Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

BACKGROUND: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. METHODS: Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. RESULTS: Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. CONCLUSIONS: In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.

Low-dose prostacyclin has potent capillary permeability-reducing effect in cat skeletal muscle in vivo.

The dose-response effects of intravenous infusion of prostacyclin on capillary permeability (the capillary filtration coefficient technique), hydrostatic capillary pressure, transcapillary filtration, and vascular tone were analyzed in vivo on cat skeletal muscle from a normal and an increased permeability level. Increased permeability was accomplished by intra-arterial infusion of tumor necrosis factor-alpha or histamine. Permeability effects of bradykinin were also analyzed. Prostacyclin decreased capillary permeability by 8% at a dose of 0.1 ng.kg-1.min-1 and at most by 30% below control attained at 2 ng.kg-1.min-1, also with no effect on vascular tone and hydrostatic capillary pressure. The permeability increase by tumor necrosis factor-alpha and histamine (by 54 and 73%) was more than counteracted by the simultaneous infusion of prostacyclin at 2 ng.kg-1.min-1. The vasodilator effect of tumor necrosis factor-alpha was also restituted. Indomethacin (prostacyclin inhibitor)-induced increase in capillary permeability (25%) was more than restituted by prostacyclin at 2 ng.kg-1.min-1. Surprisingly, bradykinin decreased capillary permeability. We conclude that endogenous prostacyclin may be a physiological regulator of capillary permeability and that low-dose prostacyclin infusion may have clinical relevance in states of increased permeability.

Low-dose prostacyclin is superior to terbutaline and aminophylline in reducing capillary permeability in cat skeletal muscle in vivo.

OBJECTIVE: To analyze and compare the capillary permeability-reducing effects of prostacyclin, terbutaline, and aminophylline. DESIGN: A prospective, experimental study. SETTING: A university laboratory. SUBJECTS: Fourteen adult, anesthetized cats. INTERVENTIONS: The study was performed on an autoperfused calf muscle preparation enclosed in a plethysmograph, with continuous recordings of tissue volume, arterial and venous blood pressures, and blood flow. The capillary filtration coefficient was used as a measure of capillary hydraulic permeability, and measured at different doses of intravenous infusions of prostacyclin, terbutaline, and aminophylline. These analyses were made from normal and from raised permeability levels, the latter by prior and simultaneous infusion of tumor necrosis factor-a (TNF-a) or histamine. All three of the drugs analyzed were given at low doses, without vasodilator effect, and at doses with a clear vasodilator effect. MAIN RESULTS: Prostacyclin infusion reduced capillary permeability to a value of about 25% below the initial control value, and this level was reached both from normal and increased permeability levels. The maximal reduction level was obtained at a low nonvasodilator dose of 2 ng/kg/min. Terbutaline and aminophylline had no significant effect on capillary filtration coefficient when tested from the initial control permeability level. From a TNF-alpha-raised permeability level (about 50% above control) and from a histamine-raised permeability level (about 60% above control), both drugs induced small reductions in the capillary filtration coefficient. CONCLUSION: Low-dose prostacyclin effectively reduces hydraulic capillary permeability in cat skeletal muscle and is superior to terbutaline and aminophylline.

Role of prostacyclin and nitric oxide in regulation of basal microvascular hydraulic permeability in cat skeletal muscle.

The effects of prostacyclin, nitric oxide (NO) and beta2-receptor stimulation on capillary filtration coefficient (CFC) and vascular tone were analyzed in an autoperfused cat skeletal muscle in vivo preparation, to evaluate if these substances are involved in regulation of basal microvascular hydraulic permeability. CFC was increased from control (100%) to 124% with the prostacyclin-synthase inhibitor tranylcypromine and restored by simultaneous infusion of prostacyclin at 0.1 ng.kg-1. min-1, with further reduction to 76% at 1 ng. kg-1.min-1. Prostacyclin at these doses did not influence vascular tone. NO inhibition by L-NAME increased CFC to 116% of control, with a vascular resistance increase of 45%. CFC was restored by simultaneous infusion of the NO precursor L-arginine. L-arginine given alone reduced CFC to 86% of control. Tranylcypromine and L-NAME given together increased CFC to 141% of control and CFC was reduced to 86% by prostacyclin at 1 ng.kg-1. min-1 with no significant further reduction by adding L-arginine. Adrenaline alone, in a vasodilating dose verifying beta2 stimulation, or when followed by simultaneous beta-blockade with propranolol, did not influence CFC. We conclude that NO and especially prostacyclin are involved in bi-directional regulation of basal microvascular hydraulic permeability and can account for up to 30-40% increase or decrease from a basal value. Physiological beta2 stimulation has no effect on basal hydraulic permeability. The permeability-reducing effects of prostacyclin and NO are additive. NO, but not prostacyclin, is involved in regulation of basal vascular tone.

Beneficial effects of low-dose prostacyclin on cat intestinal perfusion during endotoxemia as evaluated with microdialysis and oxygen transport variables.

OBJECTIVE: To evaluate the effects of low-dose prostacyclin on intestinal perfusion during endotoxemia. DESIGN: A randomized, blinded experimental study. SETTING: A university laboratory. SUBJECTS: Sixteen anesthetized cats. INTERVENTIONS: The animals received endotoxin by continuous intravenous infusion (0.5 mg/kg plus 0.5 mg x kg(-1) x hr(-1)) and a continuous volume replacement throughout the experiment. Four hours after the start of endotoxin, the animals were randomized to receive an infusion of either prostacyclin at a dose of 1 ng x kg(-1) x min(-1) (prostacyclin group) or vehicle (control group) during the next 4 hrs. MEASUREMENTS AND MAIN RESULTS: Intestinal vascular resistance was calculated from systemic arterial pressure, central venous pressure, and superior mesenteric artery blood flow, and intestinal oxygen delivery and uptake were calculated from superior mesenteric artery and vein blood samples and blood flow. Interstitial lactate, pyruvate, glucose, and glycerol in the ileal wall were measured by using microdialysis. There were no differences in baseline values between the groups. Systemic blood pressure decreased initially but recovered and remained stable in both groups. In the control group, intestinal vascular resistance increased from 10.9 +/- 1.0 to 24.7 +/- 5.3 mm Hg x mL x min(-1) x kg(-1) (p <.05) at 8 hrs, and oxygen delivery decreased from 2.6 +/- 0.2 to 1.3 +/- 0.3 mL x min(-1) x kg(-1) (p <.05). Simultaneously, microdialysis lactate increased from 1.6 +/- 0.1 to 3.6 +/- 0.5 mmol/L (p <.05) with concomitant pyruvate increase and unchanged lactate/pyruvate ratio. Blood lactate increased and pH decreased. In the prostacyclin group at 8 hrs, intestinal vascular resistance of 6.9 +/- 0.8 mm Hg x mL x min(-1) x kg(-1) was lower and intestinal oxygen delivery of 3.2 +/- 0.3 was higher (p <.05) than in the control group at 8 hrs. Intestinal oxygen uptake of 0.54 +/- 0.10 mL x min(-1) x kg(-1) was higher than in the control group, in which oxygen uptake was 0.26 +/- 0.04 mL x min(-1) x kg(-1). Lactate, pyruvate, and pH were normalized at 8 hrs in the prostacyclin group. CONCLUSION: Low-dose prostacyclin has beneficial effects on small intestinal perfusion during endotoxemia in this experimental cat model.

Reflection coefficient for albumin and capillary fluid permeability in cat calf muscle after traumatic injury.

Surgery and traumatic injury are often followed by tissue oedema and a low plasma albumin concentration, indicating leakage of fluid and proteins from the intravascular to the interstitial space. Transcapillary leakage can be referred to as an increase in capillary hydraulic conductance and/or a decrease in the reflection coefficient for plasma macromolecules. This study evaluates if time-dependent variations in the reflection coefficient for albumin and capillary hydraulic conductance can be confirmed experimentally following a surgical trauma using a blood perfused cat skeletal muscle in vivo preparation. The hydraulic conductance was estimated by the capillary filtration coefficient, and was used to evaluate variation in capillary fluid permeability. According to the Starling fluid equilibrium, the ratio between the reflection coefficients for albumin on two occasions can be calculated from the maximum osmotic absorption rates induced by a fixed intravenous bolus infusion of albumin (0.5 g kg(-1)) and from the capillary filtration coefficients. We found a decrease in the reflection coefficient of about 30% up to 10 h after the preparation. The capillary filtration coefficient showed no significant change over time, but decreased by 5-10% following the albumin infusion. We conclude that: (1) the reflection coefficient for albumin is reduced after a trauma, whereas the effects on the capillary fluid permeability are small, (2) albumin in plasma contributes to preserve normal capillary fluid permeability and, (3) the model seems to be useful for evaluation of relative variations in the reflection coefficient for albumin.

[Infections in the intensive care unit in reykjavik city hospital.].

OBJECTIVE: To identify infection rates, sites, pathogens, modes of acquisition and outcome in the Intensive Care Unit (ICU) of Borgarspitalinn. PATIENTS AND METHODS: Two hundred patients admitted longer than 24 hours were studied prospectively. Definitions of infections were based on criteria from the Centers of Disease Control. RESULTS: Seventy eight patients (39%) had a total of 128 infections. Sixty one percent were ICU acquired, 19% community acquired and 23% were other nosocomial infections. Thus, 24% of the patients developed an ICU acquired infection. The most common infections were pneumonia 30%, urinary tract infection 30%, septicemia 7% and intraabdominal infections 7%. The most common organisms isolated were S. epidermidis, E. coli, enterococci, S. aureus, S. pneumoniae, H. influenzae and P. aeruginosa. Infected patients stayed significantly longer in the unit, 7.9 days, but non- infected patients stayed 2.9 days. Infections were not related to age or gender, but were significantly associated with tracheal intubation, central lines, treatment with H2-blockers, and underlying heart- or lung disease. ICU mortality for infected patients was 13%, for non-infected patients 7% (p=ns), but 81% and 91% of infected and non-infected patients, respectively, survived to hospital discharge (p<0.05). CONCLUSIONS: Nearly 40% of the ICU patients had an infection in the unit, 24% of the patients with ICU acquired infections. The need for continuing specific and accurate control and prevention of infections in the ICU setting is clear.

Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurements.

BACKGROUND: The endogenous substance prostacyclin is a substance with the potential to improve microcirculation and oxygenation around contusions in the brain following a head trauma by its vasodilatory, antiaggregatory and antiadhesive effects. Microdialysis measurements of local concentrations of selected interstitial substances in the brain, and measurements of venous jugular bulb oxygenation reflecting overall brain oxygenation, might be useful to evaluate possible therapeutic effects of a specific therapy, such as treatment with prostacyclin. METHODS: This case report study on six patients, of whom five were given prostacyclin, includes cerebral microdialysis measurements of interstitial lactate (n=5), pyruvate (n=3), glycerol (n=5) and glucose (n=4), and is combined with measurements of venous jugular bulb oxygenation in three of the patients. One microdialysis catheter was placed adjacent to a contusion, and in four of the patients another catheter was also placed in the contralateral less injured side for comparison. Low-dose prostacyclin infusion (0.5-1.0 ng kg(-1) min(-1)) was started when lactate concentrations in the more injured side was raised at a constant level for more than 10 h. The study also includes one patient used as control to whom no prostacyclin was given. RESULTS: Lactate was markedly lower in the less injured than in the more injured area of the brain. During the prostacyclin infusion elevated lactate and lactate/pyruvate ratio were reduced. Elevated glycerol decreased, a low glucose increased and jugular bulb blood oxygenation increased following start of prostacyclin. The control patient showed an increase in lactate and lactate/pyruvate ratio. CONCLUSION: The microdialysis data combined with the jugular bulb oxygenation data indicated that low-dose prostacyclin exerts effects compatible with improved oxygenation and reduced cell damage in the severely traumatised brain.