[Sepsis therapy. A dilemma in times of limited financial resources].
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Biomedical subjects
Publications and source records attributed to H Forst.
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Glucocorticoids are frequently used in clinical anaesthesiology and intensive care because of their antiallergic, antiinflammatory and antioedematous properties and anaphylactic reactions are rare. We report on a 62-year-old asthmatic patient with evidence of aspirin sensitivity. We administered 100 mg of hydrocortisone-21-hemisuccinate (Pharmacia & Upjohn, Erlangen, Germany) dissolved in 100 ml 0.9% sodium chloride solution for perioperative corticoid substitution. The patient immediately developed severe bronchospasm and anaphylactic shock requiring intubation and mechanical ventilation. He received adrenaline, isoflurane, ketamine and inhalational fenoterol. He then developed atrioventricular block type III for which we transcutaneously paced the patient. Subsequently he was tested via skin prick tests, intracutaneous tests and i.v.-challenges resulting in the patient having positive reactions to hydrocortisone-21-hemisuccinate. Thus when allergic-like reactions result from glucocorticoid therapy one should consider corticoid allergy as a differential diagnosis.
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One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorised as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic, or combined toxicity. Knowledge of the mechanism by which a given drug interaction occurs is often clinically useful and may help to avoid serious adverse events and perioperative morbidity. Although every tissue has some ability to metabolise drugs, the liver is the principal organ of drug metabolism and at the subcellular level the cytochrome P450 enzyme system is the main source of drug interaction. This article reviews the basic principles of drug metabolism and the role of cytochrome P450 in this scenario. Drugs frequently used in anaesthesia and critical care medicine such as benzodiazepines, opioid analgesics, antihypertensive and antiarrhythmic agents, antibiotics and antifungal drugs, antiemetics, histamine-receptor-antagonists, theopylline and paracetamol will be considered. The development of methods and tools which are practical and also economic, are of utmost importance since drug interaction is predictable if the metabolic pathway and the activity (genetic polymorphism) of the enzyme is known.
Laparoscopic surgery of the gallbladder has increasingly replaced open techniques due to postoperative benefits (less pulmonary complications, less postoperative pain, earlier mobilisation). Specific intraoperative effects of pneumoperitoneum have led to some uncertainty if cardiac and/or pulmonary high-risk cases should be done laparoscopically. We describe anaesthesiological management of a 72 year old patient with a unilateral leftsided honeycomb lung (two very large cysts) to undergo laparoscopic cholecystectomy. Vital capacity was reduced to 45%, forced expiratory 1 second volume to 41%, preoperative bloodgas analysis revealed a paO2 of 64 mmHg and a paCO2 of 40 mmHg. Under spontaneous breathing the patient was fiberoptically intubated with a left sided double lumen tube (Mallinckrodt, Athlone/Irland; 37 Ch) using balanced anaesthesia. The healthy right lung was hand ventilated with 100% oxygen to avoid excessive airway pressures (peak airway pressure 27 mbar, mean airway pressure 22-24 mbar). The diseased left lung was passively insufflated with oxygen. The intraabdominal pressure was limited to 10 mmHg. Muscle relaxation was achieved with atracurium under monitoring using a nerve stimulator. The paCO2 increased from 40 to 57 mmHg during the operation, but returned to normal immediately postoperatively. All other ventilatory and hemodynamic parameters were uneventful during the 35 minute procedure. The patient was extubated at the end of the procedure and monitored on the intensive care ward for one night. A postoperative chest X-ray revealed a mediastinal shift of 2 cm to the right, healthy side as well as an atelectasis on this side. The shift was most likely due to hypoventilation of the right lung, with the ensuing atelectasis drawing the mediastinum to the right. Under physiotherapy this shift had resolved by the next morning. The patient could be discharged from hospital on day seven and fully recovered. Especially the severely cardiopulmonary compromised patient benefits from a laparoscopic procedure, due to less postoperative reduction of pulmonary function. Careful and individually adapted monitoring and anaesthetic techniques are necessary to successfully counteract the special implications of pnemoperitoneum.
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We report on a case of a lumbar epidural abscess with staphylococcus aureus following a catheter epidural anaesthesia in a previously healthy and not immunosuppressed 34-year-old female. The indication for the epidural anaesthesia was mobilization of the right knee following arthrotomy due to chronic synovitis. On postoperative day 7 the patient experienced lumbar pain, headache and meningism. Magnetic resonance imaging revealed an epidural abscess at the height of the 3rd and 4th lumbar vertebrae. A right-sided intralaminar fenestration with debridement and drainage of the abscess was carried out immediately after confirmation of the diagnosis. The patient was discharged from hospital on postoperative day 21 without any neurological sequelae. This is another addition to the published cases of epidural abscess following a epidural technique. It underlines the need for a proper aseptic technique, to abandon frequent changes of bacterial filters, daily examination of the entry site of the catheter and strategies for close and continuous monitoring of patients following epidural anaesthesia.
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OBJECTIVE: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock. DESIGN: Prospective, randomized, double-blind, single-center study. SETTING: Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital. PATIENTS: Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score. INTERVENTIONS: All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group. CONCLUSIONS: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.
The aim of the present study was to investigate the pattern of ventricular dynamic contraction and its relation to changes of transseptal pressure gradient during ventilation with positive end-expiratory pressure (PEEP). For that purpose, left (LV) and right ventricular (RV) pressures as well as ventricular shortening in septal-lateral (s.l.) direction were assessed in 8 dogs (RV n = 5) exposed to experimental acute respiratory distress syndrome (eARDS) and PEEP 10 and 20 cmH2O (P10, P20). Despite maintenance of transmural central venous pressure by volume substitution, PEEP resulted in a fall of stroke index (P10 vs. eARDS: -7%, p<0.05; P20 vs. P10: -28%, p<0.05); this was accompanied by a fall of LV end-diastolic diameter (P10 vs. eARDS: -3.1%, p<0.01; P20 vs. P10: -7.4%, p<0.01). Although the transseptal LV to RV end- diastolic pressure gradient changed only minimally, there was a significant increase of paradoxic left ventricular systolic lengthening from 3.1% at eARDS to 4.5% at P10 (p<0.05 vs. eARDS) and 8.4% at P20 (p<0.05 vs. P10). Neither RV end-diastolic diameter nor s.l. shortening were significantly influenced by P10 or P20. It is concluded, that a rearrangement of LV dynamic contraction does occur during ventilation with PEEP, which is compatible with the concept of paradoxic systolic bulging of the interventricular septum towards the lumen of the right ventricle. Since this phenomenon occurred independent from changes of the end-diastolic pressure gradient between both ventricles, we suggest that systolic septal movement to the right is an active contractile process to support the function of a stressed RV.
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We interviewed 45 patients, who answered advertisements (n = 21) or were referred by colleagues (n = 24), about their experience of intraoperative awareness using a standardized questionnaire. Auditory perceptions, hearing sounds or voices were mentioned by all patients (45 of 45): 33 of 45 patients understood and recalled conversations; 21 of 45 patients had visual perceptions; 12 of 21 recognized things or faces; 29 of 45 patients felt being touched; three patients had the sensation of moderate pain; and eight patients were in severe pain. Patients' feelings were mostly related to paralysis (27 of 45), helplessness (28 of 45), anxiety and fear (22 of 45); 18 were in severe panic. All patients (45 of 45) recognized the situation as a real event: 22 of 45 patients experienced unpleasant after effects; 11 suffered from anxiety and nightmares; and three developed post-traumatic stress disorder syndrome and required medical treatment. Twenty of 45 patients were especially attentive to emotionally relevant remarks on their own person, their disease and the course of their operation. The accuracy of sensory perception indicates a very high level of cognitive performance of patients during intraoperative awareness.
Critically ill patients frequently exhibit indirect signs of tissue hypoxia such as metabolic acidosis or elevated blood lactate levels. According to the concept of supply dependence of oxygen uptake (VO2), improvement of tissue oxygenation and secondary reduced mortality rates may be achieved in critically ill patients by an increase in systemic oxygen transport (DO2). However, a critical review of available clinical data and studies suggests that a positive correlation between calculated VO2 and oxygen delivery does not necessarily imply "pathological" oxygen-supply dependence. Possible pitfalls in the interpretation of data are mathematical coupling of data, alterations of oxygen demand, and calorigenic effects of catecholamines. Due to cellular dysfunction in specific tissues, increases in blood lactate concentration in patients with severe sepsis are not proof of tissue hypoxia. Retrospective analyses of data from survivors of critical illnesses form the basis of the therapeutic concept of maximising DO2 to supranormal values. Volume expansion, erythrocytes, catecholamines, and vasoactive agents were used to reach this aim. The results of two studies suggest that beginning the optimisation of DO2 preoperatively may be beneficial in high-risk surgical patients. There is evidence, however, that therapeutic interventions designed to achieve supranormal values of cardiac output, DO2, or VO2 in a heterogeneous population of critically ill patients do not result in reduced morbidity or mortality.
According to our own experience and published reports the frequency of red cell transfusion in intensive care units is in the range of 0.2 to 0.4 units per patient per day and is dependent upon the local strategy, the patients involved and the kind of surgery performed. The rationale for red cell transfusion is to maintain or restore the oxygen carrying capacity of the blood to avoid tissue hypoxia which occurs when oxygen delivery drops below a certain critical value. Besides bleeding, phlebotomy is also a significant source of blood loss in critically ill patients. According to several recent reviews and consensus articles there is no basis for a fixed indicator for transfusion, such as a haemoglobin concentration of < 100 gL-1. The decision to transfuse has to be made according to the patients individual status. The major adaptive mechanism in response to acute anaemia is an increase in cardiac output and hence blood flow to tissues. As a consequence even moderate degrees of acute anaemia may not be tolerated by patients with cardiac disease, whilst marked anaemia carries a considerable risk of ischaemia in patients with brain lesions or cerebral arterial stenoses. In critically ill patients it has been postulated that supply dependency of oxygen consumption occurs over a wide range of oxygen delivery, far above the critical values of oxygen delivery seen under normal conditions. Maximising oxygen delivery was therefore formulated as a goal in these patients. However, whether pathological supply dependency of oxygen delivery really exists in critically ill patients is still under discussion and recent studies found no benefit in maximising oxygen delivery to this patient group. However, individualised triggers for red blood cell transfusion are adequate for critically ill patients considering their co-morbidities and severity of disease. Finally, the decision to transfuse must also take into account the potential risks (infectious and non-infectious), as well as benefits for the individual patient. In the future, the level of transfusions may be reduced by using blood sparing techniques such as blood withdrawal in closed systems, bedside microchemistry, intravascular monitors, or autotransfusion of drainage blood in intensive care units.
Plasma and tissue concentrations of amphotericin B were determined in a patient treated with liposomal amphotericin B during liver transplant failure. A cumulative rise in amphotericin B plasma concentrations was observed accompanied by an enhanced pulmonary deposition of the drug. Failure of the liver as a major component of the reticuloendothelial system may cause elevated plasma concentrations of liposomal amphotericin B and may consequently enhance deposition of liposomes in the lungs as a substitutive clearing organ.