Initial Bolus Dose Research Articles

Appropriate dosage of unfraction heparin and low molecular weight heparin in hemodialysis patients

To investigate the appropriate dose of unfraction heparin and low molecular weight heparin (LMWH) in hemodialysis patients. Thirty-eight hemodialysis patients were enrolled and randomly allocated into four groups.The initial bolus dose for the Low-dose (LH, n = 10) and high-dose heparin (HH, n = 10) groups were 35 U/kg and 55 U/kg, respectively.The repeated maintenance dose for both groups were 10 U/kg.h and 16 U/kg.h, respectively. Fragmin were administered as single bolus (60 U/kg or 80 U/kg) at 30 minutes before hemodialysis in Low-dose LMWH(LLMWH, n = 10) and High-dose LMWH (HLMW, n = 8) group, respectively. Furthermore, the dialysis circuits in LUFH and LLMWUFH groups were primed with with 4 mg/dl heparinized saline before hemodialysis. Glass bead active clotting time (gbACT), clot rate (CR) and platelet function (PF) were examined using Sonoclot analysator at 0 h, 2 h and the end of hemodialysis at the arterial circuit and 2 h at the venous circuit. (1) LH and LUFH: the increase of gbACT and decrease of CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significant compared with baseline. While they recovered at the end of hemodialysis. No difference between the two groups at different time points was found, either. (2) LLMWH: No change were found in gbACT during hemodialysis. CR at the arterial circuit and the venous circuit were significantly decreased at 2 h and recovered at the end of hemodialysis. (3) LLMWUFH: gbACT at the arterial circuit was significantly increased only at 2 h of hemodialysis. CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significantly decreased and recovered when hemodialysis finished. (4) HH and HLMWH: gbACT were significantly increased and CR were rapidly decreased at both the arterial circuit and venous circuit at 2 h of hemodialysis. Low-dose heparin was effective and safe as anticoagulant in hemodialysis. Low-dose low-molecular-weight heparin was efficient in anticoagulation to some extent. However, High-dose low-molecular-weight heparin, high-dose heparin and flushing with heparinized saline may increase the risk of hemorrhage.

Comparison of efficacy of bupivacaine and fentanyl with bupivacaine and sufentanil for epidural labor analgesia.

Objectives:A study to compare the efficacy between fentanyl and sufentanil combined with low concentration (0.0625%) of bupivacaine for epidural labor analgesia in laboring womenMaterials and Methods:Fifty full term parturients received an initial bolus dose of a 10 ml solution containing 0.125% bupivacaine. The patients were randomly divided into two: group F received 0.0625% bupivacaine with 2.5 mcg/ml fentanyl and group S received 0.0625% bupivacaine with 0.25 mcg/ml sufentanil. Verbal analogue pain scores, need of supplementary/rescue boluses dose of bupivacaine consumed, mode of delivery, maternal satisfaction, and neonatal Apgar scores were recorded. No significant difference was observed between both groups.Results:Both the groups provided equivalent labor analgesia and maternal satisfaction. The chances of cesarean delivery were also not increased in any group. No difference in the cephalad extent of sensory analgesia, motor block or neonatal Apgar score were observed. Although mean pain scores throughout the labor and delivery were similar in both groups, more patients in fentanyl group required supplementary boluses though not statistically significant.Conclusion:We conclude that both 0.0625% bupivacaine-fentanyl (2.5 μg/ml) and 0.0625% bupivacaine-sufentanil (0.25 μg/ml) were equally effective by continuous epidural infusion in providing labor analgesia with hemodynamic stability achieving equivalent maternal satisfaction without serious maternal or fetal side effects. We found that sufentanil was 10 times more potent than fentanyl as an analgesic for continuous epidural labor analgesia.

Effect of Body Mass Index on Bleeding Frequency and Activated Partial Thromboplastin Time in Weight-Based Dosing of Unfractionated Heparin: A Retrospective Cohort Study

To assess bleeding and activated partial thromboplastin time (APTT) in relation to body mass index (BMI) in patients prescribed weight-based dosing of intravenous unfractionated heparin (UFH) for cardiac indications without a maximum (dose-capped) initial bolus or capped initial infusion rate. Consecutive patients admitted to an academic medical center from February 1, 2002, through November 31, 2003, who were treated with a UFH nomogram consisting of a 60-U/kg intravenous bolus plus an initial continuous intravenous infusion of 12 U/kg hourly and titrated to a goal APTT range corresponding to thromboplastin-adjusted target heparin levels of 0.3 to 0.7 U/mL by anti-Xa assay were evaluated for this retrospective cohort study. Patients were excluded if they concomitantly received a fibrinolytic, glycoprotein IIb/IIIa inhibitor, or any other antithrombotic agent (except warfarin). Study patients were divided into quartiles by BMI. Of the 1054 patients included in the study, 807 (76.6%) had an initial bolus dose higher than 4000 U, and 477 (45.3%) had an initial infusion rate higher than 1000 U/h. Despite a significant difference among BMI quartiles in proportion of supratherapeutic first APTT values (P<.001), no statistically significant difference was found in bleeding frequency (P=.26) or frequency of first APTT within the goal range (P=.27). Logistic regression analyses revealed that BMI was not a significant predictor of bleeding or first APTT within the goal range. We did not find any difference in the proportion of first APTT values in the goal range or an increased risk of bleeding in obese patients treated with UFH without a capped initial dose. Our data demonstrate the safe use of weight-based UFH without a capped initial bolus dose or capped initial infusion rate in patients with medical cardiac conditions.

Free and Total Digoxin in Serum During Treatment of Acute Digoxin Poisoning With Fab Fragments: Case Study

A woman ingested 10 mg of methyldigoxin in a suicide attempt and presented 19 hours after ingestion with clinical signs of glycoside intoxication. Her serum level of digoxin was 7.4 ng/mL, and antidotal therapy with Fab antibody fragments was started. The manufacturer's recommended dosing scheme was modified, with 80 mg Fab administered intravenously within 15 minutes followed by a continuous infusion at 30 mg/h. Total serum concentration of digoxin increased markedly within minutes after Fab therapy was started, while the level of free digoxin immediately decreased into the nontoxic range without recrudescent toxic effects of digoxin. The cumulative amounts of free and bound digoxin that were excreted in urine within 30 hours after ingestion were 900 microg and 1600 microg, respectively. Half-life of bound digoxin in urine was 9.9 hours; mean rate of clearance of bound digoxin in the urine was 7.0 mL/min. On the basis of these kinetic data, a smaller initial bolus dose of Fab followed by a continuous infusion may be a more tailored, cost-effective, and relatively safe therapy for patients who have overdosed on cardiac glycosides.

Development of Carotid Intraplaque Hemorrhage Demonstrated by Serial Magnetic Resonance Imaging

68-year-old man presented with a sudden onset of weakness and paresthesia of the left arm. He had a history of myocardial infarction 4 years earlier and a known renal artery stenosis. A nonenhanced computed tomographic scan of the brain showed no signs of hemorrhage or infarction. The patient underwent intravenous thrombolysis with alteplase (0.9 mg/kg body wt, 10% initial bolus dose over 1 minute, followed by infusion of the remaining 90% of the dose over 60 minutes). Soon after, the symptoms completely disappeared except for the persistence of a slight paresthesia of the left arm. Doppler ultrasonography revealed a hypoechoic plaque proximally in the right internal carotid artery causing a 50% to 69% stenosis. ECG showed sinus rhythm with complete right bundle-branch block without ST-segment or T-wave abnormalities. Transcranial Doppler imaging revealed no stenosis of the right middle cerebral artery. Serum lipid profile was within normal limits. In addition to the aspirin (100 mg once per day) and atorvastatin (40 mg once per day) he was already using, the patient was prescribed dipyridamole (200 mg twice per day) for secondary stroke prevention. Fifteen days after the initial onset of symptoms, the patient was enrolled in a clinical study investigating the natural history of carotid artery plaques. Magnetic resonance imaging scans of the brain and right carotid artery plaque were obtained, which revealed a recent discrete infarction of the right sensory region (Figure 1A and 1B) and a plaque with a large lipid-rich necrotic core with no or little hemorrhage (Figure 2A through 2D), respectively. Three months after the initial event, the patient once more presented with sudden onset of weakness and a numb feeling of the left arm. The patient again underwent intravenous thrombolysis with alteplase. However, the symptoms persisted. A nonenhanced computed tomographic scan, performed 24 hours after thrombolysis, revealed a hypodense area in the right motor region. Repeated Doppler ultrasonography showed no change in carotid plaque echogenicity and degree of luminal narrowing of the right internal carotid artery. Ten days after the onset of the second event, the patient underwent repeated magnetic resonance imaging scans of the brain and right internal carotid artery plaque. These scans confirmed recent infarction in the right motor region (Figure 1C and 1D) and revealed recent intraplaque hemorrhage (Figure 2E through 2H). Because of recurrent symptoms, the patient underwent carotid endarterectomy 20 days after the onset of the second event. Histological analysis of the excised plaque demonstrated large intraplaque hemorrhage (Figure 3A and 3B), confirming the magnetic resonance imaging findings. According to the American Heart Association, it was a type VI plaque (complex plaque with possible surface defect, hemorrhage, or thrombus). 1

The relationship between heparin level and activated clotting time in the adult cardiac surgery population

The purpose of this descriptive study was to examine the relationship between heparin levels (HL) determined by heparin protamine titration (HPT) and activated clotting time (ACT) for cardiopulmonary bypass (CPB) in an adult cardiac surgery population. We examined institutional databases for all patients who underwent CPB at a single US academic institution from February 2005 until July 2007. Baseline ACT, predicted and actual heparin dose response (HDR), target and actual ACT, heparin concentration and heparin bolus dose were recorded. We examined the ACT and HL after the initial heparin bolus dose (Post-Hep) and 10 minutes after the initiation of CPB (CPB+10). The Post-Hep and CPB+10 ACT and HL are reported for 3802 patients. The distribution of ACTs for HL of 0.7, 1.4, 2.0, 2.7 and 3.4 units heparin/mL blood at both time points are reported. Additional analysis of the relationship of HL to ACTs of 300, 350, 400 and 480 seconds is also presented.

Consensus protocol for the use of recombinant activated factor VII [eptacog alfa (activated); NovoSeven®] in elective orthopaedic surgery in haemophilic patients with inhibitors

Patients with haemophilia complicated by inhibitors have a significant burden of joint disease, which is associated with a negative impact on their quality of life. Successful elective orthopaedic surgery can result in decreased bleed frequency into a new joint, less time spent in hospital, increased mobility and improved well being. This paper describes a new protocol for use of recombinant activated factor VII (rFVIIa) in elective orthopaedic surgery, based on a review of published data as well as the personal experience of a group of expert physicians. The protocol offers guidance on the planning of the surgery and preoperative testing as well as the bolus schedule for rFVIIa and advice on the concomitant use of antifibrinolytic agents and fibrin sealants. A total of 10 operations involving 13 procedures in eight patients in five comprehensive care centres have been undertaken until now using the protocol, which employs an initial bolus dose of rFVIIa in the range of 120-180 microg kg(-1) to cover surgery. The clinical experience reported here encompasses all cases of elective orthopaedic surgery using rFVIIa as initial treatment carried out in the UK and Republic of Ireland over the last 2 years. In all cases, there was good control of haemostasis during surgery and the final outcome was rated as 'excellent' or 'extremely satisfactory' by the reporting clinicians. Although the initial cost of product to cover surgery such as arthroplasty is high, it needs to be borne in mind that this may be offset in subsequent years by savings resulting from avoidance of bleeding episodes in the affected joint.

Single Centre Experience of Surgery Management of Patients with Von Willebrand's Disease Using High Purity Von Willebrand Factor Concentrate with Low Factor VIII Content

Good haemostatic control is paramount for surgery in patients with von Willebrand's disease (VWD) and can be achieved with either desmopressin or plasma derived von Willebrand factor (VWF). Wilfactin is a plasma-derived von Willebrand factor concentrate with a low FVIII content. It was developed for the treatment of VWD and has been shown to produce safe and efficacious haemostasis, either alone or with supplementary FVIII. We report our experience in a retrospective study of all patients with VWD who underwent at least one invasive or surgical procedure during 1997 to 2001 and received Wilfactin. There were 30 evaluable patients (Table 1), all with either contraindications or unresponsive to desmopressin. The target VWF activity was 80–100 iu/dl and monitored in patients on continuous infusion and those with severe VWD or undergoing complicated procedures. Efficacy was primarily determined clinically. Thirty patients had a total of 75 surgical or invasive procedures. Of these, 64 were managed by bolus dosing and 11 by continuous infusion. Bolus dosing was given just prior to the procedure for 24 patients whose mean FVIII:C level was 47 iu/dl. Three patients had an additional priming bolus dose the day prior to the intervention and 2 patients received a bolus dose of FVIII in addition to the VWF just prior to the intervention. The mean FVIII:C of these patients was 32 iu/dl. The mean pre-operative dose per injection of VWF was 42 IU/kg. Continuous infusion was administered with an initial bolus dose of 40 iu/kg, followed by an infusion of 4 iu/kg until haemostasis or complete wound healing was achieved. The precise schedule and duration however, depended on the length and type of surgery, baseline VWF activity and post treatment values (Table 2). Of the 11 procedures managed with a continuous infusion; 5 were started the day before the procedure (D-1). Two received an extra bolus dose 12– 24 hours prior to the procedure. A FVIII bolus of 35 iu/kg with the VWF was given just prior to the intervention in 2 procedures on the same patient with severe VWD and FVIII levels of 2 iu/dl. Haemostatic efficacy for both bolus and continuous infusion was good with only one bleeding episode recorded, due to a surgical bleed requiring re-intervention. VWF activity and FVIII levels were within target range, and FVIII levels were maintained at between 90 and 175 iu/dl. No patients developed a thrombosis and there was no record of inhibitor formation to date. Our experience with Wilfactin in surgical management has been good. Bolus dosing was used primarily for minor procedures or patients with mild VWD. For more complicated procedures or severe VWD, continuous dosing was used. Only 2 patients received co-administration of FVIII. The low FVIII content in Wilfactin is reassuring in many cases, avoiding the post operative high Factor VIII levels and risk of thrombosis.Table 1. Patient demographicsNo. of patients (N)Male/Female (N)Mean age at surgery (n)Mean VWF activity (Ricof) iu/dlMean FVIII level iu/dlVWD Type 1216/1537 (6–70)29 (<10–69)54 (6–120)VWD Type 271/622 (7–37)10 (5–13)37 (23–48)VWD Type 321/149 (40–58)7 (5–10)5 (2–8)Total308/2234* (6–72)15 overall mean32 overall mean* 14 procedures in paediatric patientsTable 2. Continuous infusion: Schedule and ProceduresPatient TypeVWF Activity iu/dlFVIII:C iu/dlInterventionInfusion initiation day12–24hr Pre infusion Bolus VWF (iu)Factor VIII Bolus (iu)Treatment duration (days)3<108Orthopaedic surgeryD 0Yes 4000No5Orthopaedic surgeryD-1NoNo61A731ENT surgeryD-1NoNo23<52ENT surgeryD-1NoNo2ENT surgeryD 0NoYes D01Orthopedic surgeryD 0NoYes D021b6981Gynaecological surgeryD 0NoNo51b59120Gynaecological surgeryD-1NoNo31<1022General surgeryD 0NoNo41<1018Orthopedic surgeryD-1NoNo3Orthopedic surgeryD 0Yes 3000No3

Utility of Initial Bolus Insulin in the Treatment of Diabetic Ketoacidosis

Current guidelines for treatment of diabetic ketoacidosis (DKA) recommend administration of an intravenous bolus dose of insulin followed by a continuous infusion. This study was designed to investigate whether the initial bolus dose is of significant benefit to adult patients with DKA and if it is associated with increased complications. This was a non-concurrent, prospective observational cohort study of adult patients who presented with DKA in a 12-month period. Charts were divided into two groups depending on whether they received an initial bolus dose of insulin. Data on glucose levels, anion gap (AG), intravenous fluid administration (IVF), and length of stay (LOS) were collected. Primary outcome was hypoglycemia (need for administration of 50% dextrose). Of 157 charts, 78 received a bolus of insulin and were designated the treatment group, the remaining 79 formed the control group. Groups were similar at baseline and received equivalent IVF and insulin drips. There were no statistically significant differences in the incidence of hypoglycemia (6% vs. 1%, respectively, p = 0.12), rate of change of glucose (60 vs. 56 mg/dL/h, respectively, p = 0.54) or AG (1.9 vs. 1.9 mEq/L/h, respectively, p = 0.66), LOS in the Emergency Department (8 vs. 7 h, respectively, p = 0.37) or hospital (5.6 vs. 5.9 days, p = 0.81). Equivalence testing revealed no clinically relevant differences in IVF change, rate of change of glucose, or AG. Administration of an initial bolus dose of insulin was not associated with significant benefit to patients with DKA and demonstrated equivalent changes in clinically relevant endpoints when compared to patients not administered the bolus.

Unfractionated heparin dosing and risk of major bleeding in non–ST-segment elevation acute coronary syndromes

Unfractionated heparin (UFH) is a mainstay of treatment for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), but the practice of weight-adjusted bolus and infusion dosing has not been carefully evaluated. Using data from 31,445 high-risk patients with NSTE ACS enrolled at 420 hospitals in the CRUSADE initiative, we evaluated initial UFH dosing relative to guideline recommendations and determined factors associated with excess weight-adjusted dosing and major bleeding, overall and among subgroups. Excess dose was defined as >70 U/kg for bolus or >15 U/kg per hour for infusion. The most frequent bolus dose was 5,000 U (42.7%) and infusion dose was 1,000 U/h (46%). An excess weight-adjusted UFH bolus or infusion dose was administered 35% of the time. Factors strongly associated with excess weight-adjusted dosing were age (per 10-year increase) (odds ratio [OR] 1.11, 95% CI 1.08-1.15) and female sex (OR 1.45, 95% CI 1.33-1.59). Rate of major bleeding increased proportionally in relation to dose of UFH for both bolus and infusion, specifically when dose was above the recommended weight-adjusted range (>70 U/kg for bolus or >15 U/kg per hour for infusion). Both excess bolus (OR 1.03, 95% CI 1.00-1.06) and infusion (OR 1.16, 95% CI 1.05-1.28) were individually associated with increased bleeding. The relationship between weight-adjusted UFH dose and major bleeding did not vary independently by sex or age. In high-risk patients with NSTE ACS, initial UFH bolus and infusion dosing were frequently higher than recommended weight-adjusted ranges, particularly in patients with lower body weight. Excess bolus and infusion rate dosing was associated with more bleeding and was common among elderly and females. Attention to dosing by weight rather than standard bolus and infusion dosing should lead to improved safety in the use of UFH.

The Sophistication of Simplicity . . . Optimizing Emergency Dosing

The Sophistication of Simplicity . . . Optimizing Emergency Dosing

Abstract 1800: Unfractionated Heparin Dosing and Major Bleeding in Non-ST-Segment Elevation Acute Coronary Syndromes

Background : Unfractionated heparin (UFH) is a mainstay in the treatment of ACS, but failure to adjust UFH dosing based on pt weight is common. Methods : We used data from 31,445 high-risk ACS pts in 420 CRUSADE hospitals to assess initial UFH bolus and infusion doses relative to guidelines recommendations (60–70 U/Kg bolus and 12–15 U/Kg/h infusion). We evaluated the following: UFH excess dosing (&gt;70 U/kg bolus or &gt;15 U/kg/min infusion) vs. no excess dosing; excess dosing and major bleeding, overall and in subgroups; and factors associated with excess dosing. Results : An excess dose of UFH was given 35% of the time (8.9% excess infusion, 9.0% excess bolus, 17.1% both); more often to women, elderly, and those with low body weight (Figure). There was a digit preference for bolus doses of 5000 U (37%), and infusion doses of 1000 U/h (45%). The factors most associated with excess dosing were older age (OR 1.11, 95% CI 1.08–1.15) and female sex (OR 1.45, 95% CI 1.33–1.59). Although individually excess bolus (OR 1.03, 95% CI 1.00–1.06) and excess infusion (OR 1.16, 95% CI 1.05–1.28) each contribute to bleeding, considered together only excess infusion remained significantly associated with bleeding (OR 1.13, 95% CI 1.01–1.26). Although women and elderly bleed more, the relationship between UFH dose (bolus and infusion individually) and major bleeding did not vary across sex and age. Conclusion : In high-risk NSTE ACS pts, both UFH bolus and infusion dosing is often outside the recommended range. Excess dosing is common among elderly and women and is related to increased bleeding. Attention to dosing by weight rather than one-size-fits-all bolus and infusion dosing should improve safety in the use of UFH.

Severe Anaphylactic Reaction After Repeated Intermittent Exposure to Lepirudin

Lepirudin, a recombinant DNA derivative of hirudin, is used to prevent thromboembolic complications caused by heparin-induced thrombocytopenia type II. Anaphylactic and anaphylactoid reactions have been reported with its use in patients both with and without known previous exposure to lepirudin. We describe the case of a 57-year-old woman who received five uneventful courses of lepirudin therapy before having a severe anaphylactic reaction during administration of the intravenous bolus dose that began her sixth course. The patient experienced cardiorespiratory arrest but recovered from the reaction. The decision to administer lepirudin to a patient who has previously received it should be reached with due consideration of the risk:benefit ratio and strategies to manage risk resulting from readministration. Risk factors for an anaphylactic reaction to lepirudin may include use of an initial bolus dose, intravenous rather than subcutaneous administration, length of any single course of therapy beyond 3 days, and repeat administration of lepirudin within 100 days.

Epidural magnesium reduces postoperative analgesic requirement

Magnesium has antinociceptive effects in animal and human models of pain. Our hypothesis was that the addition of magnesium to postoperative epidural infusion of fentanyl may decrease the need for fentanyl. Fifty patients undergoing hip surgery were enrolled to receive either fentanyl (Group F) or fentanyl plus magnesium sulphate (Group FM) for 24 h for epidural analgesia. All patients were equipped with a patient-controlled epidural analgesia device and the initial settings of a demand bolus dose of fentanyl 25 microg. In Group FM, patients received 50 mg magnesium sulphate epidurally as an initial bolus dose followed by a continuous infusion of 100 mg day(-1). Ventilatory frequency, heart rate, blood pressure, pain assessment using a visual analogue scale (VAS), sedation scores and fentanyl consumption were recorded in the postoperative period. There was no significant difference between groups in the time to first analgesic requirement. Compared with Group F, patients in Group FM received smaller doses of epidural fentanyl (P < 0.05). The cumulative fentanyl consumption in 24 h was 437 (SD110) microg in Group F and 328 (121) microg in Group FM (P < 0.05). Patients in Group F showed a higher VAS score in the first hour of the postoperative period (P < 0.05). The groups were similar with respect to haemodynamic and respiratory variables, sedation, pruritus, and nausea. Co-administration of magnesium for postoperative epidural analgesia results in a reduction in fentanyl consumption without any side-effects.

The Effect of l-arginine and Aprotinin on Intestinal Ischemia–reperfusion Injury

BackgroundIntestinal ischemia/reperfusion (I/R) results in local mucosal injury, systemic injuries, and organ dysfunction. These injuries are characterized by altered microvascular and epithelial permeability and villous damage. Activation of neutrophils, platelets, and endothelial factors are known to be involved in this process. Cytokines such as TNF-α, IL-1, IL-6, and oxygen-derived free radicals are believed to be important pathogenic mediators. Capillary no-reflow is also known to play a role in I/R. The aim of our study was to examine the role of l-arginine, a known nitric oxide (NO) donor, and aprotinin, a protease inhibitor with multiple effects, on intestinal I/R. MethodsPigs weighing 20–25 kg were used. Ischemia was established by clamping the superior mesenteric artery (SMA) at its origin and was sustained for 2 hours. Duration of reperfusion was 2 hours. The animals were divided into four groups: group A, the control group, which was submitted to I/R injury only; group B, in which l-arginine was administered at a rate of 5 mg/kg/min during ischemia and continuing throughout reperfusion; group C, in which aprotinin was administered with an initial bolus dose of 20,000 U/kg during ischemia followed by a continuous dose at 50 U/hour throughout reperfusion; and group D in which both substances were administered. In all groups TNF-α, IL-1, and IL-6 levels were measured using ELISA at baseline, 2 hours of ischemia, and 1 hour and 2 hours of reperfusion. SMA blood flow was measured with a Doppler probe at baseline, 10 min, 1 hour, and 2 hours of reperfusion. Histological changes of the intestinal mucosa were examined and graded on a five-point scale in all groups. ResultsIn the control group, levels of TNF-α, IL-1, and IL-6 were significantly increased during reperfusion (p < 0.05) compared to baseline. Administration of l-arginine and aprotinin led to suppression of the release of TNF-α, IL-1, and IL-6 during reperfusion in a statistically significant manner (all p < 0.05). A synergistic or additive effect of l-arginine and aprotinin was not observed. SMA blood flow in the control group was decreased (p > 0.05) during reperfusion compared to baseline. In animals treated with l-arginine and aprotinin, SMA blood flow during reperfusion was significantly increased (p < 0.05) compared to the control group. Histologic examination of the intestinal mucosa was characterized by flattening of the villi and necrosis in the control group. In the treated animals, less severe histological changes were noted. ConclusionsAdministration of l-arginine and aprotinin may lead to amelioration of intestinal I/R injury. We did not note a synergistic or additive effect of these two substances. These findings warrant further studies in clinical settings for future treatment efforts.

Haemostatic efficacy and safety of bolus and continuous infusion of recombinant factor VIIa are comparable in haemophilia patients with inhibitors undergoing major surgery

Bolus infusion (BI) recombinant factor VIIa (rFVIIa) administration is safe and effective in the surgical management of haemophilia patients with inhibitors but has not been compared directly with continuous infusion (CI). We conducted an open-label, randomized, multicenter trial comparing the efficacy and safety of rFVIIa administered by BI or CI for the surgical management of haemophilia A or B patients with inhibitors to FVIII or FIX. Safety was compared with that of a control group of non-inhibitor patients receiving FVIII or FIX concentrates for major surgery. All inhibitor subjects received an initial bolus dose of 90 microg/kg rFVIIa and were then randomly assigned to BI (n = 12) or CI (n = 12). The BI group received 90 microg/kg rFVIIa every two hours (h) during surgery through day 5, then every four hours for days 6-10. The CI group received 50 microg/kg/h rFVIIa through day 5, then 25 mg/kg/h for days 6-10. The control group (n = 12) received FVIII or FIX per institutional protocols. Twenty-two major surgeries included orthopedic procedures on the knee (n = 13), hip (n = 3), and abdominal/pelvis procedures (n = 4). One patient with an autoimmune FVIII inhibitor randomized to the BI arm was excluded from efficacy analysis. Haemostatic efficacy of rFVIIa in each group was comparable: effective in 8/11 and 9/12 subjects in the BI and CI arms, respectively, and ineffective in three subjects in each arm. Serious adverse events were related to continued or increased bleeding. In conclusion, haemostatic efficacy and safety of BI and CI of rFVIIa are comparable for the surgical management of haemophilia subjects with inhibitors.

Diabetes

Diabetes mellitus is caused by an absolute (type I) or relative (type II) lack of insulin. Treatment was first described by Banting and Best in the form of injectable pancreatic extract (insulin) in 1922. Approximately, 6% of the world's population suffers from diabetes mellitus and this is set to rise to 300 million sufferers by 2025. Ninety seven percent will have type II diabetes. Normal carbohydrate metabolism depends upon the presence of insulin. Both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are caused by the reduced effect of insulin with a concomitant rise in counter-regulatory hormones such as glucagon, catecholamines, cortisol and growth hormone. Decreased insulin and increased epinephrine levels activate adipose tissue lipase causing lipolysis of trigylcerides into glycerol and free fatty acids (FFAs) with subsequent promotion of fatty acid transport into mitochondria where ketone body formation occurs. HHS does not have the ketogenic features of DKA and there are reduced levels of FFAs, glucagon, cortisol and growth hormone relative to DKA although this is by no means absolute. Hyperosmolarity is the prominent feature of HHS. The keystone of treatment is fluid replacement and insulin administration. Fluid to replace losses, correct the obvious hypovolaemia and then more slowly allow the patient to correct their intracellular deficit. Insulin is used in moderation. An initial bolus dose of 0.15 U/kg followed by low dose (0.1 U/kg/h) insulin infusions with gradual correction of hyperglycaemia results in a reduced mortality. With this approach there are less therapy-induced episodes of hypoglycaemia and hypokalaemia. In HHS, it is likely that insulin requirements to achieve normo-glycaemia are usually lower than DKA, although insulin resistance can occur due to the presence of counter-regulatory hormones in the acute illness. The main areas of concern in the treatment of acute diabetic hyperglycaemic episodes are: speed of glucose correction, over-aggressive fluid resuscitation and the role of bicarbonate in correcting an acidosis. The latter is a more particular consideration in DKA.

INITIATION OF A WEIGHT-BASED UNFRACTIONATED HEPARIN NOMOGRAM WITH AN INITIAL BOLUS IN MEDICAL CARDIAC PATIENTS DOES NOT INCREASE BLEEDING RATE OR PERCENT OF INITIAL APTT VALUES WITHIN GOAL RANGE

PURPOSE: The 2004 ACC/AHA guidelines for ST-elevation myocardial infarction recommend unfractionated heparin (UFH) with an initial bolus dose of 60 units/kg (maximum 4000 units) followed by a continuous intravenous infusion. Current data support the recommendation of an initial UFH infusion rate of 12 units/kg/hr (maximum 1000 units/hr), but data supporting an initial bolus are limited. We designed this study primarily to analyze the effect of an initial bolus of UFH on overall bleeding frequency and percent of initial (6 hour) aPTT values within goal range.

Physician and Patient Satisfaction for AQUAVAN® in a Randomized, Double-Blind, Multicenter, Dose-Finding Colonoscopy Study

Purpose: Fospropofol disodium (AQUAVAN® Injection, AQ) a prodrug of propofol, is being developed for use in diagnostic and therapeutic procedures requiring minimal to moderate sedation. To assess physician and patient satisfaction with sedation during colonoscopy performed during a randomized, double-blind, multicenter dose-finding study of AQ. Methods: Patients (ASA I–IV, age ≥18 years) undergoing colonoscopy were stratified by age and ASA status and then randomly assigned to receive an initial bolus dose of either fospropofol disodium (2.0, 5.0, 6.5, or 8.0 mg/kg) or midazolam (0.02 mg/kg) following pretreatment with fentanyl citrate (50 μg). Midazolam was included in the study as a safety reference. Upon completion of each procedure, the endoscopist answered a 10-question survey designed to assess satisfaction with the patient's level of sedation, comfort, anxiety, and ability to move and follow instructions during the procedure. Prior to discharge, patients completed a 7-question survey to assess their satisfaction with the sedation medications. Results: 127 patients were randomized and completed the study. A general dose-response trend in Sedation Success was observed across the AQ dosing groups. [figure1] Conclusions: A high level of satisfaction was reported by physicians and patients with the two highest doses of AQ (6.5 and 8.0 mg/kg).

The Use of Dexmedetomidine in Pediatric Cardiac Surgery

We tested dexmedetomidine, an alpha2 agonist, for its ability to decrease heart rate, arterial blood pressure, and neuroendocrinal responses during pediatric cardiac surgery. In a randomized, placebo-controlled study, 30 pediatric patients undergoing open heart surgery were randomly assigned to one of two equal groups. The control group received saline, whereas the treatment group (DEX group) received an initial bolus dose of dexmedetomidine (0.5 microg/kg) over 10 min, followed immediately by a continuous infusion of 0.5 microg.kg(-1).h(-1). Arterial blood pressure, heart rate, and sequential concentrations of circulating cortisol, epinephrine, norepinephrine, and blood glucose were measured. Relative to baseline, arterial blood pressure and heart rate decreased significantly after the administration of dexmedetomidine through skin incision. In the control group, patients' heart rate and arterial blood pressure measures increased after skin incision until the end of bypass (P < 0.05). In both groups, plasma cortisol, epinephrine, norepinephrine, and blood glucose increased significantly relative to baseline, after sternotomy, and after bypass. However, the values were significantly higher in the control group compared with the DEX group (P < 0.05). In conclusion, intraoperative dexmedetomidine infusion attenuated the hemodynamic and neuroendocrinal response to surgical trauma and cardiopulmonary bypass in pediatric patients undergoing corrective surgery for congenital heart disease.