Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus. Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure. Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain. Efficacy of continuous low-dose human atrial natriuretic peptide given from the beginning of cardiopulmonary bypass for thoracic aortic surgery. A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery. [Subcutaneous injections and intravenous infusion of sodium salt of heparin in the treatment of thrombosis of deep veins of the lower extremities]. A randomised placebo controlled trial of loop diuretics in moderate/severe pre-eclampsia, following delivery.
To evaluate the safety and relative effectiveness of two diuretic protocols in the intensive care unit (ICU).
                Prospective, randomized comparative study.
                Thirty-three cardiac and medical ICU patients with pulmonary edema or fluid overload for which aggressive diuresis was intended.
                Enrolled patients were randomized to fluid management strategies combining fluid restriction and individually adjusted diuretic therapy by either continuous or bolus infusions of furosemide, titrated to achieve negative hourly fluid balance.
                Cumulative intake minus output (primary endpoint); change in serum creatinine, and length of ICU and hospital stay (secondary endpoints). Diuresis by either protocol was feasible, safe, and effective. The main outcome measures were not significantly different for either group managed with a standardized protocol.
                Protocol-guided diuretic management, with individualized titration of dosage to defined physiologic endpoints can be readily and safely implemented in the ICU. Both continuous and bolus diuretic regimens appear equally effective in achieving negative fluid balance. Larger studies with a randomized control arm are needed before these protocols can be recommended as routine practice. Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure. To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned. Cardiac surgery performed under cardiopulmonary bypass (CPB) causes abnormalities of the renin-angiotensin-aldosterone system, resulting in decreased urine output and an accumulation of water in the third space. We studied the efficacy of continuous low-dose human atrial natriuretic peptide (hANP) in patients undergoing thoracic aortic surgery.
                We divided 40 patients undergoing thoracic aortic surgery into two groups: the hANP group, which received 0.02 microg/kg per minute of hANP and the non-hANP group, which did not. The hemodynamics, urine output, intensive care unit (ICU) and hospital stay, bleeding volume, homologous blood transfusion volume, furosemide dose, corrected KCl volume, and postoperative respiratory, hepatic, and renal function were compared in the two groups.
                The urine output during CPB and from CPB weaning to return to ICU was significantly better in the hANP group. The bleeding volume, homologous blood transfusion volume, furosemide dose, and corrected KCl volume were all significantly less in the hANP group.
                These findings support the consensus that hANP exerts its diuretic effects to their full potential when administered continuously at low doses during thoracic aortic surgery. We found it to be effective for postoperative hemostasis and for preventing ischemic reperfusion injury. We hypothesized that, in vascular surgery patients, the application of a goal-directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and/or inotropes required in such a goal-directed therapy depended on the general anaesthetic technique used.
                Patients undergoing peripheral arterial bypass grafting were randomly assigned to three groups. In group 1, haemodynamic management was performed according to routine clinical practice. In the two other groups (groups 2 and 3) a goal-directed therapy was applied aiming to maintain the pulse contour-derived cardiac index above 2.5 l m min. Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia. Haemodynamic variables, amount of fluid and administration of inotropes were assessed at different time intervals.
                The amount of fluid administered was not significantly different between the groups. Two patients in group 1, 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine (P < 0.001). None of the patients anaesthetized with sevoflurane (groups 1 and 2) experienced postoperative cardiovascular complications, whereas four patients in the total intravenous group (group 3) experienced major postoperative cardiovascular complications (P = 0.005).
                In the conditions of the present study, the application of a goal-directed therapy aiming to maintain the cardiac index above 2.5 l min m did not result in a higher tissue oxygen delivery than when applying the standard haemodynamic strategy nor did it depend on the anaesthetic technique used. Ninety-four patients with deep vein thrombosis of inferior limbs were randomly allocated to receive sodium heparin either by subcutaneous injections or by continuous intravenous infusion for six days. No significant difference was observed in the therapeutic efficiency as judged by phlebographic examinations and in rate of symptomatic pulmonary embolism between the two groups. There was one instance of major bleeding in the subcutaneous group. Minor bleedings occurred in 10 of the 48 patients treated with subcutaneous heparin and in 13 of the 46 patients receiving intravenous heparin. The results showed that subcutaneous injections of sodium heparin are as effective and safe as continuous intravenous infusion of this drug in the treatment of deep vein thrombosis. Nineteen patients with pre-eclampsia were randomised to receive 40 mg of frusemide or placebo by mouth daily for 7 days in the first post-partum week. Outcome measures included mean and maximum blood pressure, the need for additional antihypertensive treatment during that period and mean length of hospital stay. There were no statistically significant differences in outcome between the treatment and placebo groups although there was a trend to more rapid lowering of blood pressure following delivery in those receiving frusemide.
Currently available data are insufficient to confidently assess the merits of the two methods of giving intravenous diuretics. Based on small and relatively heterogenous studies, this review showed greater diuresis and a better safety profile when loop diuretics were given as continuous infusion. The existing data still does not allow definitive recommendations for clinical practice and larger studies should be done to more adequately settle this issue.