PubMed Health⌕ Search

Biomedical subjects

Donat R Spahn

Publications and source records attributed to Donat R Spahn.

At least 19 recordsLinked to original sources
PubMed2007

Novel starches: single-dose pharmacokinetics and effects on blood coagulation.

BACKGROUND: Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to their volume expansion effect and their pharmacokinetic characteristics. The goal of the current study was to determine the pharmacokinetics of CMS and CM-HES and to investigate their influence on blood coagulation in comparison with the standard low-molecular, low-substituted HES (130/0.42) used in Europe. METHODS: The study was conducted as a randomized, blinded, parallel three-group study in 30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a single dose, and serial blood sampling was performed over 20 h to measure plasma concentration and molecular weight and to assess blood coagulation. Concentration-effect relations were assessed by pharmacokinetic-pharmacodynamic analysis. RESULTS: CMS and CM-HES showed significantly higher plasma concentrations and molecular weights over 20 h (P for both<0.001) with smaller volumes of distribution and longer elimination rates during the terminal phase (P for both<0.01) when compared with HES. CMS and CM-HES impaired whole blood coagulation more than HES as assessed by Thrombelastograph analysis (Haemoscope Corporation, Niles, IL). However, similar effects of all three starch preparations on blood coagulation were found when related to the plasma concentrations in mass units. CONCLUSIONS: Carboxymethylation of starch results in an increased intravascular persistence and a slower fragmentation compared with HES. The greater impairment of blood coagulation by CMS and CM-HES seems to be caused by the higher plasma concentrations.

Animals↗
PubMed2006

Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse.

Experimental models of peripheral nerve injury have been developed to study mechanisms of neuropathic pain. In the spared nerve injury (SNI) model in rats, the common peroneal and tibial nerves are injured, producing consistent and reproducible pain hypersensitivity in the territory of the spared sural nerve. In this study, we investigated whether SNI in mice is also a valid model system for neuropathic pain. SNI results in a significant decrease in withdrawal threshold in SNI-operated mice. The effect is very consistent between animals and persists for the four weeks of the study. We also determined the relative frequency of paw withdrawal for each of a series of 11 von Frey hairs. Analysis of response frequency using a mixed-effects model that integrates all variables (nerve injury, paw, gender, and time) shows a very stable effect of SNI over time and also reveals subtle divergences between variables, including gender-based differences in mechanical sensitivity. We tested two variants of the SNI model and found that injuring the tibial nerve alone induces mechanical hypersensitivity, while injuring the common peroneal and sural nerves together does not induce any significant increase in mechanical sensitivity in the territory of the spared tibial nerve. SNI induces a mechanical allodynia-like response in mice and we believe that our improved method of assessment and data analysis will reveal additional internal and external variability factors in models of persistent pain. Use of this model in genetically altered mice should be very effective for determining the mechanisms involved in neuropathic pain.

Animals↗
PubMed2006

Complications of different ventilation strategies in endoscopic laryngeal surgery: a 10-year review.

BACKGROUND: Spontaneous ventilation, mechanical controlled ventilation, apneic intermittent ventilation, and jet ventilation are commonly used during interventional suspension microlaryngoscopy. The aim of this study was to investigate specific complications of each technique, with special emphasis on transtracheal and transglottal jet ventilation. METHODS: The authors performed a retrospective single-institution analysis of a case series of 1,093 microlaryngoscopies performed in 661 patients between January 1994 and January 2004. Data were collected from two separate prospective databases. Feasibility and complications encountered with each technique of ventilation were analyzed as main outcome measures. RESULTS: During 1,093 suspension microlaryngoscopies, ventilation was supplied by mechanical controlled ventilation via small endotracheal tubes (n = 200), intermittent apneic ventilation (n = 159), transtracheal jet ventilation (n = 265), or transglottal jet ventilation (n = 469). Twenty-nine minor and 4 major complications occurred. Seventy-five percent of the patients with major events had an American Society of Anesthesiologists physical status classification of III. Five laryngospasms were observed with apneic intermittent ventilation. All other 24 complications (including 7 barotrauma) occurred during jet ventilation. Transtracheal jet ventilation was associated with a significantly higher complication rate than transglottal jet ventilation (P < 0.0001; odds ratio, 4.3 [95% confidence interval, 1.9-10.0]). All severe complications were related to barotraumas resulting from airway outflow obstruction during jet ventilation, most often laryngospasms. CONCLUSIONS: The use of a transtracheal cannula was the major independent risk factor for complications during jet ventilation for interventional microlaryngoscopy. The anesthetist's vigilance in clinically detecting and preventing outflow airway obstruction remains the best prevention of barotrauma during subglottic jet ventilation.

Adolescent↗
PubMed2006

Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs.

BACKGROUND: Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. METHODS: Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. RESULTS: Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. CONCLUSION: High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.

Animals↗
PubMed2006

Anemia and perioperative red blood cell transfusion: a matter of tolerance.

In the past, anemia in the perioperative period has been treated by red blood cell (RBC) transfusions relatively uncritically. RBC transfusions were believed to increase oxygen delivery by increasing hemoglobin concentration. Arbitrary transfusion triggers such as the "10/30 rule" (i.e., RBC transfusion indicated below a hemoglobin concentration of 10 g/dL or a hematocrit of 30%) were applied. However, there is now increasing evidence that RBC transfusions are associated with adverse outcomes and should be avoided whenever possible. Restraining from RBC transfusions and maintaining normovolemia in patients suffering from surgical blood loss results in acute anemia. Therefore, knowing the compensatory mechanisms during acute anemia is crucial. This review focuses on acute anemia tolerance, its limits, and physiologic transfusion triggers in the perioperative period.

Acute Disease↗
PubMed2006

Key issues in advanced bleeding care in trauma.

The incidence of hemostatic abnormalities in the early hours after traumatic incident is high and represents an independent predictor of mortality. Key factors in the development of traumatic coagulopathy include the severity of injury, hypothermia, acidosis, hemorrhagic shock, hemodilution, clotting factor consumption, and fibrinolysis. Assessment of bleeding includes evaluation of the mechanism of injury, vital signs, biochemistry, detection of external and internal bleeding sources, injuries found upon secondary investigation, and response to treatment. Priority in treating the bleeding trauma patient should be given to prevention of further bleeding, hypothermia, acidosis, coagulopathy, and maintenance of tissue oxygenation, achieved by careful physical handling, damage control surgery, analgesia, maintenance of normothermia, correction of coagulopathy, control of blood pH, and serum calcium. Priority during initial treatment is to restore tissue perfusion and achieve hemostasis in vital functions; other nonvital procedures may generally be delayed. This state-of-the-art review aims to address key issues in acute control of bleeding in the trauma patient.

Hemorrhage↗
PubMed2006

Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding--a European perspective.

INTRODUCTION: Our aim was to develop consensus guidelines for use of recombinant activated factor VII (rFVIIa) in massive hemorrhage. METHODS: A guidelines committee derived the recommendations using clinical trial and case series data identified through searches of available databases. Guidelines were graded on a scale of A-E according to the strength of evidence available. Consensus was sought among the committee for each recommendation. RESULTS: A recommendation for use of rFVIIa in blunt trauma was made (grade B). rFVIIa might also be beneficial in post-partum hemorrhage (grade E), uncontrolled bleeding in surgical patients (grade E) and bleeding following cardiac surgery (grade D). rFVIIa could not be recommended for use: in penetrating trauma (grade B); prophylactically in elective surgery (grade A) or liver surgery (grade B); or in bleeding episodes in patients with Child-Pugh A cirrhosis (grade B). Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child-Pugh B and C cirrhosis (grade C). Monitoring of rFVIIa efficacy should be performed visually and by assessment of transfusion requirements (grade E), while thromboembolic adverse events are a cause for concern. rFVIIa should not be administered to patients considered unsalvageable by the treating medical team. CONCLUSIONS: There is a rationale for using rFVIIa to treat massive bleeding in certain indications; however, only adjunctively to the surgical control of bleeding once conventional therapies have failed. Lack of data from randomized, controlled clinical trials, and possible publication bias of the case series data, limits the strength of the recommendations that can be made.

Blood Substitutes↗
PubMed2005

Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons.

The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression of voltage-gated sodium channels (VGSCs) and a modification of sodium currents. To investigate whether the beta2 subunit of VGSCs participates in the generation of neuropathic pain, we used the spared nerve injury (SNI) model in rats to examine beta2 subunit expression in selectively injured (tibial and common peroneal nerves) and uninjured (sural nerve) afferents. Three days after SNI, immunohistochemistry and Western blot analysis reveal an increase in the beta2 subunit in both the cell body and peripheral axons of injured neurons. The increase persists for >4 weeks, although beta2 subunit mRNA measured by real-time reverse transcription-PCR and in situ hybridization remains unchanged. Although injured neurons show the most marked upregulation,beta2 subunit expression is also increased in neighboring non-injured neurons and a similar pattern of changes appears in the spinal nerve ligation model of neuropathic pain. That increased beta2 subunit expression in sensory neurons after nerve injury is functionally significant, as demonstrated by our finding that the development of mechanical allodynia-like behavior in the SNI model is attenuated in beta2 subunit null mutant mice. Through its role in regulating the density of mature VGSC complexes in the plasma membrane and modulating channel gating, the beta2 subunit may play a key role in the development of ectopic activity in injured and non-injured sensory afferents and, thereby, neuropathic pain.

Animals↗
PubMed2005

Current status of artificial O2 carriers.

This article describes currently evaluated artificial O2 carriers, summarizes their efficacy, and discusses their side effects, based on and restricted to published data. For compounds in phase III testing, approximately 500 to 1000 patients have been dosed, and similar numbers of control patients have been investigated. For compounds in phase I or II testing, the number of patients dosed is significantly less. Unfortunately, there is a significant amount of nonpublished data, which renders the overall assessment difficult, and the direct comparison among different types of artificial O2 carriers is significantly limited by the virtual nonexistence of studies that directly compare different products.

Emulsions↗
PubMed2005

The effect of clonidine on perioperative blood coagulation.

STUDY OBJECTIVE: To evaluate the influence of perioperative stress protection by clonidine on blood coagulation. DESIGN: Prospective, randomized, double-blinded, placebo-controlled clinical trial. SETTING: University hospital. PATIENTS: 50 patients scheduled for elective gynecoabdominal surgery. INTERVENTIONS AND MEASUREMENTS: Patients were randomly assigned to control (placebo) or clonidine group (single intravenous clonidine dose; 4 microg/kg(-1) or 3 microg/kg(-1) for age >65 years). Three measurement time points were defined: before administration of placebo/clonidine and anesthesia induction, (t1; baseline measurement); after surgery, before emergence of anesthesia (t2); and at the first postoperative day, 24 hours after anesthesia induction (t3). Blood coagulation was analyzed at all time points measuring international normalized ratio, platelets, thrombin-antithrombin complex, von Willebrand factor, soluble thrombomodulin, d-dimers, plasminogen activator inhibitor 1, and Thrombelastograph analysis. MAIN RESULTS: In the postoperative period (t2, t3), hypercoagulability was present in all patients compared with baseline measurements (t1) but without differences between the control and clonidine group. Regarding hematologic, laboratory blood coagulation, and Thrombelastograph parameters, there was no statistically and clinically relevant difference throughout the study period between the 2 groups. No hemodynamic adverse events of clonidine were observed in the perioperative period. Until day of discharge, no thrombotic or thromboembolic events were reported in both groups. CONCLUSIONS: Preoperative administration of a single dose of clonidine has no effect on perioperative blood coagulation.

Abdomen↗
PubMed2005

Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients.

Positive end-expiratory pressure (PEEP) applied during induction of anesthesia prevents atelectasis formation and increases the duration of nonhypoxic apnea in nonobese patients. PEEP also prevents atelectasis formation in morbidly obese patients. Because morbidly obese patients have difficult airway management more often and because arterial desaturation develops rapidly, we studied the clinical benefit of PEEP applied during anesthesia induction. Thirty morbidly obese patients were randomly allocated to one of two groups. In the PEEP group, patients breathed 100% O(2) through a continuous positive airway pressure device (10 cm H(2)O) for 5 min. After induction of anesthesia, they were mechanically ventilated with PEEP (10 cm H(2)O) for another 5 min until tracheal intubation. In the control group, the sequence was the same but without any continuous positive airway pressure or PEEP. We measured apnea duration until Spo(2) reached 90% and we performed arterial blood gases analyses just before apnea and at 92% Spo(2). Nonhypoxic apnea duration was longer in the PEEP group compared with the control group (188 +/- 46 versus 127 +/- 43 s; P = 0.002). Pao(2) was higher before apnea in the PEEP group (P = 0.038). Application of positive airway pressure during induction of general anesthesia in morbidly obese patients increases nonhypoxic apnea duration by 50%.

Adolescent↗
PubMed2005

Bronchial aspiration in patients after weight loss due to gastric banding.

Laparoscopic gastric banding is a surgical treatment of morbid obesity. There are no specific recommendations concerning anesthesia induction in patients having gastric banding. After recent experience of two bronchial aspirations during anesthetic induction in patients with gastric banding, we concluded that esophago-gastric peristalsis in these patients is altered. Such patients should consume only liquid meals the day before the operation, and we propose a rapid-sequence induction as the anesthetic technique. In patients with an expected difficult airway, an awake intubation may be considered.

Adult↗
PubMed2005

Artificial O2 carriers: status in 2005.

Donor blood is a limited resource and its transfusion is associated with significant adverse effects. Therefore, alternatives have been searched, the ultimate being artificial oxygen (O2) carriers. There are two main groups of artificial O2 carriers: hemoglobin based and perfluorocarbon emulsions. The hemoglobin molecule in hemoglobin based artificial O2 carriers needs to be stabilized to prevent dissociation of the alpha2beta2-hemoglobin tetramer into alphabeta-dimers in order to prolong intravascular retention and to eliminate nephrotoxicity. Other modifications serve to decrease O2 affinity in order to improve O2 off-loading to tissues. In addition, polyethylene glycol may be surface conjugated to increase molecular size. Finally, certain products are polymerized to increase the hemoglobin concentration at physiologic colloid oncotic pressure. Perfluorocarbons are carbon-fluorine compounds characterized by a high gas dissolving capacity for O2 and CO2 and chemical and biologic inertness. Perfluorocarbons are not miscible with water and therefore need to be brought into emulsion for intravenous application. Development, product specification, physiologic effects, efficacy to decrease the need for donor blood in surgery and side effects of the following products are described: Diaspirin cross-linked hemoglobin (HemAssist), human recombinant hemoglobin (rHb1.1 and rHb2.0), polymerized bovine hemoglobin-based O2 carrier (HBOC-201), human polymerized hemoglobin (PolyHeme), hemoglobin raffimer (Hemolink), maleimide-activated polyethylene glycol-modified hemoglobin (MP4) and perflubron emulsion (Oxygent). In addition, enzyme cross-linked poly-hemoglobin, hemoglobin containing vesicles (nano-dimension artificial red blood cells) and an allosteric modifier (RSR13) are discussed. The most advanced products are in clinical phase III trials but no product has achieved market approval yet in the US, Europe or Canada.

Allosteric Regulation↗
PubMed2004

Allogeneic blood transfusions: benefit, risks and clinical indications in countries with a low or high human development index.

The risks associated with allogeneic red blood cell (RBC) transfusions differ significantly between countries with low and high human development indexes (HDIs). In countries with a low HDI, the risk of infection (HIV, HBV, HCV and malaria) is elevated. In contrast, in countries with a high HDI, immunological reactions (haemolytic transfusion reactions, alloimmunization and immunosuppression) are predominant. Therefore the overall risk associated with RBC transfusions in low HDI countries is much more significant than that in high HDI countries. In view of these risks, the limited efficacy of RBC transfusion and its high costs, this procedure should be used sparingly and rationally. Therefore RBC transfusion protocols adapted to the local situation are essential. Such protocols should distinguish between physiological and haemoglobin-based transfusion triggers. In countries with a high HDI, relative tachycardia and hypotension, despite normovolaemia, ST-segment changes suggestive of myocardial ischaemia and an Hb level <6 g/dl can serve as general guidelines for transfusion. Higher haemoglobin transfusion triggers should be used for patients aged >80 years and those with coronary artery or cerebrovascular disease. In countries with a low HDI, clinical signs of circulatory failure or myocardial ischaemia and an Hb level <5 g/dl can serve as transfusion guidelines.

Adult↗