H. Hjelmqvist

Early- versus late-onset shock in European intensive care units

We investigated the possible differences in epidemiology, clinical course, management, and outcome between early and late occurrence of shock using data from the Sepsis Occurrence in Acutely Ill Patients Study, a large European multicenter study, which prospectively collected data from all adult intensive care unit (ICU) patients admitted to a participating center within a 2-week period in 2002. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor agents. Early and late shock were defined as onset of shock within the first 2 days in the ICU or later, respectively. Of 3,147 patients, 1,058 (33.6%) had shock at any time, of whom 462 (43.7%) had septic shock. Patients with late shock had a higher incidence of respiratory (87.4 vs. 69.7%, P < 0.001) and hepatic (15.5 vs. 8.7%, P < 0.05) failure, and more often received dopamine (44.7% vs. 34.5%, P < 0.05) and albumin (31.1% vs. 20.3%, P < 0.001) than patients who developed shock early. Intensive care unit and hospital mortality rates were greater in patients who developed shock late, rather than early (52.4% vs. 36.8% and 55.3% vs. 43%, respectively, P < 0.02). In a multivariable analysis, late shock was associated with an independent risk of higher ICU mortality in shock patients (odds ratio, 2.6; 95% confidence interval, 1.6-4.3, P < 0.001). These observations have important implications in establishing individual prognosis as well as in the design and interpretation of clinical trials.

Central and regional hemodynamics during uncontrolled bleeding using hypertonic saline dextran for resuscitation.

The effects of hypertonic (7.5%) saline/6% dextran 70 (HSD) on central and regional hemodynamics were studied during uncontrolled intra-abdominal bleeding in 16 anesthetized pigs. Ultrasonic flow probes were placed proximally and distally to an aortic injury to indicate the incidence and extent of rebleeding after injecting 4 mL kg(-1) (N = 8) and 2.65 mL kg(-1) (N = 8) of HSD 10 min after the vascular injury was induced. The initial aortic bleeding reduced the blood flow rates to 71% of baseline in the skin, 53% in the splanchnic region, 42% in the upper aorta, and 15% in the kidney. Cardiac output dropped to 46% and the mean arterial pressure to 57% of baseline. The injection of HSD was followed by a prompt increase in all blood flow rates, but rebleeding started within 2 min in 13 of the pigs (81%). A second period of rebleeding occurred in six of them. The rebleeding averaged 300 mL, which is 62% of the blood lost when the aortic injury was induced. There was no significant difference between the treatment groups with respect to these blood losses or to the oxygen consumption, which was not restored by HSD. Five animals in each treatment group died after about 70 min, while the remaining six pigs (38%) survived the 120 min study period. These results suggest that HSD in the recommended dose, and even two-thirds thereof, promotes rebleeding when given shortly after a low energy intra-abdominal aortic injury. The fluid seems to have no beneficial effect on this type of uncontrolled hemorrhage.

Acute hemodynamic effects of induced hypothermia in hemorrhagic shock: an experimental study in the pig.

Hypothermia (HT) is used in certain surgical procedures to reduce metabolism and protect the brain, but in trauma victims accidental HT is considered harmful. Recent animal studies indicate that HT has protective effects in hemorrhagic shock. The aim of the present study was to examine how induced HT modifies the hemodynamic pattern in hemorrhagic shock. Twenty pigs with a body weight of between 17 and 24 kg (mean 20.8) were anesthetized, 50% of their blood volume was withdrawn, and hypothermia (30 degrees C) was induced in half of them (HT group) while the others served as controls. Central hemodynamics was monitored during 4 h via an arterial line and a pulmonary artery catheter. Blood samples were obtained for measurement of leukocyte and platelet counts. Three of the control pigs died while all the animals in the HT group survived the experiment. The hemorrhage resulted in a marked increase in heart rate and a drop in cardiac output and mean arterial pressure. HT slowed the heart rate and induced a further reduction of cardiac output, which parallelled the depression of the core temperature, while the stroke volume did not change in any of the groups. A significant decrease in mean arterial pressure and the leukocyte count became apparent 2 h after the induction of HT. HT aggravated the hypokinetic situation resulting from hemorrhagic shock but without increasing the mortality.

Central application of a nitric oxide donor activates heat defense in the rabbit

In chronically instrumented, conscious rabbits at moderately warm ambient thermal conditions, infusion of the NO-donor SIN-1 into the anterio-ventral 3rd cerebral ventricle (1-2 microg/min per kg BW, 2-4 microl/min, 30 min) initiated a co-ordinated activation of autonomic heat loss mechanisms, as indicated by the rise in ear skin temperature and by increases in panting frequency and respiratory evaporative water loss, while oxygen consumption decreased slightly. The heat loss responses were similar to those attributed to NO in studies employing systemic application of NO-donors. Different from NO acting peripherally, which causes arterial hypotension and tachycardia, centrally acting NO induced arterial hypertension and bradycardia. The observation of the same heat loss responses despite opposing circulatory actions suggests that NO is specifically involved in thermoregulation as a central activator of heat defense mechanisms.

Acute Metabolic and Endocrine Effects of Induced Hypothermia in Hemorrhagic Shock: An Experimental Study in the Pig

BACKGROUND Hypothermia is considered harmful in trauma patients. In surgery, hypothermia is occasionally used to reduce metabolism and protect the brain. Recent studies in animals have also shown protective effects of hypothermia in hemorrhagic shock. The aim of this study was to evaluate the metabolic and endocrine effects of induced hypothermia in hemorrhagic shock. METHODS Half of the individually calculated blood volume was removed from 17 anesthetized piglets. They were then randomized to normothermia or hypothermia and followed for 4 hours after hemorrhage. RESULTS In the hypothermic pigs, arterial PO2 increased from 10.3 +/- 0.7 to 16.4 +/- 0.9 kPa, but it remained unchanged in the normothermic group. The serum levels of potassium increased from 3.9 +/- 0.2 to 5.0 +/- 0.2 mmol/L in the normothermic group. In the hypothermic pigs, the potassium levels temporarily decreased from 3.8 +/- 0.1 to 3.0 +/- 0.1 mmol/L but then returned to baseline levels. The levels of serum catecholamines surged in both groups during hemorrhage. They remained elevated in normothermic pigs but declined in the hypothermic group. CONCLUSION In porcine hemorrhagic shock, induced hypothermia increases arterial oxygen tension and stabilizes serum levels of potassium and catecholamines.

Haemodynamics and fluid balance after intravenous infusion of 1.5% glycine in sheep

With the aim of studying the pathophysiological background of the “TUR syndrome”, we gave six conscious ewes an intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min. Isotonic saline infusions served as controls. Central haemodynamics were monitored. The plasma concentrations of protein, K, Na and vasopressin, and plasma osmolality were measured repeatedly for up to 4 h. The urinary excretions of Na, K and osmoles were also followed. Both infusions caused an elevation of the mean arterial pressure. With glycine, the pressure increased from 93 ± 4 to 112 ± 12 mmHg (12.4 ± 0.5 to 14.9 ± 1.6 kPa) (mean ± s.d.). The pulmonary capillary wedge pressure increased from 7±3 to 16±3 mmHg (0.9 ± 0.4 to 2.1 ± 0.4 kPa) and remained slightly elevated. The central venous pressure rose from 2 ± 3 to 11 ± 3 mmHg (0.3 ± 0.4 to 1.5 ± 0.4 kPa) but returned to baseline within 30 min after the infusion. Infusion of glycine resulted in a decrease in the plasma Na concentration from 144 ± 3 to 114 ± 4 mmol/l. The plasma osmolality decreased from 290 ± 2 to 280 ± I mosmol/l, and remained low. There was a median 6‐fold increase in plasma vasopressin concentration, while saline did not elicit vasopressin release. Despite the absence of electrolytes in glycine solution, the urinary excretion of sodium amounted to 106 ± 40 mmol. We conclude that i.v. infusion of 1.5% glycine solution in sheep causes a transient circulatory strain and natriuresis. Moreover, a vasopressin‐mediated reduction of maximal water excretion contributes to persisting hypoosmolality.

Hemodynamic effects of vasopressin antagonism and angiotensin I converting enzyme inhibition during halothane anesthesia in sheep

The hemodynamic effects of separate and combined intravenous administration of the vasopressin (AVP) V1‐receptor antagonist SK&F 100273 (10 μg/kg) and the angiotensin I converting enzyme inhibitor captopril (20 mg+ 1 mg/h) were studied in 12 sheep during stable halothane anesthesia (1.5% end‐tidal conc.). The separate blockade of either V1‐receptors or angiotensin II (ANG II) synthesis induced a small (7–10%), but significant, fall in mean systemic arterial pressure (MSAP), whereas the combined treatment caused a 30% reduction in blood pressure. The changes in systemic vascular resistance paralleled those of the MSAP. Consequently, the cardiac output was largely unaffected by the interference with AVP effects and/or ANG II synthesis. The halothane anesthesia effectively increased the plasma levels of AVP and ANG II, and plasma renin activity without any relation to changes in MSAP. When either the AVP effects or ANG II synthesis were blocked separately, there was a slight tendency for a compensatory increase of the unimpeded hormonal system. It is concluded that halothane anesthesia increases the plasma levels of AVP and ANG II in sheep, and that the maintenance of the arterial pressure is dependent on the concurrent vasopressor effects of the two hormones in this situation.

The endothelin receptor antagonist tezosentan improves renal microcirculation in a porcine model of endotoxemic shock

Background: Impaired renal microcirculation has been suggested as a factor contributing to the development of renal dysfunction in sepsis. This study was conducted to elucidate the role of endothelin‐1 (ET‐1)in mediating reductions in renal microcirculatory blood flow during endotoxemic shock.

Anesthesia aggravates lung damage and precipitates hypotension in endotoxemic sheep.

Beneficial anti-inflammatory properties have been ascribed to volatile anesthetics in septic conditions, but no studies have compared anesthesia to the conscious state in a large-animal model. The aim of this study was to investigate the effect of isoflurane anesthesia on cardiovascular and respiratory function, leukocyte activation, and lung damage in a model of endotoxemia in sheep. Conscious (n = 6) and anesthetized (n = 6) sheep were made endotoxemic by continuous infusion of LPS for 48 h. Central hemodynamics were monitored continuously, and blood samples were collected regularly. Activation of leukocytes was assessed by surface expression of CD11b and plasma myeloperoxidase concentration. Lung damage was determined by electron microscopy, cell count in bronchoalveolar lavage fluid, and analysis of lung vascular permeability. Four additional animals (two conscious and two anesthetized) went through the same protocol but did not receive LPS. LPS infusion induced a hyperdynamic sepsis. The drop in total peripheral resistance was compensated by an increase in heart rate and cardiac output in the conscious group, whereas anesthetized sheep failed to compensate in this way. Endotoxemic isoflurane-anesthetized sheep also showed signs of aggravated lung edema formation and tissue damage together with enhanced neutrophil activation and lung tissue accumulation. Our data suggest that isoflurane in conjunction with mechanical ventilation blunts cardiovascular compensatory mechanisms in sepsis and enhances leukocyte activation, which may contribute to lung edema formation and tissue damage.

Renal function during intravenous infusion of urological irrigating fluids in the sheep

Background: Oliguria or anuria is an important sign of the transurethral resection syndrome, but the mechanism is not clear.