[The chapters "Stop the bleed-prehospital" and "Coagulation management and volume therapy (emergency departement)" in the new S3 guideline "Polytrauma/severe injury treatment"]. / Die Kapitel "Stop the Bleed ­ Prähospital" sowie "Gerinnungsmanagement und Volumentherapie (Schockraum)" in der neuen S3-Leitlinie "Polytrauma/Schwerverletzten-Behandlung".

The S3 guideline on the treatment of patients with severe/multiple injuries by the German Association of the Scientific Medical Societies was updated between 2020 and 2022. This article describes the essence of the new chapter "Stop the bleed-prehospital" and the revised chapter "Coagulation management and volume therapy".

[Hypovolemic and hemorrhagic shock]. / Hypovolämisch-hämorrhagischer Schock.

The term "shock" refers to a life-threatening circulatory failure caused by an imbalance between the supply and demand of cellular oxygen. Hypovolemic shock is characterized by a reduction of intravascular volume and a subsequent reduction in preload. The body compensates the loss of volume by increasing the stroke volume, heart frequency, oxygen extraction rate, and later by an increased concentration of 2,3-diphosphoglycerate with a rightward shift of the oxygen dissociation curve. Hypovolemic hemorrhagic shock impairs the macrocirculation and microcirculation and therefore affects many organ systems (e.g. kidneys, endocrine system and endothelium). For further identification of a state of shock caused by bleeding, vital functions, coagulation tests and hematopoietic procedures are implemented. Every hospital should be in possession of a specific protocol for massive transfusions. The differentiated systemic treatment of bleeding consists of maintenance of an adequate homeostasis and the administration of blood products and coagulation factors.

[Management of hemorrhage in patients treated with direct oral anticoagulants]. / Management von Blutungen unter Therapie mit direkten oralen Antikoagulanzien.

The introduction of nonvitamin K antagonistic, direct oral anticoagulants (DOAC) made thromboembolic prophylaxis easier for patients. For many physicians, however, there is still uncertainty about monitoring, preoperative discontinuation, and restarting of DOAC therapy. Guidelines for the management of bleeding are provided, but require specific therapeutic skills in the management of diagnostics and therapy of acute hemorrhage. Small clinical studies and case reports indicate that unspecific therapy with prothrombin complex concentrates (PCC) and activated PCC (aPCC) concentrate may reverse DOAC-induced anticoagulation. However, PCC or aPCC at higher doses potentially provoke thromboembolic complications. However, idarucizumab, a specific, fast-acting, antidote for dabigatran, provides immediate and sustained reversal with no intrinsic or prohemostatic activity. This review article provides an overview of the pharmacology and potential risk of DOAC and the management in the perioperative period with a focus of current concepts in the treatment of DOAC-associated bleeding.

[Approaches to pre-hospital bleeding management : Current overview on civilian emergency medicine]. / Ansätze zur prähospitalen Gerinnungstherapie : Aktuelle Übersicht für die zivile Notfallmedizin.

Severe bleeding is a typical result of traumatic injuries. Hemorrhage is responsible for almost 50% of deaths within the first 6 h after trauma. Appropriate bleeding control and coagulation therapy depends on an integrated concept of local hemostasis by primary pressure with the hands, compression, and tourniquets accompanied by prevention of hypothermia, acidosis and hypocalcemia. Additionally, permissive hypotension is accepted for suitable patients and tranexamic acid should be administered early. Multiple publications prove that prehospital transfusion of blood products (e. g. red blood cells and plasma) and coagulation factors (e. g. fibrinogen) is feasible and safe, but only required for <5% of polytrauma patients in the civilian setting.

[Care for severely injured persons : Update of the 2016 S3 guideline for the treatment of polytrauma and the severely injured]. / Versorgung von Schwerverletzten : Update der S3-Leitlinie Polytrauma/Schwerverletzten-Behandlung 2016.

In 2011 the first interdisciplinary S3 guideline for the management of patients with serious injuries/trauma was published. After intensive revision and in consensus with 20 different medical societies, the updated version of the guideline was published online in September 2016. It is divided into three sections: prehospital care, emergency room management and the first operative phase. Many recommendations and explanations were updated, mostly in the prehospital care and emergency room management sections. These two sections are of special interest for anesthesiologists in field emergency physician roles or as team members or team leaders in the emergency room. The present work summarizes the changes to the current guideline and gives a brief overview of this very important work.

[Anesthesiological approach to postpartum hemorrhage]. / Anästhesiologisches Vorgehen bei peripartaler Blutung.

Peripartum hemorrhage (PPH) is a frequent obstetric emergency situation with increasing incidence in the last decades. It requires a fast, coordinated and interdisciplinary management. This life-threatening situation is often recognized too late and not adequately treated (too little is done too late); therefore, it is important to be aware of the most important risk factors for PPH known as the 4 Ts (i.e. tonus, trauma, tissue and thrombin). Due to the special patient population there is only little evidence-based data on hemostatic therapy in this situation; therefore, the currently available studies on the therapy of PPH is discussed.

[Coagulation therapy in multiple trauma without point-of-care testing]. / Gerinnungstherapie beim Polytrauma ohne Point-of-care-Testung.

Analysis of blood coagulation with thrombelastometry (ROTEM™) and thrombelastography (TEG™) and analysis of thrombocyte function by a Multiplate™ assay is possible in only a few hospitals in Germany. Recently, the grade of recommendation (GoR) for point-of-care (POC) testing in official guidelines was increased and is now classified as GoR 1C. If a POC-based option is not available alternatives must be used. Besides blood products (RBC, FFP, TC), coagulation factor concentrates are used to treat trauma-induced coagulopathy. The benefits of therapy with factor concentrates are fewer immunological and infection side effects as well as faster effects after administration of specific coagulation factors. A good outcome in patients with multiple trauma is only possible by an adequate transfusion regime and administration of coagulation factors.

[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).

[Peripartum hemorrhage, diagnostics and treatment : Update of the S2k guidelines AWMF 015/063 from August 2022]. / Peripartale Blutungen, Diagnostik und Therapie : Update der S2k-Leitlinie AWMF 015/063 vom August 2022.

The current S2k guidelines on the diagnostics and treatment of peripartum hemorrhage are summarized in this article from the perspective of anesthesiology based on a fictitious case report. The update of the guidelines was written under the auspices of the German Society of Gynecology and Obstetrics with the participation of other professional societies and interest groups from Germany, Austria and Switzerland and published by the AWMF in 2022 under the register number 015/063.

[Coagulation management in the treatment of multiple trauma]. / Gerinnungsmanagement bei der Polytraumaversorgung.

In recent years a new understanding of trauma-associated hemorrhaging and trauma-induced coagulopathy has been achieved. This coagulopathy is multifactorial with the predominant mechanisms being tissue trauma, shock and hypoperfusion which can lead to hyperfibrinolysis by activation of the endothelium. Routinely tested coagulation parameters, such as prothrombin time and partial thromboplastin time, are frequently employed for decision making but remain problematic as they do not give any information on clot stability, lysis or platelet function. Thrombelastometry seems to be a useful alternative. A pro-active anticipatory approach is required for a successful outcome to be achieved as rescue correction is more difficult than prevention. While the pathophysiological conception of causal relationship of the mentioned therapeutic options is conclusive, an evidence-based validation by randomized controlled studies is mostly lacking. The emergency and anesthesiological concept of damage control resuscitation consists of limiting volume therapy with crystalloids and colloids to reach a mean arterial pressure > or =65 mmHg (higher for head injuries), active (re-)warming management, the prevention of a pH< or =7.2 and a base excess (BE) < or =-6 mmol/l. The early and sufficient application of hemostatic drugs is essential. Because erythrocytes play a substantial role in the coagulation process, hemoglobin (Hb) values of around 6. 2 mmol/l (10 g/dl) and/or a hematocrit of 30% should be strived for when massive non-arrested hemorrhaging occurs. After severe multiple trauma a fibrinogen deficit develops and must be adequately compensated. If coagulation therapy is carried out using fresh frozen plasma sufficient quantities (20-30 ml/kgBW) must be administered to correspondingly raise the coagulation factors. Prothrombin complex concentrates can be helpful to optimize thrombin generation during severe hemorrhaging. Because hyperfibrinolysis occurs more often than previously assumed during severe trauma, an anti-fibrinolytic therapy should be used especially for patients with an instable circulation. The platelet count should not go below 100,000/microl when hemorrhaging occurs after multiple trauma. For thrombocytopathic patients with diffuse bleeding desmopressin (DDAVP) is a therapeutic option and the "off label" use of recombinant activated factor VIIa (rFVIIa) remains an option for individual situations with stringent indications and when the above named measures to optimize the coagulation situation have been taken.

[Intrathecal baclofen therapy. Overdose during replacement of a medication pump]. / Intrathekale Baclofentherapie. Uberdosierung beim Wechsel der Medikamentenpumpe.

This case report reviews the anesthesiological complications of intrathecal baclofen (ITB) therapy. An 11-year-old boy with spasticity and apallic syndrome needed general anesthesia for exchange of a baclofen pump but 2 h later he became increasingly hypothermic, hypotonic with bradycardy and dyspnea. The cause was an intra-operative bolus of ITB. Reduction of the baclofen administration rate caused disappearance of all symptoms without any residual effects. The ITB is an increasingly used therapeutic option for multiple sclerosis and cerebral palsy. Therefore, emergency personal and anesthesiologists must be aware of the possible side effects of this medication.

Behavioral transitions modulate hippocampal electroencephalogram correlates of open field behavior in the rat: support for a sensorimotor function of hippocampal rhythmical synchronous activity.

A clear relationship exists between moment-to-moment behavioral elements and hippocampal rhythmical synchronous activity (RSA) (theta rhythm). However, behavioral elements are not isolated events but are part of behavioral sequences in a context of behavioral activity. By concurrently monitoring open field behavior and hippocampal EEG, EEG correlates of open field behavior in relation to preceding and following behavior were studied in Sprague Dawley rats to determine whether the behavioral context influences EEG correlates of behavior. Results show that preceding and subsequent behavioral patterns influenced the spectral power correlates of behavior. RSA power was increased when a "type 1 behavior" (voluntary movement) preceded the behavior compared with when a "type 2 behavior" (automatic movement, awake immobility) preceded it. The modulating effect of behavioral transitions was shown for several types of behaviors, and systematic modulation of hippocampal EEG correlates of behavior was demonstrated. The present report shows that the strong and systematic relationship between hippocampal RSA and behavior is modulated by the behavioral-sequential context. Thus, in addition to the well established relationship between RSA and motor activity, a second nonmotor process seems to contribute to hippocampal RSA. A likely candidate is a sensory process, which is in accordance with theories on the sensorimotor function of hippocampal RSA.

The relationship between hippocampal EEG theta activity and locomotor behaviour in freely moving rats: effects of vigabatrin.

The relationship between hippocampal electroencephalogram (EEG) theta activity and locomotor speed in both spontaneous and forced walking conditions was studied in rats after vigabatrin injection (500 mg/kg i.p.). Vigabatrin increased the percentage of time that rats spent being immobile. During spontaneous walking in the open field, the speed of locomotion was increased by vigabatrin, while theta peak frequency was decreased. Vigabatrin also reduced the theta peak frequency during forced (speed controlled) walking. There was only a weak positive correlation (r=0.22) between theta peak frequency and locomotor speed for the saline condition. Furthermore, vigabatrin abolishes the weak relationship between speed of locomotion and theta peak frequency. Vigabatrin and saline did not differ in the slope of the regression line, but showed different offset points at the theta peak frequency axis. Thus, other factors than speed of locomotion seem to be involved in determination of the theta peak frequency.

Somatostatin analog octreotide (SMS 201-995) prevents the decrease in blood pressure after oral glucose loading in the elderly.

In elderly subjects blood pressure (BP) may fall after a meal. The mechanism of this phenomenon is unknown, but it has been suggested that it may be mediated by insulin and/or vasoactive gut hormones. We studied in normo- and hypertensive elderly subjects the effects of the synthetic long-acting somatostatin analog octreotide (SMS 201-995) on the BP reduction that follows oral glucose administration in subjects who are recumbent and on their postglucose plasma vasoactive intestinal polypeptide (VIP) and insulin concentrations. After placebo treatment, mean arterial pressure fell by 15 +/- 1 mm Hg (P less than 0.001) in the 10 hypertensive subjects and by 7 +/- 2 mm Hg (P less than 0.01) in the 10 normotensive subjects. In contrast, when 50 micrograms octreotide were given sc, BP did not change significantly in either group. Oral glucose did not induce a rise in plasma VIP after either octreotide or placebo administration. The postglucose rises in plasma glucose concentrations were similar after octreotide and placebo treatments in both groups. After placebo administration the postglucose plasma insulin levels increased from 79 to 519 pmol/L in the hypertensive subjects and from 63 to 464 pmol/L in the normotensive subjects, whereas after octreotide treatment plasma insulin increased little in either group. These data indicate that treatment with octreotide holds promise for patients with symptomatic postprandial hypotension, and that VIP does not seem to play a role in this phenomenon.

Nitrendipine versus hydrochlorothiazide in hypertensive patients over 70 years of age.

The effects of nitrendipine and hydrochlorothiazide were studied in hypertensive elderly patients. Blood pressure was reduced (p less than 0.01) by both nitrendipine (13/10 +/- 4/3 mm Hg [n = 15], mean +/- SE) and hydrochlorothiazide (25/11 +/- 4/2 mm Hg [n = 16]). After hydrochlorothiazide, plasma glucose, uric acid, and renin activity increased and plasma potassium levels decreased. Edema and flushing were the main adverse reactions during nitrendipine. The response of blood pressure and heart rate to head-up tilt were not significantly different under both treatments. However, the effects of both drugs on diastolic blood pressure and norepinephrine responses to head-up tilt differed significantly. We conclude that, in the elderly, hydrochlorothiazide lowers systolic blood pressure more effectively than nitrendipine. However, nitrendipine does not have any of the potentially harmful metabolic side effects that were found during hydrochlorothiazide therapy. The clinical significance of a lower vasoreactivity during nitrendipine, as was found with the head-up tilt test, has to be established.