[Escalation and de-escalation concept for intensive care beds in hospitals reserved for COVID-19]. / Eskalations­/Deeskalationskonzept zur COVID-19-bedingten Freihaltung von Intensivkapazitäten an Kliniken.

BACKGROUND: Since the spread of Severe Acute Respiratory Syndrom Corona Virus 2 (SARS-CoV­2) in Germany, intensive care beds have been kept free for patients suffering from Corona Virus Disease (COVID-19). Also, after the number of infections had declined, intensive care beds were kept free prophylactically; however, the percentage of beds reserved for COVID-19 differ in the individual federal states in Germany. The aim of this article is to define a necessary clearance quota of intensive beds for COVID-19 patients in Germany. An escalation and de-escalation scheme was created for rising and falling numbers of infected patients. METHODS: Data from the COVID-19 resource board of the state of Baden-Württemberg, the daily situation report of the Robert Koch Institute (RKI), the register of COVID-19 intensive care beds of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) as well as the daily report of COVID-19 Baden-Württemberg from April to November 2020 were used for the calculation. RESULTS: At the end of November 2020 approximately 13.5% of intensive care beds in Germany were used by COVID-19 patients. Of all persons tested positive for SARS-CoV­2, 1.5% were admitted to an intensive care unit. The hospitalization rate was 6% and the mean age of infected persons was 43 years. Based on these numbers hospitals are recommended to keep 10% of intensive care beds available for COVID-19 patients in the case of less than 35 new infections/100,000 in the catchment area, 20% should be kept free in case of an advanced warning level of 35 new infections/100,000 inhabitants and 30% for a critical limit of 50 new infections/100,000 inhabitants. Further internal hospital triggers, such as the occupancy of the intensive care beds with COVID-19 patients, should be considered. CONCLUSION: If the number of infections is low a general nationwide retention rate of more than 10% of intensive care beds for COVID-19 patients is not justified. Locally increasing numbers of infections require a local dynamic approach. If the number of infections increases, the free holding capacity should be increased according to a step by step concept in close coordination with the local health authorities and other internal hospital triggers. In order not to overwhelm hospital capacities in the event of local outbreaks, a corresponding relocation concept should be considered at an early stage.

[Provisioning of personal protective equipment in hospitals in preparation for a pandemic]. / Bevorratung persönlicher Schutzausrüstung in Kliniken zur Vorbereitung auf eine Pandemie.

BACKGROUND: At the beginning of the SARS-CoV­2 outbreak, personal protective equipment (PPE) was scarce worldwide, leading to the treatment of patients partially without sufficient protection for the medical personnel. In order to be prepared for a new epidemic or pandemic or a "second wave" of COVID-19 outbreak and to meet a renewed deficiency of PPE, considerations were made on how personnel and patients can be better protected by appropriate provisioning. OBJECTIVE: The aim of this study was to develop a tool to predict the necessary amount of PPE to be in stock at a transregional university hospital for a certain period of time during a pandemic. MATERIAL AND METHODS: The consumption of PPE needed for every patient was calculated based on the following data of the Ulm University Hospital: the total consumption of healthcare workers' PPE for April 2020 recorded by the materials management department and the number of patients suffering from COVID-19 and their treatment days. From the amount of PPE necessary for every patient in the intensive care unit (ICU) or in an infection ward, a PPE calculator was created in which the estimated amount of PPE can be calculated with the input variables "patients in intensive care unit", "patients in infection ward" and "treatment days". To validate the PPE calculator, the actual consumption of PPE for May 2020 at the Ulm University hospital was compared to the theoretically calculated demand by the PPE calculator. RESULTS: In April 2020 PPE consisting of 18 different items were kept in stock at Ulm University Hospital and in total 1,995,500 individual items were used. 22 intensive care patients with 257 nursing days and in the infection ward 39 patients with 357 nursing days were treated for COVID-19 disease, leading to a total of 603.2 man-days. A total of 34,550 KN95 masks, 1,558,780 gloves and 1100 goggles or protective visors were used, with a daily average of 49 NK95 masks and 2216 gloves required per ICU patient. In May 2020, 6 ICU patients and 19 patients in infection wards were treated for COVID-19 with 34 nursing days in intensive care and 201 nursing days in infection wards. The use of PPE material was 39% lower than in the previous month but in absolute terms 82% and on average 39% higher than calculated. CONCLUSION: The developed tool allows our hospital to estimate the necessary amount of PPE to be kept in stock for future pandemics. By taking local conditions into account this tool can also be helpful for other hospitals.

[Terrorist attack training exercise-What can be learned? : Baden-Württemberg counterterrorism exercise (BWTEX)]. / Terrorismusabwehrübung ­ Was können wir daraus lernen? : Baden-Württembergische Terrorismusabwehr Exercise (BWTEX).

BACKGROUND: There is a risk of terror attacks in the Federal Republic of Germany, which might increase in the future. A timely comprehensive strategy for treatment and care of a large number of casualties helps minimize chaos and improve the outcome of patients. Adequate training is vital for successful implementation of an emergency plan. Therefore, the effectiveness of training should be assessed and evaluated; however, data collection capabilities for training events are extremely limited, so that publications on the topic are almost impossible to find. OBJECTIVE: This study aimed to collect data from a simulated terrorist attack in order to draw conclusions from a clinical point of view concerning the improvement of preclinical and clinical management, taking interface problems into consideration. MATERIAL AND METHODS: On 19 October 2019 the Ministry of the Interior, Digitalization and Migration of Baden-Württemberg conducted a large-scale simulation of a terrorist attack in the city center of Constance, called the Baden-Württemberg counterterrorism exercise (BWTEX). The simulation included an explosion of a car bomb as well as the use of firearms by terrorists. The large scale of the simulation with the high number of participants in combination with close cooperation between military and civil forces was unprecedented. The police force, the armed forces, civil protection forces, air rescue teams and staff from Constance, Friedrichshafen and Sigmaringen regional hospitals in southwest Germany worked together to treat simulated injuries to victims of the attack. The following parameters were recorded when the injured patients arrived at the hospital: prehospital triage time, prehospital triage score, initial treatment and quality of documentation on site as well as triage time, triage score, injury severity scale (ISS) score based on the specified injury pattern, treatment, and quality of documentation on hospital arrival. RESULTS: Out of a total of 84 "injured patients" 55 were admitted to hospital and 80% were triaged at the scene. Injured patients of triage category 1 (TK1 red: life-threatening injury, immediate treatment) arrived at the hospital 198 ± 50 min after the attack, injured patients of triage category 2 (TK2 yellow: severely injured, urgent treatment) after 131 ± 44 min and injured patients of triage category 3 (TK3 green: slightly injured, non-urgent treatment) arrived after 157 ± 46 min. There was no significant difference in terms of arrival time at the hospital between the triage scores (r = 0.2) or between the ISS scores (r = 0.43). The authors assume that approximately 44% of TK1 patients would have died due to avoidable time delays. Prehospital medical documentation was insufficient in 78% and insufficient in 65% in the hospitals. CONCLUSION: A mass casualty incident resulting from a terrorist attack differs greatly from a conventional mass casualty incident. The scene of the attack has to be evacuated as quickly as possible, which means that a large number of patients arrive untreated at the nearest hospitals. The setting up of treatment facilities in city centers and areas close to the city seems to be counterproductive because the time delay may result in higher mortality rates of victims. The particularities of mass casualties caused by a terrorist attack have to be incorporated into terrorist attack training.

[Exit wave plan for structured secondary patient distribution : Logistic concept for mass victims of terrorist attacks]. / Exit-Wellenplan zur geordneten sekundären Patientenverteilung : Logistikkonzept bei Massenanfall von Terroropfern.

BACKGROUND: Following a terrorist attack a second hit is to be feared. The adequate reaction of the emergency services on site is to clear the scene. Since in such cases no treatment areas are set up at the scene of the incident, the injured are quickly admitted to the nearest hospital, either by themselves or by the emergency services and are largely untreated. Therefore, the hospital has to be ready to take in a significantly larger number of injured people in a very short period of time than after a conventional mass casualty incident. Due to the conceivably large number of wounded persons the emergency department can ensure primary medical care but nowhere near all casualties admitted to the hospital can be definitively treated. OBJECTIVE: In order to provide injured patients with individual medical care after initial treatment according to the criteria of damage control resuscitation, a concept should be developed that enables a well-organized secondary transfer to receiving hospitals with appropriate equipment. MATERIAL AND METHODS: Within a radius of 100 km from Ulm, all hospitals certified by the German Society for Trauma Surgery were contacted and asked to indicate how many emergency patients of the triage categories T1 (red), T2 (yellow) and T3 (green) could be admitted and treated around the clock (24/7). Special features such as a helicopter landing pad, neurosurgical care and pediatric traumatology care were considered. RESULTS: Of the 32 hospitals within a 100 km radius of Ulm 29 (91%) provided information on the admission capacity. In these hospitals 45 T1, 121 T2 and 333 T3 patients could be admitted around the clock (24/7). A helicopter landing pad is available at 26 of the 29 hospitals (90%), 11 hospitals (38%) can treat patients for emergency neurosurgery and 18 hospitals (62%) have the possibility of pediatric traumatological emergency care. Based on this information the structured exit wave plan was developed, which enables a secondary transfer of at least 100 patients to qualified trauma centers. CONCLUSION: The University Hospital of Ulm has made preparations to admit at least 100 injured patients for initial medical treatment following a terrorist attack. This corresponds to 10% of the hospital beds as required in the literature. Together with the neighboring Military Hospital and the University and Rehabilitation Hospital Ulm up to 300 injured patients can be treated; however, the number of available intensive care unit (ICU) beds and capacities in normal wards for definitive care is much lower, therefore, patients treated according to the principles of damage control resuscitation have to be relocated. By documenting the capacity of the hospitals within a 100 km radius around Ulm and taking their specific features into account, an exit wave plan could be created that enables patient distribution for definitive care without time-consuming procedures.

[Impact assessment of inadequate hospital disaster management : Reflection based on a risk model]. / Folgen einer unzureichenden Krankenhaus-Katastrophenplanung : Betrachtung anhand eines Risikomodells.

BACKGROUND: According to legal regulations alarm and emergency plans have to be developed and kept current in hospitals. However, often neither the hospital administration, nor the medical employees and nursing staff pay the necessary attention to these alarm and evacuation plans. In particular, risks and consequences - including financial ones - due to insufficient planning, are not adequately considered. OBJECTIVES: Risks in hospitals are assessed based on a risk analysis. The risk assessment evaluates, whether the risk is acceptable, critical or unacceptable. Parameters for the risk analysis are the magnitude of damage and number of affected people. The intention of this paper is to evaluate whether there is a connection between estimated risk, quality of risk planning, and financial damage. MATERIALS AND METHODS: We visualized the risk analysis as a two-dimensional matrix. In addition, we introduced disaster planning quality as a third dimension and calculated the dependency between risk and planning quality and also between the resulting damage level and the planning quality. RESULTS: We showed that a poor disaster planning quality increases the unacceptable risk exponentially. Risk assessment can also draw conclusions about the extent of financial damage caused, for example fires, terrorist attacks or infrastructure failure. The amount of damage can be described as a function depending on the planning deficit of emergency planning. The worse the planning quality, the higher the amount of damages for non-tolerable risks can be. CONCLUSIONS: Risk management means recognizing risks, assessing risks and managing risks. In hospitals, this mostly means using a critical incident reporting system (CIRS), however risk management in the sense of disaster planning is largely unknown. With a three-dimensional risk matrix, we showed a clear correlation between the quality of disaster planning and relative risk or financial damage. To substantiate the presented theoretical considerations, however, further research must be designed and implemented.

[Stocks of dantrolene in anesthesia and intensive care units in Germany : Nationwide online survey with 1673 participants]. / Dantrolenbevorratung in Anästhesie und Intensivmedizin in Deutschland : Bundesweite Onlineumfrage mit 1673 Teilnehmern.

BACKGROUND: A malignant hyperthermia (MH) crisis is a potentially fatal complication in anesthesia and intensive care units (ICU). Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis. International anesthesiology societies recommend an initial dose of 2.0-2.5 mg/kg body weight (BW). The necessary total dosage should be titrated up to 10 mg/kg BW depending on the effectiveness. OBJECTIVE: The goal of this study was an analysis of the stocking situation of dantrolene in Germany. A national survey was conducted amongst members of the German Society of Anaesthesia and Intensive Care (DGAI). MATERIAL AND METHODS: A questionnaire consisting of 19 items was posted online to all DGAI members from 2 September to 30 September 2015. The questionnaire dealt with characterization of the participants, the administration of triggering substances in the operating room and in the ICU of the respective hospitals. The main part covered the amount of stocked dantrolene, the place of storage and emergency availability of stocked dantrolene from elsewhere. RESULTS: The questionnaire was posted online to 12,415 DGAI members with a response rate of 13.5% (n = 1673). The highest response rate was from 259 directors and heads of anesthesiology units representing 28.3%. In total 93,7% of participants use volatile anesthetics and 82,3% use succinylcholine. In the event of an MH-crisis 40.4% of participants have 36 or more vials of dantrolene available within 5 min, 27.4% have only 24 vials and 18.7% only have 12 vials. Of the anesthesiologists in outpatient surgery 70.6% have a dantrolene stock of less than 36 vials. In those cases with insufficient dantrolene stock, 35.5% of hospitals have no agreement with neighboring hospitals. In the ICU setting, 51.8% of responding participants indicated the use of volatile anesthetics, but only 25.7% stock dantrolene in the ICU. For succinylcholine, 77.3% stated using the drug in the ICU, and 26.0% have a dantrolene stock in the ICU. CONCLUSION: Almost all anesthesiologists participating in the online survey use volatile anesthethics and/or succinylcholine. Whereas almost all participants have access to dantrolene, more than half of the units have a stock of dantolene, which is less than that recommended by the DGAI. In the case of low dantrolene stock, only 61% of anesthesia departments have access to additional dantrolene within a time frame of 15min . The results of this online survey demonstrate that the stock of dantrolene may be insufficient in some German hospitals and anesthesiology practices.

[Pharmacogenetics in anesthesia and intensive care medicine : Clinical and legal challenges exemplified by malignant hyperthermia]. / Pharmakogenetik in Anästhesie und Intensivmedizin : Klinische und juristische Herausforderung am Beispiel der Malignen Hyperthermie.

Pharmacotherapy is a key component of anesthesiology and intensive care medicine. The individual genetic profile influences not only the effect of pharmaceuticals but can also completely alter the mode of action. New technologies for genetic screening (e.g. next generation sequencing) and increasing knowledge of molecular pathways foster the disclosure of pharmacogenetic syndromes, which are classified as rare diseases. Taking into account the high genetic variability in humans and over 8000 known rare diseases, up to 20 % of the population may be affected. In summary, rare diseases are not rare. Most pharmacogenetic syndromes lead to a weakening or loss of pharmacological action. In contrast, malignant hyperthermia (MH), which is the most relevant pharmacogenetic syndrome for anesthesia, is characterized by a pharmacologically induced overactivation of calcium metabolism in skeletal muscle. Volatile anesthetic agents and succinylcholine trigger life-threatening hypermetabolic crises. Emergency treatment is based on inhibition of the calcium release channel of the sarcoplasmic reticulum by dantrolene. After an adverse pharmacological event patients must be informed and a clarification consultation must be carried out during which the hereditory character of MH is explained. The patient should be referred to a specialist MH center where a predisposition can be diagnosed by the functional in vitro contracture test from a muscle biopsy. Additional molecular genetic investigations can yield mutations in the genes for calcium-regulating proteins in skeletal muscle, e.g. ryanodine receptor 1 (RyR1) and calcium voltage-gated channel subunit alpha 1S (CACNA1S). Currently, an association to MH has only been shown for 35 mutations out of more than 400 known and probably hundreds of unknown genetic variations. Furthermore, MH predisposition is not excluded by negative mutation screening. For anesthesiological patient safety it is crucial to identify individuals at risk and warn genetic relatives; however, the legal requirements of the Patients Rights Act and the Human Genetic Examination Act must be strictly adhered to. Specific features of insurance and employment law must be respected under consideration of the Human Genetic Examination Act.

[Terror attacks : Recommendations for cooperation between police, hospitals and non-police security services]. / Lebensbedrohliche Einsatzlagen : Handlungsempfehlung zur Zusammenarbeit zwischen Polizei, Kliniken und nichtpolizeilicher Gefahrenabwehr.

BACKGROUND: The risk of terrorist attacks in the Federal Republic of Germany is present and is currently increasing. Publicly funded acute care hospitals and their owners are involved in disaster control as part of their remit and are responsible for taking comprehensive precautions to ensure their operational capability in the event of disasters. This mandate must also be ensured in the event of terrorist attacks and amok incidents. For this purpose, an optimal cooperation between preclinical and clinical care is indispensable. AIM: Recommended actions for collaboration between nonclinical and clinical planning to manage a mass casualty incident in terrorist life-threatening response situations are presented. MATERIAL AND METHODS: The Inter-Hospital Security Conference Baden-Württemberg (IHSC BW) is an association of representatives of acute hospitals in Baden-Württemberg, the Ministry of the Interior, Digitalization and Migration Baden-Württemberg, the Ministry of Social Affairs and Integration Baden-Württemberg, the State Police Headquarters Baden-Württemberg and the Baden-Württemberg Hospital Association. From 2018 to 2020, the IHSC BW developed recommendations for action on cooperation between police, hospitals and non-police emergency response. The recommendations for action were agreed by the group members in 6 working sessions and initialled in two subsequent video conferences. A recommendation was considered adopted when the IHSC BW plenary assembly finally gave its approval with an absolute majority. RESULTS AND DISCUSSION: Competence-based interface solutions for a smooth cooperation between prehospital and hospital management in the care of patients who have become victims of a terrorist attack are to be demanded. For preliminary planning, the establishment of a local safety conference at the county disaster control authority level with the following participants is recommended: disaster control authority, fire department, regional police headquarters, chief emergency physician, rescue services and disaster control officers of affected clinics. It is recommended to set up a joint command and situation center (CSC), where management personnel from the police, rescue service, fire department and disaster control can meet to organize the handling of the incident jointly, competently and without loss of time. From this CSC, a liaison officer should then provide the clinics with information at regular intervals. Exercises should take place regularly. Cross-organizational exercises are particularly important, and this is one of the tasks of the local safety conference.

[Resilience against IT attacks in hospitals : Results from an exercise in a German university hospital]. / Resilienz gegen IT-Angriffe an Kliniken : Ergebnisse einer Stabsrahmenübung an einem Universitätsklinikum.

BACKGROUND: According to the legal definition healthcare systems and their components (e.g., hospitals) are part of the critical infrastructure of modern industrial nations. During the last few years hospitals increasingly became targets of cyber attacks causing severe impairment of their operability for weeks or even months. According to the German federal strategy for protection of critical infrastructures (KRITIS strategy), hospitals are obligated to take precautions against potential cyber attacks or other IT incidents. OBJECTIVE: This article describes the process of planning, execution and results of an advanced table-top exercise which took place in a university hospital in Germany and simulated the first 3 days after a cyber attack causing a total failure of highly critical IT systems. MATERIAL AND METHODS: During a first stage lasting about 8 months IT-dependent processes within the clinical routine were identified and analyzed. Then paper-based and off-line back-up processes and workarounds were developed and department-specific emergency plans were defined. Finally, selected central facilities such as pharmacy, laboratory, radiology, IT and the hospitals crisis management team took part in the actual disaster exercise. Afterwards the participants were asked to evaluate the exercise and the hospitals cyber security using a questionnaire. On this basis the authors visualized the hospital's resilience against cyber incidents and defined short-term, medium-term and long-term needs for action. RESULTS: Of the participants 85% assessed the exercise as beneficial, 97% indicated that they received adequate support during the preparations and 75% had received sufficient information; however, only 34% had the opinion that the hospital's and their own preparedness against critical IT failures were sufficient. Before the exercise took place, IT-specific emergency plans were present only in 1.7% of the hospital facilities but after the exercise in 86.7% of the clinical and technical departments. The highest resilience against cyber attacks was not surprisingly reported by facilities that still work routinely with paper-based or off-line processes, the IT department showed the lowest resilience as it would come to a complete shutdown in cases of a total IT failure. CONCLUSION: The authors concluded that the planning phase is the most important stage of developing the whole exercise, giving the best opportunity for working out fallback levels and workarounds and through this strengthen the hospitals resilience against cyber attacks and comparable incidents. A meticulous preparedness can minimize the severe effects a total IT failure can cause on patient care, staff and the hospital as a whole.

[Inhalational analgosedation in the intensive care unit : Risk of malignant hyperthermia]. / Inhalative Analgosedierung auf der Intensivstation : Gefahr einer malignen Hyperthermie.

BACKGROUND: According to the 2010 S3 Guidelines, analgosedation is an option for ventilated patients in intensive care units (ICU). Therefore, adverse effects of volatile anesthetics can occur in areas outside of surgical medical fields. OBJECTIVE: The aim is to inform ICU physicians about the clinical and legal challenges of a life-threatening pharmacogenetic reaction to inhalational anesthetics, malignant hyperthermia (MH). DISCUSSION: Consequences of an MH crisis for doctors, patients, and relatives regarding patient rights legislation, as well as insurance and employment issues with respect to the German Genetic Diagnostics Act are discussed.

Radiological validation of tracheal tube insertion depth in out-of-hospital and in-hospital emergency patients.

We performed a 5-year, retrospective study using records of 1081 patients admitted to the trauma emergency room at a University Hospital to investigate the occurrence of tracheal tube malpositioning after emergency intubation in both the inpatient and outpatient settings, using chest radiographs and CT scans in the trauma emergency room. Prehospital patients and inpatients referred from peripheral hospitals were compared. This study showed that tracheal tube misplacements occur with an incidence of 18.2%, of which almost a third (5.7%) were placed in a main bronchus. We further show that tracheal intubation in emergency patients approximates the misplacement rates in the prehospital or in-hospital settings. We speculate that the skill level of the operator may be critical in determining the success of tracheal intubation. Based on our findings, all efforts should be made to verify the tube position with immediate radiographic confirmation after admission to the emergency room.

Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Binding of a Bolton-Hunter substituted homostatine analog to affinity-immobilized human renin.

The binding of a Bolton-Hunter reagent substituted homostatine analog, SDZ 213-776, to human renin was investigated at pH 6.5 and 7.4. At both pH values, SDZ 213-776 bound to human renin in a reversible and saturable manner. The binding characteristics conformed to a one-site binding model. The dissociation constant Kd, obtained at equilibrium, was four-fold lower at pH 6.5 that at pH 7.4 (0.94 nM vs 3.7 nM). Under non-equilibrium conditions, only the association kinetic constant k+1 was affected by pH. The results of the binding assay at pH 6.5 correlated well with those obtained in enzymatic assay at the same pH.

Influence of continuous haemofiltration on haemodynamics and central blood volume in experimental endotoxic shock.

In order to assess the influence of continuous haemofiltration (HF) on haemodynamics and central blood volume in endotoxic shock, endotoxinaemia was invoked in 20 swine (28-32 kg). 15 min after doubling the mean pulmonary pressure, the animals were randomly assigned to receive either a zero-balanced veno-venous HF with an ultrafiltration and replacement rate of 600 ml/h (HF group, n = 10) or to observe the spontaneous course (E group, n = 10) under a constant infusion of endotoxin for 4 h. A trend to a higher survival rate in the HF group (6/10 vs. 3/10; E group) during the observation period was evident, but not statistically significant. Early initiation of HF during endotoxic shock modifies the haemodynamic response, lowering the pulmonary artery pressure (PAP), PCWP, pulmonary (PVR) and systemic vascular resistance (SVR), compared to the spontaneous course, whereas the decrement of central blood volume was comparable in both groups. These changes cannot be explained by effects of the HF on the volume status, but supports and additional effect by the filtration of small and medium-sized molecules.

The consequences of continuous haemofiltration on lung mechanics and extravascular lung water in a porcine endotoxic shock model.

Endotoxinaemia (E. coli endotoxin, 0.111.B4) and pulmonary hypertension were evoked in 20 swine, randomly assigned to receive either zero-balanced venovenous haemofiltration (HF) with an ultrafiltration and replacement rate of 600 ml/h (HF group, n = 10) or to undergo an uninfluenced spontaneous course (E group, n = 10) during a constant infusion of endotoxin until the end of the experiment. Endotoxin-induced pulmonary dysfunction was assessed on the basis of extravascular lung water (EVLW) using a thermo-dye technique via a fiberoptic intra-aortic probe, gas exchange and lung mechanics, the latter derived by a pressure-volume loop (P/V loop) of the respiratory system (super syringe, flow 30 ml/s, tidal volume 600 ml). A comparable increase in alveolo-arterial oxygen difference and a constant EVLW was observed in both groups. The progressive deterioration of hysteresis area and compliance parameters by endotoxinaemia was significantly blunted by HF. Independent of an impact on pulmonary oedema zero-balanced HF modifies endotoxin induced lung injury, probably by the convective transport of mediator substances.

The effect of basic fibroblast growth factor on glutamate-injured neuroarchitecture and arachidonic acid release in adult hippocampal neurons.

During development in culture, basic fibroblast growth factor (bFGF) protected immature primary hippocampal neurons against glutamate-induced neurotoxicity. We investigated the effects of bFGF on mature, differentiated rat hippocampal neurons cultured for 10-12 days after an 8-min exposure to 500 microM glutamate. Seven days post-injury, hippocampal cells demonstrated severe reductions in cellular viability and axonal and dendritic outgrowth, which were accompanied by a marked increase in [3H]arachidonic acid (ARA) release from prelabelled neurons. bFGF applied post-injury attenuated cell death and cytoarchitectural destruction at all concentrations used (500 pg/ml, 1, 10, 20 ng/ml). However, neurite elongation and branching processes were only significantly protected by 10 ng/ml bFGF. [3H]ARA release decreased in a dose-related fashion within a concentration range of 1-10 ng/ml bFGF. 20 ng/ml bFGF was not superior to 10 ng/ml bFGF. Therefore, bFGF's neurotropic actions appear to be concentration-dependent. Our data suggest that bFGF applied post-injury may have a neuroprotective potential for mature, differentiated, completely polarized hippocampal neurons.

Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: An experimental study of the underlying pathophysiology.

The present study examines intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral circulation immediately after experimental head injury in an animal model. The underlying systemic hemodynamic changes were also observed. To produce a standardized head injury, a fluid-percussion device was applied to the dura at the midline of 10 piglets. Seven other nontraumatized animals served as a control group. Hemodynamic parameters as well as ICP and CPP were recorded on-line, one value every 1.4 seconds. Cerebral blood flow (CBF) and cerebral vascular resistance (CVR) were measured three times using a microsphere technique. Immediately after head injury, the traumatized animals showed a sudden increase in ICP, with a maximum of 40 torr at 3 to 5 minutes, while there was a pronounced decrease in CPP from 85 to 40 torr. The CBF in the various brain areas fell from 55 to 22 ml/min/100 gm within 5 minutes after the impact, and CVR increased to 300% of control values within 90 minutes. The findings of this study demonstrated that cerebral circulation is critically jeopardized within a few minutes after trauma. This, in combination with a subsequent increase in CVR, makes the early development of ischemic brain damage very likely. In traumatized patients, treatment prior to hospital admission must therefore be directed at prevention of this fatal course.

The respiratory aspect of the treatment of brain injury associated with acute alcohol intoxication--results of an animal experiment.

The effects of spontaneous respiration and mechanical ventilation were examined by investigating the interaction between elevated intracranial pressure and alcohol intoxication. Ethanol (200 ml 48%) was infused in 11 young pigs with elevated cerebral pressure during mechanical ventilation (group 1), 7 young pigs with elevated cerebral pressure during spontaneous respiration (group 2), and 4 young pigs without elevated cerebral pressure during spontaneous respiration (group 3). While the behavior of intracranial pressure during mechanical ventilation in the animals from group 1 was inhomogeneous with a tendency to rise (29-34 mmHg), cerebral pressure (28-55 mmHg) increased drastically in the animals from group 2. This increase was associated with a sharp rise of Pa,CO2 (37.6-73.3 mmHg) and a decrease of Pa,O2 (74 mmHg to 13 mmHg). None of the animals in group 2 survived. Pa,CO2 also rose in alcoholized animals without elevated cerebral pressure (group 3) (41.9-63.9 mmHg); intracranial pressure, however, remained within the normal range. All animals in group 3 survived. Our findings indicate that elevated intracranial pressure and alcohol intoxication have a cumulative or potentiating effect on depression of the respiratory center. Respiratory depression can be prevented by mechanical ventilation and, therefore, a further rise of intracranial pressure generally avoided.

Spectral analysis of ventricular fibrillation and closed-chest cardiopulmonary resuscitation.

This study was designed to assess the interference by closed-chest cardiopulmonary resuscitation (CPR) on the ventricular fibrillation (VF) ECG signal in a porcine model of cardiac arrest and to elucidate which variable of VF spectral analysis reflects best myocardial blood flow and resuscitation success during CPR. Fourteen domestic pigs were allocated to receive either 0.4 U/kg vasopressin (n = 7) or 10 ml saline (n = 7) after 4 min of VF and 3 min of CPR. Using radiolabeled microspheres, myocardial blood flow was determined during CPR before, and 90 s and 5 min after, drug administration. Using spectral analysis of VF, the median frequency, dominant frequency, edge frequency and amplitude of VF were determined simultaneously and before the first defibrillation attempt. Using filters in order to specify frequency ranges, stepwise elimination of mechanical artifacts resulting from CPR revealed that at a frequency bandpass of 4.3-35 Hz, median fibrillation frequency has a sensitivity, specificity, positive and negative predictive value of 100% to differentiate between resuscitated and non-resuscitated animals. The best correlation between myocardial blood flow and fibrillation frequency was found at a median frequency range of 4.3-35 Hz. We conclude that spectral analysis of VF can provide reliable information relating to successful resuscitation. In this model after elimination of oscillations due to mechanical CPR, median fibrillation frequency best reflects the probability of resuscitation success.

Effects of epinephrine and vasopressin on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation.

OBJECTIVE: This study was designed to assess whether median frequency of ventricular fibrillation (VF) correlates with myocardial blood flow and defibrillation success during cardiopulmonary resuscitation (CPR) after epinephrine or vasopressin administration. METHODS AND RESULTS: After 4 min of VF and 3 min of CPR, 14 pigs received 0.045 mg/kg epinephrine or 0.4 U/kg vasopressin. Using radio-labeled microspheres, median myocardial blood flow during CPR before, and 90 s and 5 min after drug administration (DA) was 15.5 (12.6, 23.1; 25th percentile, 75th percentile), 26.4 (18.5, 29.1), 16.9 (14.9, 19.1) mL min-1 100 g-1, respectively, in the epinephrine, and 16.9 (15.4, 18.9), 48.1 (36.9, 68.9) (P < 0.05 vs. before DA), 52.3 (38.5, 65.0) mL min-1 100 g-1, respectively, in the vasopressin group. Using spectral analysis of VF, median frequency of VF was 11.0 (10.7, 11.8), 11.3 (9.6, 13.1), 10.2, (8.8, 11.4) Hz, respectively, in the epinephrine, and 10.1 (10.0, 10.5), 11.7 (11.1, 14.2) (P < 0.05 vs. before DA), 13.2 (11.5, 13.9) Hz, respectively, in the vasopressin group at the same points in time. Median frequency correlates significantly with myocardial blood flow in the epinephrine (n = 21); rs = 0.772; P < 0.001) and in the vasopressin group (n = 21; rs = 0.905; P < 0.001). Median fibrillation frequency before the first defibrillation was 13.0 (12.2, 13.2) Hz in resuscitated (n = 8) and 9.2 (8.3, 10.2) Hz (n = 6) in non-resuscitated animals (P < 0.01). CONCLUSIONS: We conclude that median frequency of VF reflects myocardial blood flow and the chance of successful defibrillation during closed-chest CPR after vasopressor treatment in a porcine model of VF.