Manual Infusion Research Articles

The Rationale for Combining Normothermic Liver Machine Perfusion with Continuous Renal Replacement Therapy to Maintain Physiological Perfusate during Ex Vivo Organ Perfusion.

Background: The possibility of keeping liver grafts viable and functioning until transplantation has been explored since the 1950s. However, the current modalities of Normothermic Machine Perfusion (NMP) have shown several limitations, such as the inability to correct electrolytes and pH derangements efficiently. Combining NMP with continuous kidney replacement therapy (CKRT) might provide a promising new model to overcome these issues. Methods: An NMP that covers the organ perfusion, oxygenation, carbon dioxide removal, and thermal balance was connected to a CKRT circuit to ensure physiological hydro-electrolytes, acid-base balance, and catabolite removal from the perfusate. Results: The integration of NMP and CKRT maintains a neoplastic liver in a perfusion system with physiological perfusate for 100 h. CKRT re-established and maintained the hydro-electrolyte and acid-base status throughout the 100 h of perfusion. Significant limitations were the need for frequent monitoring of electrolytes and acid-base disorders and the loss of low molecular weight nutrients, which have to be replenished by manual infusion into the system. Conclusions: This novel CKRT-NMP integrated system may represent a practical and versatile model to support organs' perfusion and extend preservation times. Further experiments are needed to fix monitoring and adjusting processes.

Determining the Relationship between Delivery Parameters and Ablation Distribution for Novel Gel Ethanol Percutaneous Therapy in Ex Vivo Swine Liver.

Ethyl cellulose-ethanol (ECE) is emerging as a promising formulation for ablative injections, with more controllable injection distributions than those from traditional liquid ethanol. This study evaluates the influence of salient injection parameters on forces needed for infusion, depot volume, retention, and shape in a large animal model relevant to human applications. Experiments were conducted to investigate how infusion volume (0.5 mL to 2.5 mL), ECE concentration (6% or 12%), needle gauge (22 G or 27 G), and infusion rate (10 mL/h) impacted the force of infusion into air using a load cell. These parameters, with the addition of manual infusion, were investigated to elucidate their influence on depot volume, retention, and shape (aspect ratio), measured using CT imaging, in an ex vivo swine liver model. Force during injection increased significantly for 12% compared to 6% ECE and for 27 G needles compared to 22 G. Force variability increased with higher ECE concentration and smaller needle diameter. As infusion volume increased, 12% ECE achieved superior depot volume compared to 6% ECE. For all infusion volumes, 12% ECE achieved superior retention compared to 6% ECE. Needle gauge and infusion rate had little influence on the observed depot volume or retention; however, the smaller needles resulted in higher variability in depot shape for 12% ECE. These results help us understand the multivariate nature of injection performance, informing injection protocol designs for ablations using gel ethanol and infusion, with volumes relevant to human applications.

Target-controlled infusion - Past, present, and future.

Target-controlled infusion (TCI) is a novel drug delivery system wherein a microprocessor calculates the rate of drug to be infused based upon the target plasma or effect site concentration set by the operator. It has found its place in the operation theaters and intensive care units (ICUs) for safe administration of intravenous anesthesia and analgosedation using drugs like propofol, dexmedetomidine, opioids, and so on. Operating a TCI device requires the user to have a primitive understanding of drug pharmacokinetics and pharmacodynamics and an awareness of the practical problems that can arise during its administration. Ongoing research supports their usage in other clinical settings and for various other drugs such as antibiotics, vasopressors, and so on. In this article, we review the underlying principles and commonly used drugs for TCI, the practical aspects of its implementation, and the scope of this technology in future. TCI technology is increasingly being used in the field of anesthesiology and critical care due to the myriad advantages it offers when compared to manual infusions. It is, therefore, essential for the reader to understand the relevant principles and practical aspects related to TCI technology, as well as to be aware of the commonly used TCI models.

Recovery time in target controlled infusion versus manual infusion of propofol in total intravenous anaesthesia for endoscopic retrograde cholangio-pancreatography procedure using laryngeal mask airway-gastro: A randomised comparative study.

This study aimed to compare manual infusion versus target-controlled infusion (TCI) in total intravenous anaesthesia (TIVA) utilising laryngeal mask airway (LMA)-gastro during endoscopic retrograde cholangio-pancreatography (ERCP) procedures. This was a single-blind randomised trial. Patients were randomly allocated into two groups. TCI group included 27 patients, where TCI of propofol was implemented with the Schnider pharmacokinetic model driven by a computer-controlled syringe pump. The TIVA group included 27 patients with a loading dose of 2 mg/kg of propofol, followed by manual infusion of 15 mg/kg/h for the first 15 min, 13 mg/kg/h for the next 15 min, then 11 mg/kg/h for 30 min and 10 mg/kg/h for 60 min and finally maintained at 9 mg/kg/h. The primary objective was to compare recovery time following cessation of propofol infusion in both groups. The difference in the total dose of propofol, time to achieve anaesthesia induction, first attempt success rate, ease of LMA-gastro insertion, ease of insertion, success rate of endoscope device and post-anaesthesia care unit (PACU) discharge time were the secondary objectives. T-test and Chi-square test were used for statistical analysis. The time required for the recovery was significantly less in the TCI group than in the TIVA group (mean ± standard deviation; 11.60 ± 2.27 versus 15.4 ± 3.25 minutes, P < 0.001). The duration of ERCP, ease of LMA and endoscope insertion were comparable between the groups. There was no post-operative recall of intra-operative events in the groups. TCI offers earlier recovery than TIVA in patients undergoing ERCP procedures using LMA-gastro.

Postoperative Nausea and Vomiting According to Target-Controlled or Manual Remifentanil Infusion in Gynecological Patients Undergoing Pelviscopic Surgery: A Randomized Controlled Trial

We compared the incidence of postoperative nausea and vomiting (PONV) and postoperative outcomes, according to the remifentanil infusion method, during surgery in patients with a high-risk of PONV. Ninety patients undergoing elective gynecological pelviscopic surgery were randomly allocated to either target-controlled infusion (TCI, T) or manual (M) infusion. The primary outcome was the incidence of PONV until postoperative day (POD) 2. The secondary outcomes were perioperative heart rate (HR), blood pressure (BP), numerical rating scale pain scores up to POD2, and postoperative hospital length of stay. Forty-four patients in the T group and 45 patients in the M group were analyzed. The total dose of remifentanil infusion was significantly higher in the T group (T group: 0.093 (0.078-0.112) μg/kg/min; M group: 0.062 (0.052-0.076) µg/kg/min, p < 0.001). Within POD2, the overall PONV was not significantly different (27 (61.4%) vs. 27 (60.0%), p = 0.895). The HR (82 ± 11.5/min vs. 87 ± 11.1/min, p = 0.046) and mean BP (83 ± 17.2 mmHg vs. 90 ± 16.7 mmHg, p = 0.035) were significantly lower in the T group after tracheal intubation. The other postoperative outcomes were comparable between the two groups. Although the total remifentanil infusion dose was higher in the T group than in the M group, the postoperative outcomes were similar. If stable vital signs are desired during tracheal intubation, remifentanil infusion with TCI should be considered.

Alternatives to remifentanil for the analgesic component of total intravenous anaesthesia: a narrative review.

Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required. We provide an overview of both target-control and manual infusion regimes for the alternative opioids: alfentanil, sufentanil and fentanyl. The optimal combination of hypnotic-opioid dose, titration sequence and anticipated additional postoperative analgesia required depend on the chosen combination. In addition, we include a brief discussion on the role of non-opioid adjuncts in total intravenous anaesthesia, suggested doses and expected reduction in propofol dose.

The Impact of Low Cardiac Output on Propofol Pharmacokinetics across Age Groups-An Investigation Using Physiologically Based Pharmacokinetic Modelling.

Background: pathophysiological changes such as low cardiac output (LCO) impact pharmacokinetics, but its extent may be different throughout pediatrics compared to adults. Physiologically based pharmacokinetic (PBPK) modelling enables further exploration. Methods: A validated propofol model was used to simulate the impact of LCO on propofol clearance across age groups using the PBPK platform, Simcyp® (version 19). The hepatic and renal extraction ratio of propofol was then determined in all age groups. Subsequently, manual infusion dose explorations were conducted under LCO conditions, targeting a 3 µg/mL (80–125%) propofol concentration range. Results: Both hepatic and renal extraction ratios increased from neonates, infants, children to adolescents and adults. The relative change in clearance following CO reductions increased with age, with the least impact of LCO in neonates. The predicted concentration remained within the 3 µg/mL (80–125%) range under normal CO and LCO (up to 30%) conditions in all age groups. When CO was reduced by 40–50%, a dose reduction of 15% is warranted in neonates, infants and children, and 25% in adolescents and adults. Conclusions: PBPK-driven, the impact of reduced CO on propofol clearance is predicted to be age-dependent, and proportionally greater in adults. Consequently, age group-specific dose reductions for propofol are required in LCO conditions.

Effect-site concentration of remimazolam at loss and recovery of responsiveness during general anesthesia: a simulation study

BackgroundThe objective of this study was to investigate the effect-site concentration (Ce) of remimazolam at loss of response (LOR) and recovery of response (ROR) in patients underwent general anesthesia using simulation. In addition, the relationships between patient’s factors and simulated Ce at LOR and ROR were examined.MethodsThe medical records of 81 patients who underwent elective surgery under general anesthesia using remimazolam with simulation of Ce between August 4, 2021 and October 12, 2021, were retrospectively reviewed. Remimazolam was administered as an induction dose of 6 or 12 mg/kg/h until the patient became unresponsive, followed by 0.3–2 mg/kg/h to maintain BIS values below 60. Simultaneously, simulations of manual infusion mode were performed using Asan Pump software and the Ce of remimazolam was simulated using the Schüttler model. Whenever infusion rate of remimazolam was manually changed, the simulated Ce was confirmed almost simultaneously. LOR and ROR, defined as unresponsive and eye-opening to verbal commands, respectively, were recorded in the Asan Pump program.ResultsThe median (1Q, 3Q) simulated Ce at LOR and ROR were 0.7 (0.5, 0.9) and 0.3 (0.2, 0.4) μg/ml, respectively. LOR was achieved in 1.9 min after remimazolam infusion with cumulative doses of 0.3 mg/kg. There was a significant relationship between age and simulated Ce at ROR (Ce at ROR = –0.0043 × age + 0.57, r = 0.30, P = 0.014). ConclusionsFor optimal dosage adjustment, simulating Ce while administering remimazolam with a weight-based dose during anesthesia is helpful. Elderly patients may recover from anesthesia at lower Ce of remimazolam.

Recanalization of thrombosed aneurysmal hemodialysis arterovenous fistulas using a hybrid technique based on data from a single center

ObjectiveTo explore the technical specifications and clinical outcomes of thrombosed aneurysmal haemodialysis arteriovenous fistula (AVF) treated with ultrasound-guided percutaneous transluminal angioplasty combined with minimal aneurysmotomy.MethodsThis case series study included 11 patients who had thrombosed aneurysmal AVF and underwent salvage procedures over a 13-month period. All procedures were performed under duplex guidance. Minimal aneurysmotomy was performed, along with manual thrombectomy and thrombolytic agent infusion, followed by angioplasty to macerate the thrombus and sufficiently dilate potential stenoses. A successful procedure was defined as immediate restoration of flow through the AVF.ResultsThe 11 patients (four males and seven females) had a mean age of 49.6 years ± 11.9 years. Six patients (54.5%) had two or more aneurysms. The mean aneurysm maximal diameter was 21.5 mm (standard deviation: ± 5.0 mm), and the mean thrombus length was 12.9 cm (8–22 cm). Ten (83.3%) of the 12 procedures were technically successful. The mean duration of operation was 150.9 minutes (standard deviation: ± 34.2 minutes), and mean postoperative AVF blood flow was 728.6 ml/min (standard deviation: ± 53.7 mi/min). The resumption of hemodialysis was successful in all 11 cases, with a clinical success rate of 100%. The primary patency rates were 90.0% and 75.0% at three and four months over a mean follow-up time of 6.3 months (3–12 months). The secondary patency rates were 90.4% at three and four months.ConclusionA hybrid approach combining ultrasound-guided percutaneous transluminal angioplasty and minimal aneurysmotomy might be a safe and effective method for thrombosed aneurysmal AVF salvage.

A Qualitative Study on the Benefits of Tumescence in Cadaveric Dissection with Faculty &amp; First‐year Medical Students at SHSU‐COM

Hands‐on cadaver dissection is considered essential to the optimal education of future physicians, and the quality of students’ dissections has been directly related to their performance on national board exams. Some centers, however, have reduced or even eliminated cadaver dissections due to time constraints and safety concerns. To address such concerns while optimizing the benefits of hands‐on learning, we introduced tumescence into our first‐year anatomy lab. This involved the manual infusion of cadaver wetting solution into subcutaneous and interstitial tissue planes using a syringe and a blunt‐tipped canula. This technique was utilized by our students and faculty during the Clinical Anatomy course. A qualitative survey of students and faculty regarding the benefit, if any, of the tumescence was subsequently carried out and a thematic analysis of the responses was performed. The most frequent theme which surfaced in the survey was an increased ease and efficiency of dissection with the use of tumescence. In addition, the themes of separation, spaces, and planes, were common, reflecting in the respondents, an increased appreciation of tissue planes and relationships. The survey lent support to the conclusion that cadaver tumescence can improve the quality and speed of dissections safely, while increasing the appreciation of natural tissue planes.

Electronic Infusion Flow Regulator with Occlusion Detection

Infusion is one medical equipment that provides several fluids into the body through a needle into a vein to replace fluids or food substances lost from the body. The use of manual infusion to determine the number of drops given to the patient and the calculation manually. The purpose of this research is to design an automatic infusion flow control device equipped with occlusion detection. This module consists of an Arduino Mega 2560, DC motor (stepper NEMA 17), optocoupler module, 4x4 keypad, and TFT. Infusion drops are detected by the optocoupler sensor. The microcontroller will process the detection results and send a DC motor command to move according to the settings entered. The unit of flow rate used in the module is ml/min. After measuring using an IDA calibration device with the Fluke brand type IDA 4 plus on the occlusion parameter, the average time is 41 seconds and the results of the flow rate have the largest deviation of 0.15 ml/min at the time setting of 6 hours and the volume of 500. While the smallest deviation is 0.12 ml /min on setting time 4 hours and volume 500 ml. From the results of measurements that have been carried out, this module is expected to help nurses regulate the infusion. The results in the future this module can be developed again with the appearance of the flow rate results can be directly displayed without having to wait for the drops to stabilize.

Comparison of the effects of inhalational and total intravenous anesthesia on quality of recovery in patients undergoing endoscopic transsphenoidal pituitary surgery: a randomized controlled trial

Background: Endoscopic transsphenoidal pituitary surgery has shown promising results. However, fast and high-quality recovery after this procedure remains a challenge for neuroanesthesiologists. This study aimed to compare the quality of recovery after transsphenoidal pituitary surgery between patients who received inhalational anesthesia with sevoflurane and patients who received propofol-based total intravenous anesthesia (TIVA).Methods: Eighty-two patients undergoing transsphenoidal pituitary surgery were randomized to receive either sevoflurane inhalation with manual infusion of remifentanil (sevoflurane group) or effect-site target-controlled infusion of propofol and remifentanil (TIVA group). The primary outcome was the 40-item Quality of Recovery (QoR-40) score on postoperative day 1. The QoR-40 questionnaire was completed by patients the day before surgery and on postoperative days 1 and 2. Emergence agitation and recovery characteristics were also assessed.Results: There were no significant differences between the groups in the global QoR-40 scores on both postoperative days 1 and 2 (difference -8.7, 95% CI -18.0 to 0.7, and P = 0.204; -3.6, 95% CI -13.0 to 5.8, and P > 0.999, respectively). The time to verbal response and time to extubation were significantly shorter in the sevoflurane group than in the TIVA group (P < 0.001 and P < 0.001, respectively). However, the incidence of emergence agitation was lower in the TIVA group than in the sevoflurane group (P < 0.001).Conclusions: Both inhalational anesthesia with sevoflurane and propofol-based TIVA were appropriate anesthetic techniques for patients undergoing endoscopic transsphenoidal pituitary surgery in terms of the quality of recovery up to 2 days postoperatively. Rapid emergence was observed in the sevoflurane group, while smooth emergence was observed in the TIVA group.

Comparison of Postoperative Recovery after Manual and Target-Controlled Infusion of Remifentanil in Bariatric Surgery.

Background and Objectives: Early postoperative recovery after surgery is a key point for patients’ safety and comfort. Moreover, operating room turnover depends on recovery time. Our aim was to assess which method of remifentanil administration, manual (MI) or target-controlled infusion (TCI), could reduce patient time in recovery room. In this study, patients’ recovery times were registered and compared among the groups. Materials and Methods: We enrolled 31 morbidly obese patients in this prospective study. All of them had undergone bariatric surgery at the Hospital of Lithuanian University of Health Sciences Kauno Klinikos in 2020. Sevoflurane/remifentanil anaesthesia was performed for all patients. The patients were randomly assigned to the manual infusion (MI) (control group) or target-controlled infusion (TCI) group for the method of the administration of remifentanil. While the patients were waking up after the surgery, we recorded spontaneous breathing and airway reflexes recovery time, time of extubation, eye opening, recovery of orientation and beginning of the following oral command. For the TCI group, we also documented remifentanil concentrations in the blood (automatic infusion pump). Results: Patients did not differ in demographic values and duration of remifentanil infusion. We found that remifentanil consumption in the TCI group was lower, p = 0.02. Despite lower remifentanil consumption in the TCI group patients, they demonstrated longer total recovery time than the control group patiens: 14 (12–20) vs. 10 (6–16), p = 0.001. Conclusions: The study showed that, upon comparing the TCI method with MI, manual infusion produced better results in postoperative patient recovery. Additionally, higher doses of remifentanil were consumed using MI. In conclusion, the dosage recommended by highly qualified anaesthesiologists is favourable for morbidly obesity patients when compared to the TCI method.

The comparison of different drip cholangiography: a randomised trial.

This study investigated the advantages and disadvantages of contrast media administration by gravity drip and manual push injection during cholangiography. A total of 100 patients who presented to the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, for a cholangiography between June 2019 to June 2020 were enrolled in this study. Patients were randomly divided into 2 treatment groups. One group of patients with manual injection of contrast (the N group, n=50), received the contrast agent via the traditional manual injection method whereby the doctor injects 50 mL of prepared contrast agent into the right side of the patient while continuously observing the effects on the bile duct. The other group of patients with gravity drip administration of contrast media (the O group, n=50), received the contrast agent via gravity drip at a rate of 80 drops per minute, and both clinicians and radiologists monitored the entire cholangiography process from a safe distance. Patients were followed up and angiographic satisfaction was assessed after two weeks. All 100 patients completed cholangiography without allergic reaction to the contrast medium. In the traditional injection group (N group), nine patients experienced upper abdominal discomfort with nausea, abdominal pain, chills, high fever, and other symptoms, and residual gallstones were observed in 12 patients. In patients in the gravity drip group (O group), four patients felt upper abdominal discomfort accompanied by nausea, abdominal pain, chills, high fever, and other symptoms, with residual gallstones detected in six patients. Patients who underwent gravity drip cholangiography had significantly reduced adverse reactions compared to patients who underwent traditional manual infusion cholangiography. Furthermore, gravity drip cholangiography resulted in clearer images and reduced X-ray exposure for medical staff. Thus, increased implementation of gravity drip cholangiography in the clinical setting should be considered. Chinese Clinical Trial Registry ChiCTR1800018202.

Design of Automation for Infusion Monitoring Using a Weight Sensor (Load Cell) Based on AT-MEGA 328 Microcontroller

The development of medical equipment with advanced technology can provide convenience in providing services to the community. One of the equipment that is in the hospital and most often used is an IV. In its use, manual infusion is used to determine the volume of the infusion and must be monitored every hour or even minute by the nurse. This is considered quite difficult, especially in the era of the Covid-19 pandemic where minimal interaction is required from 2 individuals. This is done by utilizing sensor technology to monitor the patient's condition so that the frequency of the nurses checking the condition of the infusion is getting less. Therefore, in this research, manufactured of an infusion monitoring system using aweight sensor (Load Cell) based on the ATMEGA 328 microcontroller was carried out. The sensor of this monitoring system uses a Load Cell Weight Sensor with the HX711 module which is integrated into the ARDUINO UNO MCU. The output of the system is displayed on a 16 x 2 mm LCD as well as a Macro Excel which will display the percentage value of intravenous fluids in the PC and real-time automatic data logging into the macro excel. The infusion used uses Nacl fluid infusion. The test results of the system as a whole show that the data for measuring levels (%) of intravenous fluids can be sent and displayed on the LCD and PC. The incoming data is converted into a table at certain time intervals according to the user's choice into the operator. The experiment was carried out 10 times by looking at changes in the contents of the infusion fluid over time in 11 stages where the LED lights up when the weight of the infusion reaches 40 - 46 grams. Then, the buzzer and LED have turned on when the weight of the infusion is less than 5 grams. From the experiment, it can be concluded the 10% setpoint alarm works well, i.e. when the infusion load is less than the 1% set point, the buzzer and LED will light up until the intravenous fluid is replaced with a new one.

Design of Gas Detection System Based on STM32 Infusion Set

Aiming at the low efficiency and low quality detection level of the manual infusion set, a gas detection system for infusion set based on STM32 single-chip microcomputer was designed. The detection system includes hardware system design and software system design. The hardware system is based on the STM32F103 single-chip microcomputer. It mainly designs the gas pressure sensor acquisition circuit and the multi-way solenoid valve control circuit. The software system uses a C ++ real-time operating system to ensure system monitoring's real-time performance and validity. Test data is transmitted to the upper computer and displayed via USB serial communication. The experiment proves that the infusion set gas detection system can perform gas detection on the infusion set. The system has the characteristics of stability and high accuracy. The relative error of the experimental measurement is within ±5%, and the detection efficiency is better than manual detection.

Comparison of the target-controlled infusion and the manual infusion of propofol anesthesia during electroconvulsive therapy: an open-label randomized controlled trial

BackgroundTarget-controlled infusion (TCI) of propofol is a well-established method of procedural sedation and has been used in Japan for anesthesia during electroconvulsive therapy (ECT). However, the usefulness of the TCI of propofol for ECT has yet to be determined. This study aimed to compare the TCI and manual infusion (MI) of propofol anesthesia during ECT.MethodsA total of forty psychiatric inpatients receiving bitemporal ECT were enrolled in the present study and randomized into the TCI group (N = 20) and the MI group (N = 20). Clinical Global Impression (CGI) and Montreal Cognitive Assessment (MoCA) scores were measured before and after ECT. The clinical outcomes, anesthesia-related variables, and ECT-related variables were compared between the two groups. Generalized estimating equations (GEEs) were used to model the comparison throughout the course of ECT.ResultsA total of 36 subjects completed the present study, with 18 subjects in each group. Both the groups didn’t significantly differ in the post-ECT changes in CGI and MoCA scores. However, concerning MoCA scores after 6 treatments of ECT, the MI group had improvement while the TCI group had deterioration. Compared with the MI group, the TCI group had higher doses of propofol, and longer procedural and recovery time. The TCI group seemed to have more robust seizures in the early course of ECT but less robust seizures in the later course of ECT compared with the MI group.ConclusionsThe present study does not support the use of TCI of propofol for anesthesia of ECT.Trial registration(ClinicalTrials.gov): NCT03863925. Registered March 5, 2019 - Retrospectively registered.

Low-dose intracoronary alteplase during primary percutaneous coronary intervention in patients with acute myocardial infarction: the T-TIME three-arm RCT

Background Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction and is independently associated with adverse outcomes. Objective To determine whether or not a strategy involving low-dose intracoronary fibrinolytic therapy infused early after coronary reperfusion will reduce microvascular obstruction. Design This was a multicentre, randomised, double-blind, parallel-group, placebo-controlled, dose-ranging trial. Setting The trial took place at 11 hospitals in the UK between 17 March 2016 and 21 December 2017. Participants Patients with acute ST-segment elevation myocardial infarction and a symptom onset to reperfusion time of ≤ 6 hours were eligible for randomisation. Radial artery access was a requirement, and further angiographic criteria included a proximal-to-middle coronary artery occlusion or impaired coronary flow in the presence of a definite thrombus in the culprit coronary artery. Exclusion criteria included a functional coronary collateral supply to the infarct-related artery, any contraindication to fibrinolysis and lack of informed consent. Additional exclusion criteria for safety were (1) requirement for immunosuppressive drug therapy for ≤ 3 months and (2) treatment with an antimicrobial agent. Intervention A total of 440 participants were randomly assigned 1 : 1 : 1 to treatment with placebo (n = 151), 10 mg of alteplase (n = 144) or 20 mg of alteplase (n = 145) administered by manual infusion directly into the infarct-related coronary artery over 5–10 minutes. The intervention was scheduled to happen after reperfusion and before stent implantation. Outcomes The primary outcome was the amount of microvascular obstruction (percentage of left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging at 2–7 days after enrolment. The primary analysis was the comparison between the 20 mg of alteplase group and the placebo group; if this comparison was not significant, the comparison of the 10 mg of alteplase group with the placebo group was considered as a secondary analysis. Sample size A total of 618 patients (minimum of 558 patients). Recruitment was halted on 21 December 2017 given that conditional power for the primary outcome based on a prespecified analysis of the first 267 randomised participants was &lt; 30% in both treatment groups (futility criterion). Methods The primary outcome was compared between groups using a stratified Wilcoxon rank-sum test (van Elteren test), stratified by the location of the myocardial infarction. Results Among the 440 patients (mean age of 60.5 years; 15% women), the primary end point was measured in 396 (90%) patients, 17 (3.9%) withdrew, seven died and all other patients were followed up to 3 months. The amount (mean percentage of left ventricular mass) of microvascular obstruction was 2.3% versus 2.6% versus 3.5% in the placebo, 10 mg of alteplase and 20 mg of alteplase groups, respectively. In the primary analysis, microvascular obstruction did not differ between the 20 mg of alteplase group and the placebo group: 3.5% versus 2.3%, estimated difference 1.16% (95% confidence interval –0.08% to 2.41%; p = 0.32). In the secondary analysis, microvascular obstruction did not differ between the 10 mg of alteplase group and the placebo group: 2.6% versus 2.3%, estimated difference 0.29% (95% confidence interval –0.76% to 1.35%; p = 0.74). By 3 months, major adverse cardiac events (cardiac death, non-fatal myocardial infarction and unplanned hospitalisation for heart failure) had occurred in 15 (10.1%) patients in the placebo group, 18 (12.9%) in the 10 mg of alteplase group and 12 (8.2%) in the 20 mg of alteplase group. Conclusions Adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction compared with placebo. Limitations Premature discontinuation of enrolment limited the power of the secondary and safety analyses. Future work Low-dose intracoronary alteplase or tenecteplase could be compared with placebo at the end of primary percutaneous coronary intervention in patients with an ischaemic time of &lt; 4 hours. Trial registration This trial is registered as ClinicalTrials.gov NCT02257294. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 5. See the NIHR Journals Library website for further project information.

Effect of warming and infusion of red blood cell concentrates on markers of haemolysis: An ex vivo simulation study

BackgroundTransfusion of red blood cell (RBC) concentrates is a common procedure to restore blood volume and tissue oxygen delivery in patients with trauma. Although RBC warmers may prevent hypothermia, some warming or infusion equipment may lead to haemolysis and patient injury. ObjectivesThe aim of this study was to test the effect of (i) RBC warming and (ii) administration via manual vs. pump infusion on haemolysis. MethodsThis experimental ex vivo study studied haemolysis markers of RBC injury. The sample consisted of 90 RBC infusions in two simulations, randomly, 45 warmed RBC infusions and 45 nonwarmed RBC infusions, in two or three stages: before the intervention (baseline—warming, N= 45; nonwarming, N= 45), after water bath warming at 42 °C (warmed, N= 45), and then after the warmed or nonwarmed RBCs were infused by manual or pump infusion at a rate of 100 mL/h (infusion—warming, N= 45; nonwarming, N= 45). ResultsWarmed RBCs showed significantly lower total haemoglobin (Hb) and haematocrit levels and increase in free Hb levels, haemolysis levels, and lactate dehydrogenase (LDH) activity (all p<0.05) than baseline RBCs. Pump infusion RBCs were associated with reduced total Hb and increased free Hb, haemolysis, and potassium (K) levels (all p<0.05) compared with warmed RBCs. In contrast, manual infusion of warmed RBCs resulted in significantly reduced total Hb levels and increased LDH activity (both <0.05). After infusion, total Hb, free Hb, haematocrit, haemolysis, and LDH values were significantly different for warmed vs. nonwarmed RBCs (p<0.05). ConclusionsHaemolysis biomarkers increase with RBC warming and infusion, especially when using infusion pumps. Critically ill patients should be carefully monitored for possible complications during and after RBC infusion.

Safety and Tolerability of Manual Push Administration of Subcutaneous IgPro20 at High Infusion Rates in Patients with Primary Immunodeficiency: Findings from the Manual Push Administration Cohort of the HILO Study

PurposeTo evaluate the safety and tolerability of IgPro20 manual push (also known as rapid push) infusions at flow rates of 0.5–2.0 mL/min.MethodsPatients with primary immunodeficiency (PID) with previous experience administering IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) were enrolled in the Hizentra® Label Optimization (HILO) study (NCT03033745) and assigned to Pump-assisted Volume Cohort, Pump-assisted Flow Rate Cohort, or Manual Push Flow Rate Cohort; this report describes the latter. Patients administered IgPro20 via manual push at 0.5, 1.0, and 2.0 mL/min/site for 4 weeks each. Responder rates (percentage of patients who completed a predefined minimum number of infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated.ResultsSixteen patients were treated; 2 patients (12.5%) discontinued at the 1.0-mL/min level (unrelated to treatment). Responder rates were 100%, 100%, and 87.5% at 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Mean weekly infusion duration decreased from 103–108 to 23–28 min at the 0.5- and 2.0-mL/min flow rates, respectively. Rates of treatment-related treatment-emergent adverse events (TEAEs) per infusion were 0.023, 0.082, and 0.025 for the 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Most TEAEs were mild local reactions and tolerability (infusions without severe local reactions/total infusions) was 100% across flow rate levels. Serum IgG levels (mean [SD]) were similar at study start (9.36 [2.53] g/L) and end (9.58 [2.12] g/L).ConclusionsSubcutaneous IgPro20 manual push infusions at flow rates up to 2.0 mL/min were well tolerated and reduced infusion time in treatment-experienced patients with PID.Trial RegistrationNCT03033745