Rapid Fluid Infusion Research Articles

Pressure Infusor Assisted Arthrocentesis

Temporomandibular joint internal disorders commonly present with limited mouth opening and pain. Treatment options range from invasive surgical procedures to minimally invasive interventions. This technical note aims to introduce a modification to the arthrocentesis technique in which a pressure infusion cuff (VBM Classic Infusor, Medizintechnik GmbH, Germany) is used for irrigation instead of syringes or peristaltic pumps. A pressure infusion cuff (bag) is an inflatable bag with a hand pump and a sphygmomanometer that allows monitorization of the pressure, and it is intended to apply pressure on I.V. fluid bags to assist with rapid infusion of fluids. This allows the operator to maintain an efficient and stable flow pressure throughout the procedure while avoiding occupational hand and wrist problems resulting from manual irrigation with syringes. Furthermore, pressure monitoring, as read on the sphygmomanometer of the cuff, facilitates the manipulation of the needles and adjustment of the pressure should the patient experiences discomfort. This increases the patient’s compliance, physician’s comfort and allows the collection of quantitative data in clinical studies.

Iatrogenic Hyperhydration in Sickle Cell Disease Patients Admitted for Acute Pain Crisis Management: A Retrospective Analysis from a Single Institution

Background: Parenteral fluids are an important component of acute pain crisis management in sickle cell disease patients. However, lack of uniform guidelines for fluid replacement coupled with underlying host comorbidities result in risk to patients from complications associated with hyperhydration. Contributing factors include inappropriate choice of fluid, rapid fluid infusion rates with prolonged time periods and inadequate monitoring of signs of hyperhydration. Complications of fluid replacement include excessive weight gain, extremity swelling, pulmonary edema and heart failure. In our study we examined the prevalence of hyperhydration in sickle cell anemia patients admitted for acute pain crisis management at our hospital. Methods: We conducted a retrospective chart review on EPIC of sickle cell anemia patients treated for acute pain crisis in the inpatient unit of John Dempsey Hospital, University of Connecticut between January 2022-December 2022, following IRB approval. To capture patients with signs and symptoms of hyperhydration and its clinical consequences, we looked at surrogate markers such as excessive weight gain during admission, signs of fluid retention, charting of patient fluid intake and output, increased oxygen use, diuretic (Lasix) administration, bronchodilator use, abnormal chest x ray findings indicative of fluid overload pattern, activation of rapid response team for patients developing acute symptoms of fluid overload, and urgent patient transfer to a higher level of care including intensive care unit. Results: 256 admitted patient charts were analyzed representing a total of 95 unique sickle cell disease patients. The median length of hospital stay (LOS) was 3 days. 168 patients had LOS from 3 to 10 days. We observed that 10.7% of the patients experienced an increase in oxygen requirements during their hospital stay. Daily weight was collected in only 27 patients (10.5%) for 3 or more days limiting its usefulness to detect subclinical hyperhydration( figure 1). 69 patients (27%) received parenteral Lasix injection for acute symptoms whose chest x rays also showed pulmonary edema or pleural effusions. 13 patients (18%) were transferred to a higher level of care that included 9 patients to step-down unit and 4 to intensive care for endotracheal intubations and ventilatory support. The median hospital stay was 4 days in patients requiring Lasix compared to 3 days in those who did not. Conclusion : Hyperhydration is undesirable complication associated with fluid administration of sickle cell anemia patients admitted with acute vaso-occlusive pain crisis. It occurs in a significant proportion of affected patients that can result in life threatening complications and prolonged hospitalization. Hyperhydration were missed in this retrospective analysis since daily weight measurements were not available in the majority of patients. Strict charting of fluid intake and output, choice of half normal saline for hydration, as well as clinical monitoring of signs and symptoms of subclinical hyperhydration will help reduce this complication and improve patient outcomes. Improving awareness of this complication among health care providers is important towards achieving this goals. Findings from this study are used to design a prospective quality improvement project in our hospital to improve outcomes and reduce hospitalization in sickle cell anemia patients admitted for acute vaso-occlusive pain crisis.

Rehydration Rates and Outcomes in Overweight Children With Diabetic Ketoacidosis.

The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients. We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the amount of fluid received in these groups. Obese children and youth were more likely to receive fluids at rates slower than dictated by protocol. Overweight and obese children and youth in the fast fluid arms, who received fluids per the study protocol based on their measured weight, had similar rates of mental status changes or clinically apparent cerebral injury as those with normal weights. Risk of hypophosphatemia was increased in those receiving larger initial bolus volumes and reduced in those receiving higher rehydration rates. No other metabolic outcomes were associated with rehydration. Protocol adherence data in the FLUID Trial suggest that physicians are uncomfortable using weight-based fluid calculations for overweight or obese children. However, higher rates of fluid infusion were not associated with increased risk of mental status changes or cerebral injury, suggesting that physicians should not limit fluid resuscitation in obese children and youth with DKA.

Effects of rapid fluid infusion on hemoglobin concentration: a systematic review and meta-analysis

BackgroundRapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration.MethodsOur protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic.ResultsSixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as “low” for randomized controlled trials (RCTs) and ‘low to moderate’ for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI − 1.45 to − 1.12; p < 0.001; I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI − 1.69 to − 1.42; p < 0.001; I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI − 1.03 to − 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb.ConclusionsHb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation.

184EMF Implementation of a Novel Fluid Resuscitation Device for the Care of Sepsis Patients: Processes and Perceptions in the Out-of-Hospital Setting

Early fluid infusion is a key performance metric in the care of sepsis patients, yet this benchmark is often unmet. Emergency Medical Services (EMS) transports one-third of sepsis patients, presenting an opportunity for increased achievement of fluid goals. To enhance sepsis care, one large urban EMS system (∼120,000 EMS responses/year) introduced a novel rapid fluid infusion device, LifeFlow® Plus, to its sepsis protocol (∼700 patients/year). The study objective is to assess the implementation of this device in EMS fluid administration for out-of-hospital sepsis care.

A pressure-resistant peripherally inserted central catheter is as useful as a central venous catheter for rapid fluid infusion: an in vitro study

BackgroundAlthough peripherally inserted central catheters (PICCs) have been widely used, they have not been frequently used in anesthesia practice. The central venous pressure measured via PICCs are reportedly as accurate as that measured via central venous catheters (CVCs), but the findings concerning rapid infusion are unclear. This study examined whether or not pressure-resistant PICCs could be used for rapid fluid infusion. MethodsThe in-line pressure was measured in similar-sized double-lumen catheters—4-Fr PICC (55, 45 and 35 cm) and 17-G CVC (20 and 13 cm)—at flow rates of saline decided using a roller pump system. We also examined the flow rate at an in-line pressure of 300 mmHg, which is the critical pressure at which hemolysis is considered to occur during blood transfusion.ResultsThe pressure-resistant PICCs obtained a high flow rate similar to that of CVCs, but the in-line pressures increased in proportion to the flow rate and catheter length. Flow rates at an intra-circuit pressure of 300 mmHg were not significantly different between the 45-cm PICC and 20-cm CVC.ConclusionPressure-resistant PICCs can be used for rapid fluid infusion.

Short-Term Volume Loading Effects on Estimated Intracranial Pressure in Human Volunteers.

BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.

Systematic review and meta-analysis: safety of ultrasound-guided peripheral venipuncture and catheterization.

Vascular punctures are widely used in clinical applications; however, clinical trials have identified complications and poor prognosis for patients undergoing common peripheral vein puncture as compared to ultrasound-guided peripheral venipuncture and catheterization. Ultrasound-guided peripheral venipuncture and catheterization is accurate, simple, has fewer associated complications, and will gradually take the place of common peripheral vein puncture. To study the safety of ultrasound-guided peripheral venous catheterization, a meta-analysis was conducted of relevant articles dating from establishment date of the database (such as PubMed, MEDLINE and EMBASE) to March 2021, with the search keywords being peripheral venipuncture, ultrasound guidance, vascular injury rate, and hematoma formation rate. A total of 8 trials were used to determine accuracy indicators, which included puncture failure rate, arterial injury rate, hematoma formation rate, pneumothorax incidence rate, and hemothorax incidence rate. There were statistically significant differences between the two methods for peripheral venipuncture and catheterization in terms of puncture failure rate [odds ratio (OR) =0.08; 95% CI: 0.04-0.16; P<0.00001], incidence of vascular injury (OR =0.15; 95% CI: 0.07-0.32; P<0.00001), probability of hematoma formation during the puncture process (OR =0.24; 95% CI: 0.08-0.69; P=0.008), and probability of pneumothorax during puncture (OR =0.10; 95% CI: 0.02-0.55; P=0.008). Eight articles were included for meta-analysis. Ultrasound-guided peripheral venipuncture and catheterization is a commonly used puncture method for patients needing rapid fluid infusion with pressure or a pressure pump, repeated transfusion of blood product, or multiple daily venous blood drawing test. The results were very clear, and the puncture failure rate and other complications of ultrasound-guided peripheral venipuncture catheterization were low.

Dosing Heat: Expected Core Temperature Change with Warmed or Cooled Intravenous Fluids.

Emergent modification of a patient's body temperature is crucial in certain disease or injury states. Advanced targeted temperature management techniques such as central venous catheter devices are not universally available, however, virtually all medical centers have access to intravenous fluids. This study approximates the change in body temperature for a given volume of room temperature, chilled, or heated isotonic crystalloid bolus. Using thermodynamic principles, a mathematical model was created to approximate change in body core temperature in response to a given volume and temperature of intravenous fluid. The model assumes rapid fluid infusion and the previously published specific heat capacity of the human body of 3.47 J/kg · °C. Values were calculated under conditions of varying body temperatures from profound hypothermia to hyperthermia (18°C-45°C). Various crystalloid temperatures representing iced, room temperature, and warmed (4°C, 20°C, 42°C) were used in the calculations. Each 30 mL/kg dose of 20°C crystalloid is expected to cool a hyperthermic (38°C-45°C) patient by 0.6°C-0.9°C. Each 30 mL/kg dose of 4°C crystalloid is expected to cool a hyperthermic (38°C-45°C) patient by 1.2°C-1.4°C. Each dose of 42°C crystalloid is expected to warm a hypothermic patient by 0.2°C-0.8°C. Using the results in this study, clinicians may roughly estimate the effect of temperature management with varying doses of intravenous fluids and thus assess the benefits of this technique. Risk should be evaluated based on inevitable coadministered volume and electrolytes. Individuals with volume-sensitive conditions such as heart, liver, or kidney failure deserve particular attention. Based on a mathematical model, typical expected core temperature change is about 0.2°C-1.4°C per 30 mL/kg crystalloid bolus, depending on patient and fluid temperature.

Tension pneumoperitoneum caused by intestinal perforation from underlying colon cancer: a case report

BackgroundTension pneumoperitoneum, a form of abdominal compartment syndrome, is an important clinical condition. Increased pressure in the intraperitoneal cavity leads to respiratory and circulatory instability. Most of the reported cases include complications due to active air infusion into the peritoneal cavity or trauma; however, few reports are available on tension pneumoperitoneum caused by perforation from colon cancer. We present a case of a patient with tension pneumoperitoneum caused by gastrointestinal perforation owing to colon cancer.Case presentationA 63-year-old Japanese man with altered mental state was brought to our emergency department. He was in shock, and an abdominal radiograph suggested gastrointestinal perforation. Despite rapid fluid infusion and inotropic support, his condition deteriorated. His abdomen was tensely distended; abdominal computed tomography showed significant intra-abdominal gas. Following immediate needle decompression, his circulatory status improved. Emergent laparotomy revealed an approximately 10-cm tumor (adenocarcinoma) in the colon, which caused the perforation.ConclusionsA perforated wall or the surrounding omental fat that acts as a one-way valve could lead to tension pneumoperitoneum without active air infusion. Although tension pneumoperitoneum is a life-threatening condition, it is reversible if prompt diagnosis and immediate decompression are performed. Physicians should always consider this condition as one of the causes of shock or cardiopulmonary arrest, even without an apparent medical history of active air infusion or trauma.

Massive obstetric hemorrhage during cesarean section in a patient after conception by frozen-thawed embryo transfer: a case report

BackgroundPlacenta accreta is a major cause of massive obstetric hemorrhage during cesarean section. In recent years, pregnancy by in vitro fertilization-embryo transfer has been reported as a risk factor for placenta accreta.Case presentationA 36-year-old G1P0 woman with systemic lupus erythematosus became pregnant by frozen-thawed embryo transfer. Emergency cesarean section was performed under general anesthesia due to the diagnosis of non-reassuring fetal status. The placenta invaded the myometrium and completely covered the entire anterior uterine wall. Following birth, 3000 mL of blood loss required rapid fluid infusion and blood transfusion. Total hysterectomy was performed because the placenta could not be separated from the uterine wall. Histological examination revealed placenta accreta/increta.ConclusionsWhen performing cesarean section on patients who have undergone frozen-thawed embryo transfer, preoperative examinations to assess for placenta accreta should be performed, and the anesthetic management should include sufficient planning for massive obstetric hemorrhage.

The Use of a Rapid Fluid Infusion System in Children

Fluid resuscitation is the cornerstone of treatment for pediatric shock caused by conditions such as sepsis, dehydration, trauma, and anaphylaxis. Children presenting to the Emergency Department (ED) in shock have a high risk of mortality, and each hour of delay in shock reversal doubles the odds of death1,2. Pediatric Advanced Life Support (PALS) guidelines emphasize the importance of providing rapid fluid resuscitation to prevent the progression to hypotensive or refractory shock3. PALS and other septic shock guidelines recommend that patients receive a 20 mL/kg bolus of crystalloid immediately upon recognition of hypovolemic or distributive shock, with 20 mL/kg to be delivered within 5 minutes and up to 60 mL/kg within the first 15-60 minutes3-6. Studies based on these guidelines show that earlier fluid delivery directed at reversal of shock reversal leads to decreased morbidity7-9, mortality2,7,9-12, and hospital length of stay (LOS)9,11-13. Unfortunately, timely fluid delivery is often not achieved due to the technical challenges of obtaining adequate vascular access and delivering fluid boluses quickly in patients with shock or hypotension11,14-16. Current methods of fluid bolus delivery in the pediatric emergency care setting include infusion pumps, gravity drip, pressure bags, rapid infusers, and the push-pull syringe technique17,18. Each of these methods are limited by speed, ease of use, or safety concerns. Infusion pumps provide a maximum rate of 999 mL per hour, which for a 25kg child would provide a 60 mL/kg bolus in 90 minutes. In most patients, infusion pumps are therefore too slow to provide adequate fluid resuscitation. Gravity drip rates are unpredictable and inadequate for the treatment of shock and hypotension. For example, up to 50 minutes are required for one liter of fluid to flow through a 22G intravenous (IV) line, and up to 200 minutes via the intraosseous (IO) route19-22. A pressure cuff may speed flow modestly, but requires constant re-inflation, makes volume of infusion difficult to track, and carries the risk of inadvertent air embolism3,20,22-25. Rapid infusers can deliver fluids very quickly but are expensive, require frequent training, are not readily available in many emergency care settings, and importantly do not provide adequate flow with the small gauge IV or intraosseous (IO) access typical of pediatric resuscitation19,26. Due to the limitations of these common fluid delivery methods, pediatric emergency providers commonly use a syringe and 3-way stopcock to repeatedly draw fluid from the container of crystalloid and then deliver to the patient. This technique is referred to as the “push-pull” method and is recommended in the PALS guidelines3. An alternate technique involves disconnecting and reconnecting multiple pre-filled 60mL syringes, which often requires two providers18. Both methods may be associated with increased risk of nosocomial infection due to the difficulty of maintaining syringe sterility27-31. The LifeFlow® infuser (410 Medical, Inc; Durham, NC) is a new manually operated device for rapid fluid bolus delivery that overcomes some of these common barriers. The device is currently FDA-cleared for infusion of crystalloid and colloid fluids, and is in use at our center for emergency resuscitation. Using common IV gauges LifeFlow can deliver fluid 2 to 4 times faster than standard techniques, and allows providers to observe a clinical response immediately by improvements in vital signs, mental status and skin perfusion29,32-34. This study describes the use of the LifeFlow device in a busy academic children’s hospital ED with 74,000 patient visits per year.

Targeted temperature management: State of the Art

One of the indicated elements of post-resuscitation care is therapeutic hypothermia or temperature treatment management. the survivability of out-of-hospital cardiac arrest (OHCA) till admission to hospital is only 23%. Efficient thermoregulatory mechanisms are the basis for maintaining optimal body temperature. Therapeutic hypothermia shows normalizing effect on metabolic processes disturbed in ischaemic conditions, including improving metabolism and maintaining glucose balance in the brain, lowering the concentration of lactates, limiting the secretion of free radicals in damaged neurons, lowering the production of pro-inflammatory cytokines, stabilizes the blood-brain barrier and reduces endothelial dysfunction preventing ischaemic damage to tissues and organs. Hypothermia has a wide multidirectional effect on the human body, which can be useful in patients. Most available scientific studies show the efficacy and benefits of hypothermia in patients with out-of-hospital sudden cardiac arrest, including especially with ventricular fibrillation. The delay in the initiation of therapeutic hypothermia and reaching target temperature significantly increased the odds of a poor neurological outcome. Current American Heart Association (AHA) and European Resuscitation Council (ERC) resuscitation guidelines recommend that targeted temperature management should be implemented in all adult coma patients with return of spontaneous circulation (ROCS) after sudden cardiac arrest. The target temperature should be between 32°C and 36°C and then maintained for at least 24 hours. In patients with coma after TTM, fever should be actively prevented. For patients with out-of-hospital cardiac arrest, it is not recommended to routinely cool patients in prehospital conditions with a rapid intravenous infusion of cold fluids after ROSC.

Abstract 448: Predicting Blood Pressure Response to Fluid Bolus Therapy Using Neural Networks with Clinical Interpretability

Background: Fluid bolus therapy (FBT), the rapid infusion of fluid, has been recommended as the primary-line treatment for acute hypotensive episode (AHE) that occurs in about 41% of patients in ICU. However, previous studies have reported that approximately one-third of the acute hypotensive patients do not successfully respond to FBT treatment. Avoiding the administration of FBT that will not successfully resolve AHE might prevent an inappropriate increase of the total fluid volume administered to ICU patients, potentially reducing their risk for severe organ dysfunction and increased mortality. Methods: Our study utilized regression models and attention-based recurrent neural network (RNN) algorithms and two large-scale information system databases, the multi-clinical MIMIC-ICU one and the multi-center Philips eICU CRD one, to predict the successful response to FBT among hypotensive patients in ICUs. We investigated both time-aggregated modeling and time-series modeling using RNN with the attention mechanism (AM) for clinical interpretability. The successful FBT is defined by intensive care experts as the presence of the maximum mean atrial pressure (MAP) &gt; 1.15 * average (MAP) at least once, where maximum(MAP) is the maximal MAP from the FBT starting time to two hours after FBT, and average (MAP) is the average MAP from 30 minutes before FBT until 10 minutes after FBT. Results: The stacked RNN with AM yielded the highest accuracy of 0.852 and area under the curve (AUC) value of 0.925 when trained and tested on the MIMIC-ICU dataset. The top features learned from regression include the patient's respiratory rate, diastolic pressure, temperature, and bicarbonate and base excess levels in blood. Preliminary results from training and testing the RNN on the Philips eICU-CRD database yielded an accuracy of 0.812 and AUC value of 0.769. We were also able to identify timesteps close to the time of FBT administration as clinically meaningful using the RNN models with AM. Conclusion: This is the first study that utilizes machine learning for identifying hypotensive patients in ICUs who will have sufficient blood pressure recovery after FBT. Utilizing AM and identifying the top features learned also provided clinical interpretability to the models we used.

Children and Adults with Steroid-Refractory Acute Graft-Versus-Host Disease Respond to Treatment with the Mesenchymal Stroma Cell Preparation “MSC-FFM”: Treatment Results for 92 Consecutive Patients

Introduction: Since the seminal paper of LeBlanc in 2008, despite several negative studies, the scientific community has retained optimism with respect to the usefulness of mesenchymal stroma cells (MSCs) in refractory acute graft-versus-host disease (GvHD). A prevailing theme of past studies was that, while pediatric GvHD responded to MSCs, adult GvHD did not. As reported, we developed proprietary protocols GMP-quality MSC production from bone marrow (BM) mononuclear cells expanded in platelet lysate-enriched media.Patients and Methods: We present treatment data with MSC-FFM for 61 children/adolescents and 31 adults with either “only” steroid-refractory (SR) GvHD (27%) or GvHD which had additionally proven refractory to up to five additional lines of therapy (MR-GvHD) (73%). Pediatric patients tended to have more MR-GvHD than adults. Patients from 23 centers in 6 countries were included. Most patients had severe GvHD (37% °III, 59% °IV, Glucksberg scale). 31 patients (34%) were female,61 male (66%). 69 have a malignant disease (75%), and 23 a non-malignant (25%) disease as indication for transplantation. Donors were MSD (n=21, 23%), MUD (n=56, 61%), haploidentical (n=14, 15%), and 1 MMUD (1%).Patients received myeloablative conditioning with TBI-, Treosulfan-, Busulfan- and Fludarabine-based regimen, with serotherapy, mostly ATG. 89% of patients had had immunosuppression for GvHD prophylaxis, 13% CSA alone, 49% CSA+MTX or MMF; or others (n=15, 16%). Median onset of aGvHD was at 40 days (range: 6-280 d), another 28 days (range: 5-380) until the first infusion of MSC-FFM. Recommended dose and interval is 4 weekly doses of 1-2M MSC/kg body weight; the average patient received only 3 doses, the interval approximately staggered as recommended, with a median dose of 1.4M MSC/kg. Any reduction in GvHD activity by at least one full grade was classified as a partial (PR), absence of any degree of GvHD as a complete response (CR).Results: Day-28 response rates were 84%/25%/59% overall (OR)/CR/PR for children and 80%/35%/45% for adults resulting in a day-28 response rate for the entire cohort: 82%/28%/54%). At last follow-up (LFU) many of the pediatric responders had continued to improve from partial to complete response to response rates of 84%/59%/25% OR/CR/PR, in adults responses were largely unchanged (77%/35%/42%; LFU for the entire cohort: 81%/51%/30%). GvHD °III and °IV were equally likely to respond or resolve. Looking at response rates of SR- vs. MR-GvHD, of the SR-GvHD 96% responded (MR-GvHD: 81%), as well as early and LFU responses in SR-GvHD were more likely to be complete responses (60% and 72% for SR-GvHD, 16% and 43% for MR-GvHD, day-28 and LFU, respectively).Day-28-response was highly predictive of long-term responsiveness, in that only one non-responder on day 28 achieved a response long term, and only two initial partial responders' GvHD relapsed to the same degree of severity as before MSC treatment.The historical expected survival probability for patients with steroid-refractory severe GvHD being in the order of 20% at 6 months. The patients reported here with °III or °IV aGVHD achieved 6-month overall survival probabilities of 65% and 61%, respectively. In total 6 patients relapsed and died (of note: only 69 patients were at risk), 28 deaths were treatment-related. 6-month overall survival rates for children and adults were 68% and 54%, respectively (n.s.). In terms of adverse reactions to MSC-FFM, one case each of spontaneously remitting headache and nausea/vomiting were reported shortly after infusion of the thawed cells. Both events occurred in children and were possibly related to the rapid infusion of DMSO-containing ice-cold fluid and not the active substance.Conclusion: MSC-FFM emanates as a highly efficacious treatment for severe pediatric and adult advanced GvHD, with OR in excess of 80% and survival rates approximating those of patients without GvHD. The very low relapse mortality may suggest that severe GvHD effectively suppresses leukemic recurrence. Better and faster responses of SR- vs. MR-GvHD make a case for early treatment with MSC-FFM. DisclosuresBader:Medac: Patents & Royalties, Research Funding; Cellgene: Consultancy; Neovii: Research Funding; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau. Kuci:Medac: Patents & Royalties. Kuci:Medac: Patents & Royalties. Bug:Amgen: Honoraria; Jazz Pharmaceuticals: Other: Travel Grant; Neovii: Other: Travel Grant; Astellas Pharma: Other: Travel Grant; Janssen: Other: Travel Grant; Celgene: Honoraria; Novartis Pharma: Honoraria, Research Funding. Lang:Miltenyi Biotec: Patents & Royalties, Research Funding. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Seifried:Medac: Other: BSD owns IP and is contract manufacturer; Uniqure BV: Research Funding. Bonig:Kiadis Pharma: Consultancy.

Rapid fluid administration: an evaluation of two techniques.

ObjectiveRapid administration of fluid remains a cornerstone in treatment of shock and when caring for trauma patients. A range of devices and technologies are available to hasten fluid administration time. While new devices may optimize fluid delivery times, impact on subjective experience compared to traditional methods is poorly documented. Our study evaluated administration time and provider experience using two unique methods for fluid administration.Materials and methodsProspective comparison of objective and subjective outcomes using a novel infusion device (LifeFlow® Rapid Infuser) and the traditional push–pull syringe method in a simulated model of rapid fluid infusion. Ten paired trials were conducted for each of three intravenous catheter gauges. Providers administered 500 mL of isotonic crystalloid through an intravenous catheter with both LifeFlow and a push–pull device. Administration time was compared between devices using paired t-tests. Participants’ subjective physical demand, effort, pain, and fatigue using each device were recorded using 21-point visual analog scales and compared between devices using sign-rank tests.ResultsFluid administration time was significantly decreased with LifeFlow compared to the push–pull device with the 18-gauge catheter (2.5±0.8 vs 3.8±1.0 minutes; 95% CI of difference: 0.9, 1.8 minutes; P<0.001). Findings were similar for other catheter sizes. No improvements in subjective experience were noted with the LifeFlow device. Increased physical demand with the LifeFlow device was noted with 18 and 22 gauge catheters, and increased fatigue with the LifeFlow device was noted for all catheter sizes.ConclusionThe LifeFlow device was faster than the push–pull syringe method in our simulated scenario. However, provider subjective experience was not improved with the LifeFlow device.

Does Intravenous Infusion Influence Diagnostic Ultrasound-Induced Pulmonary Capillary Hemorrhage?

Pulmonary diagnostic ultrasound (US) can induce pulmonary capillary hemorrhage (PCH) in mammals. This singular biological effect of diagnostic US imaging was discovered more than 25 years ago but remains poorly understood. Our objective here was to investigate rapid infusion of intravenous fluids as a possible stressor for capillaries, which might enhance pulmonary diagnostic US-induced PCH. Rats were anesthetized with Telazol (Zoetis, Inc, Kalamazoo, MI), which yielded relatively low pulmonary diagnostic US-induced PCH, or Telazol and xylazine, which yielded relatively high pulmonary diagnostic US-induced PCH. Groups of rats were not infused or infused either with normal saline, 10% mannitol, or 5% albumin. Rats were scanned in a warmed water bath with B-mode US for 5 minutes with a 7.6-MHz linear array set to different mechanical index values to obtain exposure response information. Pulmonary capillary hemorrhage was observed as comet tail artifacts in the image and measured on the lung surface. For Telazol anesthesia, all of the PCH results were very low, with no significant differences at the maximum output with an in situ peak rarefactional pressure amplitude of 2.1 MPa (on-screen mechanical index, 0.9). The addition of xylazine to the Telazol anesthetic significantly enhanced the PCH (P < .001) without infusion and likewise for the mannitol and albumin infusion. Saline infusion eliminated this enhancement, with significantly reduced PCH for Telazol-plus-xylazine anesthesia (P < .001); however, both mannitol and albumin infusion resulted in significantly more PCH than saline infusion (P < .01). These results show PCH dependence on the specific intravenous infusion fluid and illustrate the complex importance of physiologic parameters for US-induced PCH.

Intravenous fluid therapy in acute pancreatitis: a critical review of the randomized trials.

Fluid management is a cornerstone of treatment in acute pancreatitis (AP). Identification of existing randomized prospective trials of patients with AP, in which intravenous fluid management was a significant parameter in the experimental design, was undertaken using the PubMed and ENDOBASE databases. Included patients in the seven studies identified were on the whole very unwell with deaths occurring in six trials. Fluid regimens in AP included crystalloid alone, combinations of crystalloid and colloid and in two studies, plasma. In most studies, patients with premorbid major organ failure and advanced age were excluded. Study entry within 6 h of presentation occurred in three trials. Initial fluid administration rates varied from 1 to 2 mL/kg/h to 15 mL/kg/h. Rapid fluid rates were associated with increased morbidity and mortality except in one study in which a high fluid regimen (20 mL/kg bolus within 4 h of presentation followed by 3 mL/kg) led to a better clinical outcome than a more conservative regimen. Use of Ringer's lactate led to improved surrogate outcome markers compared to that of normal saline in one study. Administration of colloid as part of the fluid management was associated with lower morbidity and lower fluid requirements. Rapid infusion of crystalloid very early in the course of AP may be beneficial but rapid infusion of fluid later in the course of the illness may be deleterious. Colloid administration and the use of Ringer's lactate solution in preference to normal saline may improve outcome.

Use of resuscitative endovascular balloon occlusion of the aorta in a patient with gastrointestinal bleeding.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) was developed for controlling intra-abdominal arterial bleeding before definitive bleeding control, and is commonly used in patients with ruptured abdominal aortic aneurysms. Although there is limited evidence for other uses of REBOA, we used REBOA in a patient with massive gastrointestinal bleeding. A 53-year-old man with hematochezia was admitted to our emergency department with an initial systolic blood pressure (SBP) of 83 mmHg. His SBP decreased to 40 mmHg in 10 minutes despite rapid fluid infusion. We decided to resuscitate the patient with REBOA in the emergency department and then move him to an intervention room after stabilization. After aortic occlusion, SBP abruptly increased from 57 to 108 mmHg, and the patient could be transferred to an intervention room. The patient was admitted to intensive care, but died of massive rebleeding 24 hours after admission to the emergency department.

Central Venous Access in the Pediatric Population With Emphasis on Complications and Prevention Strategies.

Central venous catheters are often necessary in the pediatric population. Access may be challenging, and each vessel presents its own unique set of risks and complications. Central venous catheterization is useful for hemodynamic monitoring, rapid fluid infusion, and administration of hyperosmolar medications, including vasopressors, antibiotics, chemotherapy, and parenteral nutrition. Recent advances have improved the catheters used as well as techniques for insertion. A serious complication of central access is infection, which is associated with morbidity, mortality, and significant financial costs. Reduction of catheter-related bloodstream infections is realized with use of ethanol locks, single lumens when appropriate, and prudent adherence to insertion and maintenance bundles. Ultrasound guidance used for central venous catheter placement improves accuracy of placement, reducing time and unsuccessful insertion and complication rates. Patients with central venous catheters are best served by multidisciplinary team involvement.