Biomedical subjects

A Hoeft

Publications and source records attributed to A Hoeft.

At least 19 recordsLinked to original sources

PubMed2006

Role of Toll-like receptor 4 for the pathogenesis of acute lung injury in Gram-negative sepsis.

BACKGROUND AND OBJECTIVE: Proinflammatory cytokines as well as nitric oxide (NO) play a major role in mediating the response to lipopolysaccharide (LPS). The present study tested the hypothesis that LPS induces proinflammatory cytokines in the lung via the Toll-like receptor 4 (TLR4)/CD14 signalling cascade. METHODS: Control mice and TLR4-deficient (TLR4-D) mice were used to test TLR4-mediated effects of LPS. Both strains received either Escherichia coli LPS (20 mg kg-1 intraperitoneal) or saline and their lungs were collected at different time points. Pulmonary nuclear factor kappaB (NFkappaB) activation was investigated with electromobility shift assay. mRNA expression of inflammatory mediators and their corresponding receptors were detected with Ribonuclease Protection Assay. Protein expression was detected by ELISA and western blotting. Inducible NO synthase (iNOS) expression was monitored by RT-PCR and iNOS activity by conversion of l-arginine to citrulline. Immune cells were sampled by bronchoalveolar lavage (BAL) and classified. RESULTS: LPS application induced CD14-, but not TLR4 protein expression in control mice. Activation of pulmonary NFkappaB was observed within 60 min in control, but not in TLR4-D mice. Six hours of LPS administration induced a significant increase in pulmonary tumour necrosis factor alpha-, interleukin-1beta- and interleukin-6 mRNA and protein expression in control mice compared to TLR4-D mice. Furthermore, LPS induced a significantly higher increase of the iNOS expression and catalytic activity in control mice than in TLR4-D mice. BAL revealed an increase in total cell count in all LPS treated mice. CONCLUSION: Our findings suggest that TLR4 plays a key role for regulating the expression of relevant cytokines within the lung during endotoxic shock.

Animals↗

PubMed2006

[Theophylline (aminophylline) and asystole. Case report and a brief review of the literature].

We report the use of the non-specific adenosine antagonist theophylline (aminophylline) during a prolonged intraoperative cardiopulmonary resuscitation (CPR) due to myocardial infarction. In the 2005 guidelines of the European Resuscitation Council the general use of theophylline during CPR is not recommended, but in the case of an atropine and epinephrine resistant asystole, especially as a result of inferior myocardial infarction, theophylline might be a useful adjunct during CPR.

Aged, 80 and over↗

PubMed2006

Reduction in anaesthetic drug consumption is correlated with mean titrated intra-operative Bispectral Index values.

BACKGROUND: Several studies have shown a reduction in anaesthetic drug consumption with Bispectral Index (BIS) titration compared with standard clinical practice. However, the amount of reduction varied widely between 1% and 40%. We investigated the correlation between reduction in anaesthetic drug consumption and mean titrated BIS values. METHODS: An analysis upon randomized controlled trials cited until January 2006 in MEDLINE and other databases investigating the potential reduction in anaesthetic (hypnotic) drug consumption with BIS titration was performed. Investigations with a marked difference (> 15%) in opioid drug consumption between the BIS group and the standard practice group were excluded. Correlations between amount of reduction in hypnotic drug use and the mean titrated BIS value were analysed with linear regression. RESULTS: Fourteen manuscripts covering 2582 patients were included into the analysis. The mean BIS value in the standard clinical practice group averaged over all studies was 43.6 +/- 3.2 and the mean BIS value in the BIS-titrated group was 49.9 +/- 5.4. The amount of reduction in hypnotic drug use correlated significantly with the mean BIS values in the BIS-titrated groups (r =0.68) and with the differences between the mean BIS value in the BIS-titrated group and the mean BIS value in the standard clinical practice group (r = 0.70). Every point of BIS difference between the two groups resulted in a reduced hypnotic drug use of approximately 2%. CONCLUSION: Despite differences in the study designs and in the drugs used, a linear correlation between the mean titrated BIS value and the hypnotic drug saving potential was found.

Anesthetics↗

PubMed2005

[Accidental urban hypothermia. Severe hypothermia of 20.7 degrees C].

In emergency medicine accidental hypothermia (<35 degrees C) is a common epiphenomenon of many medical conditions. In contrast, severe hypothermia (<28 degrees C) occurs very seldom and presents a difficult medical situation. Here we present a female patient with severe urban hypothermia (core temperature of 20.7 degrees C) and circulatory arrest. An overview of the emergency treatment, rewarming strategy with extracorporeal circulation and the clinical course will be given. The survival of the patient and the favorable neurological outcome will be discussed considering the current literature. Due to the paucity of treatment guidelines or clear prognostic criteria of withholding or withdrawing treatment in severe hypothermia, the decision of prolonged resuscitation and rewarming strategy is solely dependent on the individual judgement and medical experience of the physician. The positive clinical outcome which can be gleaned from case reports or single retrospective studies should encourage the emergency physician to selectively rewarm a severe hypothermic patient with extracorporeal circulation under prolonged CPR.

Adult↗

PubMed2005

Schmidt syndrome presenting as acute liver failure.

The Schmidt Syndrome (Type II Autoimmune-Syndrome) is characterised by an autoimmune adrenalitis in combination with a chronic lymphocellular thyreoiditis resulting in insufficiency of these organs in adulthood. Combination with diabetes is possible. The diagnosis is usually established by clinical examination and analysis of serum hormone levels (adrenocorticotropin hormone [ACTH], cortisol, thyroid stimulating hormone [TSH], triiodothyronine [fT3], thyroxine [fT4]). In the present case, initial diagnosis was rapid progressive liver failure of unknown origin with consecutive multiple organ dysfunction syndrome including dysfunction of heart, lungs, and kidneys. Frequent and less frequent causes of liver failure were ruled out, e.g. viral or autoimmune hepatitis, Budd-Chiari-syndrome, toxic, or drug induced liver failure. In retrospect, the multiple organ dysfunction syndrome was caused by hypoperfusion due to severe hypovolemia and hypoperfusion was induced by adrenocortical insufficiency proven by endocrinological testing. The clinical course of this case stresses the importance of the hormone balance in the critical ill patient. The guideline for treatment of patients with assumed hormonal dysregulation should include a full hormone status prior to substitution. The present case report also illustrates the importance of clinical signs and careful consideration of the medical history in detecting an autoimmune endocrine disease.

Diagnosis, Differential↗

PubMed2004

[Cytokines and heart failure].

Chronic heart failure is a major cause for mortality and morbidity in western civilizations. Previous hypothesises regarding the pathogenesis of chronic heart failure did not sufficiently explain the aetiology and the progression of the disease. However, it has been shown that a group of peptides called cytokines are expressed during chronic heart failure and that cytokines might play an important role for the pathogenesis. The expression of cytokines can be modulated from specific ACE-inhibitors as well as from different beta-blockers and angiotensin type 1 antagonists. Numerous investigations have shown that cytokines depress left ventricular function and can be responsible for different characteristics of chronic heart failure. The present article resumes experimental and clinical investigations and recent pharmacologic attempts for the treatment of chronic heart failure. The previous results demonstrate the importance to further investigate anti-inflammatory approaches to treat chronic heart failure.

Apoptosis↗

PubMed2004

Detection and differentiation of in vitro-spiked bacteria by real-time PCR and melting-curve analysis.

We introduce a consensus real-time PCR protocol for the detection of bacterial DNA from laboratory-prepared specimens such as water, urine, and plasma. This prototype detection system enables an exact Gram stain classification and, in particular, screening for specific species of 17 intensive care unit-relevant bacteria by means of fluorescence hybridization probes and melting-curve analysis in a one-run experiment. One strain of every species was tested at a final density of 10(6) CFU/ml. All bacteria examined except Staphylococcus aureus and Staphylococcus epidermidis could be differentiated successfully; S. aureus and S. epidermidis could only be classified as "Staphylococcus species." The hands-on time for preparation of the DNA, performance of the PCR, and evaluation of the PCR results was less than 4 h. Nevertheless, this prototype detection system requires more clinical validation.

Bacteria↗

PubMed2003

Opioid-induced respiratory depression is associated with increased tidal volume variability.

BACKGROUND AND OBJECTIVE: mu-agonistic opioids cause concentration-dependent hypoventilation and increased irregularity of breathing. The aim was to quantify opioid-induced irregularity of breathing and to investigate its time-course during and after an opioid infusion, and its ability to predict the severity of respiratory depression. METHODS: Twenty-three patients breathing spontaneously via a continuous positive airway pressure (CPAP) mask received an intravenous (i.v.) infusion of alfentanil (2.3 microg kg(-1) min(-1), 14 patients) or pirinitramide (piritramide) (17.9 microg kg(-1) min(-1), nine patients) until either a cumulative dose of 70 microg kg(-1) for alfentanil or 500 microg kg(-1) for pirinitramide had been achieved or the infusion had to be stopped for safety reasons. Tidal volumes (VT) and minute ventilation were measured with an anaesthesia workstation. For every 20 breaths, the quartile coefficient was calculated (Qeff20V(T)). RESULTS: Both the decrease of minute volume and the increase of Qeff20V(T) during and after opioid infusion were highly significant (P < 0.001, ANOVA). Patients in which the alfentanil infusion had to be terminated prematurely had lower minute volumes (P = 0.002, t-test) and higher Qeff20V(T) (P = 0.034, t-test) than those who received the complete dose. Changes in the regularity of breathing measured as Qeff20V(T) parallel those of minute ventilation during and after opioid infusion. CONCLUSIONS: Opioids cause a more complicated disturbance of the control of respiration than a mere resetting to higher PCO2. Furthermore, Qeff20V(T) appears to predict the severity of opioid-induced respiratory depression.

Adult↗

PubMed2003

Differential expression of alpha- and beta-defensins in human peripheral blood.

BACKGROUND: Human defensin peptides with broad-spectrum antimicrobial activity have been implicated in the human defence response towards microbial invasion. Two families of defensins designated alpha- and beta-defensins, respectively, have been identified. Little is known about the expression of both defensin families in human peripheral blood. The purpose of this study was to examine the expression of alpha- and beta-defensin genes in human peripheral blood. MATERIAL AND METHODS: Fifty-one healthy blood donors were screened for defensin expression. Blood from defensin responders was stimulated by lipopolysaccharide or heat-inactivated Pseudomonas aeruginosa ex vivo. Levels of mRNA were assessed by semiquantitative RT-PCR. Southern blot analysis and sequencing were used to confirm the identity of defensin gene transcripts. Western blotting analysis was used to detect the expression of defensin peptides. RESULTS: beta-defensin was undetected in human peripheral blood without stimulation. Following stimulation by lipopolysaccharide or heat-inactivated bacterial cells, the majority (88.2%) of healthy individuals had a detectable expression for beta-defensin-1 gene and 39.2% for beta-defensin-2 gene, compared with none for beta-defensin-3. beta-defensin-1 and -2 mRNAs in the stimulated human peripheral blood of responders became detectable at 3 h and showed a maximum at 6 h following induction by 100 ng mL-1 of lipopolysaccharide or bacterial cells. In contrast, human alpha-defensins 1-3 mRNA are constitutively expressed in peripheral leukocytes but not up-regulated by lipopolysaccharide or bacterial cells. CONCLUSIONS: In human peripheral blood, beta-defensin-1 and -2 genes were transiently transcribed and translated following the induction of lipopolysaccharide or heat-inactivated bacterial cells, whereas alpha-defensins 1-3 genes were constitutively transcribed, and beta-defensin-3 gene was not expressed. The inducible expression of beta-defensin-1 and -2 genes showed interindividual variability.

Adult↗

PubMed2003

Piritramide and alfentanil display similar respiratory depressant potency.

BACKGROUND: The question whether some opioids exert less respiratory depression than others has not been answered conclusively. We applied pharmacokinetic/pharmacodynamic (PKPD) modeling to obtain an estimate of the C50 for the depression of CO2 elimination as a measure of the respiratory depressant potency of alfentanil and piritramide, two opioids with vastly different pharmacokinetics and apparent respiratory depressant action. METHODS: Twenty-three patients received either alfentanil (2.3 microg x kg(-1) x min-1, 14 patients, as published previously) or piritramide (17.9 microg x kg(-1) x min(-1), nine patients) until significant respiratory depression occurred. Opioid pharmacokinetics and the arterial PCO2 (PaCO2) were determined from frequent arterial blood samples. An indirect response model accounting for the respiratory stimulation due to increasing PaCO2 was used to describe the PaCO2 data. RESULTS: The following pharmacodynamic parameters were estimated with NONMEM [population means and interindividual variability (CV)]: k(elCO2) (elimination rate constant of CO2) 0.144 (-) min(-1), F (gain of the CO2 response) 4.0 (fixed according to literature values) (28%), C50 (both drugs) 61.3 microg l-1 (41%), k(eo alfentanil) 0.654 (-) min(-1) and k(eo piritramide) 0.023 (-) min(-1). Assigning separate C50 values for alfentanil and piritramide did not improve the fit compared with a model with the same C50. CONCLUSION: Since the C50 values did not differ, both drugs are equally potent respiratory depressants. The apparently lower respiratory depressant effect of piritramide when compared with alfentanil is caused by slower equilibration between the plasma and the effect site. Generalizing our results and based on simulations we conclude that slowly equilibrating opioids like piritramide are intrinsically safer with regard to respiratory depression than rapidly equilibrating opioids like alfentanil.

Adult↗

PubMed2003

[Comparison of the emergency medical services systems of Birmingham and Bonn: process efficacy and cost effectiveness].

OBJECTIVE: Due to rising health care costs there is a need to verify that the treatment by Emergency Medical Services (EMS) systems is efficient and cost effective. The integration of emergency physicians is inherent part of out-of-hospital emergency care and regulated by law in Germany but not in England and the United States of America. Aim of this study therefore was to conduct a cost performance analysis by evaluating the underlying structure, the costs incurred and the achieved performance in two EMS systems with paramedics or emergency physicians on scene. METHODS: The study was carried out in West-Birmingham, a part of the West-Midlands-Ambulance-Service (WMAS), and the EMS of Bonn. Pre defined questionnaires, EMS protocols, calculations of purchasing power parity and recent publications concerning out-of-hospital resuscitation (CPR) were used to evaluate the operating costs, to describe the structure and to measure the quality of performance. Significance was assumed at p < 0.01 for CHI(2)- or t-test, respectively. RESULTS: Birmingham used state of the art technology for dispatch and logistics whereas Bonn trusted in high qualified personnel. In the 1st quarter 1997 the Mainz-Emergency-Evaluation Score could be achieved before (MEES A) and after preclinical treatment (MEES B) in 3502 and 3422 patients in Birmingham and Bonn, respectively. In Birmingham 7.5 % and in Bonn 17 % of all patients could be improved by the EMS treatment, respectively (p < 0.01). Looking at severely ill patients (MEES A < 22) the EMS in West-Birmingham achieved an improvement in 27.9 % of these patients with an averaged change in MEES of 0.9 +/- 1.7 points in all of them. In contrast the Bonn EMS improved the status in 47.8 % of these patients and MEES A could be improved considerably by 2.3 +/- 3.4 points (p < 0.01). Pharmacological treatment was less frequently used in Birmingham than in Bonn (12.9 % vs. 32.4 %, respectively; p < 0.01). At equal incidences of CPR attempts discharge rate after CPR was only 4 % in WMAS compared to 14.7 % in Bonn-North (p < 0.01). Per inhabitant and year total costs amounted to 10.43 euro for the EMS system in Birmingham, which is 42 % less than in Bonn. Unit hour utilisation reached 0.6 in Birmingham and only 0.33 in Bonn. In severely ill patients the improvement of MEES A by 0.1 points cost per inhabitant and year 1.16 euro in Birmingham and only 0.65 euro in Bonn. The survival of one patient after CPR was calculated to 0.7 euro in Birmingham and 0.17 euro in Bonn. CONCLUSIONS: The provider of the EMS in West-Birmingham--WMAS--organised a reliable system with high efficiency concerning unit hour utilisation and response time reliability. In the EMS of Bonn, in contrast, the complex therapy by the emergency physicians improved MEES considerably and increased probability of survival after CPR at a higher level of efficiency. Further investigations however are necessary to evaluate the presented parameter of efficiency.

Allied Health Personnel↗

PubMed2002

Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury.

OBJECTIVE: To investigate the kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury (ALI). DESIGN: Prospective observational cross-over study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twelve mechanically ventilated patients with ALI. INTERVENTIONS: Mechanical ventilation was transiently changed from a lung protective setting with PEEP of 15 cmH(2)O and a V(T) of 5 ml/kg predicted body weight to a more conventional ventilatory setting with PEEP of 5 cmH(2)O and V(T) of 12 ml/kg predicted body weight for a period of 6 h. MEASUREMENTS AND RESULTS: We examined the profile of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor in the plasma of all patients, and in the bronchoalveolar lavage (mini-BAL) fluid of six of these patients. Measurements were performed at baseline, 1 h, and 6 h after each change of the ventilatory setting. Switching to conventional mechanical ventilation was associated with a higher PaO(2) ( P < 0.05) and a marked increase ( P < 0.05) of measured plasma cytokines in patients with and without mini-BAL with a maximum after 1 h. Similarly, intraalveolar cytokine concentrations increased with conventional mechanical ventilation. While plasma cytokine levels returned to baseline values, intraalveolar cytokine concentrations further increased when lung protective mechanical ventilation was reestablished. CONCLUSIONS: In patients with ALI, initiation of low PEEP and high V(T) mechanical ventilation is associated with cytokine release into circulation which occurred within 1 h. It is independent from BAL procedures and can be reversed by reinstitution of lung protective mechanical ventilation.

Bronchoalveolar Lavage Fluid↗

PubMed2002

Perioperative monitoring of indocyanine green clearance and plasma disappearance rate in patients undergoing liver transplantation.

INTRODUCTION: Indocyanine green (ICG) elimination tests have been repeatedly suggested as an early predictor of graft function in patients with liver transplantation. Conventionally, ICG clearance (ClICG) is measured by a series of blood samples with subsequent laboratory analysis. More recently bedside techniques have become available to measure ICG concentrations in vivo and in addition to ClICG, the plasma disappearance rate of ICG (PDRICG) is increasingly being used. The aim of this study was to assess and to compare the normal time courses of ClICG and PDRICG in liver transplant recipients. METHODS: ClICG and PDRICG were measured perioperatively and at various times up to 24 h after liver transplantation. The bedside transpulmonary indicator dilution technique with an arterial fiberoptic-thermistor catheter was used to assess the ICG concentration time curve together with total circulating blood volume (Vd circ). RESULTS: Similar patterns of the time courses of ClICG and PDRICG with a fast recovery of ICG elimination in the early reperfusion period were observed. Compared to healthy subjects, ClICG was supranormal and PDRICG was slightly subnormal. In this study, Vd circ was increased at baseline and remained increased during surgery. CONCLUSIONS: PDRICG and ClICG are well suited to monitor onset and maintenance of graft function in patients undergoing liver transplantation. The PDRICG values measured tend to be relatively lower than ClICG because of an increased blood volume in these patients. By knowing these differences it is justified to monitor liver function in a very simple manner with PDRICG.

Adult↗

PubMed2002

Effects of induction of anaesthesia with sufentanil and positive-pressure ventilation on the intra- to extrathoracic volume distribution.

BACKGROUND AND OBJECTIVE: Induction of general anaesthesia in combination with positive-pressure ventilation is often associated with a significant decrease of arterial pressure. A decreased preload may contribute to this phenomenon. The aim was to investigate whether a change in cardiac filling occurs following the induction of general anaesthesia with sufentanil under typical clinical conditions. METHODS: Fifteen patients scheduled for elective coronary bypass grafting were studied immediately before surgery. In addition to standard monitors, a transpulmonary double-indicator dilution technique measured in vivo intrathoracic blood volume, global end-diastolic volume and total circulating blood volume. For induction of anaesthesia 2 microg kg(-1) sufentanil was given. Measurements were performed awake and after the induction of anaesthesia, intubation and mechanical ventilation of the lungs. RESULTS: To maintain arterial pressure during the induction period within -20% of baseline pressure, on average 22 +/- 6mLkg(-1) crystalloids and 8 +/- 6mLkg(-1) colloids were given. Despite these amounts of fluid, cardiac filling was decreased, whereas circulating blood volume increased significantly. Both central venous pressure and pulmonary capillary wedge pressure increased. CONCLUSIONS: Induction of general anaesthesia with positive-pressure ventilation is regularly associated with a blood volume shift from intra- to extrathoracic compartments. Even in low-dose opioid monoanaesthesia with sufentanil--often regarded as relatively inert in haemodynamic terms--the phenomenon could be demonstrated as the primary cause of the often-observed decrease of arterial pressure. It seems, therefore, rationally justified to restore cardiac filling by generous administration of intravenous fluids, at least in patients with unaffected cardiac pump function. During induction of anaesthesia, central venous pressure and pulmonary capillary wedge pressure do not reliably indicate cardiac filling.

Adjuvants, Anesthesia↗

PubMed2002

Application of semilinear canonical correlation to the measurement of the electroencephalographic effects of volatile anaesthetics.

BACKGROUND AND OBJECTIVE: The common parameters of the electroencephalogram quantify a shift of its power spectrum towards lower frequencies with increasing anaesthetic drug concentrations (e.g. spectral-edge frequency 95). These ad hoc parameters are not optimized for the content of information with regard to drug effect. Using semilinear canonical correlation, different frequency ranges (bins) of the power spectrum can be weighted for sensitivity to changes of drug concentration by multiplying their power with iteratively determined coefficients, yielding a new (canonical univariate) electroencephalographic parameter. METHODS: Electroencephalographic data obtained during application of volatile anaesthetics were used: isoflurane (n = 6), desflurane (7), sevoflurane (7), desflurane during surgical stimulation (12). Volatile anaesthetic end-tidal concentrations varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The canonical univariate parameter and spectral-edge frequency 95 were determined and their correlation with the volatile anaesthetic effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modelling, were compared. RESULTS: The canonical univariate parameter with individually optimized coefficients, but not with mean coefficients, was superior to the spectral-edge frequency 95 as a measure of anaesthetic drug effect. No significant differences of the coefficients were found between the three volatile anaesthetics or between the data with or without surgical stimulus. The coefficients for volatile anaesthetics were similar to the coefficients for opioids, but different from coefficients for propofol and midazolam. CONCLUSIONS: The canonical univariate parameter calculated with individually optimized coefficients, but not with mean coefficients, correlates more accurately and consistently with the effect site concentrations of volatile anaesthetics than with spectral-edge frequency 95.

Analysis of Variance↗

PubMed2001

Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis.

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) as a marker of severity of systemic inflammation in patients with severe sepsis and critically ill postsurgical patients. DESIGN: Prospective observational study in consecutive patients with severe sepsis, critically ill nonseptic postsurgical patients, and healthy blood donors. SETTING: A surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 19 patients with severe sepsis, 18 critically ill nonseptic postsurgical patients, and 10 healthy blood donors. MEASUREMENTS AND RESULTS: MIF plasma levels of patients and participants were measured. Interleukin 6 plasma levels were monitored as a control marker of inflammation. The median MIF plasma level was four to five times higher in patients with severe sepsis (2.70 ng/ml, range 0.31-19.59) and in critically ill nonseptic postsurgical patients (2.43 ng/ml, range 0.49-4.31) than in healthy blood donors (0.56 ng/ml, range 0.16-1.68). MIF plasma levels did not differ between the patient groups. CONCLUSIONS: MIF serves as a general marker for systemic inflammation in septic and nonseptic acute critical illness, but MIF does not discriminate for severity or differentiate between infectious and noninfectious origins of an acute critical illness.

Adolescent↗

PubMed2001

Increased susceptibility to apoptosis in circulating lymphocytes of critically ill patients.

BACKGROUND AND AIMS: Lymphocyte apoptosis may influence immune responsiveness in systemic inflammation. Therefore, we investigated whether early signs of apoptosis (i.e., annexin-V binding and cell shrinkage) in peripheral lymphocytes were different among patients with severe sepsis, critically ill, nonseptic patients after major surgery, and healthy individuals. PATIENTS/METHODS: Ten patients with severe sepsis and ten critically ill, nonseptic patients after major surgery admitted to a surgical intensive care unit in a university hospital were included in the study. In addition, ten healthy blood donors were included for comparison. We investigated early signs of apoptosis using flow cytometric measurement of annexin-V binding to the cell surface and cell shrinkage of peripheral lymphocytes. RESULTS: The percentage of apoptotic lymphocytes determined as annexin-V positive and propidium iodide negative cells was increased in freshly prepared cells of patients with severe sepsis (11.4 +/- 0.5%) and critically ill, nonseptic patients after major surgery (18.5 +/- 2.0%) relative to healthy blood donors (4.4 +/- 0.5%) (P < 0.05). No significant difference between patients with severe sepsis and patients after major surgery were found. Annexin-V binding increased significantly after OKT-3 stimulation of lymphocytes in patients with severe sepsis (34.4 +/- 1.6%), patients after major surgery (33.8 +/- 3.4%), and healthy blood donors (21.1 +/- 2.8%). No significant difference among groups was detected following OKT-3 stimulation. Furthermore, freshly isolated peripheral lymphocytes of patients with severe sepsis and critically ill, nonseptic patients after major surgery revealed a significantly higher proportion of cell shrinkage than in healthy blood donors (55.0 +/- 2.2%, 21.5 +/- 2.4% vs 3.6 +/- 0.7%; P < 0.05). CONCLUSION: Circulating lymphocytes of critically ill patients show a high degree of early signs of cellular apoptosis. This may contribute to hyporesponsiveness of immune cells in systemic inflammation.

Adult↗

PubMed2001

Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index.

STUDY OBJECTIVE: To identify and quantify the interaction between propofol and remifentanil during surgical procedures with a bispectral index (BIS) of 50 that was chosen as a continuous surrogate measure for "adequate depth" of anesthesia. DESIGN: Prospective, open-label study. SETTING: Department of orthopedics of a university hospital. PATIENTS: 20 patients undergoing orthopedic surgery. INTERVENTIONS: Anesthesia was induced and maintained with propofol and remifentanil, both administered by target-controlled infusion (TCI). Initial target concentrations of propofol (1.5-8 microg/mL) and remifentanil (2-15 ng/mL) were chosen and alternated in order to maintain the BIS between 45 and 55. If constant target concentrations had been maintained for 20 minutes and the BIS did not depart from the desired range, blood samples were taken to determine propofol concentrations, and the BIS value was recorded. Isobolographic interaction models were fitted to the infusion rates of remifentanil and propofol, predicted target concentrations of both drugs, and measured propofol concentrations versus predicted remifentanil concentrations. MAIN RESULTS: The isobole for the interaction of propofol and remifentanil in the concentration range investigated (propofol 1.5-8 microg/mL and remifentanil 1-30 ng/mL) is a concave up hyperbola ((0.15. C(prop))(3.13). C(rem) = 1) with C(prop) = propofol plasma concentration [microg/mL] and C(rem) = remifentanil blood concentration [ng/mL]). Use of predicted (=TCI target) concentrations or the respective infusion rates did not alter the general shape of the interaction isobole. CONCLUSIONS: The interaction between propofol and remifentanil for maintenance of a BIS value between 45 and 55 during surgery is synergistic. This finding applies regardless of whether measured concentrations (for propofol), predicted concentrations of the infusion device, or infusion rates are used as model input. Notably, the interaction isobole of the (clinically readily available) infusion rates provides a useful dosing recommendation for the coadministration of propofol and remifentanil during maintenance of anesthesia.

Adult↗