Exogenous adrenomedullin prevents and reverses hypodynamic circulation and pulmonary hypertension in ovine endotoxaemia.

BACKGROUND: Hypodynamic septic shock is associated with a poor prognosis. The present randomized-controlled laboratory experiment was designed to test the hypothesis that the vasodilatory peptide hormone adrenomedullin (ADM) is a useful agent to prevent and reverse the development of hypodynamic circulation in ovine endotoxaemia. METHODS: Twenty-four healthy ewes were chronically instrumented for haemodynamic monitoring and randomly allocated to either the control, treatment, or prophylaxis group (n = 8 each). After a baseline (BL) measurement in the healthy state, all sheep were subjected to a continuous endotoxin infusion started at 10 ng kg(-1) min(-1) and doubled every hour six times. After 4 h of endotoxin challenge, the treatment group received ADM (50 ng kg(-1) min(-1)) for the remaining 3 h of the experiment. The prophylaxis group received a simultaneous infusion of endotoxin and ADM (50 ng kg(-1) min(-1)) from the beginning to the end of the 7 h intervention period. RESULTS: In the control and treatment groups, the ewes exhibited a hypodynamic circulation at 4 h (>20% reduction in cardiac index, both P < 0.01 vs BL). Endotoxin also increased mean pulmonary arterial pressure (MPAP) and arterial lactate concentrations. Prophylactic infusion of ADM prevented the occurrence of pulmonary hypertension and hypodynamic circulation and thereby blunted the increase in arterial lactate concentrations. In the treatment group, ADM administration increased CI (P < 0.001) and reduced both MPAP (P = 0.023) and arterial lactate concentrations (P < 0.001 each at 7 h) when compared with the control group. CONCLUSIONS: This study demonstrates that exogenous ADM prevents and reverses hypodynamic circulation, attenuates pulmonary hypertension, and limits lactic acidosis in ovine endotoxaemia.

Processing of stored packed red blood cells using autotransfusion devices decreases potassium and microaggregates: a prospective, randomized, single-blinded in vitro study.

The aim of the study was to compare the potential of autotransfusion devices to reduce non-infectious complications related to transfusion of long-stored packed red blood cells (PRBC; n= 57), such as changes in electrolytes, blood cells and the load of free microaggregates. Following a baseline measurement, a blood pool of three PRBC was divided into three equal volumes and washed with either the Haemonetics Cell Saver (HCS) or the continuous autotransfusion system (C.A.T.S), using the quality (CATS(quality)) and emergency (CATS(emergency)) mode. After the washing procedure, measurements for electrolytes, blood cells and free microaggregates were repeated (n= 19 each). Compared with baseline, the investigated autotransfusion devices reduced the median load of potassium (baseline: 52 mEq L(-1); HCS: 4 mEq L(-1); CATS(quality): 4 mEq L(-1); CATS(emergency): 17 mEq L(-1); each P < 0.001), restored a physiologic electrolyte balance and significantly decreased the load of leucocytes, glucose and protein. Whereas the quantity of microaggregates was not reduced by HCS, CATS(emergency) decreased the load of cell fragments below 7.8 microm (P < 0.05 vs. baseline). Using CATS(quality) decreased the load of cell fragments not only to a diameter below 7.8 microm (P < 0.001 vs. baseline) but also of microaggregates between 7.8 and 17.6 microm (P < 0.05 vs. baseline). In situations where long-stored PRBC have to be transfused, the procedure described here may be feasible to reduce clinically relevant side effects, i.e. hyperkalaemia and microvascular obstruction secondary to free cell fragments. This approach could be especially useful in patients undergoing massive transfusion and/or suffering from renal failure.

Anaesthetic strategies to reduce perioperative blood loss in paediatric surgery.

In adults, a number of measures to reduce perioperative blood loss have been established. These techniques serve to reduce patients' exposure to homologous blood. Most adults are concerned with this issue especially since many patients became infected with human immunodeficiency virus (HIV) during the 1980s through exposure to blood components. While blood-saving strategies are widely used in adults, they are mostly neglected in infants. However, it is these young patients with their whole life in front of them who, it could be argued, would benefit especially from any potentially avoidable infection (HIV, hepatitis, etc.) or immunological complications. In infants and small children, these blood-sparing techniques may not be as effective as in adults and technical limitations may prevent their application. However, some of these measures can be used and may serve to prevent or reduce exposure to homologous blood. In the following review, blood-saving techniques established in adults are described and their applicability for paediatric patients discussed.

Intraoperative washing of long-stored packed red blood cells by using an autotransfusion device prevents hyperkalemia.

IMPLICATIONS: Long-stored packed red blood cells (PRBCs) have a large potassium load. In patients with end-stage renal failure, the transfusion of such PRBCs may cause a critical increase in plasma potassium levels. Washing PRBCs with an autotransfusion device allows for a marked decrease in potassium load, thus preventing hyperkalemia.

Alanyl-glutamine dipeptide does not affect hemodynamics despite a greater increase in myocardial heat shock protein 72 immunoreactivity in endotoxemic sheep.

The possible beneficial effect of supplemental glutamine (Gln) in critically ill patients has been suggested to be mediated by the induction of the cytoprotective heat shock proteins (HSP)32 and HSP72. There is evidence that HSP72 and HSP32 have opposite effects on the hemodynamic situation during endotoxemia. Therefore, the effect of Gln supplementation on the cardiovascular system is not clear. We investigated the effect of alanyl-Gln (Ala-Gln) dipeptide on cardiovascular function in healthy and endotoxemic sheep. Ten sheep catheterized for chronic studies received Ala-Gln 700 mg/(kg x d) [equal to 470 mg/(kg x d)Gln] on 4 consecutive days, and 10 sheep received NaCl (9 g/L) as the control solution. On d 4, four sheep of each group were killed and myocardial samples were taken for immunohistochemistry. The remaining sheep received a continuous infusion of endotoxin [Salmonella typhosa, 10 ng/(kg x min)]. Hemodynamic parameters were measured before application of Ala-Gln or the control solution, and during endotoxemia. Myocardial HSP72 immunoreactivity was determined by immunohistochemistry. After 24 h of endotoxemia, the sheep exhibited a hyperdynamic circulation. No difference was found in the hemodynamic parameters between treatment and control group. Ala-Gln treated sheep had a greater increase in myocardial HSP72 immunoreactivity compared with controls after (P < 0.05) but not before endotoxemia. In summary, Ala-Gln increased HSP72 immunoreactivity after endotoxemia, but did not alter hemodynamic parameters. Thus, Ala-Gln supplementation does not seem to aggravate the hyperdynamic circulation in endotoxemic shock.

Fat elimination from autologous blood.

Bowl-based autotransfusion devices reduce the amount of fat found in shed blood, but cannot completely eliminate fat particles. When fat is seen on the surface of the processed blood, this blood should be filtered with a leukocyte removal filter before retransfusion.

Cost containment through L-alanyl-L-glutamine supplemented total parenteral nutrition after major abdominal surgery: a prospective randomized double-blind controlled study.

BACKGROUND & AIMS: Glutamine is recognized as a conditionally essential amino acid. Recent studies indicate that glutamine-containing total parenteral nutrition improves nitrogen economy, enhances gastrointestinal and immune functions and shortens hospital stay. METHODS: Thirty-seven patients (19 w and 18 m; age 61. 4+/-10.4 years; BMI 23.7+/-2.8 kg/m(2)) following major abdominal surgery receiving an isonitrogenous isoenergetic TPN with or without alanyl-glutamine supplementation (0.5 g/kg BW/day), were evaluated in a double-blind, randomized, controlled trial over a five-day period by measuring nitrogen balance, selected biochemical parameters and length of hospital stay. RESULTS: Supplemental alanyl-glutamine improved the overall mean (-3.5+/-1.6 vs. -5.5+/-1. 4 g N;P<0.05) and cumulative nitrogen balance (-14.1+/-9.1 vs. -21.7+/-11.4 g N;P<0.05) compared with the isonitrogenous, isoenergetic standard regimen. Alanyl-glutamine normalized plasma glutamine concentration and reduced the length of hospital stay (12.8+/-2.6 vs. 17.5+/-6.4 days;P<0.05). CONCLUSIONS: The results of the study confirm that supplementation with synthetic alanyl-glutamine dipeptide is associated with cost containment due to shortened hospitalization and improved nitrogen economy.

Comparative hemodynamic effects of three different parenterally administered lipid emulsions in conscious dogs.

OBJECTIVE: To compare the hemodynamic side effects of three structurally different lipid emulsions. DESIGN: Randomized, controlled, prospective animal study. SETTING: University research laboratory. SUBJECTS: Six chronically instrumented mongrel dogs. INTERVENTIONS: On separate days, all animals were submitted to three different treatments, in a randomized order. After baseline measurements, either a long-chain triglyceride emulsion (treatment 1), a mixed medium-chain triglyceride/long-chain triglyceride emulsion (treatment 2), or an omega3 polyunsaturated fatty acid long-chain triglyceride (PUFA) emulsion (treatment 3) was administered intravenously over 30 mins. MEASUREMENTS AND MAIN RESULTS: Global and regional hemodynamics (sonomicrometry) were recorded for 2 hrs after baseline measurements. Arterial blood gases and plasma concentrations of hemoglobin, triglycerides, total protein, and glucose were recorded for 2 hrs. Long-chain triglycerides did not affect the cardiovascular performance in awake animals. However, medium-chain triglycerides/long-chain triglycerides and omega3 PUFA caused marked increases in systemic vascular resistance (from 1833 +/- 154 to 3277 +/- 163 mm Hg/dynexsec5, p < .05), heart rate (from 89 +/- 6 to 158 +/- 10 beats/min, p < .05), and depressed ventricular performance (wall-thickening fraction [as percentage from baseline] decreased to 53 +/- 9%, p < .05). CONCLUSIONS: Commercially available lipid emulsions can cause profound cardiovascular side effects at high doses, depending on their composition. Whereas long-chain triglyceride emulsions have virtually no effects on hemodynamics in normal dogs, medium-chain triglyceride/long-chain triglyceride, and omega3 PUFA emulsions should be used with caution in critically ill patients with compromised cardiovascular function.

Fat elimination during intraoperative autotransfusion: an in vitro investigation.

UNLABELLED: Intraoperative autotransfusion of scavenged blood is an established method to reduce the need for perioperative homologous blood transfusion. However, if fat particles contaminate blood suctioned from the wound site, no reliable method is available to remove them during the washing and concentration of the recycled blood. A new generation of autotransfusion devices (e.g., continuous autotransfusion system [CATS]), based on separation chambers used in cell separators or plasmapheresis devices, allows continuous procession of the collected blood, in contrast with the discontinuous process used in conventional autotransfusion devices such as the Cell Saver 5. Theoretically, the continuous system should be more efficient than the discontinuous system in eliminating fat. Outdated, 36-day-old packed red blood cells, 600 mL, were mixed with 500 mL of lactated Ringer's solution and 200 mL of soya oil. Soya oil was used because it has a fatty acid composition similar to that of fat found in bone marrow. The blood mixture was then washed and concentrated by using either the CATS or the Cell Saver 5. Six samples were processed by each device. The CATS eliminated the soya oil (200 mL) completely, whereas the Cell Saver 5 delivered 30.3 +/- 7.8 mL soya oil into the retransfusion bag. The new generation of autotransfusion devices allows complete removal of fat particles. IMPLICATIONS: Autotransfusion devices serve to wash and retransfuse blood scavenged from the wound site. However, they cannot completely remove fat particles. This in vitro investigation showed that a new device completely removes fat particles and thus prevents retransfusion of fat.

Strategies to reduce the need for peri-operative blood transfusion.

Therapeutic regimens involving the transfusion of blood components are a matter of debate, not only with regard to patients' safety, but also with regard to cost-effectiveness. The following different measures to reduce the use of blood components and their efficacy are discussed: autologous transfusion, including predonation, isovolaemic haemodilution and peri-operative retransfusion; toleration of a lower haematocrit; and measures to reduce blood loss. In particular, a combination of these methods may be most effective at reducing transfusion needs.

Long-chain triglycerides improve recovery from myocardial stunning in conscious dogs.

OBJECTIVES: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in parallel with the normalization of contractile performance. Assuming a causal role for this metabolic disturbance in the pathogenesis of stunning, we questioned whether exogenous administration of high dose triglycerides during reperfusion of postischaemic myocardium, could improve its functional recovery. METHODS: Thirteen dogs were chronically instrumented to measure global and regional haemodynamics and to produce a 10 min episode of regional myocardial ischaemia. In 7 dogs, Intralipid 20% was administered i.v. during the reperfusion phase. Contractile recovery of stunned myocardium was compared with control saline treatments. The series were repeated in another 6 animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during reperfusion. RESULTS: Contractile recovery of stunned myocardium was faster and more extensive when Intralipid was administered during reperfusion than with saline treatment (wall thickening fraction 86 +/- 6% of preischaemic controls versus 52 +/- 11% at 90 min post-reperfusion; P < 0.05). Oxfenicine pretreatment completely abolished this beneficial effect. CONCLUSIONS: Exogenous administration of triglycerides during reperfusion of postischaemic myocardium improves functional recovery from stunning. This beneficial effect most likely operates through enhanced FFA availability and/or oxidation since it could be abolished by selective inhibition of the carnitine palmitoyl I enzyme.

Nitric oxide synthase inhibition restores vasopressor effects of norepinephrine in ovine hyperdynamic sepsis.

To investigate the hypothesis that nitric oxide synthase (NOS) inhibition restores the vasopressor response to norepinephrine (NE) in ovine hyperdynamic sepsis, eight sheep were chronically instrumented. In the non-septic portion of the study, NE was titrated to achieve an increase in mean arterial pressure (MAP) by 15 mm Hg ("small dose"). Small-dose NE was repeated 1 h after administration of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; bolus 5 mg/kg, followed by 1 mg.kg-1.h-1). After 3 days of recovery, sepsis was induced by a continuous endotoxin infusion (Salmonella typhosa, 10 ng.kg-1.h-1). Three animals died during this period (data excluded). After 24 h, small-dose NE was given. If MAP increased less than 15 mm Hg, the NE dose was increased to achieve the targeted MAP change ("large dose"). Finally, both doses of NE were given after L-NAME administration. To increase MAP by 15 mm Hg in nonseptic animals, the rate of NE infusion was 0.18 +/- 0.03 microgram.kg-1.min-1 (small dose). During L-NAME infusion, this NE dose increased MAP by 32 +/- 8 mm Hg. In septic animals, small-dose NE increased MAP by only 9 +/- 2 mm Hg (P < 0.05 versus nonseptic state). To increase MAP by 15 mm Hg, the NE dose had to be increased to 0.34 +/- 0.06 microgram.kg-1.min-1 (large dose). During L-NAME infusion, NE administration increased MAP by 16 +/- 2 mm Hg and 28 +/- 4 mm Hg (small and large dose, respectively). Thus, L-NAME restored the vasopressor response to NE in sepsis, and increased the vasopressor response to NE in a similar fashion in healthy and septic sheep.

Investigation of the pharmacokinetics and analgesic effects of an intramuscular injection of sustained-release sufentanil for postoperative pain: an open study.

STUDY OBJECTIVES: To investigate the pharmacokinetics after an intramuscular (IM) injection of sufentanil in thin vegetable oil in postsurgical patients and to determine whether sustained-release IM sufentanil can provide safe and sufficient analgesia of long duration in these patients. DESIGN: Open study. SETTING: University hospital. PATIENTS: 10 ASA physical status I and II patients aged 18 to 65 years who were scheduled for elective surgery. INTERVENTIONS: All patients were premedicated with lorazepam and anesthetized with a general anesthetic technique containing nitrous oxide, fentanyl, and isoflurane. As soon as significant pain [visual analog scale score of 5 or greater (range, 0 = no pain to 10 = worst pain imaginable)] occurred during the early postoperative period, the patient received an IM injection of sustained-release sufentanil. MEASUREMENTS AND MAIN RESULTS: During the first 48 hours following surgery, blood samples were taken for determination of plasma sufentanil concentrations. Blood pressure, heart rate, respiratory rate, pain scores, and sedation scores were documented at the same time. The IM administration of sufentanil in thin vegetable oil provided sufficient pain relief, although the onset of analgesia was rather slow (+/- 1 hour). The analgesic effect was still apparent 48 hours later. Plasma concentration of sufentanil at the different time points varied from 0.021 to 0.142 ng/ml, with a mean maximal peak concentration of 0.103 ng/ml. The plasma concentration 48 hours after injection varied from 0.026 to 0.074 ng/ml. CONCLUSIONS: Although an IM injection of sufentanil in thin vegetable oil is effective for postoperative pain relief, it is associated with wide interindividual variability in plasma concentration of sufentanil and long duration of action.

Quality of washed salvaged red blood cells during total hip replacement: a comparison between the use of heparin and citrate as anticoagulants.

A randomized, prospective study comparing heparin with citrate (ACD) as anticoagulant during red blood cell saving was performed in 10 ASA grade I-II patients undergoing primary total hip replacement. Blood samples were taken before and after surgery and at several steps during cell saving. In the heparin group, salvaged red cells showed normal values, with the exception of decreased filtrability and moderate hemolysis. More differences in red cell quality were found in the ACD group. Mean corpuscular volume was higher (110 vs 95 x 10(-12) mL), red cell distribution was increased (17% vs 13%), osmotic resistance was lower (0.54 vs 0.43 g NaCl/L at 50% hemolysis), antioxidative reserve capacity was lower (1.9 vs 4.6 U glutathione reductase per gram of hemoglobin) and there was more hemolysis (15% vs 11%). Despite the small volume of autologous blood retransfused (388 +/- 92 mL), the differences in vitro produced significantly higher free hemoglobin levels in the patients' plasma at the end of the operation (58 vs 23 mg/dL). We conclude that heparin is preferable to citrate as an anticoagulant during autotransfusion with cell washing and immediate retransfusion.

A balanced view on intra- and postoperative blood salvage.

Increasing fear of transfusion related HIV infection, due to recent problems in West European countries, could result in an exaggerated confidence in autologous transfusion techniques. The author, being an anesthesiologist working in a blood bank since one year, tries to put forward a balanced opinion. After a short historical overview, the three main groups of blood salvage techniques are presented: intraoperative blood salvage without and with cell washing as well as postoperative salvage. For each group the following items are discussed: careful technique, quality of the autologous blood, indications, side effects, limitations, efficiency and cost. It is demonstrated that blood salvaging is not the first choice in a global blood sparing and safety program. Some sort of routine quality control should be instituted and if necessary (the safest possible) homologous blood should be preferred. Finally, a practical proposal for elective surgery is roughly made, stressing the life saving potential of blood salvaging in emergency situations.

Embolization of arteriovenous malformations of the brain: preliminary experience.

Transcatheter embolization was performed in 8 young patients (mean age 24.5 years) with intracerebral arteriovenous malformations. In total 12 arteries were embolized in 10 sessions. Clinical complaints of the patients included epilepsy in 4, sudden coma in 3 and severe sudden neurological deficit in 1. Intracerebral hemorrhage was documented in 4 patients and subarachnoid hemorrhage in 1. In all patients, prior to embolization a superselective Wada-test was performed under wake-up anesthesia. Embolization was performed with a mixture of acrylic glue and lipiodol. In one patient a detachable balloon was added. In 6 patients embolization of all the feeding arteries was possible, with total obliteration of the arteriovenous malformations in 4 and subtotal embolization (> 90%) in 2. In 2 patients reduction of the size of the arteriovenous malformation by one third was followed by total surgical removal of the lesion. In 1 patient reflux of the embolization material in the anterior choroidal artery caused severe neurological deficit with good clinical recuperation.