A multi-centre, double-blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety of liposomal PGE1 (TLC C-53) in patients with acute respiratory distress syndrome (ARDS), and determine its efficacy in improving oxygenation and reducing ventilator dependency. DESIGN: A multi-centre, randomized, double-blind, placebo-controlled clinical study. SETTING: Thirty-one hospitals in six European countries. PATIENTS: One hundred two patients with ARDS. INTERVENTIONS: Patients were randomized in a 2:1 ratio to receive infusions of either the study drug TLC C-53 or placebo. Infusions were given over 60 min every 6 h for 7 days. The dose of study drug started at 0.6 microg/kg per h, rising over 24 h to a maximum dose of 1.8 microg/kg per h. MEASUREMENTS AND MAIN RESULTS: Seventy patients received the study drug and 32 placebo. Sixty-nine patients (47 treatment, 22 placebo) completed the study protocol. Patients were monitored for changes in the PaO2/FIO2 ratio, changes in lung compliance, time to off-ventilator and 28-day mortality, in addition to basic haematological and haemodynamic parameters. There were no significant differences in demographics and baseline characteristics between the two groups. There were no differences in the time to off-ventilation (16 days with treatment, 16.6 days with placebo, p=0.94) or in 28-day mortality (30% with treatment, 28% with placebo, p=0.78). There was a difference in the time to achieve a PaO2/FIO2 ratio above 300 in favour of TLC C-53 (10.3 versus 26.5 days) but this was not statistically significant (p=0.23). CONCLUSIONS: TLC C-53 was generally well-tolerated but failed to reduce mortality or duration of mechanical ventilation.

Determinants of psychotropic drug usage in a general intensive care unit.

During a 3-month period, determinants of psychotropic drug utilization (sex, age, length of stay, reason for admission, disease severity) and data on psychotropic consumption (type of medication--antidepressants, benzodiazepines and antipsychotics--dosage and length of treatment) were retrospectively collected in a general intensive care unit of a Dutch university hospital. Daily exposure to psychotropics was standardized in number of Defined Daily Doses (DDD). Benzodiazepines were used by 35.8% of all patients (137) during their stay in the ICU whereas 17.5% of all patients used a neuroleptic agent. Antidepressants were hardly prescribed. High doses of benzodiazepines (9.9 DDDs) and low doses of antipsychotics (0.5 DDDs) were prescribed, which probably reflect the unusual nature of this critically ill group of patients compared with the reference group for DDD's. Clear patterns of determinants of psychotropic drug use in ICU patients were found and both benzodiazepines, antipsychotics and combined use of these agents could be associated with the determinants assessed. The time patterns we found in terms of length of stay give clues for further investigations in order to rationalize psychotropic drug use in the management of severely ill and complex patients.

Postcardiac surgery low cardiac output syndrome: dopexamine or dopamine?

OBJECTIVE: To compare the efficacy and safety of dopexamine with dopamine in the treatment of low cardiac output syndrome after cardiac surgery. DESIGN: This was a multicentre, double-blind, randomised, parallel-group study conducted in intensive care units at centres in Holland and Belgium. Patients were randomised to receive dopexamine (up to 2.0 micrograms/ kg per min) or dopamine (up to 6.0 micrograms/kg per min) for 6 h after low cardiac output syndrome was confirmed. RESULTS: 70 patients were enrolled (35/group) and there was no significant differences in the operative procedures or haemodynamics at entry into the study. Clinical efficacy, defined as a cardiac index > 2.5 l/min per m2 with urine production > 0.5 ml/kg per h and stable haemodynamics for two consecutive readings 1 h apart, was achieved by 90 and 87% of patients in the dopexamine and dopamine groups, respectively. However, more patients maintained clinical efficacy over the 6-h period in the dopexamine group, which was statistically significant at 1-2 h and approached significance at all other time points. Safety was assessed by comparing the adverse events and concomitant medication. Fewer patients on dopexamine had cardiac events compared with dopamine-treated patients (25 vs 38 events), although there was no difference in the pattern of rhythm disturbance. Fewer patients in the dopexamine group required concomitant vasodilating drugs (18 vs 30). CONCLUSION: Taking the proportion of patients achieving clinical efficacy, the time to achieve it and the maintenance of it along with the adverse event profile, dopexamine was shown to be an effective and safe drug to use in the management of low cardiac output syndrome after coronary artery bypass graft surgery and may be superior to dopamine.

Rapid diagnosis of acute meningococcal infections by needle aspiration or biopsy of skin lesions.

OBJECTIVES: To evaluate the usefulness of Gram staining and culture of skin lesions in patients with acute meningococcal infections. DESIGN: Retrospective study. SETTING: Community hospital and intensive care unit of a teaching hospital. SUBJECTS: 51 patients admitted from 1989 to 1993 with proved meningococcal infections and microbiological examination of specimens from skin lesions. INTERVENTIONS: Needle aspiration of a skin lesion before start of antibiotic treatment in 26 patients in the community hospital; punch biopsy of skin lesion after start of antibiotic treatment in 25 patients in the teaching hospital. MAIN OUTCOME MEASURES: Detection of meningococci by Gram staining of specimens from skin lesions according to category of infection (meningococcaemia, meningitis, meningitis with shock, or septic shock without meningitis). RESULTS: Bacteria were detected in the specimen from haemorrhagic skin lesions by culture or Gram staining, or both in 32 (63%) patients. The sensitivity of the Gram stain was 51% and did not differ significantly from its sensitivity in detecting bacteria in cerebrospinal fluid. In meningococcal sepsis, however, a Gram stained skin lesion was significantly more sensitive (72%) than Gram stained cerebrospinal fluid (22%). In patients with meningitis skin lesions gave positive results on staining more often if shock was present. The results for punch biopsy specimens were not affected by antibiotics as Gram staining gave positive results up to 45 hours after the start of treatment and culture gave positive results up to 13 hours. CONCLUSION: Microbiological examination of skin lesions is informative, especially in patients with sepsis and inconclusive results from cerebrospinal fluid, and may provide a diagnosis in such patients within 45 minutes. It differentiates well between meningitis with and without haemodynamic complications, and the result is not affected by previous antibiotic treatment.

Catecholamines in critical care. The commonly used catecholamines: receptor and clinical profile, indications and dosages.

The pharmacology, pattern of receptor activation and resulting clinical impact of the currently most widely used intravenous catecholamines are reviewed. A brief physiological description of the alpha, beta and dopaminergic receptors is used in order to explain the clinical effects of norepinephrine, epinephrine, isoproterenol, dopamine, dobutamine and dopexamine. Each drug is discussed separately according to receptor profile, indications, dosages and current application in critical care. Tables are provided for comparison of relative strengths of these drugs regarding receptor activation, haemodynamic effects, organ perfusion and recommended dosages. The use of combinations of catecholamines to meet a variety of circulatory demands is commented upon.

Prolonged infusion of varied doses of dopexamine hydrochloride for low cardiac output after cardiac surgery.

Circulatory failure after cardiac surgery often calls for active hemodynamic management with fluids, inotropes, and vasodilators. Dopexamine hydrochloride is a new combined beta 2-adrenergic and DA1-dopaminergic receptor agonist and an inhibitor of the uptake-1 mechanism of endogenous catecholamines. As a result, it exerts inotropic and vasodilator effects on the heart and systemic vasculature. The effects were examined over a mean of 22 hours, using 1 to 4 micrograms/kg/min of dopexamine to treat low cardiac output states following coronary bypass and valvular/ventricular repair surgery. In 8 out of 14 patients, low cardiac output was readily reversed by 1 microgram/kg/min of dopexamine. Six patients required higher doses (2 to 4 micrograms/kg/min) to achieve a satisfactory cardiac index. Significant changes from control values were observed throughout the infusion for heart rate (67 to 102 beats/min), cardiac index (2.0 to 3.4 L/min/m2), and systemic vascular resistance (1,545 to 914 dyne.s.cm-5). Pulmonary vascular resistance, pulmonary artery wedge pressure, and right atrial pressure were also significantly reduced during the infusion. Most of these changes reversed when dopexamine was discontinued, suggesting a drug-specific effect and a lack of tolerance. Nausea was a frequent complaint, but was no more frequent than in a random sample of similar patients. Titration of dopexamine, 1 to 4 micrograms/kg/min, was efficacious in producing circulatory improvement in patients with a low cardiac output after cardiac surgery.

Plasma and whole blood exchange in meningococcal sepsis.

The present study describes the effect of plasma exchange or whole blood exchange (PEBE) on the survival rate among patients with fulminant meningococcal sepsis and on the level of circulating endotoxin. Since 1989 all patients with meningococcal disease and hypotension who were admitted to our intensive care unit were treated with PEBE. Results for our patients were compared with those for a historical control group conventionally treated between 1984 and 1989 (n = 10; mortality rate, 60%); the expected mortality rate, which was based on the Niklasson prognostic score and was calculated for seven patients in this control group, was 73%. A total of 15 patients were treated with PEBE, three (20%) of whom died, whereas the prognostic score (calculated for 14 patients) for this group was 62%. In two of the fatal cases, PEBE was started after a delay of greater than or equal to 40 hours. In the remaining 13 patients, PEBE was started within 5-30 hours after the first hospital admission. The mortality rate among this group was 8% (one of 13 patients); this rate was significantly different from that among the control group (P = .025). For seven patients treated with PEBE, plasma endotoxin concentrations were sequentially measured. The overall half-life (+/- SEM) of endotoxin was 181 +/- 18 minutes. This is approximately the same as reported values for patients who were not treated with PEBE. It is concluded that early initiation of PEBE may improve the rate of survival among patients with meningococcal infection and hypotension but that the mechanism of the beneficial effect is most likely not based on the elimination of endotoxin.

[Results of intensive care treatment in patients with hematologic malignancies; relation to infections]. / Resultaten van intensive care-behandeling bij patiënten met een hematologische maligniteit; het verband met infecties.

In a retrospective study we determined the factors that influence the outcome of patients requiring intensive care (IC) for the complications of the treatment of haematological malignancies. All consecutive patients suffering from haematological malignancy admitted to the IC unit of the University Hospital Nijmegen over a 4 year period (1986-1989) were studied; 39 patients (21 female, 18 male) with a median age of 41 year (range 18-71). Various clinical variables were assessed at admission and related to the outcome of IC treatment in terms of death or survival. Previously, 33 patients had undergone chemotherapy. Eight (21%) survived. One of a subgroup of 13 bone marrow transplantation patients survived. Hypoxaemic respiratory failure requiring mechanical ventilation was the most frequent reason for admission (20 patients of whom four recovered). The second most frequent reason was combination of respiratory failure and septic shock (eight patients, none recovered). Three out of five patients admitted with septic shock survived. The need for mechanical ventilation had the highest predictive power for a poor prognosis (p = 0.002). Mortality increased with increasing APACHE II score (p = 0.03). When more than four major organ systems were affected (seven patients), mortality was 100%. Granulocytopenia (leucocyte count less than 1 x 10(9)/l) at admission turned out to be of no prognostic significance, but absence of leucocyte recovery was a prognostically bad sign (p = 0.05). A considerable number of patients (20) suffered from a non-bacterial (opportunistic) infection, carrying a high mortality (only two patients survived: one with candida, one with a cytomegalovirus infection).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous infusion of midazolam during anaesthesia and postoperative sedation after maxillofacial surgery.

The clinical effects and pharmacokinetics of 24 h infusion of midazolam (MDZ) during major maxillofacial surgery and postoperative observation in an Intensive Care Unit (ICU) were studied in 20 patients. During anaesthesia, infusion of MDZ at 5 mg/h combined with 67% nitrous oxide, 1.8 (s.d. = 0.8) mg of fentanyl, and 26.5 (s.d. = 11.4) mg of vecuronium, adequately suppressed clinical responses to surgical nociceptive stimuli. Postoperatively, infusion of MDZ was continued in the ICU at 5 mg/h until 9 a.m. of the first postoperative day for sedation of the intubated but spontaneously breathing patients. The depth of sedation in the ICU was scored from 1-5 (1 = "awake and tense", 5 = "unable to communicate"). During infusion the sedation score decreased from 3.8 after ICU arrival to 2.2 at 8 a.m. of the first postoperative day. Neither ventilatory nor circulatory depression were observed. After cessation of MDZ, recovery from sedation was fast. The degree of amnesia was low. During constant rate infusion no increase in plasma concentration of either MDZ or metabolites occurred. T1/2 beta of MDZ after cessation was 125 min (range 90-320) and its total body clearance was 10.5 ml/kg/min (s.d. = 3.1). The volume of distribution, clearance and T1/2 beta were significantly longer in women than in men. It was concluded that 24 h of MDZ infusion at 5 mg/h caused satisfactory ICU sedation with fast recovery, but that individual tailoring of the infusion rate may still improve the quality of sedation.

Intermittent jaundice: a rare complication of a solitary nonparasitic liver cyst.

A case of a solitary nonparasitic liver cyst, presenting with intermittent jaundice, is described in a 61-year-old female. Twice during the condition's 19-month course deep jaundice developed, spontaneously subsiding to a state of mild icterus. Diagnosis was suggested by ultrasonography and scintigraphy, whereas retrograde cholangiography and arteriography did not contribute. At laparotomy a single large benign multilocular cyst was partially removed.