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Continuous intravenous infusions of lorazepam versus midazolam for sedation during mechanical ventilatory support: a prospective, randomized study.

OBJECTIVE: To evaluate the efficacy of continuous infusions of lorazepam vs. midazolam for sedation in the intensive care unit (ICU). DESIGN: Prospective, randomized study. SETTING: Large, urban university hospital. PATIENTS: Twenty adult medical ICU patients receiving mechanical ventilatory support. INTERVENTIONS: Patients were randomized to receive either lorazepam or midazolam. The infusion rate was adjusted at the bedside by the ICU nurse according to a standardized study protocol to achieve and maintain sedation at Ramsay's sedation level 2 or 3. MEASUREMENTS AND MAIN RESULTS: Ten patients were randomized to receive lorazepam and ten to receive midazolam. The groups were similar in demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, ICU admission diagnosis, underlying disease processes, and supplemental analgesic administration. The mean time to achieve initial adequate sedation was 124 mins for lorazepam and 105 mins for midazolam. The mean infusion rate at the point of initial sedation was 0.06 mg/kg/hr for lorazepam and 0.15 mg/kg/hr for midazolam. The maximum and mean infusion rates for the entire study period were 0.1 and 0.06 mg/kg/hr, respectively, for lorazepam and 0.29 and 0.24 mg/kg/hr, respectively, for midazolam. The number of infusion rate adjustments per day was 1.9 mg/kg/hr for lorazepam and 3.6 mg/kg/hr for midazolam. Of the surviving patients, the mean time to return to baseline mental status after discontinuation of the benzodiazepine infusion was 261 mins for lorazepam and 1815 mins for midazolam. The mean volume of fluid per day required to deliver the maximum dose of benzodiazepine was 1.2 L for lorazepam (maximum 2.4 L) and 1.3 L for midazolam (maximum 3.6 L). CONCLUSIONS: While there was a tendency to a longer time required for return to baseline mental status in patients receiving midazolam, this was not statistically significant. Findings of interest concerning both midazolam and lorazepam were: a) time to achieve sedation in medical ICU patients is often prolonged; b) actual dose requirements necessary to maintain sedation in this patient population are larger than the current literature describes; c) time to awaken after discontinuation of the infusion was occasionally delayed for > 24 hrs; d) large volumes of fluid were required to deliver these doses of drug via this route of administration.

Adult↗

Kinetics and dynamics of lorazepam during and after continuous intravenous infusion.

OBJECTIVE: To evaluate the kinetics and dynamics of lorazepam during administration as a bolus plus an infusion, using electroencephalography as a pharmacodynamic end point. METHODS: Nine volunteers received a 2-mg bolus loading dose of lorazepam, coincident with the start of a 2 microg/kg/hr zero-order infusion. The infusion was stopped after 4 hrs. Plasma lorazepam concentrations and electroencephalographic activity in the 13- to 30-Hz range were monitored for 24 hrs. RESULTS: The bolus-plus-infusion scheme rapidly produced plasma lorazepam concentrations that were close to those predicted to be achieved at true steady state. Mean kinetic values for lorazepam were as follows: volume of distribution, 126 L; elimination half-life, 13.8 hrs; and clearance, 109 mL/min. Electroencephalographic effects were maximal 0.5 hr after the loading dose, were maintained essentially constant during infusion, and then declined in parallel with plasma concentrations after the infusion was terminated. There was no evidence of tolerance. Plots of pharmacodynamic electroencephalographic effect vs. plasma lorazepam concentration demonstrated counterclockwise hysteresis, consistent with an effect-site equilibration delay. This was incorporated into a kinetic-dynamic model in which hypothetical effect-site concentration was related to pharmacodynamic electroencephalographic effect via the sigmoid Emax model. The analysis yielded the following mean estimates: maximum electroencephalographic effect, 12.7% over baseline; 50% effective concentration, 13.1 ng/mL; and effect-site equilibration half-life, 8.8 mins. CONCLUSION: Despite the delay in effect onset, continuous infusion of lorazepam, preceded by a bolus loading dose, produces a relatively constant sedative effect on the central nervous system, which can be utilized in the context of critical care medicine.

Adult↗

Continuous insulin intravenous infusion therapy for VLBW infants.

Very low birth weight (VLBW) infants less than 1,000 g often experience hyperkalemia and hyperglycemia during the initial hospital course. Hyperkalemia has been noted in 44% to 50% of infants less than 800 g birth weight or less than 28 to 29 weeks' gestation. Hyperglycemia occurs 18 times more frequently in infants less than 1,000 g than in those weighing more than 2,000 g. Insulin has been used for VLBW infants less than 1,000 g to manage hyperkalemia, control hyperglycemia, and optimize parenteral nutrition. A protocol for using exogenous insulin therapy for VLBW infants is described.

Humans↗

Hemodynamic effects of a constant intravenous infusion of piroximone in patients with severe congestive heart failure.

The hemodynamic effects and serum levels of piroximone (MDL 19,205), a new inotropic agent with vasodilating properties, were measured in 10 patients with chronic severe congestive failure during a constant 48-h infusion. The initial five patients (group A) received piroximone at 10 micrograms/kg/min; however, because a sustained increase in heart rate greater than or equal to 25% from baseline developed in two patients and an episode of paroxysmal supraventricular tachycardia developed in another, the last 5 patients (group B) received an 8 micrograms/kg/min infusion. Because the steady-state hemodynamic alterations of group A prior to the onset of tachyarrhythmias were similar to those of group B, these results were combined. A significant increase in cardiac output from 3.65 +/- 0.31 (SE) to 5.20 +/- 0.49 L/min and decrease in pulmonary capillary wedge pressure (27 +/- 2 to 20 +/- 2 mm Hg), right atrial pressure (18 +/- 2 to 11 +/- 2 mm Hg), and systemic vascular resistance (1811 +/- 172 to 1293 +/- 80 dynes.s.cm-5) occurred (all p less than 0.05) without a significant change in mean arterial pressure. The peak plasma piroximone level was lower in the eight patients who did not develop a sustained increase in heart rate greater than or equal to 25% above baseline (2.1 +/- 0.5 micrograms/ml; range 1.6-2.9 micrograms/ml) than in the two who did (5.0 and 5.8 micrograms/ml). The latter two patients had the highest serum creatinine levels in the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Serum concentrations of erythromycin after intravenous infusion in preterm neonates treated for Ureaplasma urealyticum infection.

Erythromycin is receiving renewed attention as an alternative for treatment of neonatal infections caused by Ureaplasma urealyticum because of recently proved abilities of this organism to produce systemic disease in this population. Although erythromycin has been used clinically for almost 40 years, very little is known about its activity in the preterm neonate. Fourteen neonates, birth weights < or = 1500 g and < or = 15 days of age, from whom U. urealyticum was isolated from the lower respiratory tract were randomized to receive erythromycin lactobionate either 25 or 40 mg/kg/day in four divided doses at 6-hour intervals scheduled for a total of 10 days. Blood samples collected at multiple time points after initial and steady state doses were assayed for erythromycin by liquid chromatography. Minimal inhibitory concentrations (MICs) of erythromycin for the U. urealyticum isolates were determined. MICs ranged from 0.031 to 2 micrograms/ml; MIC90 = 2 micrograms/ml. Serum erythromycin concentrations met or exceeded most MICs, with peak values of 3.05 to 3.69 and 1.92 to 2.9 micrograms/ml for the 40- and 25-mg/kg/day dosage groups, respectively. Pharmacokinetic parameters were calculated after the initial dose and at steady state for both dosage groups and compared. No adverse effects thought to be related to administration of erythromycin were observed. These preliminary findings showed that erythromycin is well-tolerated, has favorable pharmacokinetic activity in the preterm neonate and should be further investigated for treatment of ureaplasmal infections.

Bacteriological Techniques↗

Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L-arginine during the early reperfusion period in pig liver transplantation.

BACKGROUND: The release of liver arginase after orthotopic liver transplantation (OLT) causes a deficiency of L-arginine and nitrite in the plasma. This deficiency is possibly related to pulmonary hypertension and reduced hepatic blood flow, which are commonly observed in the immediate reperfusion period. The aim of this study was to evaluate the impact of L-arginine supplementation on metabolic and hemodynamic parameters during liver reperfusion after OLT in pigs. METHODS: Thirteen pig OLTs (control group, n=6; arginine group, n=7) were performed by a standard technique. Cold ischemic time was 20 hr. L-Arginine was infused at a dosage of 500 mg/kg body weight into the donor pigs (30 min before liver explantation) and also into the recipients (over a period of 3 hr from the beginning of the reperfusion period). At the end of the experimental study, the pigs were killed with an overdose of potassium. RESULTS: In the control group, liver revascularization increased plasma arginase concentrations (+615%) and reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%). Infusion of L-arginine increased plasma levels of L-arginine from 94+/-21 micromol/L to 1674+/-252 micromol/L (P<0.001), L-ornithine from 46+/-8 micromol/L to 2215+/-465 micromol/L (P<0.001), and L-citrulline from 58+/-8 micromol/L to 116+/-34 micromol/L (P<0.001), but had no effect on plasma levels of nitrite and nitrate. Administration of L-arginine in the donor pigs did not produce any systemic or organ-specific hemodynamic alterations. Infusion of L-arginine into the recipient pigs improved cardiac performance (increase in heart rate [+61%, P=0.017] and cardiac index [+53%, P=0.005], reduction in pulmonary capillary wedge pressure [-54%, P=0.014]). Moreover L-arginine infusion increased oxygen consumption (+65%, P=0.003), reduced pulmonary vascular resistance index (P=0.001), stimulated portal venous blood flow (P=0.014), and elevated body temperature during the reperfusion period (P=0.007). CONCLUSIONS: From these data, we conclude that the infusion of L-arginine during OLT improves the hemodynamic performance of the heart, lung, and liver.

Animals↗

Decreasing errors in pediatric continuous intravenous infusions.

OBJECTIVE: To evaluate the effect of a Web-based calculator and decision-support system on infusion ordering errors and to estimate error frequency in pharmacy infusion preparation. DESIGN: Data on ordering error frequency and typology were collected before and after implementation of an online infusion ordering system. Data on pharmacy preparation errors of infusions were collected. SETTING: A children's hospital at an academic medical center. PATIENTS: None. Data were abstracted from infusion orders. INTERVENTIONS: Introduction of a voluntary-use Web-based calculator into infusion ordering workflow. Observation only. MAIN OUTCOME MEASURES: Number and type of errors in handwritten and calculator-generated orders. Number and type of errors in pharmacy infusion preparation. RESULTS: Before calculator deployment, 129 sequential handwritten infusion orders were collected over 5 weeks. After deployment, of 162 sequential infusion orders, 88% (142) were calculator-generated. Calculator-generated infusion orders contained 83% fewer (p < .001) orders containing one or more errors than handwritten orders. Calculator-generated orders contained no high-risk errors (incorrect decimal, dose, or unit of measure) when compared with handwritten orders and were associated with fewer pharmacy interventions. In 118 sequential pharmacy infusion preparations over 4 wks, there were no errors observed. CONCLUSION: A Web-based calculator reduced significantly the total number of errors and eliminated all high-risk errors in the prescribing process for continuous pediatric infusions. With no observed errors in pharmacy preparation, this study provides data to support the use of computerized ordering as an independent safe and viable method for ordering continuous pediatric infusions.

Chi-Square Distribution↗

Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatory dysfunction in experimentally induced pancreatitis in the rat.

OBJECTIVE: To evaluate the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis. SUMMARY BACKGROUND DATA: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue. METHODS: In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0-16). RESULTS: In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P < 0.001; 95% confidence interval for difference 17.5-45.3). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3-8.5 vs. 8-10.75, P < 0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3-8.5 vs. 6.5-10.25, P < 0.006)]. CONCLUSIONS: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.

Acute Disease↗