions maintained glucose measurements within the target range of 4 to 10 mmol/L more often than any other medication regimen, with 60% of measured values falling within the target range. The use of a sliding-scale insulin regimen maintained 52% of glucose measurements within the target range. Oral hypoglycemic agents performed relatively poorly, with only 12% to 29% of glucose measurements within range. The coadministration of corticosteroids led to worse glycemic control across all medication regimens. This study confirmed that ICUs should continue using the standard protocol of IV insulin infusion to achieve recommended blood glucose targets in critically ill patients with COVID-19, particularly those receiving corticosteroids.

Predictors of Postoperative Morphine Milligram Equivalents in Cardiac Surgery

ObjectivesGiven both the short- and long-term deleterious effects of opioids, there has been increased focused on reducing the use of postoperative opioid analgesia. As patients undergoing cardiac surgery often require high levels opioids postoperatively, understanding risk factors for increased postoperative opioid use may be helpful for the development of patient specific opioid sparing pain regimens for this patient population. DesignThis study was a retrospective analysis of data from our electronic medical records and the Society of Thoracic Surgeon's database. SettingThis was a single-institution study at an academic medical center. ParticipantsAll patients undergoing open adult cardiac surgery were included. Exclusion criteria were patients with continuous IV narcotic drips and operative mortality. InterventionsAs this was a retrospective study, no interventions were conducted on the participants. Measurements and Main ResultsData for patient's postoperative opioid requirements was extracted from the electronic medical record. Total opioid use on postoperative days 0-3 was converted to morphine milligram equivalent (MME) via standard conversion factors. A total of 1,604 patients were included in the study. 456 patients were female, and 1,066 underwent coronary artery bypass grafting. Patients undergoing CABG had 31.0% increased use of MME (P<.001), patients with liver disease had 76.3% increased use of MME (P=.005), and patients with patient-controlled analgesia had 48.8% increased use of MME (P<.001) during postoperative days 0-3. Younger age (P<.001) and increased BMI (P<.001) were also associated with increased MME prescription. ConclusionsPatients undergoing CABG, patients with liver disease, patients with patient-controlled analgesia, in addition to younger age and increased BMI, are associated with increased narcotic use after cardiac surgery. Implementation of more aggressive perioperative multimodal opioid sparing regimens should be considered for these patient groups.

The Acute Impact of Propofol on Blood-Brain Barrier Integrity in Mice.

We investigated whether short term infusion of propofol, a highly lipophilic agonist at GABAA receptors, which is in widespread clinical use as anesthetic and sedative, affects passive blood-brain barrier (BBB) permeability in vivo. Mice were anesthetized with an intraperitoneal injection of ketamine/xylazine followed by a continuous IV infusion of propofol in lipid emulsion through a tail vein catheter. Control groups received ketamine/xylazine anesthesia and an infusion of Intralipid, or ketamine/xylazine anesthesia only. [13C12]sucrose as a permeability marker was injected as IV bolus 15min after start of the infusions. Brain uptake clearance, Kin, of sucrose was calculated from the brain concentrations at 30min and the area under the plasma-concentration time curve. We also measured the plasma and brain concentration of propofol at the terminal time point. The Kin value for propofol-infused mice was significantly higher, by a factor of 1.55 and 1.87, compared to the Intralipid infusion and the ketamine/xylazine groups, respectively, while the control groups were not significantly different. No difference was seen in the expression levels of tight junction proteins in brain across all groups. The propofol plasma concentration at the end of infusion (10.7µM) matched the clinically relevant range of blood concentrations reported in humans, while concentration in brain was 2.5-fold higher than plasma. Propofol at clinical plasma concentrations acutely increases BBB permeability, extending our previous results with volatile anesthetics to a lipophilic injectable agent. This prompts further exploration, potentially refining clinical practices and ensuring safety, especially during extended propofol infusion schemes.

Treatment of Severe Hyperglycemia in Extremely Preterm Infants Using Continuous Subcutaneous Insulin Therapy

Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of intravenous (iv) insulin treatment. The aim of this study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Clinical data from extremely premature infants (<28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia in the neonatal intensive care unit were included. Blood glucose levels during CSII, as well as the nutritional intake and insulin intake were recorded. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Normoglycemia rates were best in the iv insulin-cohort (n=22, 50.3%) compared to the CSII group (n=15, 15.6%). Hypoglycemia was very rare in both groups (0.4% vs. 0.0%). CSII therapy appears to require higher insulin doses compared to continuous iv therapy to achieve a similar effect. Subcutaneous Insulin therapy in extremely preterm infants is feasible, at least for prevention of hypoglycemia. However, dose control needs to be improved. The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII in this population.

Abstract A005: Enhanced DNA damage and disruption of repair by iodinated thymidine analogues with Tipiracil for clinical radiation sensitization

Abstract IUdR incorporation into cellular DNA enhances radiation induced DNA damage and impairs repair pathways. IUdR has been explored as a clinical radiation sensitizer in Phase I and II clinical trials of sarcomas and gliomas, showing clinical activity. A major barrier to acceptance of this therapy has been the poor pharmacokinetic (PK) profile of IUdR which has a blood plasma half-life of less than 10 minutes. Continuous IV infusion of IUdR has been used to achieve clinically relevant DNA incorporation into tumor cells, but technical limitations of delivery and acute toxicities in rapidly proliferating normal tissues presented barriers to advancing this approach. To improve the PK profile of IUdR, a prodrug strategy has been employed leading to the development of ropidoxuridine (IPdR), which improved the PK profile, demonstrated oral bioavailability of the active metabolite IUdR, showed less normal tissue toxicity, and provided tumor radiation sensitization. IPdR plus XRT has been tested in Phase 0 and Phase 1 clinical trials and a phase II trial is proposed for glioblastoma treatment. We report here a second approach to improve the PK profile of orally administered IUdR by combining these iodinated thymidine analogs with the metabolism inhibitor, Tipiracil (TPI) which inhibits thymidine phosphorylase, the primary enzyme responsible for irreversible IUdR degradation, and is currently used in the FDA approved combination drug Lonsurf. Oral co-administration of IUdR and TPI in rats dramatically improved the PK profile of IUdR, increasing the half-life of the compound to 1.5 hours and boosting the maximum plasma concentration by approximately 8-fold. We studied the effects of Tipiracil on the metabolism of IUdR by varying the molecular ratio of IUdR/TPI from 2:1 up to a ratio of 10:1 and discovered that the plasma concentration of IUdR plateaued between a ratio of 5:1 and 10:1. This new combination therapy of IUdR/TPI yields a PK profile of IUdR that is relevant to clinical treatment in combination with RT and offers to expand potential clinical radiation sensitizer applications. Citation Format: Scott Grindrod, Alfredo Velana, Tyvin Rich, Mira Jung, Dalong Pang, Anatoly Dritschilo. Enhanced DNA damage and disruption of repair by iodinated thymidine analogues with Tipiracil for clinical radiation sensitization [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A005.

Pain Management in Blast Crisis Phase of Chronic Myeloid Leukemia: A Case Report

Background: Chronic myeloid leukemia (CML) is a slow-growing type of cancer that begins in the bone marrow's blood-forming cells and is caused by a chromosomal mutation that is assumed to develop spontaneously. As CML advances into the rapid or blast phase, it can cause significant pain. This study aimed to describe pain management in the blast crisis (BC) phase of CML.&#x0D; Case presentation: A 48-year-old female diagnosed with CML in the BC phase complained of severe pain in the head, shoulders, back, and tailbone area with a numeric rating scale (NRS) of 9/10. The patient received multimodal analgesic therapy with continuous IV fentanyl at a rate of 0.25 mcg/kg/hour and ketamine at 1.3 mcg/kg/minute for 24 hours. The dosage was gradually increased through titration with a target NRS of 4/10. On the fifth day, we replaced fentanyl with morphine at 0.04 mg/kg/hour and ketamine at 1.3 mcg/kg/minute, and we reduced the titration dose according to the patient’s NRS, and her pain was controlled with NRS 3-4/10 after 7 days of treatment. On the 9th day, she was discharged with oral therapy.&#x0D; Conclusion: Multimodal analgesia has been shown to effectively reduce the intensity of the pain in blast crisis phase.

Pediatric Patients with High-Risk B-Cell ALL in First Complete Remission May Benefit from Less Toxic Immunotherapy with Blinatumomab - Results from Randomized Controlled Phase 3 Trial AIEOP-BFM ALL 2017

Background: One of the key questions in trial AIEOP-BFM ALL 2017 focused on the reduction of treatment-related complications by replacing parts of the highly intensive consolidation phase by two courses of Blinatumomab (Blina) in a prospective randomized trial. Herein, we report the toxicity profile of B-cell acute lymphoblastic leukemia (B-ALL) patients (pts) with high-risk (HR) characteristics pending final outcome data. Patients and Methods: 728 pts with HR B-ALL were enrolled from July 15, 2018 to October 31, 2022 in this multicenter trial run in 8 different countries. Patients were included in the HR group in view of the presence of at least one of the following criteria: induction failure; high levels of minimal residual disease (MRD) at day 15 of induction, or at the end of induction (EOI), or at the end of consolidation (EOC); presence of KMT2A::AFF1, of IKZF1+ and positive MRD at EOI (Stanulla et al, JCO 2018), TCF3::HLF, or hypodiploidy. B-ALL pts with one or several of these characteristics represented 20.8% of all pts aged 0-18 years of age with B-ALL. After a 4-drug induction phase, and two weeks of consolidation treatment, patients were randomized to receive Bortezomib in addition to standard consolidation (not part of this report). Before treatment continued with intensive consolidation block HR-1', MRD was analyzed in order to identify patients eligible for subsequent hematopoietic stem cell transplantation (HSCT) based on MRD results. After block HR-1', all B-ALL HR pts were randomized to receive either two courses of consolidation (blocks HR-2', and HR-3'), or two 28-day courses of Blina at 15µg/m 2/d administered by continuous IV infusion (with a 2-week treatment-free interval). Two intrathecal injections of methotrexate (MTX) for CNS prophylaxis were given on days 1 and 29 of each Blina course, respectively. Out of 728 HR B-ALL pts, 619 pts were eligible for randomization [reasons for non-eligibility were: Event (death or relapse) before randomization was due (26), Down syndrome (25; scheduled for a non-randomized intervention with Blina), presence of TCF3::HLF (3; could receive any alternative therapy including Blina), discontinuation/substantial change of preceding therapy (23) or other protocol exclusion criteria (32)]. 572 pts were randomized (92.4% of those eligible). One pt assigned to the experimental arm (EA) and 4 pts assigned to the control arm (CA) received the other arms, respectively. Results: Toxicity was evaluated in randomized pts according to treatment administered during the randomized phase, respectively, until next element started: 268 pts were treated in the control and 281 in the EA (see Table). 16 of them switched in/after the first Blina cycle to the HR blocks due to toxicity or poor response to Blina (due to increasing MRD, &amp;gt;=1x10 -4). Medically relevant adverse reactions of special interest (ARSI) according to MedDRA (specified in the protocol) were evaluated in the randomized treatment phases (CA: HR-2‘/HR-3‘ block, EA: 2 Blina cycles). ARSI were recorded in 61 of 268 pts in the CA (22.8%, 71 ARSI) and in 29 of 281 pts in the EA (10.3% [p&amp;lt;0.001], 33 ARSI); 3 of the 33 ARSI in the EA were related to HR blocks and were observed in 3 of the 16 pts that switched to HR blocks. Life-threatening SAR were seen in 14 pts of the control group (5.2%) and in no patient in the EA (p&amp;lt;0.001). Conclusions: Taken together, these results show for the first time in newly diagnosed pts with HR B ALL, the favorable toxicity profile previously reported with Blinatumomab in pediatric relapsed ALL (Locatelli F et al, JAMA 2021; Brown P et al, JAMA 2021). We have demonstrated that the toxicity profile of Blinatumomab is much more favorable as compared to the intensive chemotherapy approach using HR-blocks. If upcoming analyses of outcome data will show no inferiority of the EA, blinatumomab replacement of some of the intensive chemotherapy blocks will become the new standard of care for treatment if newly diagnosed patients with HR B-ALL.

Abstract 18979: Calm Before the Storm: Exploring the Risk of Torsades De Pointes With Dexmedetomidine Administration

Introduction: Corrected QT interval (QTc) prolongation is the known side effect of multiple medications especially in antipsychotic and antiarrhythmic family. Patients with either inherited or secondary prolonged QTc should be monitored closely as they can develop life threatening complications like Torsades de-pointes and ventricular fibrillation. Here we present a case of cardiac arrest secondary to dexmedetomidine. Case: A 49-year-old female with history of bipolar disorder was admitted to intensive unit for seizure after intentional ingestion of uncounted amount of diphenhydramine pills. Patient was intubated for airway protection and started on propofol. Her vitals at the time of admission included the pulse rate of 76, blood pressure of 102/49 mmHg. Her urine drug screen was positive for TCA and cannabinoids. Her ECG at the time of admission was significant for prolonged QTC of 600msec that improved to 460msec in the consecutive ECGs after administration of total of 4mg intravenous magnesium. Continuous EEG was negative for seizure and she was weaned off sedation. After awakening, she became agitated, after pushes of benzodiazepines, was eventually started on dexmedetomidine. Twenty minutes after starting low dose dexmedetomidine, patient was noted to be in cardiac arrest. Reviewing telemetry prior to event, revealed the R on T phenomenon and Torsades de pointes that lasted for few seconds with progression into ventricular fibrillation. Discussion: Currently dexmedetomidine is labeled with a low to possible risk of Torsade de pointes and QTC prolongation. Dexmedetomidine induced Torsade de pointes might be explained by bradycardia in patients which causes further prolongation of QT interval. Studies have shown that continuous IV infusion of dexmedetomidine at rate of 0.3 mcg/kg/hour can worsen QTC prolongation. Conclusions: In this case we present a case of VFib arrest secondary to Torsade after twenty minutes of infusion of dexmedetomidine without any sign of bradycardia prior to the event. This carries a significant importance as it shows this drug carries a potential risk of QTc prolongation similar to previous studies. Whether this side effect is dose dependent or not requires further investigation.

Updated Results from a Phase I Dose Escalation Study of the Rapidly-Switchable Universal CAR-T Therapy UniCAR-T-CD123 in Relapsed/Refractory AML

Introduction CAR-T efficacy in AML has been limited by a lack of ideal target antigens as well as the aggressive and resistant nature of disease. CD123 expression on leukemic blasts has been observed in about 80% of AML patients. However, the antigen is also expressed on non-malignant hematopoietic cells including neutrophils and endothelial cells. As consequence, targeting of CD123 with conventional CAR-T has been shown to result in persistent cytopenias, capillary leakage syndrome, CRS, and ICANS. AVC-101 (UniCAR02-T-CD123) is an adapter CAR-T, consisting of a universal CAR-T cell (UniCAR-T) and a CD123 targeting module (TM). The TM binds to the CAR-T cell via a peptide tag and induces T cell activity against CD123 bearing cells. Due to the short half-life of the TM, interruption of its continuous IV administration will rapidly switch T cell activity off, and mitigate toxicities as shown previously. Since the presentation of initial results, the study was amended to include a stricter and prolonged schedule of TM consolidation cycles. Given the excellent safety enabled by the switchable mechanism, additional dose levels (DL) of TM were added. Methods Key inclusion criteria included rrAML patients with ECOG ≤ 1, CD123 expression in ≥ 20% of blasts, and no suitable approved treatment option available or MRD positive AML patients. Initial dosing was applied using an adaptive Bayesian optimal interval design for drug-combination trials, escalating either cell dose or TM concentration based on posterior probability calculation of AEs. Dose escalation for the two additional dose levels was guided by a classical 3+3 design. Patients received standard Flu/Cy lymphodepletion (LD) for 3 days and TM was administered as continuous infusion, whereas UniCAR-T cells were given as one-time infusion on cycle 1 day 1. After completion of the initial 20-day induction cycle, responding patients were allowed to receive up to 3 consolidation cycles of 12 days continuous TM infusion with 7-14 days treatment free intervals in between cycles. Results As of this time 19 patients have received the induction cycle, 8 patients have also received at least one consolidation cycle (1-3, total 13 cycles). Patients were heavily pretreated with a median of 4 (2-7) prior treatment lines. Twelve of these patients had received a prior allogeneic (Allo) stem cell transplantation (SCT). Most of the patients (60%) were in adverse risk category according to ELN classification. In the initial escalation phase, 19 patients were treated in 16 dose cohorts. We observed a single DLT at DL 8 (reversible drop in fibrinogen levels, reported earlier) but no DLTs occurred in 11 patients treated in the yet highest dose cohort of 4 mg/day TM and 500 million UniCAR-T. Treatment was generally well tolerated irrespective of age and prior treatments. CRS was observed in 12 patients, mostly grade 1 or 2. Three grade 3 CRS and 1 grade 2 ICANS were reported, all resolving within 24 hrs from interruption of TM administration. Treatment-related AEs were most frequent in cycle 1, none were reported in cycles 3 and 4. No treatment-induced lasting myelosuppression was observed, and no patient required SCT support for WBC reconstitution. ORR in the first 19 patients was 53% (8/15) for the rrAML population and 75% (3/4) for the MRD population. Since the last presentation, extended administration of TM (20-day induction followed by three 12-day consolidation cycles 1-2 weeks apart) initiated by protocol amendment resulted in durable, ongoing responses approaching 5 months, longer than any prior. A 64-year-old MRD+ patient (#19) with 4 prior lines of therapy experienced a 3-log reduction in MRD levels (NPM1 mutation by qPCR) in both bone marrow and blood (Figure 1) and became transplant eligible. Re-administration of TM resulted in a significant re-expansion of UniCAR-T (Figure 2) without further cell dosing or LD. Another patient (#20) with overt hematological relapse after AlloSCT achieved a CR, ongoing at 5 months. Full safety and efficacy results of the additional 2 dose cohorts with prolonged TM consolidation will be presented at the meeting. Conclusions AVC-101 continues to be safe and tolerable. Repeated dosing of TM in consolidation cycles resulted in robust re-expansion of UniCAR-T with deeper remissions of extended durability. The switchable mechanism provides proven rapid reversal of safety events, enabling higher dose levels.

SAT157 Management Of Spontaneous Hypoglycemia In Dialysis-dependent Chronic Kidney Disease Using Diazoxide

Abstract Disclosure: A. Schledwitz: None. S.S. Habbsa: None. F. Sotomayor Villanueva: None. Y. Kim: None. Background: Patients with end-stage renal disease (ESRD) are at increased risk of spontaneous hypoglycemia due to decreased renal insulin clearance. Due to its inhibitory effect on pancreatic beta cell insulin secretion, oral diazoxide has been used to treat hypoglycemia due to insulinoma or congenital hyperinsulinemic hypoglycemia, but few cases detail the use of diazoxide in the ESRD population. Here, we present 4 cases of spontaneous hyperinsulinemic hypoglycemia in ESRD successfully treated with diazoxide. Clinical Cases: A 66-year-old man with ESRD presented with altered mental status secondary to severe hypoglycemia despite continuous IV 20% dextrose. Labs revealed glucose 50 mg/dL, insulin 7 (0-3 mcIU/mL), C-peptide 7.8 (0-0.6 ng/mL), proinsulin 35.7 (0-5 pmol/L), beta-hydroxybutyrate [bOH] 0.4 (0-2.7 mg/dL), negative sulfonylurea panel, normal cosyntropin stimulation test and undetectable insulin antibodies, without radiographic evidence of insulinoma. He was started on diazoxide 50 mg TID and remained euglycemic for the remainder of his course. On similar readmission 3 months later, he was restarted on diazoxide with resolution of hypoglycemia within 1 day. A 66-year-old male with ESRD and T1DM treated with pancreas transplant presented with toe gangrene and persistent hypoglycemia. Fasting labs revealed insulin 4, C-peptide 4.5, proinsulin 4.5, and bOH 4.5, without radiographic evidence of insulinoma. He maintained euglycemia 4 days after diazoxide 70 mg BID was started. A 67-year-old male with T2DM and ESRD was admitted for osteomyelitis and 2 years of episodic symptomatic hypoglycemia despite dietary adjustments. Labs showed glucose 59, insulin 7, C-peptide 5.2, proinsulin 7.5, bOH 0.04, and unremarkable imaging. Within 1 day of starting diazoxide 100 mg daily, his blood glucose stabilized, and he was discharged. Finally, a 42-year-old male with ESRD presented with 4 years of persistent episodic hypoglycemia, now refractory to continuous IV dextrose. He was found to have glucose 64, insulin 15, C-peptide 11.5, proinsulin 29, and bOH 0.1, with imaging revealing bulky pancreas without a discrete mass. His hypoglycemic episodes resolved within 1 day of starting diazoxide 100 mg daily. He was readmitted 3 months later for catheter site infection and had no episodes of hypoglycemia with continuation of diazoxide. Conclusion: Diazoxide may be a viable option for the treatment of refractory spontaneous hypoglycemia in patients with dialysis dependent ESRD. Presentation: Saturday, June 17, 2023

Effect of Intra Operative Intravenous Lidocaine Infusion on Control of Pain and Recovery of Intestinal Function Following Surgical Appendectomy

Abstract Background Intravenous lidocaine infusion has been shown to facilitate postoperative recovery after major abdominal surgery. This current randomized controlled study will assess the effect of intraoperative intravenous lidocaine infusion on pain intensity, bowel function and cytokine response after surgical appendectomy. Aim of the Work To determine the role of intraoperative lidocaine infusion in reducing perioperative pain and analgesia requirement and enhancing the recovery of intestinal function in patients undergoing surgical Appendectomy. Patients and Methods The current prospective randomized double-blinded study was conducted at the surgery department, Faculty of Medicine, Ain Shams University and it included 40 patients who were undergone urgent open appendectomy and met the selection criteria. They were classified into 2 groups: Group L: patient who received IV bolus injection of lidocaine (1.5 mg/kg slowly over 10 min) 30 minutes before the skin incisions followed by a continuous IV infusion at the rate of 2 mg/kg/h via infusion pump(B-BRAUN), Group S (control): patient who received 0.9% normal saline in equal volume and in the same manner. Results There was statistically significant difference between the studied groups regarding time to pass flatus. Patients within lidocaine group pass flatus significantly earlier than those with control group. There is statistically non-significant difference between the studied groups regarding postoperative complications. Conclusion From the current study, it was concluded that perioperative IV lidocaine injection had significant effect in reduction of postoperative pain and increased the main pain free period also noticed IV lidocaine decreased opioid requirement and time to pass flatus so shorten hospital stay. Perioperative IV lidocaine had no effect on postoperative complications and IV lidocaine during incision and extubation attenuated hemodynamic response.

Can You Establish the Cause of This Patient's Shortness of Breath?

Mr. B is a 56-year-old man diagnosed with metastatic HER2-positive gastroesophageal adenocarcinoma. He received front-line leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) and trastuzumab for 10 months before restaging imaging revealed progressive disease. He then received second-line trastuzumab deruxtecan. His treatment was complicated by several admissions felt to be unrelated to his cancer therapy. He was discharged after an episode of pneumonia on a steroid taper with prophylactic trimethoprim/sulfamethoxazole. Once he recovered, he was given a fourth dose of chemotherapy. About a week later, wheezes were noticed on physical exam, and he was given a 5-day course of levofloxacin. Around the same time, he also finished his steroid taper. Twelve days after his dose of chemotherapy, he presented to the emergency room with 3 to 4 days of progressive shortness of breath and dry cough following the completion of levofloxacin without symptom improvement. A CT scan showed increasing airspace opacities and multifocal areas of consolidation. Blood, nasal, and sputum cultures were negative. A bronchoscopy was performed that did not reveal findings concerning for capillaritis. He was ultimately diagnosed with drug-induced pneumonitis/interstitial lung disease (ILD). Mr. B continued to experience worsening hypoxic respiratory failure despite continuous IV steroids. He was discharged to an inpatient hospice facility where he passed away 2 weeks later. Drug-induced pneumonitis/ILD should be considered in all patients receiving trastuzumab deruxtecan who develop progressive shortness of breath or other respiratory complaints.

285-LB: LEAP2 Reduces Preprandial and Postprandial Glucose Levels and Ad Libitum Food Intake in Obese Men

The naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP2) has gained interest as a ghrelin receptor antagonist. Recently, we reported food intake and plasma glucose-lowering effects of exogenous LEAP2 in lean healthy males. Here, we investigated the effects of LEAP2 infusion on ad libitum food intake and postprandial glucose tolerance in obese men. Twenty obese men (mean (SEM) age 44.2 (2.2) years; BMI 36.3 (0.8) kg/m2; body fat percentage 37.4 (0.9)%) were enrolled in this randomized, double-blind, placebo-controlled, crossover study comprising two experimental days. Experimental days involved a ~5-hour intravenous (iv) infusion of LEAP2 or placebo during which a liquid mixed meal test (MMT) and a subsequent ad libitum meal test were performed. Plasma glucose measures included fasted (preprandial), Cmax and Tmax values as well as area under the curve (AUC) during MMT. Ad libitum food intake was measured in kilojoule (kJ) and kJ/kg body weight. Compared to placebo, LEAP2 infusion lowered preprandial plasma glucose (mean (SEM): 5.03 (0.08) vs. 5.19 (0.06) mmol/L, P=0.0095) as well as Cmax (6.58 (0.18) vs. 6.98 mmol/L (0.18), P=0.0001) and AUC for plasma glucose during MMT (1,506 (33.4) vs. 1564 (30.4) min×mmol/L, P=0.0005), but not Tmax. Ad libitum food intake was reduced by ~13% during LEAP2 infusion compared to placebo (2,939 (266) vs. 3,378 (258) kJ, P=0.0118; 25.0 (2.4) vs. 28.4 (2.0) kJ/kg body weight, P=0.0140). We conclude that a continuous iv LEAP2 infusion reduces pre- and postprandial plasma glucose concentrations as well as ad libitum food intake in obese men. Disclosure A. Englund: None. C. A. Hagemann: Employee; Gubra ApS. L. S. Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. F. K. Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck.

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). A multicenter, single-blind, randomized, noninferiority trial. Twenty-one centers across China from December 2020 to June 2021. A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. One hundred thirty-five ICU patients were randomly allocated into ciprofol (n = 90) and propofol (n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 μg/kg, maintenance dose: 0.02-0.15 μg/kg/min). Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time (p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

Continuous subcutaneous insulin infusion via an insulin pump in extremely premature neonates—a case series

Extremely preterm infants are prone to hyperglycemia which is associated with increased mortality and morbidity. Insulin sensitivity is variable in extreme prematurity, and its monitoring, prevention, and treatment are a significant challenge in the NICU. Frequent changes in fluid composition and volumes, as well as large growth and adaptational nutrient requirements are limited by difficult vascular access and blood sampling and risk of drug incompatibilities. Insulin treatment requires specific access and significantly increases fluid intake and sampling. Clinicians, therefore, often compromise by reducing glucose intake and accepting higher glycemia. We report a case series of 11 extremely low birth weight (ELBW) preterms, born between 23 5/7 and 27 6/7 weeks of gestation, treated for transient hyperglycemia during the first 2 weeks of life by continuous subcutaneous insulin infusion (CSII). Insulin concentration was 10 IU/ml, administered via 13 mm Accu-Chek® Tenderlink catheters and a commercial insulin pump (Accu-Chek® Combo, Roche Diabetes Care). Insulin treatment was initiated when glycemia was > 252 mg/dL (14 mmol/l) in two consecutive blood glucose determinations, except for one case when glycemia was 234 mg/dL (13 mmol/l), despite a previous decrease in glucose infusion rate. The starting dose for the CSII was between 0.01 and 0.08 IU/kg/h. The average duration of the CSII was 5 days (1–16 days). CSII in extreme preterm neonates with hyperglycemia was clinically feasible and practical by sparing IV lines and volume and appeared as more rapidly effective than continuous IV administration. No adverse events like hypoglycemia or skin infection were recorded.

Continuous IV infusion of anakinra.

Objective: A review of the use of continuous IV infusion of anakinra; a description of the protocol for continuous IV infusion of anakinra in the treatment of cytokine storm developed over the past 4years at a tertiary level academic medical center in the United States. Methods: We reviewed published reports of continuous IV infusion of anakinra in cytokine storm and summarize this method of treatment in other diseases. As well, over the past 4 years, continuous IV infusions of anakinra were administered at our tertiary level academic medical center in the United States (Regions Hospital, St. Paul, Minnesota) for approximately 400 patient days of treatment primarily for the cytokine storm associated with macrophage activation syndrome (MAS) in adults. This updated protocol is presented. While this a single center protocol, it may serve as an initial guide for further refinement of protocols in MAS and other conditions. Conclusion:Continuous IV infusion of anakinra has advantages over subcutaneous infusions and may be important in controlling severe life-threatening cytokine storm as seen in macrophage activation syndrome. This has the potential to be an important therapy for other syndromes including Cytokine Release Syndrome related to CAR T-cell therapy. Close collaboration between Rheumatology, Pharmacy and Nursing allows this treatment to be delivered rapidly and efficiently.

An Unreported homozygous variant within Lipopolysaccharide responsive beige-like anchor (LRBA) gene in a child exhibiting with infantile type 1 diabetes mellitus

We report a patient who was born at term as the first son of consanguineous Saudi parents. He developed IDDM at the age of 7 months; the initial symptoms included fever and vomiting. The laboratory findings indicated pronounced ketoacidosis, initial fluid replacement with normal saline, followed by continuous IV insulin infusion. After a while, the baby was out of DKA. Our endocrinologist advised us to start administering S/C insulin NPH 1 unit BID. Fortunately, we suspected a primary immune deficiency acer a few days from the first presentation. The WES revealed A homozygous likely pathogenic variant was identified in the LRBA gene. The result is consistent with a genetic diagnosis of autosomal recessive CVID type 8 with autoimmunity. The LRBA protein regulates the expression of CTLA-4, which is a potent immune checkpoint receptor expressed by activated and regulatory by the T-cells. CTLA-4 blocks the stimulation/proliferation of T-cells and modulates immune responses.

Patient Controlled Analgesia for Vaso-Occlusive Episodes in Children: A Retrospective Study.

To describe Patient-Controlled Analgesia (PCA) administration in pediatric patients admitted with sickle cell vaso-occlusive episode (VOE). This single-center retrospective study included all inpatient hematology admissions for VOE between 2014 and 2020. PCA-ratio was calculated as the ratio of bolus over continuous IV opioids dose, and time to PCA adjustment as time between first PCA order and a subsequent order that increased dosing or changed opioid medication. A total of 866 encounters (172 unique patients) with PCA for VOE were included. The mean age was 15.4 years old (SD=5.0). On average, after admission (hospital arrival), the first opioid dose was given at 1 hour, PCA started at 3.5 hours, and mean length of stay was 4.3 days (SD=2.5). The mean initial PCA-ratio was 1.7 (SD=0.6). There were no significant associations between age, gender, initial pain score, or admission hemoglobin and PCA-ratio (linear regression model P=0.443). In 24.7% of encounters, the PCA was adjusted within 6 hours. After adjusting by age and gender, lower admission pain scores (OR=1.15, P=0.004), lower PCA-ratio (OR=2.1, P=0.003), longer time to PCA start (OR=1.2, P=0.001), and no adjuvant ketamine (OR=2.4, P < 0.001) were associated with PCA unadjusted within 6 hours. At our institution, patients with VOE received opioids and PCA within the first hours of admission. PCAs were started at a ratio of 1.5-1.8, considered normal continuous. While no specific PCA-ratio was clearly superior for pain control, lower ratios (high continuous infusion) were associated with not requiring PCA adjustments at 6 hours. Prospective studies are needed.

Successful treatment of breast metastasis from primary transverse colon cancer: A case report

The incidence of colon cancer is increasing worldwide. Treatments for colon cancer include surgery and surgery combined with chemotherapy and radiotherapy, but the median survival rate is still poor. Colon cancer most commonly metastasizes to the lymph nodes, lungs, liver, peritoneum, and brain, but breast metastasis is rare. There is no agreement on its treatment. A 23-year-old woman was admitted to our hospital for further treatment with a history of acute abdominal pain, nausea, and vomiting. Her physical examination and computed tomography scan revealed an abdominal tumor. Transverse colectomy was successfully performed. Histopathological examination revealed that the tumor was a mucosecretory adenocarcinoma with signet ring cells. The patient inadvertently found a mass in the outer upper quadrant of the right breast after four cycles of XELOX chemotherapy [oxaliplatin 130 mg/m2, d1, intravenous (iv) drip for 2 h; capecitabine 1000 mg/m2, po, bid, d1-d14]. After discussion with the patient, we performed a lumpectomy and frozen biopsy. The latter revealed that the breast tumor was intestinal metastasis. Genetic testing showed wild-type RAS and BRAF. So we replaced the original chemotherapy with FOLFIRI [irinotecan 180 mg/m2, d1, iv drip for 3-90 min; leucovorin 400 mg/m2, d1, iv drip for 2 h; 5-fluorouracil (5-FU) 400 mg/m2, d1 and 5-FU 1200 mg/(m2 d) × 2 d, continuous iv drip for 46-48 h] + cetuximab (500 mg/m2, d1, iv drip for 2 h). Serum levels of tumor markers returned to normal after several treatment cycles, and there was no evidence of tumor recurrence or metastasis. Breast metastasis from colon cancer is rare. Radical breast surgery should be avoided unless needed for palliation. Chemotherapy combined with targeted therapy should be the first choice.