International Programme for Resource Use in Critical Care (IPOC)--a methodology and initial results of cost and provision in four European countries.

BACKGROUND: A standardized top-down costing method is not currently available internationally. An internally validated method developed in the UK was modified for use in critical care in different countries. Costs could then be compared using the World Health Organization's Purchasing Power Parities (WHO PPPs). METHODS: This was an observational, retrospective, cross-sectional, multicentre study set in four European countries: France, UK, Germany and Hungary. A total of 329 adult intensive care units (ICUs) participated in the study. RESULTS: The costs are reported in international dollars ($) derived from the WHO PPP programme. The results show significant differences in resource use and costs of ICUs over the four countries. On the basis of the sum of the means for the major components, the average cost per patient day in UK hospitals was $1512, in French hospitals $934, in German hospitals $726 and in Hungarian hospitals $280. CONCLUSIONS: The reasons for such differences are poorly understood but warrant further investigation. This information will allow us to better adjust our measures of international ICU costs.

[Intensive care medicine today]. / Intensivmedizin heute.

Physicians, nurses and many other allied health professions join in intensive care as a team for the treatment of patients whose vital functions are either endangered or impaired. Apart from continuous monitoring, which represents the smallest common denominator of all types of intensive-care treatment, intensive-care therapy also encompasses continuous treatment and support of failing organ functions and likewise continuous intensive nursing. The complexity of intensive-care medicine is a strong argument against intensive-care becoming a medical specialty of its own. Nevertheless, the coordination of intensive care-medicine by an experienced intensive care physician is of utmost importance. The present situation in intensive-care medicine is characterised by an increasing tension between new and fascinating medical possibilities (such as right and left ventricular assistance device systems, liver support, pharmacologic treatment of sepsis, avoidance of the complications of critical illness) on the one hand, and limited budgets on the other hand. This conflict is reflected by two basic fears within the population: firstly, the fear that not everything medically possible is being done for the patient due to economic reasons, secondly, a fear of futile treatment at the end of life, merely prolonging inevitable death. Accordingly, ethical questions regarding intensive-care are emerging at all levels of the health system.

Hydroxyethyl starch does not cross the blood-brain or the placental barrier but the perineurium of peripheral nerves in infused animals.

Therapy with hydroxyethyl starch (HES) is associated with a high incidence of persistent pruritus due to HES storage in cutaneous nerves. Up to now it has been unknown if HES also accumulates in the extracutaneous peripheral or central nervous system. To study this, five rats including one pregnant one were infused with a single dose (34-150 mg) of HES (70/200/450 kDa molecular weight) conjugated with fluorescein isothiocyanate (FITC). In addition, four sheep were infused with a cumulative dosage of 30 g, 120 g, and 420 g HES (200 kDa), respectively. After 7-13 days, biopsies from the adult rats, four fetal rats and sheep were taken from various organs. The specimens were analyzed by light, electron, and confocal laser scanning microscopy. Typical HES storage vacuoles were found in macrophages of the skin, liver, spleen, lung, and kidney. HES storage in healthy animals was not associated with signs of either inflammation or apoptosis contrary to a previously described animal hemorrhagic shock model. Beyond that, fetus biopsies did not show any storage phenomenon, confirming that HES does not cross the placental barrier. Deposits of HES could be detected in Schwann cells of cutaneous nerve fibers as well as in perineural and endoneural cells of sciatic nerve in one rat (HES 450 kDa) and three of four sheep. No HES storage was found in the central nervous system. Our findings clearly demonstrate that storage of HES is detectable only in small peripheral nerves, suggesting a cutaneous origin of the HES-induced pruritus.

Success rate of unilateral spinal anesthesia is dependent on injection flow.

BACKGROUND AND OBJECTIVES: The dependence of unilateral spinal anesthesia on injection flow is controversial. We hypothesized that it is possible to achieve strictly unilateral sympathetic block (as assessed by temperature measurements of the limbs) and unilateral sensory and motor block, respectively, during spinal anesthesia by a slow and steady injection of a hyperbaric local anesthetic solution. METHODS: Forty-four patients (American Society of Anesthesiologists [ASA] physical status I-III) undergoing surgery of one lower extremity were randomly assigned to one of two groups. Dependent on the patients' height, 1.4 to 1.7 mL hyperbaric bupivacaine 0.5% was injected manually with the patient in the lateral decubitus position, which was maintained for 30 minutes after injection. Injection flow was approximately 0.5 mL/min in group I ("air-buffered" injections performed by 4 mL air between the local anesthetic and the syringe's plunger, n = 25) and approximately 7.5 mL/min in group II ("conventional" injections, n = 19). Sympathetic block was defined as a temperature increase of more than 0.5 degrees C at the foot. Any reduction in the ability to move the hip, knee, or ankle as well as loss of temperature discrimination and/or pinprick even in one dermatome on the nondependent side was considered as a bilateral block. RESULTS: Before surgery, significant differences (P < .05) were observed for unilateral motor paralysis (92% in group I v 68.4% in group II), unilateral sensory block (48.0% v 10.5%), and unilateral sympathetic block (72% v 42.1%). Strictly unilateral spinal anesthesia was found to be significantly more frequent in group I (40% v 5.3%). Significant hemodynamic differences between the groups were not detected. CONCLUSIONS: For hyperbaric spinal anesthesia, the injection flow is an important factor in achieving unilateral sympathetic block. A slow injection proves useful to restrict spinal anesthesia to the side of surgery.

Minimal flow sevoflurane and isoflurane anaesthesia and impact on renal function.

BACKGROUND AND AIM: Compound A generation and accumulation in sevoflurane anaesthesia is dependent on fresh gas flow. We investigated the extent of generation of compound A. METHODS: After Institutional Review Board approval and informed consent, patients with normal renal function were randomized to receive either sevoflurane (n = 33) or isoflurane (n = 43) minimal flow anaesthesia (0.5 L min-1) for at least 2 h under standardized conditions. Compound A concentrations were quantified and blood and urine samples were taken to assess renal involvement. Both groups were comparable. RESULTS: No significant differences concerning blood chemistry and urine measurements were found. The maximum mean compound A concentration was observed 90 min after flow reduction being 40 +/- 9 p.p.m. at a corresponding mean sevoflurane concentration of 2.1 +/- 0.5 vol%. Mean inspiratory compound A exposure was 102 +/- 33 p.p.m h-1. CONCLUSION: Compound A concentrations using 0.5 L min-1 fresh gas flow and a heated absorber were higher than previously published values using an inflow of 1 L min-1. Compound A exposure was similar to other clinical studies which did not show changes in renal and hepatic function.

Intra-articular clonidine analgesia after knee arthroscopy.

Recently, it was suggested that peripherally-mediated analgesia can be accomplished by the intra-articular delivery of the mu-opioid morphine or of the a2-agonist clonidine. This clinical study assesses the potential peripheral analgesic effect of the combination of morphine and clonidine after intra-articular administration. Sixty patients (American Society of Anesthesiologists status I or II) undergoing arthroscopic repair of the knee during general anaesthesia were randomized to receive after operation, in a double-blind manner, either 1 mg morphine intra-articularly (group 1); 150 microg clonidine intra-articularly (group 2); or 1 mg morphine + 150 microg clonidine intra-articularly (group 3); or normal saline intra-articularly (group 4) in a volume of 30 mL, respectively. Visual analogue pain scores (VAS), duration of analgesia as defined by first demand for supplemental analgesics, subsequent 24 h consumption of postoperative supplementary analgesics, and patient satisfaction were evaluated. Co-administration of morphine + clonidine (group 3) resulted in a significant VAS reduction at 2 h after injection compared with the other groups. There was a tendency towards a lower need for supplementary rescue analgesia and towards a more prolonged analgesia in group 3 (211 min +/- 224 min SD) compared with group 1 (173 min +/- 197 min SD) and group 4 (91 min +/- 21 min SD). More patients were very satisfied with the postoperative analgesic regimen receiving the combination of morphine and clonidine (group 3) at 24 h postoperatively. Thus we conclude, that the peripheral co-delivery of an opioid and an a2-agonist will result in improved postoperative pain relief, when compared with each single agent given alone.

[Indications for central versus peripheral regional anesthesia]. / Differentialindikation zentraler und peripherer Leitungsanästhesien.

Serious neurological complications caused by spinal hematoma or abscess following central neuraxial block have been reported more often during the last years. In contrast, severe complications are extremely rare associated with peripheral nerve blocks. Concerned about the safety of spinal and epidural anesthesia, we encourage the use of peripheral regional techniques for procedures on the lower extremity and especially for postoperative regional analgesia. Motor block due to lumbar epidural anaesthesia using high concentrations of local anesthetic makes spinal hematoma or abscess difficult to recognize. Therefore, low concentrations of local anesthetic should be used for postoperative epidural analgesia. Any increase in motor block following neuraxial blockade should raise the suspicion of a spinal compression (e.g. hematoma or abscess). Other symptoms are back pain, radicular pain or paresthesia and incontinence. Disastrous neurological injuries can only be prevented by immediate diagnosis (MR, CT or myelography) and therapy (surgical decompression).

[Concept for continuing medical education of the European Union of Medical Specialists--EUMS]. / Fortbildungskonzept der Union Européenne des Médecins Spécialistes--UEMS.

In Europe, emerging national structures of continuing medical education (CME) have to be connected in an umbrella structure of national authorities featuring the international exchange of accreditation and credits. In this umbrella structure, following topics need to be addressed: harmonization of the system of accreditation of providers of formally planned CME, the formulation of basic requirements for providers of formally planned CME, the system of quality assessment of the provided CME, and the system of awarding of CME credits to individual specialists.

Ethical dilemmas in intensive care: can the problem be solved?

There is a lack of consistency in ethical decision-making with regard to forgoing life-support, which demands increased efforts to improve clinical competence in end-of-life care, e.g. by proactive ethics consultation or early exploration and documentation of the patient's wishes and preferences. Another current ethical issue is the allocation of limited resources; recent guidelines provide a useful framework for bedside practitioners and health policy makers.

[Is there a means for cost reduction in intensive care fluid therapy without a loss of quality?]. / Ist eine Kostenreduktion in der Flüssigkeitstherapie bei Wahrung der Qualität in der Intensivtherapie möglich?

Cost reduction in fluid therapy may be possible without a loss in quality of medical therapy if the following principles are adhered to. 1: Compare the prices of different manufacturers. 2: The greater the product unit, the cheaper the milliliter. Adherence to this principle is limited by hygienic and logistic considerations. 3: 0.9% NaCl-solution is cheaper than Ringer's lactate-solution. Lactated Ringer's solution should be used, only, if there are contraindications against the higher solute concentrations and tonicity of 0.9% NaCl. 4: Crystalloids are cheaper than colloids. When choosing between these two options intravasal duration of action and specific adverse events must be considered. 5: Cost reduction by differential indication of artificial colloids. Comparing prices, one must consider risk of anaphylactoid/anaphylactic reactions, duration of action, limitation of dosage and possible hemostasis disorders. 6: Restrictive use of albumin. Albumin is the most expensive colloid. There are no reasons for routine use.

Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep.

OBJECTIVE: The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep. DESIGN: 12 sheep were instrumented for chronic study. Six sheep received LG-nitro-arginine-methylester (L-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h). MEASUREMENTS AND RESULTS: Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of L-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of L-NAME increased mean arterial pressure (MAP) from 76.1 +/- 4.2 mmHg to normal values of 95.8 +/- 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 +/- 3.0 to 88.6 +/- 4.7 mmHg (p < 0.05). This increase in MAP was associated in the L-NAME group with a more prominent drop in cardiac index (from 10.2 +/- 0.4 to 7.0 +/- 0.51.min-1.m-2; p < 0.05) than in the PHP group (from 10.7 +/- 0.2 to 9.3 +/- 0.61.min-1.m-2). During the first 90 min of infusion, cardiac index remained lower in the L-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the L-NAME group. CONCLUSION: These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with L-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated.

Arterio-venous carboxyhemoglobin difference suggests carbon monoxide production by human lungs.

Carbon monoxide is hypothesized to be produced by the enzyme heme oxygenase predominantly in liver and spleen, bound to hemoglobin, and excreted by the lungs. Thus, venous carboxyhemoglobin is expected to be higher or equal to arterial carboxyhemoglobin. Unspecific inflammatory stimuli have been shown to induce heme oxygenase in lung tissue possibly leading to pulmonary carbon monoxide production. Arterial and central venous carboxyhemoglobin levels were measured in critically ill patients on the third day of ICU stay (n = 59) as well as in otherwise healthy humans prior to orthopedic surgery (n = 29). Arterial and central venous carboxyhemoglobin were higher in ICU patients than in healthy humans, respectively. In both groups, arterial carboxyhemoglobin was significantly higher than central venous carboxyhemoglobin. The arteriovenous carboxyhemoglobin differences were similar in both groups. The data suggest (a) increased CO-generation in critical illness and (b) pulmonary CO-production in healthy and critically ill humans.

Haemodynamic effects of dopexamine and nitric oxide synthase inhibition in healthy and endotoxaemic sheep.

Chronically instrumented awake healthy sheep (n = 6) received the synthetic catecholamine, dopexamine, during or without a background infusion of the nitric oxide synthase inhibitor. L-nitro-arginine-methylester (L-NAME). Three days later, hypotensive-hyperdynamic circulation was induced and maintained by continuous infusion of Salmonella typhosa endotoxin (10 ng/kg per min). After 24 h of continuous endotoxin infusion, the dopexamine L-NAME protocol was repeated. In healthy and endotoxaemic animals with and without nitric oxide synthase inhibition dopexamine caused the same haemodynamic changes: heart rate and cardiac output increased, mean arterial pressure and systemic vascular resistance decreased. L-NAME infusion induced normalisation of the hypotonic-hyperdynamic circulation in endotoxaemic animals. Dopexamine reduced some adverse effects of L-NAME treatment, like increased pulmonary vascular resistance and decreased oxygen delivery. In conclusion the haemodynamic effects of dopexamine are independent of the amount of nitric oxide production. Dopexamine may attenuate some of the adverse effects of nitric oxide synthase inhibition.

[Spinal and regional anesthesia in bacteremia]. / Rückenmarknahe Regionalanästhesien bei Bakteriämie.

Bacteraemia and septicaemia are generally thought to be relative or absolute contraindications for central neural axis (CNA) blocks. Postulated mechanisms for haematogenous infection of the central nervous system (CNS) caused by subarachnoid or epidural puncture might be an accidental vessel puncture, a change of pressure in the subarachnoid space, and the induction of a "locus minoris resistentiae." Infectious complications of diagnostic lumbar puncture, spinal or epidural anaesthesia are very rare. Although in animals meningitis can be induced by subarachnoid puncture during bactaeremia, there is no study that proves an increased risk for bacteraemic patients. Transient bacteraemia is common, especially in urological and obstetrical-gynecological procedures that are often done in regional anaesthesia, but the incidence of infectious complications is low. This review investigates the few published cases in which a haematogenous infection of the CNS may have been caused by regional anaesthesia. Based on current knowledge, bacteraemia cannot be an absolute, but only a relative contraindication for CNA blocks. Antibiotic chemoprophylaxis should be given before the puncture and the patients must be closely followed after the anaesthesia, particularly for the development of spinal epidural abscess. Because of the possibly increased risk of infectious complications, informed consent should be obtained from the patient.

Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Subarachnoid haemorrhage is commonly associated with natriuresis and hyponatraemia. One possible explanation for these features is a defect in the central regulation of renal sodium reabsorption with increased secretion of a natriuretic factor. We investigated whether excess sodium secretion in patients with subarachnoid haemorrhage is related to increased secretion of natriuretic peptides or to the presence of digoxin-like immunoreactive substances. METHODS: We measured the plasma concentrations of digoxin-like immunoreactive substances (by a fluorescence polarisation immunoassay) and natriuretic peptides, aldosterone, renin, and antidiuretic hormone (by radioimmunoassay) in ten patients with aneurysmal subarachnoid haemorrhage, ten patients undergoing elective craniotomy for cerebral tumours, and 40 healthy controls of similar age and sex distribution. Samples were collected before surgery, 1 h, 4 h, and 12 h after surgery, then daily until 7 days postoperatively in the two groups of patients. FINDINGS: All patients with subarachnoid haemorrhage, but none of the tumour patients, showed increased urine output and urinary excretion of sodium (p = 0.018 for comparison of means of curves to 7 days). The patients with subarachnoid haemorrhage had much higher plasma concentrations of brain natriuretic peptide (BNP) than controls, on admission (mean 15.1 [SE 3.8] vs 1.6 [1.0] pmol/L, p < 0.001) and throughout the study period, accompanied by lower than normal aldosterone concentrations and normal plasma concentrations of atrial and C-type natriuretic peptides (ANP, CNP). The patients with tumours had similar plasma concentrations of ANP, BNP, and CNP to the controls. We did not detect digoxin-like immunoreactive substances in either group of patients. INTERPRETATION: Salt-wasting of central origin may induce hyponatraemia in patients with aneurysmal subarachnoid haemorrhage, possibly as a result of increased secretion of BNP with subsequent suppression of aldosterone synthesis.