Adjustment Of Infusion Rate Research Articles

A Survey of Acute Pain Service Structure and Function in United States Hospitals

Although the number of U.S. hospitals offering an acute pain service (APS) is increasing, the typical structure remains unknown. This survey was undertaken to describe the structure and function of the APS in U.S. hospitals only. We contacted 200 non-teaching and 101 teaching U.S. hospitals. The person in charge of postoperative pain management completed and returned the survey. Seventy-four percent of responding hospitals had an organized APS. An APS was significantly more formally organized in academic/teaching hospitals when compared to non-teaching hospitals. Pain assessments included “pain at rest” (97%), “pain on activity” (63%), and reassessment after pain therapy intervention (88.8%). Responding hospitals utilized postoperative pain protocols significantly more commonly in teaching hospitals when compared to non-teaching and VA hospitals. Intravenous patient controlled analgesia (IV-PCA) was managed most commonly by surgeons (75%), while epidural analgesia and peripheral nerve block infusions were exclusively managed by anesthesiologists. For improved analgesia, 62% allowed RNs to adjust the IV-PCA settings within set parameters, 43% allowed RN adjustment of epidural infusion rates, and 21% allowed RN adjustment of peripheral nerve catheter local anesthetic infusion rates.

Unfractionated Heparin Dosing for Venous Thromboembolism in Morbidly Obese Patients: Case Report and Review of the Literature

Unfractionated heparin infusion therapy is often administered using a weight-based dosing strategy for the treatment of venous thromboembolism. In the last several decades, the prevalence of obesity in the United States has increased significantly. The applicability of weight-based heparin dosing recommendations in the obese and morbidly obese population is uncertain, as limited data are available. We describe a 388-kg man who was started on an intravenous infusion of heparin according to hospital protocol for suspected pulmonary embolism. The patient was given a 5000-unit heparin bolus followed by an initial heparin infusion rate of 1500 units/hour, the maximum initial rate specified in the protocol. After additional infusion rate adjustments, a therapeutic activated partial thromboplastin time (aPTT) was reached 55 hours later with a heparin infusion rate of 3650 units/hour. Due to concerns of heparin-induced thrombocytopenia, heparin therapy was discontinued, and fondaparinux 5 mg/day was started. However, heparin therapy was restarted 4 days later for persistent, refractory hypoxemia and recurrent concerns of possible pulmonary embolism. During this second course, a therapeutic aPTT was achieved with a heparin infusion rate of 3550 units/hour. The patient developed bloody pulmonary secretions (with a therapeutic aPTT), necessitating the discontinuation of the heparin infusion. The patient later died after developing pulseless electrical activity. Standard weight-based heparin dosing protocols that specify maximum doses for initial bolus and infusion rates can result in significant delays in time to achieve therapeutic anticoagulation in the obese and morbidly obese patient. Despite limited data on heparin dosing in obesity, we recommend the use of a dosing weight to determine initial heparin dosing when treating venous thromboembolism in morbidly obese patients. It is reasonable to consider one of the following formulas: dosing weight = ideal body weight (IBW) + 0.3(actual body weight [ABW] - IBW), or dosing weight = IBW + 0.4(ABW - IBW).

Groundbreaking Summit

Groundbreaking Summit

Evaluation of Compliance with a Paper-based, Multiplication-factor, Intravenous Insulin Protocol

Hyperglycemia is common in critically ill patients and is an independent risk factor for in-hospital morbidity and mortality. To assess compliance with a paper-based, multiplication-factor, intravenous insulin protocol. A retrospective chart review was conducted in a 720-bed urban, academic medical center in Boston, Massachusetts. During a 1-month period, compliance with and the consequent safety and efficacy of the Brigham and Women's Hospital paper-based, multiplication-factor, intravenous insulin protocol was evaluated. The primary endpoint of protocol compliance, defined as correct adjustment to insulin infusion rate and correct timing of bedside blood glucose concentration (BBGC) checks +/-10 minutes of prespecified BBGC check according to the Brigham and Women's Hospital Intravenous Insulin Protocol (BHIP), was 47.2%. Seventy-two patients met inclusion criteria. Appropriate adjustment of infusion rates occurred 68.2% (1206/1768) of the time. Compliance with the timing of BBGC checks was found to be the majority of protocol violations. BBGCs were monitored +/-5 minutes of indicated time per the protocol 26.2% (463/1768) of the time. Blood glucose concentration checks within extended timing of +/-10 minutes of indicated time per the protocol occurred 793 (44.8%) times. Blood glucose concentration monitoring took place greater than 20 minutes past indicated time 450 (25.5%) times. In 1768 measurements, blood glucose concentrations between 40 and 60 mg/dL occurred 23 (1.3%) times in 12 (16.7%) patients. Blood glucose concentrations 40 mg/dL or less were detected 3 (0.17%) times in 2 (2.7%) patients. None of these hypoglycemic events led to documented complications. Overall, a rather low level of compliance with a paper-based, multiplication-factor, intravenous insulin protocol was observed, which warrants further investigation. Compliance rates in this evaluation were found to be similar to the rates observed in previously evaluated fixed-dose intravenous insulin protocols. Protocol noncompliance may be associated with hypo- and hyperglycemia.

Estimation of Future Glucose Concentrations with Subject-Specific Recursive Linear Models

Estimation of future glucose concentrations is a crucial task for diabetes management. Predicted glucose values can be used for early hypoglycemic/hyperglycemic alarms or for adjustment of insulin injections or insulin infusion rates of manual or automated pumps. Continuous glucose monitoring (CGM) technologies provide glucose readings at a high frequency and consequently detailed insight into the subject's glucose variations. The objective of this research is to develop reliable subject-specific glucose prediction models using CGM data. Two separate patient databases collected under hospitalized (disturbance-free) and normal daily life conditions are used for validation of the proposed glucose prediction algorithm. Both databases consist of glucose concentration data collected at 5-min intervals using a CGM device. Using time-series analysis, low-order linear models are developed from patients' own CGM data. The time-series models are integrated with recursive identification and change detection methods, which enables dynamic adaptation of the model to inter-/intra-subject variability and glycemic disturbances. Prediction performance is evaluated in terms of glucose prediction error and Clarke Error Grid analysis (CG-EGA). Prediction errors are significantly reduced with recursive identification of the models, and predictions are further improved with inclusion of a parameter change detection method. CG-EGA analysis results in accurate readings of 90% or more. Subject-specific glucose prediction strategy has been developed. Including a change detection method to the recursive algorithm improves the prediction accuracy. The proposed modeling algorithm with small number of parameters is a good candidate for installation in portable devices for early hypoglycemic/hyperglycemic alarms and for closing the glucose regulation loop with an insulin pump.

Antithrombin Alfa in Hereditary Antithrombin Deficient Patients at High Risk for Thromboembolic Complications

Antithrombin alfa (ATryn®) is approved in EU for the prophylaxis of venous thromboembolism in patients with hereditary AT deficiency (HD) undergoing surgery. Pregnant HD patients are often also treated with AT replacement therapy, as the peri-partum period provides a high risk of developing venous thromboembolic complications. Population PK analysis of the peri-partum and peri-operative data of HD patients treated in a previous study of antithrombin alfa found that a significantly different pharmacokinetic profile exists in pregnancy compared to surgery, suggesting pregnant HD patients would require a revised dosing algorithm to achieve and maintain the target AT activity level (80–120%). Additionally, the therapeutic drug monitoring (TDM) guidelines were optimized for all patients. Both these revisions were applied in a multi-center, multinational, single arm, open label study with antithrombin alfa treatment for the prevention of peri-operative and peri-partum thromboembolic events in HD patients. Adult patients with HD, who had a personal history of venous thromboembolic events (VTE) and were in a high-risk situation for the occurrence of VTE were included. Pregnant women about to deliver (spontaneous, induced or cesarean section) were given a 15 minute IV loading dose calculated as: Loading dose (IU/kg) = (100 minus pretreatment antithrombin activity in %) divided by 1.25. Maintenance dose immediately followed loading dose: Maintenance dose (IU/hour/kg) = (100 minus pretreatment antithrombin activity in %) divided by 5.43. Loading and maintenance dose for surgical patients were calculated as: Loading dose (IU/kg) = (100 minus pretreatment antithrombin activity in %) divided by 2.28; Maintenance dose (IU/hour/kg) = (100 minus pretreatment antithrombin activity in %) divided by 10.22. TDM was used to check plasma AT activity and adjust infusion rate accordingly. AT activity had to be checked 2 and 6 hours after start of loading dose or change of infusion rate, and thereafter 1 or 2 times per day. When AT activity levels were <80% or >120%, infusion rate was respectively increased or decreased by 30%. Twelve pregnant HD patients and 6 surgical patients (M/F=14/4) were treated in the study. Median age was 34.5 (range 21–62). Delivery procedures included 4 cesarean sections. Surgical procedures included major joint replacement (2), neurosurgery, femoropopliteal bypass, laparoscopic cholecystectomy and pulmonary thromboendarterectomy (on cardiopulmonary bypass). Patients were treated for a median of 3.2 days (range 0.9–14) and needed a median of 1 (range 0–6) infusion rate adjustments. All but 1 patient used other anticoagulants (17 heparin, 9 Vit K antagonist, 1 platelet aggregation inhibitor). All patients were examined for VTE during treatment and on the 7th day post-treatment. Signs and symptoms indicative for a VTE had to be followed up with appropriate diagnostic assessment tools. Patient sera were collected up to 90 days post-treatment to test for an immunological reaction to antithrombin alfa or goat milk proteins. One pregnant patient was only treated for 1 day and therefore excluded from the per protocol population. No patient (per protocol or ITT) suffered a confirmed VTE during treatment or up to 7 days post-treatment. Adverse events were usually mild, and as can be expected in surgical and delivery patients. Serious adverse events assessed related to study drug were haemarthrosis and intra-abdominal hemorrhage, both recovered. No confirmed specific immune reaction to antithrombin alfa or goat milk proteins occurred in the 17 patients tested. It was concluded that antithrombin alfa is safe and efficacious in preventing VTE and the revised dosing algorithm performed well in pregnant patients. This abstract is presented by the authors on behalf of the “antithrombin alfa study group”.

Considerations for Drug Dosing Post Coronary Artery Bypass Graft Surgery

Acute physiologic changes after bypass graft surgery may temporarily result in reduced drug elimination and dosing requirements for the desired effect. Substantially lower doses for drugs such as the direct thrombin inhibitor argatroban may need to be considered when initiating therapy soon after surgery if the therapeutic window is narrow and impaired liver, kidney, or cardiac function is present. Initial dosing approaches, with follow-up infusion rate adjustments and allowances for the extended time needed to establish and maintain an activated partial thromboplastin time value in the target ratio range, also need to consider the risk of thrombosis or bleeding complications. The duration of reduced dosing may depend on several variables, and, as systems recover, the dosage may need to be adjusted upwards. Retrospective analysis for identifying heparin-induced thrombocytopenia may be difficult in situations where other causes of thrombocytopenia are present, suggesting that posttest scoring methods also be considered to confirm its presence until better, validated methods become available.

Effects of remifentanil infusion regimens on cardiovascular function and responses to noxious stimulation in propofol-anesthetized cats

To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats. 8 adult cats. On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, i.v.) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 microg/kg/ min, i.v.) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (> or = 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II). In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 microg of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 microg of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 microg/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes. Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 microg/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.

Acute MDMA and ethanol interaction effects on psychomotor performance

Introduction: A considerable percentage of young people expose themselves to 3,4‐methylenedioxy‐methamphetamine (MDMA or ‘ecstasy’). Alcohol is relatively commonly used in combination with MDMA (Barrett et al., 2005). As a percentage of MDMA users admit to driving under influence (Riley et al., 2001), the assessment of the effects of co‐administration of these substances on psychomotor performance is warranted.Hypothesis: We hypothesized that the co‐administration of MDMA and ethanol would ameliorate the impairment induced by ethanol alone.Methods: We performed a double‐blind, randomized, placebo‐ controlled study in 16 healthy volunteers (9 male, 7 female) in the age of 18–29 years. MDMA 100 mg was given orally and blood alcohol concentration (BAC) was maintained at 0.6‰ by a three hour 10% alcohol infusion regime (adjustment of infusion rate according to regular sampled breath alcohol concentration). Saccadic and smooth pursuit eye movements, a validated measure of ethanol induced sedation (van Steveninck et al., 1999), were recorded using Nihon Kohden® and Cambridge Electronic Design (CED®) hardware and Spike2® software at 1 : 35 post drug administration. Results were statistically evaluated using GLM in SPSS® 11.5.Results: Results are presented in table 1. Saccadic peak velocity was increased after MDMA (p=0.000). Co‐administration showed significant increase in peak saccadic velocity compared to placebo (p=0.004), although significantly less then the increase as observed after MDMA alone (p=0.003). Smooth pursuit was significantly impaired after ethanol compared to placebo (p=0.000) and MDMA (p=0.000), co‐adminstration also impaired score compared to placebo (p=0.000) and MDMA (p=0.000). Eye movement scores per drug Eye movements Placebo Ethanol MDMA Ethanol + MDMA Mean SD Mean SD Mean SD Mean SD Peak saccadic ◆, ♠ *, •, ♠ *, •, ◆ velocity (deg/s) 458,1 66,1 452,8 54,8 543,5 76,3 497,2 65,8 Saccadic reaction time (ms) 190,8 25,3 194,4 26,1 193,0 24,9 191,6 24,9 Average smooth *, ◆ •, ♠ *, ◆ pursuit (%) 49,08 12,00 37,56 9,72 52,74 14,30 38,90 9,85 *=Significant vs. placebo, • =Significant vs. ethanol, ◆=Significant vs. MDMA, ♠ = Significant vs. MDMA + ethanol. Conclusions: MDMA induced arousal as measured by the saccadic peak velocity when administered alone and, to a lesser degree, in combination with ethanol. Co‐administration of MDMA with ethanol however could not ameliorate the deterioration of psychomotor accuracy by ethanol as measured by smooth pursuit eye movements. These findings suggest that although MDMA might ameliorate ethanol induced sedation it does not ameliorate impaired psychomotor skills. This might give a false sense of improved performance while intoxicated and thus increases risks of for example road accidents.

The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects

In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (±SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 ± 0.1 vs 3.9 ± 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 ± 0.04 vs 0.21 ± 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 ± 0.13 vs 0.96 ± 0.09 mmol/L; P < .05), free glycerol (1.30 ± 0.07 vs 0.76 ± 0.08 mmol/L; P < .001), and β-OH butyrate (1.61 ± 0.44 vs 1.17 ± 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 ± 0.62 vs 3.15 ± 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of infused TG during the steady-state period ( r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.

Closed-Loop Resuscitation of Burn Shock

Fluid therapy for burn shock is adjusted to establish a target level of urinary output. However, the means for adjusting infusion rate are not defined. Our objective was to compare the performance of automated computer-controlled resuscitation with manual control for burn resuscitation. Sheep with a 40% TBSA full-thickness burn, administered under halothane anesthesia, were resuscitated to restore and maintain normal sheep urinary outputs in a target range of 1 to 2 ml/kg per hour over the course of 48 hours using closed-loop resuscitation (n = 10) or manual hourly adjustment of infusion rate (n = 11). The automated closed-loop resuscitation system is based on a proportional-integral-derivative algorithm, which adjusted infusion rate based on continuous monitoring and changes in urinary output. Mean urinary outputs over the course of 48 hours were in target range and were virtually identical at 1.9 +/- 0.5 ml/kg per hour for the closed-loop group and 2.0 +/- 0.7 ml/kg per hour for the technician group. Mean infusion rates and infused volumes also were similar. The closed-loop group exhibited significantly lower hourly variation for both urinary output and infusion rate compared hourly control. Hourly targets were achieved in 41% of the measurements in technician group compared with 48% for the closed-loop group (P = .23). Hourly urinary output in the technician group was undertarget by 25% as opposed to 16% with the closed-loop group (P = .02). Automated closed-loop control of infusion rates after burn injury produced urinary outputs in target ranges with less variation and less under target values than manual hourly adjustments. Closed-loop resuscitation may provide an improvement over current resuscitation regimens.

An Audit of Morphine versus Fentanyl as an Adjunct to Ropivacaine 0.2% for High Thoracic Epidural Analgesia

When used as an adjunct to local anaesthetic, opioid administered via the epidural route can improve the quality of analgesia. Reports of respiratory depression associated with epidural morphine use as a sole agent in the 1980s led to an increased use of lipophilic opioids, especially fentanyl. Although fentanyl is commonly used, controversy exists about its efficacy and site of action. It is possible that low-dose morphine may be more effective than fentanyl, without increasing the risk of respiratory depression. A retrospective audit was conducted of 200 consecutive patients undergoing coronary artery bypass surgery who received high thoracic epidural analgesia. One hundred patients who received fentanyl 2 microg/ml with 0.2% ropivacaine, prior to a change in our technique, were audited, followed by 100 patients who received 20 microg/ml morphine with 0.2% ropivacaine. Outcome measures included the incidence of Visual Analogue Score (VAS) > or =4/10; infusion rate adjustments; and side-effects. Patients receiving fentanyl were more likely to experience pain > or =4/10 (P' = 0.002); the infusion rate was higher (P' = 0.024); required more rate adjustments (P' = 0.001); a greater need for noradrenaline (P' = 0.001) and antiemetic drugs (P' = 0.001). There were no significant differences between the groups for sedation scores or the incidence of respiratory depression. This audit suggests morphine 20 microg/ml may be superior to fentanyl 2 microg/ml, as an adjunct to 0.2% ropivacaine. We found a reduced number of infusion interventions and less inadequate patient analgesia.

Index of Suspicion in the Nursery

Index of Suspicion in the Nursery

Clinical uses of intravenous immunoglobulin

There has been a rapid expansion in the use of intravenous immunoglobulin (IVIG) for an ever growing number of conditions. It is a product with an excellent safety record without the side effects of steroids or other immunosuppressive agents. There have been numerous recent advances in our understanding of the mechanisms of action of IVIG in many of the conditions for which it is being used, but there is still much to be learned. IVIG has had a major impact in neurology, haematology, immunology, rheumatology and dermatology. The limitations for IVIG are cost of the preparation itself and the logistical problems associated with its administration. Many of the side effects are managed easily by careful screening of the patient prior to treatment, premedication with analgesics and antihistamines and adjustment of infusion rate. It is likely, however, that side effects will be more frequent as the dose given increases and effects on plasma viscosity become greater [122]. It will be important to increase the evidence base for IVIG in many conditions to define its therapeutic role. In addition, there have been very few dose-ranging studies for hdIVIG and fewer still of which adjunctive agents (including biological agents such as rituximab and daclizumab) might offer the best therapeutic combinations. Although not established, the use of IVIG is being studied in a range of conditions including heart failure, mycobacterial infection, adult respiratory distress syndrome, transplantation, fibrosis, connective tissue disease, encephalitis, epilepsy and even Alzheimer's disease. Should IVIG prove to be of efficacy in these settings it is likely to have major implications for drug budgets as many of the conditions are very common and place great strain on the world's supply of IVIG itself. Future studies will therefore need to address questions of efficacy, pharmacoeconomics, dose, adjunctive therapies and mechanism of action which may point the way to novel treatment strategies beyond IVIG. It is also clear, however, that controlled trials in many of the rare conditions may be very difficult to carry out and approaches such as prospective disease registries may be needed.

Retrospective Audit of a Factor VIII Continuous Infusion Protocol to Examine Inhibitor Formation, Complications and Product Use.

Continuous infusion (CI) of factor concentrates has been suggested to decrease both the risk of bleeding and cost in the treatment of bleeding disorders. However, concerns have been raised with regards to the stability and sterility of products administered by CI and the risk of local thrombophlebitis. Most recently, there has been a concern about a potential association between the use of CI and the development of an inhibitor in mild hemophilia. A retrospective chart review was conducted to determine the effectiveness, safety, product use and risk of inhibitor formation of a continuous infusion protocol in the management of hemophilia A. Currently 248 patients are registered with the Provincial Hemophilia Program for Newfoundland and Labrador. These patients include 104 with mild hemophilia A, 3 with moderate hemophilia A and 5 with severe hemophilia A. The charts of twelve hemophilia A patients who received factor VIII (FVIII) by CI a total of 18 times between April 1998 and September 2003 were reviewed. All patients were affected by hemophilia A; 8 patients were diagnosed as mild, 1 as moderate and 3 as severe. The mean age of the cohort was 36.1 years and the patients' ages ranged from 4 months to 75 years. Continuous infusion was used as treatment for severe bleeds in 12 cases and as prophylaxis for surgical procedures in 6 cases. All patients received recombinant FVIII. Recommended devices such as a syringe pump and mini-pump were unavailable therefore all infusions were carried out by diluting the reconstituted concentrate in saline and delivering via IV infusion. The CI protocol followed required a bolus of 50 U/kg of FVIII followed by CI at an initial rate of 4 U/kg/hr. Based on daily FVIII levels, this maintenance dose could be adjusted, with an initial targeted FVIII level of 1.0 U/L. The maximum initial infusion rate was 6.7 U/kg/hr and the minimum was 3.2 U/kg/hr (mean 4.3 U/kg/hr). The infusion rate was reduced in 8 cases to a minimum of 1.2 U/kg/hr. Adequate FVIII levels were maintained after the reduction of the infusion rate in all cases. The mean low and high FVIII levels were 0.79 U/L and 1.23 U/L, respectively (range 0.05 to 1.82 U/L). Excluding the patient who developed an inhibitor, the FVIII level remained above the minimum acceptable level of 0.3 U/L for the duration of CI in all but one case (low 0.29 U/L). Patients required an average dose of 53,163 units (range 2651–299,137 units) of factor concentrate delivered by continuous infusion over a mean period of 8.1 days (range 2–21 days). FVIII infusion was well tolerated in all cases; there were no documented cases of significant bleeding, adverse reactions, thrombophlebitis or infection. One patient was documented to have a minor bleed from an NG tube despite adequate FVIII levels throughout the period of infusion. One patient with mild hemophilia developed a low titer inhibitor (0.8 BU) approximately 2 years after receiving FVIII by continuous infusion for 8 days. Another mild hemophilia patient was discovered to have a low titer inhibitor (1.3 BU) on the eighth day after the third infusion had begun. It is possible that CI contributed to the development of an inhibitor in this patient. CI was not found to significantly reduce product use. More rapid downward adjustment of infusion rates in response to high FVIII levels might improve product utilization.

Cefepime desensitization in a patient with cystic fibrosis

Rationale We report a case of successful parenteral desensitization to cefepime in a cystic fibrosis patient with multiple β-lactam sensitivities. A 36 year old male with cystic fibrosis experiencing a pulmonary exacerbation failed to improve on ciprofloxacin, linezolid and trimethoprim/sulfamethoxazole. He had a history of significant urticaria to penicillin, ceftazidime, aztreonam, and imipenem/cilastatin. Sputum culture revealed moderate growth of Pseudomonas aeruginosa and he was admitted to the intensive care unit for close vital sign observation during a cefepime desensitization procedure. Methods Review of patient history confirmed that the patient was not receiving a beta-blocker drug. Epinephrine and diphenhydramine were available nearby if needed. Desensitization was achieved with 5 minute infusions of cefepime, starting from an initial dose of 0.032mg, followed by a 10 minute observation period. Doses were progressively doubled in a similar fashion at 15 minute intervals to a final dose of 2 grams which was given over 15 minutes. A novel electronic ordering protocol was used for serial dilution and administration instruction. Only three concentrations were mixed for infusion: 4mg/100ml, 100mg/50ml, and 2000mg/100ml; with adjustment of infusion rate to achieve appropriate dose with 16 total doses. Results After desensitization, the patient was able to tolerate scheduled infusions of cefepime at maximum dose without complications. Conclusions Cefepime may be successfully administered to patients with a history of hypersensitivity reactions. It may be especially helpful in cystic fibrosis patients where multiple drug sensitivities are often prevalent.

Corticosteroid-sparing treatments in patients with Crohn's disease.

Conventional corticosteroid therapy effectively induces remission of Crohn's disease (CD) across a range of disease severity. However, alternative treatments are needed for patients with disease unresponsive to corticosteroids, patients requiring maintenance therapy (for which corticosteroids are ineffective), corticosteroid-dependent patients, and patients with corticosteroid-related toxicities. Thus, corticosteroid-sparing effects are an important clinical endpoint for treatments of CD. Budesonide offers comparable efficacy with less short-term toxicity than conventional corticosteroids (prednisone, prednisolone); this agent has also demonstrated short-term remission maintenance efficacy, while potentially enabling withdrawal of more toxic corticosteroids in corticosteroid-dependent patients. However, budesonide has not shown long-term maintenance benefit in clinical studies, and the risk for and implications of budesonide dependency need further evaluation. The immunomodulators, azathioprine and 6-mercaptopurine, are most effective for maintenance of remission in quiescent disease, but may be useful in conjunction with other therapies in inducing remission in active CD; methotrexate may be considered an alternative because of its efficacy in inducing and maintaining remission. In clinical trials, treatment with azathioprine/6-methotrexate has enabled corticosteroid withdrawal in 55% of patients, and methotrexate, in 39% of patients with corticosteroid-dependent CD, while maintaining clinical response. Monitoring for infrequent hematological or hepatic toxicity is recommended during use of these immunomodulators. Infliximab is effective for induction and maintenance of remission in patients with refractory CD participating in randomized placebo-controlled studies and, in open-label experience, has enabled corticosteroid withdrawal in approximately three quarters of patients. This biological agent is generally well tolerated. Infusion reactions are the most commonly occurring side effects; such reactions may require adjustment of infusion rate and/or treatment with an antihistamine or acetaminophen. The investigational biological agent CDP-571 has also shown corticosteroid-sparing efficacy in patients with CD. In conclusion, recent research has helped identify corticosteroid-sparing treatments that can provide benefit in patients with corticosteroid-dependent and/or corticosteroid-refractory CD or patients at risk for corticosteroid-induced toxicities.

Total intravenous anesthesia with remifentanil, propofol and cisatracurium in end-stage renal failure.

To compare recovery parameters of total intravenous anesthesia (TIVA) with remifentanil and propofol, hemodynamic responses to perioperative events, and pharmacodynamic parameters of cisatracurium in 22 end-stage renal failure and 22 normal renal function patients. Anesthesia was induced with 2-3 mg x kg(-1) propofol and 1 microg x kg(-1) remifentanil and maintained with 75 microg x kg(-1) x min(-1) propofol and propofol initial infusion of 0.2 microg x kg(-1) x min(-1) propofol. Arterial pressure and heart rate were maintained by remifentanil infusion rate adjustments. The first twitch (T1) was maintained at 25% by an infusion of cisatracurium. There was no difference in the time to maintenance of adequate respiration, date of birth recollection, first analgesic administration, between the renal failure (4.8+/-2.5, 7.8+/-3.2, 12.3+/-5.3 min respectively) and the control group (5.2+/-2.8, 8.1+/-3.1, 12.7+/-5.5 min): nor were there any differences in the time to 25% T1 recovery, T1 recovery from 25% to 75%, or cisatracurium infusion rate between the renal failure group (32.1 +/-10.8 min, 18.2+/-5.5 min, 0.89+/-0.29 microg x kg(-1) min(-1) respectively) and the control group (35.9 (7.9 min, 18.4+/-3.8 min, 0.95+/-0.22 microg x kg(-1) x min(-1)). End-stage renal failure does not prolong recovery from TIVA with remifentanil and propofol, or the recovery from cisatracurium neuromuscular block.

The Effect of Intravenous Ketoprofen on Postoperative Epidural Sufentanil Analgesia in Children

We compared the effect of IV ketoprofen and placebo as an adjuvant to epidural sufentanil analgesia after major surgery.We used a prospective, randomized, double-blinded, placebo-controlled, parallel-group study design in 54 children aged 1-15 yr who received a standardized anesthetic. Either IV ketoprofen or saline was administered in addition to an epidural sufentanil infusion, which was adjusted as required clinically. The study drug infusions were discontinued when pain scores were <3 on 0-10 scale for 6 h at a sufentanil infusion rate of 0.03 [micro sign]g [middle dot] kg-1 [middle dot] h-1. Children in the ketoprofen group had a better analgesic effect, as shown by decreased need for sufentanil (mean [10th-90th percentiles] 8.3 [3.1-15.1] [micro sign]g/kg vs 12.5 [6.2-18.9] [micro sign]g/kg; P = 0.002) and earlier possibility to discontinuation of the epidural sufentanil (11 [46%] vs 3 [13%]; P = 0.014) before the end of the 72-h study period. In the ketoprofen group, median (range) pain scores were lower during activity at 24 h (2 [0-5] vs 5 [0-7]; P = 0.01) and at 72 h (0 [0-3] vs 2 [0-6]; P = 0.033), and fewer children had inadequate pain relief during activity at 24 h (0 vs 5; P = 0.037). Children who received ketoprofen required fewer infusion rate adjustments (12 [4-20] vs 17 [6-42]; P = 0.016). In the ketoprofen group, the incidence of desaturation (1 [4%] vs 6 [26%]; P = 0.035) and fever (3 [12%] vs 11 [48%]; P = 0.008) was less than that in the placebo group. We conclude that ketoprofen improved postoperative pain in children. Implications: We compared the effect of the IV nonsteroidal antiinflammatory drug ketoprofen versus placebo as adjuvants to epidural opioid analgesia with sufentanil. The continuous IV nonsteroidal antiinflammatory drug improved pain after major surgery in children receiving an epidural opioid. Although ketoprofen reduced epidural sufentanil requirements, the incidence of opioid-related adverse effects was not changed. (Anesth Analg 1999;88:1036-41)

Adjustment of magnesium sulfate infusion rate in patients with preterm labor

Objective: Our purpose was to investigate factors that might influence serum magnesium levels during intravenous magnesium sulfate tocolytic therapy. Study Design: Thirty-three women receiving magnesium sulfate for preterm labor participated in this prospective, observational study. Gestational ages were 24 to 34 weeks. Four groups of women were identified according to the maintenance magnesium infusion rate required for arresting preterm labor after 5 g of therapy induction: 1.5, 2, 2.5, and 3 g/h. Serum magnesium samples were drawn after a predefined period of at least 18 hours of arrested preterm labor, at a minimum of every 6 hours. Variables examined included serum albumin; serum protein; serum ionized calcium; serum creatinine; creatinine clearance; 24-hour urine output; maternal height, weight, body surface area; and body mass index. Results: By use of a multivariate stepwise regression model we identified four variables that independently and significantly contributed to the model: magnesium infusion rate (P < .001); total serum protein level (P < .001); serum creatinine level (P = .009); and maternal weight squared (P = .026). Seventy-two percent of the variance was accounted for by use of these parameters. A predictive linear model, developed to relate these factors, produced the following formula: Suggested magnesium infusion rate = 0.89 × Serum magnesium concentration (mg/dL) – 3.16 × Serum creatinine (mg/dL) – 0.66 × Serum total proteins (g/dL) + 0.0001 × (maternal weight)2 (kg) + 2.30. Conclusions: Serum creatinine, serum protein, and maternal weight can be used to adjust the dose of magnesium sulfate in patients with premature labor to achieve therapeutic serum levels of magnesium more rapidly and safely. (Am J Obstet Gynecol 1998;179:994-8.)