[Safety of cell salvage in tumor surgery : Systematic review with meta-analysis]. / Sicherheit der maschinellen Autotransfusion in der Tumorchirurgie : Systematisches Review mit Metaanalyse.

BACKGROUND: Allogeneic blood transfusion is avoidable in many oncological interventions by the use of cell salvage or mechanical autotransfusion (MAT). As irradiation is elaborate and expensive, the safety of leucocyte depletion filters (LDF) for autologous blood from the surgical field might be a more acceptable alternative for the prevention of cancer recurrences. A previous meta-analysis could not identify an increased risk of cancer recurrence. The aim of this review article is to provide an update of a previous meta-analysis from 2012 as well as a safety analysis of cell salvage with LDF due to the improved data situation. MATERIAL AND METHODS: This systematic review included all studies in PubMed, Cochrane, Cochrane Reviews and Web of Science on cell salvage or autotransfusion combined with outcomes, e.g. cancer recurrence, mortality, survival, blood transfusion, length of hospital stay (LOS) after the use of MAT without irradiation and with or without LDF. The grades of recommendations (GRADE) assessment of underlying evidence was applied. RESULTS: A total of seven new observational studies and seven meta-analyses were found that compared unfiltered or filtered cell salvage with autologous predeposition, allogeneic transfusion or without any transfusion. No randomized controlled trials have been completed. A total of 27 observational and cohort studies were included in a meta-analysis. The evidence level was low. The risk of cancer recurrence in recipients of autologous salvaged blood with or without LDF was reduced (odds ratio, OR 0.71, 95% confidence interval, CI 0.58-0.86) as compared to non-transfused subjects, allogeneic or predeposited autologous transfusion. The transfusion rate could not be assessed due to the substantial selection bias and large heterogeneity. Cell salvage does not change mortality and LOS. Leucocyte depletion studies reported a removal rate of cancer cells in the range of 99.6-99.9%. CONCLUSION: Randomized controlled trials on a comparison of MAT and allogeneic blood transfusion as well as LDF and irradiation would be desirable but are not available. From observational trials and more than 6300 subjects and various tumors, cell salvage in cancer surgery with or without LDF appears to be sufficiently safe. The efficacy of leucocyte depletion of autologous salvaged blood is equivalent to irradiation. Unavailability of radiation is not a contraindication for cell salvage use in cancer surgery. By usage of leucocyte depleted salvaged autologous blood, the risks of allogeneic transfusion can be avoided.

[Dealing with massive bleeding and associated perioperative coagulopathy: recommendations for action of the German Society of Anaesthesiology and Intensive Care Medicine]. / Umgang mit Massivblutungen und assoziierten perioperativen Gerinnungsstörungen : Handlungsempfehlung der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin.

Massive bleeding with coagulopathy and hemorrhagic shock poses a potential threat to life in numerous clinical settings. Optimal treatment including the prevention of exsanguination necessitates a standardized and interdisciplinary approach. Several studies have shown the importance of massive transfusion protocols and standardized coagulation algorithms to improve survival of severely bleeding patients and to avoid secondary complications. Thus, the Helsinki declaration for patient safety in anesthesiology demands the implementation of clinical practice guidelines for the treatment of patients requiring massive transfusion. This paper introduces a standardized algorithm for the treatment of patients with massive bleeding which was developed in consensus with the German Society of Anaesthesiology and Intensive Care Medicine (DGAI).

[Artificial blood - coming soon or never reaching clinical maturity?]. / Gibt es eine Zukunft für künstliche Blutersatzstoffe?

Formerly developed resuscitation fluids solely imitated the main function of the blood -oxygen transport. A research driven by the army requested an oxygen carrier that does not need cross typing and cooled storage. Artificial oxygen carriers (AOC) use either the molecular oxygen bondage to hemoglobin: HBOC- "hemoglobin based oxygen carriers" or the physical dissolution of oxygen in the blood plasma compartment by hyperbaric pressure in perfluorocarbon emulsions (PFC). Decades of preclinical and clinical research did pass but the results were disappointing- in Russia, a not well designed PFC is available locally and the only approved HBOC in South Africa is not being used much. Other products, just prior to filing for FDA approval, did not achieve convincing study results and research and production was stopped. Some trials have been stopped by the FDA for safety reasons, half of trials with the primary endpoint reduction of allogeneic transfusion requirement were unsuccessful or offset by an increased blood requirement later. However, some ventures currently are trying to use the knowledge gained so far and are investigating third and fourth generation products of artificial blood components. These imitate the cellular structure of red cells as micells, nanocapsules, (ABC- artificial blood cells) or gas bubbles (microbubbles), admixture of volume substitutes such as starches, gelatin or albumin or use hyperbaric oxygenation [38]. Artificial platelets are in clinical phase IIa, recombinant albumin in phase III. In this article, a short overview about the current situation on artificial blood products is given. The critical point for the break through for artificial blood products did not come yet but could be ahead-

[Epidural anesthesia in obstetrics: an accidentally placed intrathecal catheter--remove it or use it?]. / Geburtshilfliche PDA: akzidentell intrathekaler Katheter--entfernen oder nutzen?

Epidural anesthesia is an established method in obstetrics. Despite constant practical experiences and established techniques, accidental penetrations of the dura and therefore malpositioning of the catheter in the intrathecal space are still present. This can result in post spinal headaches, a higher dispersion of the local anesthetic followed by life-threatening respiratory insufficiency and loss of overall conscious delivery. In consideration of these risks removal of the misplaced catheter and proper reinsertion in a higher position is standard. Thus significant emotional stress and re-exposure to the risks of the procedure for the parturient is accepted. We report of a 30-year-old primipara with secondary realized intrathecal placement. In due consideration of the current state of labor, we decided to leave the catheter in place and initiate a pain therapy applying bupivacain via this catheter immediately after the motor block had ceased. Within the first stage of labor sufficient pain relief was established. There was no change in tonicity. It resulted in a normal unproblematic vaginal birth. After an initial irritation due to the high dispersion the patient described a noticeable alleviation of pain during the adequate controlled labor.

Blood viscosity modulates tissue perfusion: sometimes and somewhere.

Each organ possesses specific properties for controlling microvascular perfusion. Such specificity provides an opportunity to design transfusion fluids that target thrombo-embolic or vasospasm-induced ischemia in a particular organ or that optimize overall perfusion from systemic shock. The role of viscosity in the design of these fluids might be underestimated, because viscosity is rarely monitored or considered in critical care decisions. Studies linking viscosity-dependent changes of microvascular perfusion to outcome-relevant data suggest that whole blood viscosity is negligible as a determinant of microvascular perfusion under physiological conditions when autoregulation is effective. Because autoregulation is driven to maintain oxygen supply constant, the organism will compensate for changes in blood viscosity to sustain oxygen delivery. In contrast, under pathological conditions in the brain and elsewhere, increases of overall viscosity should be avoided - including all the situations where vascular autoregulatory mechanisms are inoperative due to ischemia, structural damage or physiologic dysfunction. As latter conditions are not to identify with high certainty, the risks that accompany therapeutic correction of blood viscosity are outweighing the benefits. The ability to bedside monitor blood viscosity and to link changes in viscosity to outcome parameters in various clinical conditions would provide more solid foundation for evidence-based clinical management.

Perforation of the left atrium by a chest tube in a patient with cardiomegaly: management of a rare, but life-threatening complication.

Perforation of the heart is a rare, but life-threatening complication of chest tube thoracostomy. We report the very unusual case where right-sided insertion of a Matthys catheter (6 F) due to pleural effusion resulted in a left atrium perforation. Heart injury was immediately considered as a continuous flow of bright red blood emerging through the chest drain. Diagnosis was confirmed by computertomography also revealing a massive cardiomegaly due to pre-existing mitral valve regurgitation. In two consecutive thoracotomies, first the Mathys drain was removed and the heart defect closed and then the mitral valve was replaced by a bio prosthesis. The extent of the cardiomegaly and the position of the left atrium were not detected pre-operatively by chest X-ray or ultrasonic device. Despite a nosocomial pneumonia, the patient fully recovered. This case shows that extreme caution is necessary when inserting chest tubes in patients where thorax imaging by X-ray or ultrasonic device does not provide a clear anatomical site. In order to minimise complications, a blunt puncturing procedure or Seldinger technique should be used and assisted by a Doppler ultrasonic device. Also early imaging by CT and Doppler ultrasonic technique should be attempted. This may reduce incidence of severe complications as in this case.

Effects of chronic isovolaemic haemodilution on regional cerebral blood flow in conscious rats.

BACKGROUND AND OBJECTIVE: Acute isovolaemic haemodilution increases local and mean cerebral blood flow. It is not known whether a single haemodilution has a short-term effect only or whether it affects cerebral perfusion over a longer time period. In the present study, local and mean cerebral blood flow were determined in conscious rats after a 4, 24 and 48 h period following one-time haemodilution. METHODS: Thirty-six rats were randomized to three untreated sham groups and three groups of haemodilution (4, 24 or 48 h, n = 6 for each group). Isovolaemic haemodilution with albumin 5% aimed to a target haematocrit of 0.2. Local cerebral blood flow was measured in 38 brain regions by the iodo-[14C]antipyrine method in conscious normothermic rats. RESULTS: Isovolaemic haemodilution reduced haematocrit from 0.44 to 0.20. During the following 24 and 48 h periods, haematocrit remained low (0.22 and 0.21). Mean cerebral blood flow was similar in untreated sham groups (88 +/- 12 after 4 h, 92 +/- 11 after 24 h, 96 +/- 10 mL 100 g(-1) min(-1) after 48 h). Haemodilution increased mean cerebral blood flow after 4h (184 +/- 11 mL 100 g(-1) min(-1)), after 24h (153 +/- 13 mL 100 g(-1) min(-1)) and 48h (149 +/- 15 mL 100 g(-1) min(-1)) (P < or = 0.05). Local cerebral blood flow increased in all 38 structures after 4h haemodilution but decreased with time in six of 38 brain structures after 24h and in 15 regions after 48 h (P < or = 0.05). CONCLUSIONS: A single one-time haemodilution increased mean cerebral blood flow for 2 days. However, local adaptation of cerebral blood flow to a chronic low haematocrit occurred but was heterogeneous within the brain.

Cellular immune response to autologous blood transfusion in hip arthroplasty: whole blood versus buffy coat-poor packed red cells and fresh-frozen plasma.

BACKGROUND AND OBJECTIVES: Transfusion-induced immunomodulation by autologous blood is probably related to the buffy coat. Hence, in the present study, phagocytotic and oxidation activities of peripheral blood cells were investigated in hip arthroplasty patients exposed to autologous blood. MATERIALS AND METHODS: Blood from 60 autologous donors was allocated at random to storage as whole blood (WB) or as buffy coat-poor packed red cells and fresh-frozen plasma (RCP). Phagocytotic and oxidation activities of neutrophils and monocytes, incidence of infections and length of hospital stay were compared among the groups of transfused (WB and RCP) and non-transfused (NT) patients. RESULTS: Phagocytotic activities of neutrophils and monocytes were not significantly different among the WB, RCP and NT groups. CONCLUSION: In the perioperative setting, a specific cellular immune response to autologous transfusion is not detectable.

Humoral immune response to autologous blood transfusion in hip surgery: whole blood versus packed red cells and plasma.

BACKGROUND AND OBJECTIVES: The immune response to the transfused autologous buffy coat content in whole blood has, to date, not been studied in detail. SUBJECTS AND METHODS: Patients undergoing hip arthroplasty were studied according to whether they received autologous whole blood (WB) (n = 30), autologous fresh-frozen plasma and buffy coat-poor red cells (RC) (n = 40), or no transfusion (NT) (n = 27). Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and complement SC5b-9 were analysed by enzyme-linked immunosorbent assay (ELISA) 7 days after surgery. RESULTS: There were no significant between-group differences regarding the time course of TNF-alpha, IL-6 and complement SC5b-9 plasma level changes, the infection rate, or the length of hospital stay. CONCLUSION: In comparison to the impact of surgery on cytokine and complement levels, the transfusion of autologous buffy coat is not relevant.

Effect of moderate hypothermia on experimental severe subarachnoid hemorrhage, as evaluated by apparent diffusion coefficient changes.

OBJECTIVE: The aims of this study were to investigate the early changes in the mean apparent diffusion coefficient (ADC) after severe subarachnoid hemorrhage (SAH), as a marker of ischemic damage, and to examine the effects of moderate hypothermia, induced at various time points, on ADC changes. METHODS: ADC maps were calculated from diffusion-weighted, blipped-epi, spin echo, magnetic resonance imaging sequences (2.35-T BIOSPEC 24/40 scanner; Bruker Medizin Technik GmbH, Karlsruhe, Germany) for 21 anesthetized (0.45-1% halothane, temperature-adjusted/30% oxygen/69% nitrogen) and ventilated Wistar rats. After baseline scanning, bolus injection of 0.5 ml of autologous arterial blood or artificial cerebrospinal fluid (control group), into the cisterna magna, was performed. Serial scanning was performed for 3 hours after injection, using normothermic or hypothermic (32 degrees C) rats. In an additional series of experiments, hypothermia was initiated either immediately or 60 minutes after normothermic SAH. The water contents of the removed brains were calculated using the wet/dry weight method. RESULTS: The ADC values did not change in the control group but decreased to 88.6+/-5.2% (P < 0.05 versus baseline) after SAH and remained significantly decreased throughout the experiment in normothermia. An injection of blood during hypothermia caused an initial decrease in ADC to 96.1+/-5.6% (P < 0.05 versus baseline); values continuously increased and reached normal levels within 60 minutes. Delayed hypothermia also normalized ADC values within the observation period. The brain water content in the control group was 80.3+/-0.1%, that after SAH in normothermia was 81.1+/-0.7%, and that after SAH in hypothermia was 79.3+/-0.5%. CONCLUSION: This model of severe SAH in rats causes significant ADC changes, which are reversible by application of moderate hypothermia even when it is induced after a 60-minute delay. These findings support the concept of moderate hypothermia exerting a neuroprotective effect in severe SAH.

Immune response to autologous transfusion in healthy volunteers: WB versus packed RBCs and FFP.

BACKGROUND: Storage of blood as packed RBCs and FFP is standard practice in allogeneic transfusion. Separation into components has been proposed for autologous transfusion, as well, but beneficial effects have not yet been shown. STUDY DESIGN AND METHODS: Twenty-four healthy male volunteers were randomly assigned to receive 1 unit of either autologous RBCs and FFP (RCP group) or WB (WB group) after 49 or 35 days of storage, respectively. The immune response was analyzed by ELISA for IL-6, C3a, terminal complement complex SC5b-9, TNF-alpha, and neopterin. Differential WBC counts and the phagocytosis of neutrophils and monocytes were measured by flow cytometry. RESULTS: Cell counts of monocytes (0.85 x 10(3) ng/microL) [corrected] and neutrophils (6.9 x 10(3) ng/microL) [corrected] increased 30 minutes after WB transfusion and then returned to close to the baseline values seen in the RCP group (0.47 and 2.9 x 10(3) ng/microL [corrected], respectively) throughout the monitored period (p<0.05). C3a (169 vs. 116 ng/microL) [corrected] and IL-6 (29 vs. 6 pg/mL) reached higher plasma concentrations in the WB group (n = 11) than in the RCP group (n = 10). Phagocytosis of opsonized Escherichia coli was increased in neutrophils and monocytes and lasted up to 7 days after the transfusion of whole blood. CONCLUSION: Autologous WB induces a modest immunomodulation, but this effect is not observed upon transfusion of autologous blood components.

Anaesthetic care for sickle cell disease.

Despite the high frequency of sickle cell disease in Europe, the disease is poorly managed. Critical periods are the hospital stays during which the anaesthesiologist plays an important role. Understanding the molecular basis of polymerization processes of haemoglobin S can help to avoid triggering a crisis. Differentiation of the various haemoglobin phenotypes helps to estimate the individual perioperative risk. Knowledge of the patient's history and the actual haemoglobin S level facilitates general anaesthesia, surgery and postoperative care. Damage to liver, spleen, eyes, bones, lung and central nervous system increases the perioperative risk. Preoperative preparation includes early admission, intravenous volume substitution, continuing pain therapy and prophylactic antibiotic medication. General anaesthesia seems to be better for patients with a high-risk profile rather than regional anaesthesia. Careful perioperative and postoperative monitoring should allow hypoxaemia, hypovolaemia, hypothermia, acidosis and overtransfusion to be avoided. Effective pain therapy includes a combination of opioids with peripherally acting analgesia.

Effects of xenon on cerebral blood flow and cerebral glucose utilization in rats.

BACKGROUND: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. METHODS: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. RESULTS: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. CONCLUSION: Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.

Influence of blood viscosity on blood flow in the forebrain but not hindbrain after carotid occlusion in rats.

That cerebral blood flow remains unchanged at an increased blood viscosity, as long as the vascular supply is not compromised, was tested. To induce a reduced blood supply of some parts of the brain and to keep the supply unchanged in others both carotid arteries were occluded in anesthetized, ventilated rats. By this procedure, blood supply to the rostral brain, but not to the brainstem and cerebellum, was compromised. Blood viscosity was increased by intravenous infusion of 20% polyvinylpyrrolidone (high viscosity group) or decreased by infusion of 5% albumin (low viscosity group). Cerebral blood flow was measured by the [14C]iodoantipyrine method in 50 complete coronal sections of the rostral brain and 22 complete coronal sections of the brainstem and cerebellum in each rat. In the high viscosity group, mean cerebral blood flow of the rostral brain was significantly lower (46 +/- 7 mL/100 g(-1) x min(-1)) than in the low viscosity group (82 +/- 18 mL/100 g(-1) x min(-1)). No differences could be observed in brainstem and cerebellum between both groups (162 +/- 29 mL/100 g(-1) x min(-1) vs. 156 +/- 18 mL/100 g(-1) x min(-1)). Local analysis of cerebral blood flow in different brain structures of the coronal sections showed the same identical results; i.e., in 29 of the 31 brain structures analyzed in rostral brain, local cerebral blood flow was lower in the high viscosity group, whereas no differences could be observed in the 11 brain structures analyzed in the brainstem and cerebellum. It is concluded that under normal conditions cerebral blood flow can be maintained at an increased blood viscosity by a compensatory vasodilation. When the capacity for vasodilation is exhausted by occlusion of supplying arteries, an increased blood viscosity results in a decrease of cerebral blood flow.

Mild and moderate hypothermia (alpha-stat) do not impair the coupling between local cerebral blood flow and metabolism in rats.

BACKGROUND AND PURPOSE: The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO(2) (alpha-stat). Pericranial temperature was maintained normothermic (37.5 degrees C, n=12) or was reduced to 35 degrees C (n=12) or 32 degrees C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals. RESULTS: Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%, P<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (P<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%, P<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (r=0.93), anesthetized (r=0.92), and both hypothermic groups (35 degrees C r=0. 96, 32 degrees C r=0.96, P<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/micromol during anesthesia (P<0.05), remained at 2.4 mL/micromol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/micromol, P<0.05). CONCLUSIONS: Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.