Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans.

BACKGROUND: At high concentration, the TRPV-1 agonist capsaicin de-sensitizes nociceptors and reduces the intra-epidermal nerve density. METHODS: We investigated the effects of a 5 × 10 cm capsaicin 8% patch on C- and A-delta-nociceptor activation in ten healthy subjects before and at days 1-3-7-21 after patch application. Thermal thresholds, infrared thulium-YAG laser-evoked potentials (LEP) and heat pain (numeric rating scale, NRS, 0-10), electrically induced pain (10 pulses, 1.5-fold pain threshold intensity, five randomized series of 5-10-20-50-100 Hz), and axon-reflex flare (laser Doppler imaging) were recorded. RESULTS: Thermal hypoesthesia developed upon capsaicin 8% treatment. Warmth detection thresholds increased at day 1-3, heat pain thresholds were increased by about 2.6 °C after day 3, and laser-evoked heat pain remained significantly reduced for 7 days. Axon-reflex flare responses (days 1-3), but not supra-threshold electrically induced pain were significantly reduced by the capsaicin patch. CONCLUSIONS: Axonal nociceptor function assessed by electrical excitability tests supplements threshold tests of nociceptive endings. The differential analgesic effects of 8% capsaicin patches may be attributed to the kinetics of capsaicin and the different depth of nociceptive nerve fibres, yet, the time course does not match the long-lasting analgesia observed in neuropathic pain patients treated with the same patch. WHAT DOES THIS STUDY ADD?: Axonal nociceptor function assessed by supra-threshold electrical excitability tests did not coincide with capsaicin-induced transduction changes supplementing threshold measures of terminal nociceptor endings. Threshold measurements do not reflect the sustained effect of pain relief seen in neuropathic pain patients. Capsaicin-sensitive nociceptors responsible for spontaneous pain are either not specifically tested with currently available sensory stimulation protocols or have higher capsaicin sensitivity or slower recovery under neuropathic conditions.

[Implementation of an electronic patient record. Experience in an interdisciplinary pain clinic]. / Implementierung einer elektronischen Krankenakte. Erfahrungen in einer interdisziplinären Schmerzklinik.

A complex electronic patient record was implemented in an interdisciplinary pain clinic. The goal was to create a tool that would allow structured access to the entries made by all specialty groups and permit data analysis for statistical and scientific purposes by means of integrated, coded fields. An electronic workflow was developed to facilitate the processing of documents. All entries dictated were converted to digital form and recorded directly into the electronic chart. Additional features included a structured medication list and a connection to the hospital's pre-existing electronic records. The various elements to be included in the chart were determined by an interdisciplinary team and progressively implemented using a commercially available system as a basis. In conclusion, implementation of a complex electronic patient record provides a valuable instrument for quality control, interdisciplinary collaboration and improved efficiency in a large, multimodal pain clinic.

Hypervolemic hemodilution: an alternative to acute normovolemic hemodilution? A mathematical analysis.

BACKGROUND: Hypervolemic hemodilution has been proposed as an alternative to normovolemic hemodilution to reduce homologous blood transfusions. So far, convincing data supporting this concept are unknown. MATERIALS AND METHODS: We therefore present a mathematical model calculating the efficacy of hypervolemic, normovolemic, and "no" hemodilution. Hypervolemic hemodilution constituted volume expansion (20% of estimated blood volume) maintained throughout surgery. Normovolemic hemodilution contained isovolemic exchange of blood (40% of estimated blood volume) vs colloid as well as retransfusing blood plus colloid to maintain minimal acceptable hematocrit, e.g., transfusion trigger. To determine the efficacy of each technique maximal allowable blood loss and final postoperative hematocrit were calculated. Maximal allowable blood loss referred to the amount of blood lost during surgery after which homologous blood transfusion became necessary. RESULTS: Recalculating published clinical data strongly validated the formulas used for our model. Hypervolemic hemodilution always revealed lowest maximal allowable blood losses. Normovolemic hemodilution constantly ensured highest maximal allowable blood losses. For blood losses <40% of blood volume, hypervolemic and normovolemic hemodilution provided almost identical final postoperative hematocrits. But in contrast to normovolemic hemodilution, hypervolemic hemodilution did not carry the risk of severe transient, retransfusion-induced hypervolemia. "No" hemodilution always gave lowest final postoperative hematocrits. CONCLUSIONS: Thus, hypervolemic hemodilution cannot replace normovolemic hemodilution to reduce homologous transfusions, but for blood losses <40% of blood volume hypervolemic hemodilution appears to be superior.

[Cost analysis of autologous transfusion methods--a study of 5,017 patients]. / Kostenanalyse autologer Transfusionsverfahren--eine Untersuchung bei 5017 Patienten.

PURPOSE: Cost analysis of autologous blood conservation measures compared to corresponding homologous blood products. METHODS: This study is based on data from 5,017 patients undergoing major bone and joint surgery in 1993 and participating preoperatively in autologous blood donation (ABD) (with hemoseparation (HS) into autologous packed red blood cells (APRBC) and autologous fresh-frozen-plasma (AFFP)), autologous plasmapheresis (APPH) for harvesting AFFP as well as intra-/postoperative blood salvage with mechanically processed autologous transfusion (MAT). RESULTS: Total costs for 3,110 ABD with HS amount to DM 517,586.00 resulting in about DM 167.00 per U of APRBC plus AFFP. Comparatively, costs per U of HPRBC is about DM 202.00. Break-even-point (BEP) is calculated with 2,258 U of APRBC (without considering AFFP additionally obtained by HS). Taking into account this AFFP due to coagulation in 20% lowers BEP to 1,819 U of APRBC. However, this analysis compares the "mere" cost figures only, but does not consider the extent of ABD-induced increase in rbc mass compared to that of HPRBC. Under these circumstances calculated cost per unit of APRBC is up to 90 per cent higher than for 1 U of HPRBC. Total cost for PPH with 15,570 U of AFFP amounts to about DM 1,824,162.00, resulting in about DM 115.00 per U of AFFP. Comparatively, cost per U of HFFP is about DM 136.00. BEP is calculated with 11,595 U of AFFP. However, when considering AFFP on coagulatory reasons' with 20% only, no BEP can be calculated and AFFP is not proven to be cost-efficient. Under these conditions it is about 2.8-times more expensive than HFFP; and if considering AFFP a volume substitute it is even more than twelve times more expensive than artificial colloids (e.g. HES 6%, 200/0.5). MAT--2,690 sets and patients with a total of 5,326 processing cycles--causes a total cost of about DM 1,356,161.00, resulting in about DM 504.00 per set and patient. Under our conditions MAT is not cost-efficient compared to HPRBC as it is about two times more expensive than HPRBC. For reaching cost efficiency the number of processing cycles is either to be increased from about 2 to about 4 cycles per set and patient or hematocrit of the rbc-product obtained by MAT is clearly to be increased. CONCLUSIONS: The "mere" figures of this cost analysis of APRBC versus HPRBC as well as of AFFP versus HFFP and HES appear in favour of the autologous products. However, such an analysis should consider--besides the costs--both the increase in rbc-mass obtained by ABD or MAT, versus homologous rbc, and the indication for administering AFFP. This study does not prove our autologous blood conservation measures to be cost efficient compared to homologous blood products. Therefore, these data may cause a critically reflection on established concepts of autologous transfusion measures and may initiate promoting new and more cost efficient constellations/alternatives of blood conservation measures.

[Erythropoietin therapy during frequent autologous blood donations. Dose-finding study]. / Erythropoetintherapie während häufiger Blutspenden. Eine Dosisfindungsstudie.

Avoidance of homologous blood products and patients' demand for preoperative autologous blood donation programs are increasing. As many of these patients are older, with a compromised cardiovascular system and a slow response of the erythropoietic system when anemia occurs, the feasibility and benefit of autologous blood donation is often limited. Augmentation of preoperative blood donation by therapy with recombinant human erythropoietin (rHuEPO) has been described in animal models and in patients. METHODS. In a multicenter, controlled, randomized trial, 49 patients scheduled for orthopaedic or vascular surgery received 0 (control group, n = 9), 200 (n = 10), 300 (n = 11), 400 (n = 10) or 500 (n = 9) U/kg rHuEPO (Erypo, Cilag, Sulzbach, distributor Fresenius, Oberursel, Germany) subcutaneously twice a week for 3 weeks while every week 450 ml blood was collected. Iron sulphate 100 mg was prescribed orally twice a day. Patients were ineligible if they had uncontrolled hypertension, recent myocardial infarction, haematological disorders or a history of seizures. Blood donation had to be cancelled if the haematocrit was below 30%. RESULTS. There was a significant (ANOVA) drop of the haematocrit value only in the control group, and end-point values for haematocrit and haemoglobin were significantly elevated in the 400 and 500 U/kg groups compared with the control group (Table 9). DISCUSSION. The erythropoietic stimulus of phlebotomy for autologous blood donations is often not efficient enough to guarantee a constant haematocrit. Lowering of the preoperative haematocrit jeopardizes the aim of avoidance of homologous blood transfusions. rHuEPO increased the efficiency of autologous blood collections, as predonation haematocrit values could be preserved in the high-dosage groups. As a consequence, homologous transfusions could be avoided. However, there were broad interindividual differences in the erythropoietic response, possibly due to limitations in iron availability. Adverse effects of rHuEPO therapy, such as hypertension, thrombosis or neurologic disorders, are mostly reported in patients with terminal kidney failure. No such disturbances were observed in the present study. CONCLUSION. rHuEPO ameliorates the preoperative decrease of haemoglobin and haematocrit values due to autologous blood donations in a dose-related fashion. The individually adjusted dosage of rHuEPO and iron supplementation merits further investigation.

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical basis and clinical practice. II: Perioperative retransfusion of acute blood loss; plasmapheresis]. / Perioperative Retransfusion akuter Blutverluste; Plasmapherese.

Intra- and postoperative blood-salvage with consecutive retransfusion represent an established part within the "Concept of Autologous Transfusion (CAT)". According to the processing technique of the blood salvaged there exist two different systems: Autologous Transfusion System II (ATS II) and Autologous Transfusion System III (ATS III). By using ATS II blood (with or without anticoagulation) is collected within a collecting reservoir after having passed a rough-filter-system. Passing a fine-filter-system the blood collected is retransfused into the patient without any preceding processing (autologous direct-retransfusion, ADR). Because of the activation of the coagulation proteins by the tissue and by the collection system as well as due to the destroyed red blood cells, the white blood cells, the platelets and the free plasma hemoglobin the patient is transfused with an autologous "whole-blood-like product" of minor quality. By administration of ATS III blood is collected and anticoagulated and passes a rough-filter as well; by processing the blood by means of centrifugation and separation and by washing the damaged red blood cells, a great part of the white blood cells, of the platelets and of the plasma hemoglobin (and of the anticoagulatory drug) is eliminated resulting in a washed autologous product, which mainly consists of red blood cells, which are retransfused into the patient through a fine-filter system. This means, that the autologous product obtained by the two different systems differs both regarding its quality and the plasmatic and corpuscular contents. However, undoubtedly either system is able to effectively reduce the need for homologous blood.(ABSTRACT TRUNCATED AT 250 WORDS)

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical bases and clinical practice. III. Autologous blood donation, autologous donation criteria and organizational measures]. / Eigenblutspende, autologe Spendekriterien und organisatorische Massnahmen.

This third part of a review on "Autologous Transfusion" deals with preoperative autologous blood donation, with supplemental pharmaco-therapy, with election criteria of the patient as well as with the organizational measures to be taken into account if an intensive autologous predeposit programme is routinely applied. Donation of an autologous predeposit aims at supplying the patient with autologous blood and autologous plasma, respectively, according to the expected blood loss and in order to reduce the need for homologous transfusion. Important aspects, which have to be considered if applying a routine autologous donation programme refer both to the election criteria of the patient and to the organizational programme and measures to be considered. Data in the literature reveal, that the risk of side effects for the patient (who is both the donor and the receiver of the (autologous) blood) during and after donation of an autologous predeposit is definitely not greater than the risk reported for otherwise healthy homologous volunteers. In our opinion, this means, that a patient who has been declared eligible for an elective operative intervention which makes homologous transfusion very probable, can be considered eligible for donating an autologous predeposit; additionally, he should also be eligible for acute normovolemic hemodilution, as donating an autologous predeposit with accompanying volume substitution of the predeposit 'is under hemodynamic aspects' nothing else than an acute and preoperatively performed normovolemic hemodilution. Analysing the data so far reported, volume substitution of the autologous predeposit appears to be a very important component for the patient's safety.(ABSTRACT TRUNCATED AT 250 WORDS)

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical basis and clinical practice. I. Potential risks of homologous transfusion; normovolemic hemodilution]. / Potentielle Risiken der homologen Transfusion; normovolmische Hämodilution.

This paper, which is the first part of four, deals with the potential risks of homologous blood transfusion as well as with normovolemic hemodilution, an autologous transfusion method, which is easily to be applied and not expensive. Although the various methods of autologous transfusion are well known for many years the public discussion on the "AIDS-topic" has led to a growing interest in blood-saving measures. However, in contrast to the so-called "AIDS-topic" the potential risks of a transfusion-transmitted hepatitis as well as the immunologic effects of homologous blood are of much greater importance. Moreover, high-court-sentences give the legal background for intensifying autologous transfusion and to offer it to the patients. So far there are four autologous transfusion methods to be applied routinely: 1. normovolemic hemodilution (NHD); 2. intra- and/or postoperative blood salvage (I/PBS) with or without autologous direct-retransfusion (ADR); 3. preoperative autologous plasmapheresis (PPH); 4. preoperative autologous blood donation (ABD). Moreover, drug-induced stimulation of the erythropoiesis by means of erythropoietin and the additional (intravenous) administration of iron may become a further component among autologous transfusion methods. Normovolemic hemodilution means exchange of autologous blood versus an artificial colloid. To make sure for normovolemia is to be considered a "conditio sine qua non" for "functioning" of normovolemic hemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cryopreservation of erythrocytes using hydroxyethyl starch: in vivo results of an autologous retransfusion model in humans]. / Kryokonservierung von Erythrozyten mit Hydroxyethylstärke: In-vivo-Ergebnisse im autologen Retransfusionsmodell beim Menschen.

The cryopreservation of human red blood cells (RBC) can be greatly beneficial in certain situations such as for rare blood groups, problems due to multiple antibodies, and as an interim aid during temporary shortages. Additionally, cryopreserved erythrocytes may be useful in cases of civil or military disasters. Frozen/thawed autologous RBC are of particular interest as a supplement to liquid storage for elective operations (e.g. orthopedics, vascular and transplantation surgery) to extend the preoperative collection period, which is otherwise limited to 7 weeks. In this study using 7 healthy volunteers, 500 ml of whole blood was replaced by a suspension of cryopreserved autologous RBC [2 aliquots of 216 ml each, hematocrit (HCT) 43 +/- 2% (v/v), HES (hydroxyethyl starch) concentration 11.5% (w/w)]. No washing step was performed after thawing. Viability of the red cells after thawing in terms of saline stability reached 91.9 +/- 0.7% (n = 4). In all 7 cases the frozen/ thawed autologous RBC were tolerated very well. No adverse reactions could be detected. A slight posttransfusional leukocytosis as well as a moderate increase in LDH and bilirubin were observed, but these effects disappeared within 20 h. The concentrations of platelets, electrolytes, urea, protein and creatinine within their physiological ranges. The activities of the liver enzymes and the coagulation parameters investigated remained unchanged. Initially the level of free plasma hemoglobin increased by a factor of 2. Then it decreased within 20 h, accompanied by a restoration of haptoglobin. More than 85% of the HES was eliminated from the plasma within the 1st day.

[Monitoring in hemodilution]. / Monitoring bei Hämodilution.

Normovolaemic haemodilution is an established part within the 'Concept of Autologous Transfusion'. According to the mechanisms to compensate for the dilution-induced anaemia, monitoring of haemodilution has to consider (1) maintenance of normovolaemia; (2) stability of the cardio-vascular system and of a normal pulmonary function; (3) an adequate myocardial oxygen supply. (1) Normovolaemia: Under routine clinical conditions normovolaemia is controlled by close monitoring of fluid balance (considering surgical blood loss, diuresis, and insensible perspiration). If the expected blood loss is > 2.0 litres, additional monitoring of the central venous pressure appears to be reasonable. It is not a single value of the central venous pressure (CVP) but rather its time-course that allows conclusions on changes of intravascular volume. (2) Cardio-vascular and pulmonary function: Pulmonary function is easily controlled by intermittent arterial blood gas analysis. Non-invasive and discontinuous or invasive and continuous blood pressure recording, respectively, are routinely used for monitoring of cardiovascular function. Heart rate together with the time-course of the CVP give additional information on the cardio-vascular system. Central-venous oxygen saturation is only a minor substitute for mixed venous oxygen saturation; however, its changes with time make it possible to draw conclusions on global haemodynamics and total body oxygen supply. However, in situations of extreme haemodilution--as in Jehova's witnesses--a pulmonary artery catheter has to be used for monitoring the cardio-vascular system as well as bulk oxygen parameters. (3) Myocardial oxygen supply: Monitoring for myocardial ischaemia is routinely performed by ECG. It is both the number and the kinds of leads chosen that give adequate information.(ABSTRACT TRUNCATED AT 250 WORDS)

[Autologous blood donation from the viewpoint of the anesthetist]. / Eigenblutentnahme aus der Sicht des Anästhesisten.

The anesthesiological aspect regarding autologous donation/autologous predeposition aims at the following criteria: (1) Which patient is eligible for autologous donation? (2) Which kind of monitoring should be established for the donation procedure? (3) What are the quality criteria the autologous predeposit has to meet? (4) What are the logistical aspects of an autologous predeposit program managed by an anesthesis? Under anesthesiological aspects all patients who have been declared eligible for elective surgery should be able to donate an autologous predeposit. Attention should be paid both to an adequate volume substitution, especially in patients with cardiovascular and/or coronary diseases, and to an adequate monitoring during autologous blood donation; e.g., a 3-lead ECG to monitor of cardiac rhythm and heart rate as well as close and discontinuous blood pressure control appear to be appropriate. There is no doubt that the quality criteria an autologous predeposit should meet are the same as those outlined for a homologous product; especially proof of no bacterial contamination is mandatory. Undoubtedly, an anesthesist managing an autologous predeposit program should have a broad experience in and a good knowledge of transfusion medicine.