Initial Bolus Research Articles

Lipid emulsion for the treatment of acute organophosphate poisoning: an Open-Label randomized trial

Introduction Many organophosphate (OP) pesticides are lipid-soluble; therefore, intravenous lipid emulsion (ILE) has been evaluated as a possible treatment for acute poisoning. A single bolus dose of 100 ml of 20% ILE was found safe in a pilot observational study. This randomized trial aimed to assess the effectiveness and safety of an extended dose of ILE in acute OP poisoning. Methods This was an investigator-initiated, parallel-group, open-label, randomized controlled trial conducted at PGIMER, Chandigarh (India), from January 2019 to June 2020, in patients aged above 13 years with acute OP poisoning. The primary efficacy outcome was to study the change in atropine dose requirement (total and over the first 24 h) for cholinergic crisis after giving an initial bolus dose of 100 ml of 20% ILE followed by an infusion of 100 ml of 20% ILE over 6 h in addition to the standard care. The secondary efficacy outcomes were to detect the effects on hemodynamic variables, length of hospital stay, and duration of mechanical ventilation required. The incidence of adverse events was evaluated. Results A total of 45 patients were assigned to receive either ILE (intervention group, n = 23) or normal saline (control group, n = 22) in addition to standard treatment. Baseline variables in both groups were comparable. The median dose of atropine (in mg) in the first 24 h and at complete resolution in the ILE group were similar to the control group (124.0 versus 141.8, p-value 0.916; and 150.8 versus 175.0, p-value 0.935). Hemodynamic variables (systolic and diastolic blood pressures, mean arterial pressure, and pulse rate) over 24, 48, and 72 h of treatment, length of hospital stay, and duration of mechanical ventilation were also unaffected by ILE. Case fatality was 4 and not statistically different between intervention and control groups (1 versus 3, p-value 0.346). There was no excessive fever, dyspnea, elevation of serum amylase, or pancreatitis from ILE. Conclusion ILE has no apparent benefit in acute OP poisoning. However, an extended dose appears safe for the indication.

696 Moderate sedation for transesophageal echocardiography guidance of percutaneous left atrial appendage closure: the MID-DEX protocol

Abstract Aims Left atrial appendage closure (LAAC) is usually performed under general anesthesia to allow prolonged transesophageal echocardiography (TEE) guidance. There is scarce knowledge about the feasibility and safety of moderate conscious sedation (MCS) in LAAC. We aimed to assess the feasibility, effectiveness and safety of an innovative MCS protocol of dexmedetomidine plus midazolam (MID-DEX), in a retrospective population of LAAC patients. Methods and results A total of 100 patients underwent LAAC with MCS using the MID-DEX protocol between May 2019 and January 2021 in a single centre. Clinical and procedural outcomes of these patients have been collected in the context of a retrospective registry on LAAC with the Watchman FLX device. All patients were treated preoperative with Dex, administered with initial bolus infusion (1.0 mcg/kg) in 10 min, then i.v. infusion was maintained throughout the LAAC procedure (0.2–1.0 μg/kg/h), tailored on patient’s frailty (advanced age, low body mass index) and haemodynamic status (BP, HR). Midazolam was administered to patients after Dex bolus, to induce sedation and to ease probe insertion, according to patient age and respiratory status (from 2.5 to max 10 mg). The ease of insertion of the TEE probe (one very easy—five impossible), and the duration of the TEE (m′) were recorded. Additional variables were: total amount of each drug given, time to recovery from sedation. After procedure a verbal survey about the quality of sedation, level of comfort, recall of the procedure, and future acceptance of this type of sedation was administered. The operators also rated the procedural conditions on a scale of 1–5 (5 = excellent). Mean patient age was 78.5 ± 6.96 years and 34% were women. The mean LVEF was 62.9 ± 8.9%. All patients underwent LAAC under MID-DEX MCS protocol with an acute procedural success rate of 100%. Ninety patients (90%) successfully underwent TEE under MCS; in 10 patients ICE guidance was required. Fluoroscopic time was 31 ± 21.7 min. The median required dosage of Dex infusion was 0.08–0.09 μg/kg/h and midazolam was 6.2 ± 2.4 mg. No complications were observed from MCS. There was no need for conversion to GA during the procedure. We observed five cases of bradycardia (solved by reducing to half Dex infusion) and three of hypotension (only two requiring Ringer’s solution infusion). Echocardiographist rated procedural conditions as perfect (5) in 85% of cases and good (4) in 6%. Interventionalist rated procedural comfort with 5 (excellent) in 90% of cases and 4 (good) in 3%. Patients satisfaction was high with best rate (5) in 80% with 5% of 4 (good); 12% described the procedure as fair, without memory of discomfort. Conclusions LAAC is safe and effective when performed under MCS. Thus, applying MCS may simplify the LAAC procedure, as well as reduce procedural time and procedural costs, while increasing overall patient and physician satisfaction.

A Comparison Between Dexmedetomidine and Clonidine as Adjuvants to Levobupivacaine in Labour Analgesia.

BackgroundThe epidural analgesia technique is effective for labor analgesia and combinations of various local anesthetics with lipophilic opioids like fentanyl are used. However, fentanyl can cause an increased incidence of pruritus, urinary retention, nausea, vomiting, giddiness, shivering, and respiratory depression. Dexmedetomidine and clonidine are selective alpha 2 agonists with analgesic properties and have been used via the neuraxial route with local anesthetics for the same without the side effects of fentanyl. Thus, the primary objective was to assess and compare the analgesic efficacy of the two-drug combinations by the visual analog scale (VAS) score.MethodsFifty-four primigravida women were randomly allocated in two groups of 27 each and were given an initial bolus of 10 mL of 0.125% levobupivacaine with dexmedetomidine 0.5 ug/kg in Group A and with clonidine 1 μg/kg in Group B. Subsequently, each patient received a background infusion rate of 10 mL/h, a bolus dose of 5 ml, and a lock-out interval of 10 min via a patient-controlled-analgesia (PCA) pump. The blood pressure, heart rate, and severity of pain using VAS were assessed. Durations of the stages of labor, rate of instrumental delivery, and cesarean section, side effects, maternal sedation, and neonatal Apgar scores were also recorded.ResultsVAS scores in both the groups progressively decreased to <3 by 15 min with significant differences at five, 10, 15, and 120 min being lower in group A. Onset of analgesia and time for maximum analgesia was significantly shorter in group A. There was a significant decrease in hemodynamic parameters from baseline in both groups. The fall in heart rate was significantly greater in Group A and at almost all the time intervals after baseline, diastolic blood pressure (DBP) was also lower in group A. Maternal motor blockade scores, the intensity of maternal sedation, the incidence of maternal complications, the duration of the first and second stage of labor, the rate of instrumental delivery and cesarean section, total analgesic dose and PCA bolus requirement, and neonatal Apgar scores did not show a significant difference between the two groups.ConclusionBoth dexmedetomidine and clonidine provide hemodynamically stable labor with a fall in heart rate and maternal blood pressure in the initial hours. Dexmedetomidine has the advantage of faster onset of analgesia and time for maximum analgesia.

Evaluation of high-dose insulin/euglycemia therapy for suspected β-blocker or calcium channel blocker overdose following guideline implementation.

High-dose insulin/euglycemia (HDIE) is targeted therapy for β-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality. Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher's exact tests. During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups. Hypoglycemia was reduced using an HDIE guideline and concentrated insulin.

Comparison of Adult Diabetic Ketoacidosis Treatment Protocols From Canadian Emergency Departments

BackgroundDiabetic ketoacidosis (DKA) is a common acute life-threatening complication of poorly controlled diabetes mellitus contributing to considerable mortality and morbidity. Use of standardized treatment protocols improves patient outcomes in the emergency department (ED) for many conditions, but variability in adult DKA treatment protocols has not been assessed across EDs. In this study, we compared DKA treatment protocols from adult EDs across Canada to highlight inconsistencies in recommended DKA management. MethodsED staff in Canada were solicited for their treatment protocols used to guide acute ED DKA management. Information regarding initial fluid resuscitation and maintenance fluid, potassium replacement, insulin therapy and bicarbonate administration was abstracted from each protocol, collated in a table and compared. ResultsThirty-six unique protocols were obtained representing 85 institutions (40 urban and 45 rural, with a 65.1% response rate) across Canada, with no protocol use for 4 urban centres. Similarities in protocols included the intravenous insulin infusion rate and instructions for switching to subcutaneous insulin. Variability was noted in the rate, amount and type of fluid bolus given (0.5 to 2 L of normal saline or Ringer’s lactate over 15 minutes to 2 hours), the criteria determining the amount, potassium supplementation at normo/hypokalemic ranges, when to add dextrose to maintenance fluid, insulin bolus inclusion and bicarbonate administration. ConclusionsThis is the first comparison of adult DKA treatment protocols in Canada. Although several common approaches were identified, variability was found in initial fluid boluses, initial insulin bolus and role of bicarbonate, necessitating further study to ensure local DKA protocols reflect current evidence-based best practices for optimal patient clinical outcomes.

The Intraoperative Median Effective Dose of Oxytocin for Preventing Uterine Atony in Parturients with a Prior History of Caesarean Delivery.

While oxytocin is commonly used for the prevention of uterine atony, its pharmacology may be affected by a prior history of caesarean delivery. The objective of this study was to determine the 50% effective dose (ED50) of bolus oxytocin after caesarean delivery in parturients with and without prior caesarean delivery. This was a parallel-group, double-blind, dose-response study using Dixon's up-and-down sequential allocation method to estimate the ED50 of bolus-administered oxytocin in parturients having caesarean delivery under combined spinal-epidural anaesthesia (CSE). Twenty-seven parturients with a history of prior caesarean delivery (With-PCD group) and 26 parturients with no such history (Without-PCD group) were enrolled. Oxytocin was administered as an intravenous bolus at a starting dose of 0.5 units, which was then increased or decreased by 0.25 units at a time. Uterine tone was assessed by the obstetrician as either 'adequate' or 'inadequate' 3 min after delivery of the fetus. Adverse effects, administration of additional uterotonic agents, and estimated blood loss were recorded. The ED50 of oxytocin was greater in the With-PCD group than in the Without-PCD group (0.95 units [95% CI 0.82-1.08] vs. 0.55 units [95% CI 0.38-0.73], P < 0.001). The overall incidence of adverse effects was higher in the With-PCD group than in the Without-PCD group (33.3% vs. 7.7%, P = 0.02). The initial bolus dose of oxytocin needed to prevent uterine atony was higher in parturients with prior caesarean delivery than in parturients without prior caesarean delivery. Uterine scarring may contribute to the increased oxytocin requirements of the former group. ChiCTR1900023474; investigator: Wei CN; date of registration: 30 May 2019.

Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data.

To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. Prospective, multicenter, observational study. Sixteen tertiary or university hospitals in the Republic of Korea. Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. None. The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26-2.65). Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.

Continuous Erector Spinae Plane Block as Postoperative Analgesic Technique for Robotic-Assisted Thoracic Surgery: A Case Series.

IntroductionThe erector spinae plane block (ESPB) is a recently implemented analgesic technique initially reported for thoracic analgesia and subsequently adopted for both intra- and postoperative pain management. Thoracic surgery is among the most painful surgical procedures, even when conducted with minimally invasive approach. Robotic-assisted thoracic surgery (RATS) challenges the traditional analgesic regimens as one of its aims is to decrease the patient’s length of stay (LOS) whilst achieving optimal postoperative pain management. Furthermore, there is lots of growing evidence on the impact of poorly controlled postoperative pain (PP) on the development of chronic post-surgical pain (CPSP). In these case series, we aim to describe our preliminary experience of postoperative pain management with continuous ESPB in the field of RATS.Case Series PresentationIn eight consecutive patients undergoing elective RATS procedure, we performed the ESPB after surgery with an initial bolus of local anesthetic followed by catheter insertion for continuous infusion. The infusion of local anesthetic lasted for the first two postoperative days. The effectiveness of the ESPB was evaluated through serial pain assessment with numeric rate scale (NRS) score, both at rest and during movement every 6 hours. Any analgesic rescue drug prescription was reported. We noted that the ESPB strongly reduced the prescription of opioids and of rescue analgesic. In our series, only one patient needed opioids during the first two postoperative days, and no rescue analgesic administration was noted in the remaining cases.ConclusionWe report a small but promising experience regarding postoperative pain management with continuous ESPB performed after RATS. We implemented the ESPB before surgery. Larger studies on postoperative pain management with continuous regional blocks in thoracic surgery are warranted.

Intravenous lidocaine in cancer-related neuropathic pain: case series

Introduction: Administering systemic lidocaine has been shown to deliver effective analgesia for both cancer-related and non-cancer pain. Adverse effects and toxicity are rare with controlled administration.&#x0D; Objective: To report the results obtained after the indication to manage with IV lidocaine infusion to control neuropathic pain flares in 9 cancer patients.&#x0D; Methodology: Observational, descriptive, case series-type study. A search was conducted in the files of the Pain and Palliative Care Service of the National Cancer Institute - Instituto Nacional de Cancerología - in Bogotá. Patients over 18 years old diagnosed with cancer, who experienced high intensity neuropathic pain and with the cognitive ability to rate their pain in a numerical analogue scale (NAS), without any absolute contraindications for the use of IV lidocaine were included; patients were assessed between September 27 and November 21, 2019.&#x0D; Results: 9 patients experiencing a pain flare-up which was characterized as neuropathic were registered, of which 89 % had some improvement following the administration of an initial lidocaine bolus. After one hour, 60 % reported over 40% improvement in the initial NAS. After 24 hours all patients had experienced some improvement, with a reduction of 46% in the pain scale as compared to the baseline.&#x0D; Conclusions: In this series of cases, the intravenous infusion of lidocaine as an option for the management of neuropathic pain flares seems to reduce pain intensity following the initial bolus administration.

Clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning. (ATOM-6)

Introduction For acute digoxin poisoning, it has been recommended to give bolus doses of 10–20 vials or potentially larger than needed doses calculated from dose ingested or the measured concentration. However, a recent revision of internal Poisons Information Centre guidelines prompted a change of our recommendations, specifically instead of large boluses, to use titrating repeated low doses of digoxin antibodies(Digoxin-Fab) based on bedside assessment of cardiac toxicity. Methods This is a prospective observational study of patients with acute digoxin poisoning identified through two Poisons Information Centres and three toxicology units. Patient demographics, signs and symptoms of digoxin toxicity, doses and response to Digoxin-Fab, free and bound serum digoxin concentrations. Outcomes were recorded and analysed. Results From September 2013 to September 2020, 23 patients with 25 presentations (median age 56 years, females 56%) were recruited. Median dose ingested was 13 mg(IQR: 9.5–25). Median heart rate (HR) was 41 beats/min before treatment. Initial median digoxin and potassium concentrations were 14.5 nmol/L (IQR: 10.9–20) [11.2 µg/L(IQR: 8.4–15.4)] and 5 mmol/L (IQR: 4.5–5.4 mmol/L), respectively. Gastrointestinal symptoms and acute kidney injury were present in 22 patients (88%) and 5 patients (20%), respectively. Four patients received an initial bolus dose of Digoxin-Fab of 5–20 vials. Twenty-one patients received repeated titrated doses (1–2 vials) of Digoxin-Fab and the median total dose was 4 vials (IQR: 2–7.5). Median maximal change in HR post-Digoxin-Fab was 19 beats/min. The median potassium concentration decrease post-Digoxin-Fab was 0.3 mmol/L. Total dose used in the titration group was 25% and 35% of the predicted doses based on the amount of digoxin ingested or measured serum concentration, respectively. Twelve had free digoxin concentrations measured. Free digoxin concentrations dropped to almost zero after any dose of Digoxin-Fab. Ten patients had a rebound of digoxin >2.6 nmol/L (2 µg/L). There were no deaths from acute digoxin toxicity. Conclusions The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute digoxin poisoning.

The Intestinal Barrier Function and Intra-Abdominal Pressure Depend on Postoperative Analgesia Technique in Children with Appendicular Peritonitis.

Introduction Peritonitis is one of the risk factors for the development of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). The plasma citrulline and intestinal fatty acid-binding protein (I-FABP) are informative markers of intestinal barrier function. The aim of this study was to determine the correlation of the plasma citrulline and I-FABP with intra-abdominal pressure (IAP) and their relation to analgesia techniques in children suffering from appendicular peritonitis. Materials and Methods 74 children operated for appendicular peritonitis were randomized into three groups of postoperative analgesia: “Opioids” (n = 25), intravenous morphine of 10 mcg/kg/h; “Lidocaine” (n = 23), intravenous lidocaine with initial bolus of 1.5 mg/kg and then infusion of 1.5 mg/kg/h; and “EA” (n = 26), epidurally 0.25% bupivacaine with initial bolus of 1 mg/kg and then infusion of 0.4 mg/kg/year. Retrospectively patients in each group were divided into the following subgroups: “without IAH” (n = 33), “IAH” (n = 27), and “ACS” (n = 14). We detected citrulline and I-FABP in plasma on day 1 (D1) and day 3 (D3) of hospital stay. Results The patients without IAH on D1 presented significantly higher plasma citrulline (23.7 (16.0–31.3) nmol/ml) and lower I-FABP (76.9 (32.6–121.1) pg/ml) levels compared with patients in subgroup “IAH” (9.3 (7.3–11.3) nmol/ml and 226.0 (161.8–290.3) pg/ml, respectively) and subgroup “ACS” (6.9 (5.3–8.6) nmol/ml and 1011.7 (731.9–1291.5) pg/ml, respectively). The IAP had strong inverse correlation (rs = −0.74; p < 0.00001) with citrulline and positive strong correlation (rs = 0.73; p < 0.00001) with I-FABP. The citrulline in patients with IAH during three days postoperatively increased significantly in “Lidocaine” to 72% (p=0.01) and in “EA” to 138% (p=0.02), but it decreased to 13% (p=0.37) in “Opioids” group. In children with ACS, citrulline on D3 was significantly higher than that on D1 and increased in “Lidocaine” to 59% (p=0.05) and in “EA” to 134% (p=0.001), but in “Opioids” it decreased to 30% (p=0.48). The I-FABP in patients with IAH decreased to 12% in “Lidocaine” group (p=0.86) and to 75% in “EA” group (p=0.01), but it increased to 37% (p=0.57) in “Opioids” group. During observation period, I-FABP in patients with ACS decreased significantly in “Lidocaine” to 42% (p=0.05) and in “EA” to 96% (p=0.003), but it increased in “Opioids” to 63% (p=0.22). Conclusions The IAP was inversely correlated with plasma citrulline and positively correlated with I-FABP in children with appendicular peritonitis. Epidural analgesia is the most protective for intestinal wall barrier function in patients at risk of IAH and ACS.

Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?

Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?

Protein C Infusion Therapy in an Adult Case of Severe Congenital Protein C Deficiency

Background: Severe congenital protein C deficiency (SCPCD) is a rare inherited disorder characterized by recurrent thrombosis, disseminated intravascular coagulation, and purpura fulminans. Due to limitations in traditional therapeutic options (anticoagulation, FFP, PCC), plasma-derived protein C concentrates have been used for both prophylactic and therapeutic indications. However, there are few reports of protein C infusion therapy in adults, with limited understanding of pharmacokinetics and no dosing guidelines available. We report the use of protein C concentrate in an individualized dose-finding study, in an adult patient in preparation for renal transplantation.Case: A 35 year old female (68 kg) with SCPCD (baseline PC activity < 0.10 U/mL) with an extensive personal and family history of thrombosis was to undergo renal transplant. Her thrombotic history included DVT and PE (age 4), recurrent DVT with PE (age 6), mesenteric vein thrombosis (age 6), arterial thrombosis in bowel (age 10), DVT (age 10), extensive superficial venous thrombosis (age 27), pregnancy-associated DVT (age 32), and internal jugular vein thrombosis (age 34), for which she was on long-term therapeutic Enoxaparin. She developed end-stage renal disease in March 2015 (age 33) in the setting of pregnancy-associated HELLP syndrome, and is currently awaiting a deceased donor renal transplant. In anticipation of her upcoming transplant, an intravenous protein C infusion trial was performed to establish a perioperative management plan.Results: The patient was admitted to hospital for this dose-finding study. She was administered Ceprotin® (human plasma-derived, virally-inactivated protein C concentrate) with an initial intravenous bolus (59 IU/kg) followed by an infusion (5 IU/kg/hr) to maintain a target PC level of 0.65-1.30 U/mL (see Table). Protein C activity was measured every 6 hours, and target levels were achieved over the 30-hour duration of the trial. The patient experienced no adverse events during the infusion trial.Conclusion: In this case report, target protein C levels were maintained using bolus and continuous infusion rates of protein C concentrate that were approximately half of those recommended by the manufacturer. This personalized trial, while resource-intensive, provided a feasible and safe method of preparing for a high-risk surgical procedure that could be adapted to other similar clinical situations. [Display omitted] DisclosuresCrowther:Leo Pharma: Research Funding; Shinogi: Consultancy; Boehringer Ingelheim: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Pfizer: Honoraria; Portola: Consultancy.

Does the performance of lower limb peripheral nerve blocks differ among orthopedic sub-specialties? A single institution experience in 246 patients.

Continuous peripheral nerve blocks (cPNBs) have shown promising results in pain management after orthopaedic surgeries. However, they can be associated with some risks and limitations. The purpose of this study is to describe our experience with the cPNBs regarding efficacy and adverse events in patients undergoing orthopedic surgeries on the lower extremity in different subspecialties. This is a prospective cohort study on collected data from perineural catheters for pain management after orthopedic surgeries in lower limbs. Catheters were placed by experienced anesthesiologists using sterile technique. After an initial bolus dose of 10-20mL ropivacaine 0.5% (weight adjusted), the catheters were secured and connected to disposable mechanical infusion pumps with ropivacaine 0.2% (basal infusion rate=6mL/h; weight adjusted (0.2mL/kg/h)). After catheterization, the patients were examined daily, by specially educated acute pain service nurses. Pro re nata (PRN) or fixed boluses (10mL bupivacaine 0.25%; weight adjusted) with an upper limit of 4 times/day, were administered if indicated. Patients' demographic data, physiological status, and pre-op intake of opioids and other analgesics were registered. The severity of post-operative pain was assessed with 'Numeric Rating Scale' (NRS) and 'Face, legs, Activity, Cry, Consolability' (FLACC) scale for adults and children, respectively. The need for additional opioids and possible complications were registered. We included 547 catheters of 246 patients (Range 1-10 catheters per patient). Overall, 115 (21%) femoral, 162 (30%) saphenous, 66 (12%) sciatic, and 204 (37%) popliteal sciatic nerve catheter were used. 452 (83%) catheters were inserted by a primary procedure, 61(11%) catheters employed as a replacement, and 34 catheters (6.2%) used as a supplement. For guiding the catheterization, ultrasound was applied in 451 catheters (82%), nerve stimulator in 90 catheters (16%), and both methods in 6 catheters (1.1%). The median duration a catheter remained in place was 3days (IQR=2-5). The proportion of catheters with a duration of two days was 81, 79, 73, and 71% for femoral, sciatic, saphenous, and popliteal nerve, respectively. In different subspecialties, 91% of catheters in wound and amputations, 89% in pediatric surgery, 76% in trauma, 64% in foot and ankle surgery, and 59% in limb reconstructive surgery remained more than two days. During first 10days after catheterization, the proportion of pain-free patients were 77-95% at rest and 63-88% during mobilization, 79-92% of the patients did not require increased opioid doses, and 50-67% did not require opioid PRN doses. In addition to 416 catheters (76%), which were removed as planned, the reason for catheter removal was leaving the hospital in 27 (4.9%), loss of efficacy in 69 (13%), dislodgement in 23 (4.2%), leakage in 8 (1.5%), and erythema in 4 catheters (0.73%). No major complication occurred. After orthopaedic procedures, cPNBs can be considered as an efficient method for improving pain control and minimizing the use of additional opioids. However, the catheters sometimes might need to be replaced to achieve the desired efficacy.

Initial Basal and Bolus Rates and Basal Rate Variability During Pump Treatment in Children and Adolescents

Objective:Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy.Methods:A total of 154 patients with T1DM, aged between 0 and <21 years at diagnosis, from a single center were documented. Patients were divided into five age groups according to age at pump initiation: group 1, <5 years (n=36); group 2, 5-8 years (n=20); group 3, 8-15 years (n=74); group 4, 15-18 years, (n=19); and group 5, >18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated.Results:Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86±0.23 U/kg and 0.78±0.19 U/kg, respectively and differed significantly between each age group (p<0.001; p<0.001). Mean daily basal rate/kg showed significant differences between the five groups (p<0.001). Circadian distribution of BI differed markedly among the five age groups.Conclusion:At the initiation of insulin pump therapy, circadian profiles by age group should be taken into account in pediatric patients to optimize basal rate faster and more easily.

More Effective Anticoagulation During Non-Cardiac Arterial Procedures Using Activated Clotting Time Guided Heparin Administration

Arterial thrombo-embolic complications (ATEC) are still common during and after non-cardiac arterial procedures (NCAP) despite the administration of (a fixed bolus of) heparin. These ATEC could be due to existing individual differences in heparin sensitivity. The purpose of this study was to evaluate the feasibility and safety of an ACT guided heparin dose protocol and to evaluate if a more effective target ACT can be achieved during NCAP. In this multi-center prospective study, 194 patients undergoing elective and non-elective NCAP were enrolled and received heparin according to a heparin dose protocol which aimed to obtain a target ACT of 250 seconds (s.), measured by the Medtronic HMS Plus. Patients received a standardized bolus of 5 000 IU followed by additional boluses depending on the actual ACT. Primary outcome was the ACT value reached. Secondary outcomes were incidence of all ATEC and haemorrhagic complications. The mean baseline ACT was 138 ± 17 s. The mean ACT five minutes after the initial heparin bolus of 5 000 IU was 197 ± 31 s. 48% of patients reached an ACT of 200 s. and six per cent of patients reached an ACT of 250 s. Additional dosages of heparin were administered in 72% of patients. With this ACT guided heparin protocol 86% of patients reached an ACT of 200 s. and 26% of patients reached an ACT of 250 s. A negative correlation was found between body weight and the ACT at T1 (P ˂ 0.001). ATEC and haemorrhagic complications occurred in 11.3% and 16.5% of patients. The lowest incidence of ATEC was found in patients with peak ACT between 200 and 250 s, namely 6.3%. This ACT guided heparin protocol proved to be feasible, safe and more patients reached an ACT > of 200 s. compared to a standardized heparin bolus of 5 000 IU. Further research is needed to investigate if ACT guided heparin administration could be preferable over not monitoring the anticoagulant effect of peri-procedural heparin and results in a lower incidence of ATEC, without an increase in haemorrhagic complications.

Comprehensive Intraprocedural Unfractionated Heparin Protocol During Catheter Ablation of Atrial Fibrillation in the Presence of Direct Oral Anticoagulants and Wide Spectrum of Body Mass Index.

Data on optimal dosing of unfractionated heparin (UFH) in the presence of a direct oral anticoagulant (DOAC) to achieve and maintain an activated clotting time (ACT) of ≥300 seconds during catheter ablation of atrial fibrillation (CA-AF) are limited and prevalence of obesity adds to the unpredictable response to UFH. One hundred seventeen consecutive patients undergoing CA-AF were prospectively administered weight-adjusted, weight-based UFH using a pre-specified detailed protocol and retrospectively analyzed. Due to lack of distribution of UFH into muscle or adipose tissue and lower degree of vascularity in the latter compartment, each patient's ideal and actual weights were used to determine the adjusted-weight for use in all UFH doses. A UFH bolus of 200 units/kg was administered intravenously followed by an infusion of 35 units/kg/hour. The mean age was 65 years, and 85 patients (72.6%) were male. The average body mass index (BMI) was 30 (range 18-50) kg/m2. After the initial UFH bolus dose, 99 patients (84.6%) achieved ACT ≥300 sec with a mean (± SD) of 380 ± 79 sec. The mean time to reach an ACT ≥300 in all patients was 14.6 ± 12.4 minutes. Among all measured ACT values, 423 (90.8%) were ≥300 seconds. These results were consistent within all BMI categories. There were no intraprocedural thrombotic or hemorrhagic complications. Two patients (1.7%) sustained groin vascular access site hematoma without subsequent intervention and 7 patients (6%) experienced minor oozing post-procedurally. Our comprehensive weight-adjusted, weight-based UFH protocol, during CA-AF in presence of a DOAC, rapidly achieved and maintained an effective ACT irrespective of BMI.

Variability in the Hemodynamic Response to Fluid Bolus in Pediatric Septic Shock.

Fluid boluses are commonly administered to improve the cardiac output and tissue oxygen delivery in pediatric septic shock. The objective of this study is to evaluate the effect of an early fluid bolus administered to children with septic shock on the cardiac index and mean arterial pressure, as well as on the hemodynamic response and its relationship with outcome. We prospectively collected hemodynamic data from children with septic shock presenting to the emergency department or the PICU who received a fluid bolus (10 mL/kg of Ringers Lactate over 30 min). A clinically significant response in cardiac index-responder and mean arterial pressure-responder was both defined as an increase of greater than or equal to 10% 10 minutes after fluid bolus. Forty-two children with septic shock, 1 month to 16 years old, median Pediatric Risk of Mortality-III of 13 (interquartile range, 9-19), of whom 66% were hypotensive and received fluid bolus within the first hour of shock recognition. Cardiac index- and mean arterial pressure-responsiveness rates were 31% and 38%, respectively. We failed to identify any association between cardiac index and mean arterial pressure changes (r = 0.203; p = 0.196). Cardiac function was similar in mean arterial pressure- and cardiac index-responders and nonresponders. Mean arterial pressure-responders increased systolic, diastolic, and perfusion pressures (mean arterial pressure - central venous pressure) after fluid bolus due to higher indexed systemic vascular resistance and arterial elastance index. Mean arterial pressure-nonresponders required greater vasoactive-inotrope support and had higher mortality. The hemodynamic response to fluid bolus in pediatric septic shock was variable and unpredictable. We failed to find a relationship between mean arterial pressure and cardiac index changes. The adverse effects of fluid bolus extended beyond fluid overload and, in some cases, was associated with reduced mean arterial pressure, perfusion pressures and higher vasoactive support. Mean arterial pressure-nonresponders had increased mortality. The response to the initial fluid bolus may be helpful to understand each patient's individualized physiologic response and guide continued hemodynamic management.

Abstract P30: Safety and Efficacy of Intravenous Tirofiban in Acute Ischemic Stroke With Extended Window Period

Introduction: Intravenous Thrombolysis is approved upto 4½ hrs and Endovascular Therapy upto 24 hrs in eligible Acute Ischemic Stroke (AIS) patients with Large Vessel Occlusion. There are still substantial number of AIS patients where there is no effective treatment available. In this Study we aim to test the safety and Efficacy of the reversible gp IIb/IIIa receptor inhibitor antagonist Tirofiban in AIS beyond 4 ½ hrs and within 24 hrs. Methodology: Among a total of 750 AIS patients admitted in our Stroke Unit, from July 2019 to March 2020, 100 Consecutive patients were included in this study and received Intravenous tirofiban as an initial bolus followed by infusion. Inclusion criteria were Age 18-80yrs, Window Period 4 ½ to 24 hrs. National Institute of health Stroke Scale score (NIHSS) between 5-20, No contraindication for lytic drugs. CT Brain excluding Hemorrhage or &gt; 1/3 rd infarct. Cardioembolic strokes were excluded. Efficacy Assessments: NIHSS and modified Rankin scale (mRS) performed at baseline, within 48hrs, Day-7 and Day-90. The good outcome was defined as mRS 0-1 at 3 months. The safety outcomes were assessed by the incidence of Symptomatic Intracerebral hemorrhage (SICH), Systemic Bleeding and any mortality. Results: There were 74 males, 26 females with median Age of 56 yrs (range from 18 to 80yrs). The Median NIHSS is 10 (range from 5-20), Majority (87%) had anterior circulation strokes and 13% were in Posterior circulation. One patient (1%) developed symptomatic parenchymal Hemorrhage, 4 patients (4%) had mild haemorrhagic transformation within infarct, 8 patients (8%) had nonfatal systemic bleed in the form of Hematuria. Total Mortality - 2 patients (2%), one patient died in the hospital due to cardiac arrest and another patient died at home after discharge. At 3 months, 62 patients (62%) had good outcome (mRS 0-1) and 33 patients (33%) had favourable outcome (mRS 2-3). Conclusion: In this Observational Study we found that Intravenous Tirofiban is not only safe, but effective in AIS patients with extended window period. However, Randomized Clinical Trials are needed to further clarify our observation.

P0652 / #2053: ULTRASOUND GUIDED FLUID RESUSCITATION IN PAEDIATRIC SEPTIC SHOCK - A RANDOMIZED CONTROL TRIAL

Aims & Objectives: To compare the amount of fluid bolus required in children with septic shock, given with ultrasound or clinical guidance. Secondary outcomes were shock reversal time, fluid overload rate at 24 and 72 hrs, ionotrope and ventilator requirement. Methods: It was a randomized control un-blinded pilot study, conducted at the PICU and emergency of a tertiary care Government teaching hospital, from September 2019 to June 2020. Children with congenital heart disease, dengue shock syndrome and anaphylactic shock were excluded. After recieving an initial fluid bolus of 20ml/kg, participants were randomized into ultrasound (study group) and clinical (control group). The study group recieved further fluid boluses on the basis of inferior vena cava collapsibility/distensibility, cardiac contractility and extra-vascular lung water, while children in the control group recieved further fluid boluses only under clinical guidance. Results: 55 children aged 1 month to 12 years were enrolled - 26 in study group and 29 in control group. Shock reversal time (14 ± 5.5 h vs 19.3 ± 8.5 h, p=0.02) and total fluid bolus (39 ± 16.8 vs 60 ± 26.6 ml/kg, p=0.0009) was significantly lower in the study group. However, there was no significant difference in secondary outcomes, including fluid overload rate. Conclusions: Though limited by sample size, our study demonstrated reduced need for fluid boluses and earlier shock reversal if resuscitation was guided by ultrasound. However, multicenter trials with a larger sample size are required to accurately establish the usefulness of ultrasound in fluid resuscitation in children with septic shock.