Endothelin-1 elevates regional cerebral perfusion during prolonged ventricular fibrillation cardiac arrest in pigs.
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Animals↗
Biomedical subjects
Andreas Hoeft
Publications and source records attributed to Andreas Hoeft.
Impact of CYP2D6 genotype on postoperative tramadol analgesia.
Genetic polymorphisms result in absent enzyme activity of CYP2D6 (poor metabolizers, PM) in about 10% of the Caucasian population. This study investigates whether the PM genotype has an impact on the response to tramadol analgesia in postoperative patients. A prospective study design was used and 300 patients recovering from abdominal surgery were enrolled. After titration of an individual loading dose, patients could self-administer 1 ml bolus doses of the drug combination tramadol 20 mg/ml, dipyrone 200 mg/ml and metoclopramide 0.4 mg/ml via patient-controlled analgesia (PCA). Patients' genotype was analyzed considering the most prevalent PM associated CYP2D6 mutations using a real-time PCR and hybridization based genotyping method. Demographic data, surgery related variables, pain scores, analgesic consumption and need for rescue medication were compared between extensive metabolizers (EM) and PM. The primary outcome criterion 'response' was defined as responder or non-responder status by the need for rescue medication and patients' satisfaction at the final interview. Demographic and surgery related data were comparable between EM (n=241) and PM (n=30). The percentage of non-responders was significantly higher in the PM group (46.7%) compared with the EM group (21.6%; p=0.005). Tramadol loading dose amounted to 108.2+/-56.9 and 144.7+/-22.6 mg (p<0.001) in EM and PM, respectively. More patients displaying the PM genotype needed rescue medication in the recovery room and during PCA period than patients with at least one wild type allele (21.6 versus 43.3%, p=0.02). PM for CYP2D6 showed a lower response rate to postoperative tramadol analgesia than EM. Therefore, CYP2D6 genotype has an impact on analgesia with tramadol. Pharmacogenetics may explain some of the varying response to pain medication in postoperative patients.
Adult↗
A manual slide rule for target-controlled infusion of propofol: development and evaluation.
UNLABELLED: We describe the development and evaluation of a simple slide rule that enables the bedside determination of the infusion rate for a particular target plasma concentration of propofol. The infusion rate to reach this target concentration at time (t) is the product of the target concentration, body weight, and a correction factor that depends on the time elapsed from the start of the initial infusion. Our target-controlled infusion (TCI) slide rule, constructed along this principle, performs the multiplications, analogous to the principle of the classical slide rule, as addition of logarithms. We calculated the percentage deviation of the predicted concentration obtained by STANPUMP versus predicted concentrations obtained using the infusion rates determined from the TCI slide rule. The evaluation using STANPUMP simulations showed, for a constant target concentration of 3 micro g/mL of propofol, a mean deviation of 4.05% (max, 6.97%) in the first 15 min and a mean deviation of 0.5% (max, 2.03%) between 16 and 300 min. The mean deviation after changing the target from 3 micro g/mL to 1, 2, 4, or 5 micro g/mL ranged from 1.15% to 17.76%. This pocket-sized TCI slide rule combines the advantages of minimal financial and technical cost with reasonable accuracy. IMPLICATIONS: We describe the development and evaluation of a simple slide rule that enables the bedside determination of the required infusion rate for a particular target plasma concentration. This pocket-sized target-controlled infusion slide rule combines the advantages of minimal financial and technical cost with reasonable accuracy.
Algorithms↗
Correlation of approximate entropy, bispectral index, and spectral edge frequency 95 (SEF95) with clinical signs of "anesthetic depth" during coadministration of propofol and remifentanil.
BACKGROUND: Several studies relating electroencephalogram parameter values to clinical endpoints using a single (mostly hypnotic) drug at relatively low levels of central nervous system depression (sedation) have been published. However, the usefulness of a parameter derived from the electroencephalogram for clinical anesthesia largely depends on its ability to predict the response to stimuli of different intensity or painfulness under a combination of a hypnotic and an (opioid) analgesic. This study was designed to evaluate the predictive performance of spectral edge frequency 95 (SEF95), BIS, and approximate entropy for the response to increasingly intense stimuli under different concentrations of both propofol and remifentanil in the therapeutic range. METHODS: Ten healthy male and ten healthy female volunteers were studied during coadministration of propofol and remifentanil. After having maintained a specific target concentration for 10 min, the depth of sedation-anesthesia was assessed using the responsiveness component of the Observer's Assessment of Alertness/Sedation (OAA/S) rating scale, which was modified by adding insertion of a laryngeal mask and laryngoscopy. The electroencephalogram derived parameters approximate entropy, bispectral index, and SEF95 were recorded just before sedation level was assessed. RESULTS: The prediction probability values for approximate entropy were slightly, but not significantly, better than those for bispectral index, SEF95, and the combination of drug concentrations. A much lower prediction ability was observed for tolerance of airway manipulation than for hypnotic endpoints. CONCLUSION: Approximate entropy revealed informations on hypnotic and analgesic endpoints using coadministration of propofol and remifentanil comparable to bispectral index, SEF95, and the combination of drug concentrations.
Adult↗
Effects of hypertonic saline on myocardial blood flow in a porcine model of prolonged cardiac arrest.
OBJECTIVE: To evaluate the effects of hypertonic saline (HS) on myocardial reperfusion pressure (MPP) and blood flow (MBF), and cardiac index (CI) during and after cardiopulmonary resuscitation (CPR). METHODS: In 21 domestic swine (16-23 kg) open chest cardiac massage was initiated after 10 min of ventricular fibrillation. With the onset of CPR animals randomly received HS (7.2%; 2 ml/kg per 10 min or 4 ml/kg per 20 min) or normal saline ((NS); 2 ml/kg per 10 min). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure MBF and CI before cardiac arrest (CA), during CPR and 5, 30 and 120 min after the return of spontaneous circulation. RESULTS: During CPR HS significantly increased MPP, MBF, and CI in comparison to NS (P<0.05, resp., MANOVA). Doubling the volume of HS did not improve the haemodynamic effects seen after application of 2 ml/kg per 10 min. HS-infusion significantly increased the survival rate at 120 min, 6/7 and 5/7 animals receiving 2 ml/kg per 10 min or 4 ml/kg per 20 min versus 2/7 after NS-infusion (P<0.05, chi(2)-test). CONCLUSIONS: HS applied during open chest cardiac massage enhanced MBF and CI, and significantly increased resuscitation success and survival rate. The positive effects of this promising new approach need to be confirmed in clinical studies.
Animals↗
Assessment of cardiac output, intravascular volume status, and extravascular lung water by transpulmonary indicator dilution in critically ill neonates and infants.
OBJECTIVE: To assess cardiac output, intrathoracic blood volume, global end-diastolic volume, and extravascular lung water in critically ill neonates and small infants using transpulmonary indicator dilution. DESIGN: Prospective, observational, clinical study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Critically ill neonates and small infants suffering from severe heart failure, respiratory failure, or sepsis (n = 10). INTERVENTIONS: A total of 194 transpulmonary indicator dilution measurements were done. Global end-diastolic volume, intrathoracic blood volume, and stroke volume were measured and compared with standard hemodynamic parameters during the clinical course and before and after volume loading (16 +/- 3.7 mL/kg of 10% albumin solution) in 8 of 10 patients. MEASUREMENTS AND MAIN RESULTS: A positive correlation was found for stroke volume index versus global end-diastolic volume (r = 0.76, p < 0.001) and intrathoracic blood volume (r = 0.56, p < 0.001). In contrast, no correlation was observed for stroke volume index versus central venous pressure. Volume loading resulted in significant increases in stroke volume index (p < 0.01), global end-diastolic volume (p < 0.01), and intrathoracic blood volume (p < 0.01); whereas central venous pressure, heart rate, mean arterial pressure, and extravascular lung water remained unchanged. CONCLUSION: Transpulmonary indicator dilution enables measurement of cardiac output and intravascular volume status in critically ill neonates and infants at the bedside. The effects of volume loading on cardiac preload and effective change in stroke volume can be monitored by this technique, whereas central venous pressure was not indicative of changes in intravascular volume status.
Blood Volume↗
Artifact robustness, inter- and intraindividual baseline stability, and rational EEG parameter selection.
BACKGROUND: Artifact robustness (i.e., size of deviation of an electroencephalographic parameter value from baseline caused by artifacts) and baseline stability (i.e., consistency of median baseline values) of electroencephalographic parameters profoundly influence electroencephalography-based pharmacodynamic parameter estimation and the usefulness of the processed electroencephalogram as measure of the arousal state of the central nervous system (depth of anesthesia). In this study, the authors compared the artifact robustness and the interindividual and intraindividual baseline stability of several univariate descriptors of the electroencephalogram (Shannon entropy, approximate entropy, spectral edge frequency 95, delta ratio, and canonical univariate parameter). METHODS: Electroencephalographic data of 16 healthy volunteers before and after administration of an intravenous bolus of propofol (2 mg/kg body weight) were analyzed. Each volunteer was studied twice. The baseline electroencephalogram was recorded for a median of 18 min before drug administration. For each electroencephalographic descriptor, the authors calculated the following: (1) baseline variability (= (median baseline - median effect) [i.e., signal]/SD baseline [i.e., noise]) without artifact rejection; (2) baseline variability with artifact rejection; and (3) baseline stability within and between individuals (= (median baseline - median effect) averaged over all volunteers/SD of all median baselines). RESULTS: Without artifact rejection, Shannon entropy and canonical univariate parameter displayed the highest signal-to-noise ratio. After artifact rejection, approximate entropy, Shannon entropy, and the canonical univariate parameter displayed the highest signal-to-noise ratio. Baseline stability within and between individuals was highest for approximate entropy. CONCLUSIONS: With regard to robustness against artifacts, the electroencephalographic entropy parameters and the canonical univariate parameter were superior to spectral edge frequency 95 and delta ratio. Electroencephalographic approximate entropy displayed the best interindividual and intraindividual baseline stability.
Adult↗
Relationship between intracranial pressure and critical closing pressure in patients with neurotrauma.
BACKGROUND: The driving pressure gradient for cerebral perfusion is the difference between mean arterial pressure (MAP) and critical closing pressure (CCP = zero flow pressure). Therefore, determination of the difference between MAP and CCP should provide an appropriate monitoring of the effective cerebral perfusion pressure (CPP(eff)). Based on this concept, the authors compared conventional measurements of cerebral perfusion pressure by MAP and intracranial pressure (CPP(ICP)) with CPP(eff). METHODS: Simultaneous synchronized recordings of pressure waveforms of the radial artery and blood flow velocities of the middle cerebral artery were performed in 70 head trauma patients. CCP was calculated from pressure-flow velocity plots by linear extrapolation to zero flow. RESULTS: Intracranial pressure measured by intraventricular probes and CCP ranged from 3 to 71 and 4 to 70 mmHg, respectively. Linear correlation between ICP and CCP was r = 0.91. CPP(ICP) was 77 +/- 20 mmHg and did not differ from CPP(eff); linear correlation was r = 0.92. However, limits of agreement were only +/- 16.2 mmHg. Therefore, in 51.4% of the patients, CPP(ICP) overestimated CPP(eff) by 19.8 mmHg at most. CONCLUSION: Assuming that CPP(eff) (MAP - CCP) takes into account more determinants of cerebral downstream pressure, in individual cases, the actual gold standard of CPP determination (MAP - ICP) might overestimate the CPP(eff) of therapeutic significance.
Adolescent↗
Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass.
BACKGROUND: Cardiac surgery with cardiopulmonary bypass is often associated with postoperative hemodynamic instability. In this regard beneficial effects of corticosteroids are known. The purpose of this study was to investigate whether these effects are due mainly to a modification of the intravascular and extravascular volume status or whether a more direct improvement of cardiovascular performance by corticosteroids is the underlying mechanism. METHODS: Twenty patients undergoing elective coronary bypass grafting were included in this randomized double-blind study. Patients of the treatment group received 1 mg/kg-1 dexamethasone after induction of anesthesia. In addition to the use of standard monitors and detailed fluid balance assessments, the transpulmonary double-indicator technique was used to measure extravascular lung water, total blood volume, and intrathoracic blood volume. Measurements were done after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery. RESULTS: After cardiopulmonary bypass, no relevant increase in extravascular lung water was observed, despite highly positive fluid balances in all patients. A significantly smaller increase in extravascular fluid content was observed in the dexamethasone group. Total blood volume and intrathoracic blood volume did not differ in the two groups. Patients pretreated with dexamethasone had a decreased requirement for vasoactive substances and, in contrast with the control group, no increase in pulmonary artery pressure. CONCLUSIONS: Extravascular fluid but not extravascular lung water is increased in patients after surgery with cardiopulmonary bypass. Pretreatment of adult patients with 1 mg/kg-1 dexamethasone before coronary bypass grafting decreases extravascular fluid gain and seems to improve postoperative cardiovascular performance. This effect is not caused by a better intravascular volume status.
Adult↗
The influence of genomics on outcome after cardiovascular surgery.
Recent findings in molecular research suggest that the outcome of cardiovascular surgery is at least partly determined by the individual patient's genetic predisposition to react to surgical trauma and extracorporal circulation. The activation of cellular as well as humoral cascades occurs in the perioperative period, and influences the extent of pro- and anticoagulation and pro- and anti-inflammation. These events contribute to the incidence and severity of perioperative ischaemia or organ dysfunction, and thus determine adverse outcomes in patients undergoing cardiac surgery. Candidate genes that are possibly involved in the development of adverse outcomes not only consist of genes relevant to the field of coagulation and inflammation, but also genes functioning in lipid metabolism, ion channels, membrane integrity and others. Genomic variations may prove to serve as future diagnostic tools for the risk stratification of patients undergoing cardiovascular surgery.
Journal Article↗
Real-time PCR for detection and differentiation of gram-positive and gram-negative bacteria.
We developed a consensus real-time PCR protocol that enables us to detect spiked bacterial 16S DNA from specimens such as water, urine, plasma, and sputum. The technique allows an exact Gram stain classification of 17 intensive care unit-relevant bacteria by means of fluorescence hybridization probes. All tested bacteria were identified correctly, and none gave a false-positive signal with the opposite Gram probe.
Bacterial Infections↗
Comparison of different decontamination methods for reagents to detect low concentrations of bacterial 16S DNA by real-time-PCR.
Contamination of polymerase chain reaction (PCR) reagents continues to be a major problem when consensus primers are used for detection of low concentrations of bacterial DNA. We designed a real-time polymerase chain reaction (PCR) for quantification of bacterial DNA by using consensus primers that bind specifically to the 16S region of bacterial DNA. We have tested four different methods of decontamination of PCR reagents in a project aimed at detecting bacterial DNA at low concentrations: deoxyribonuclease (DNAse) treatment, restriction endonuclease digestion, UV irradiation, and 8-methoxypsoralen in combination with long-wave UV light to intercalate contaminating DNA into double-stranded DNA. All four methods result in inhibition of the PCR reaction, and most of the decontamination procedures failed to eliminate the contaminating bacterial DNA. Only the DNAse decontamination proved to be efficient in eliminating contaminating DNA while conserving PCR efficiency. All four decontamination methods are time consuming and have the possibility of carrying new contamination into the reaction mixture. However, decontamination with DNAse may help, together with the use of highly purified PCR reagents, in detecting small amounts of bacterial DNA in clinical specimens.
Artifacts↗
Rapid and reliable method for cytochrome P450 2D6 genotyping.
BACKGROUND: Single-nucleotide polymorphisms and single-base deletions within the cytochrome P450 2D6 (CYP2D6) gene have been associated with a poor metabolizer (PM) phenotype and display a frequency of 7-10% in the Caucasian population. METHODS: We developed a reliable and rapid procedure to identify five major PM-associated mutations (CYP2D6*4, *7, and *8) and deletions (CYP2D6*3 and *6) by real-time PCR with subsequent fluorometric melting point analysis of the PCR product. These polymorphisms within the CYP2D6 gene were detected by use of two primer pairs and five different pairs of hybridization probes. DNA extracted from whole blood of 323 individuals was analyzed, and results were compared with genotypes obtained by allele-specific multiplex PCR. In case of uncertain results, additional sequence analysis was performed. RESULTS: Genotyping results by real-time PCR were 100% reliable, whereas conventional allele-specific multiplex PCR produced uncertain results for 12.1% of samples, as confirmed by sequence analysis. Costs for reagents and consumables were considerably higher for the real-time PCR technology, but labor time was reduced by 2 h compared with allele-specific PCR. The allele frequencies in the population investigated were 0.186 for allele *4, 0.026 for allele *5, 0.009 for allele *3, 0.031 for allele *6, and 0.002 for allele *8. The defective CYP2D6*7 allele was not found. In addition, three additional mutations were detected, one of them displaying a PM genotype. CONCLUSION: Genotyping of CYP2D6 by real-time PCR with fluorometric melting point analysis is a rapid and reliable method.
Cytochrome P-450 CYP2D6↗
Prone positioning, systemic hemodynamics, hepatic indocyanine green kinetics, and gastric intramucosal energy balance in patients with acute lung injury.
OBJECTIVE: To investigate the effects of prone positioning on systemic hemodynamics, intra-abdominal pressure (IAP), plasma disappearance rate of indocyanine green (PDR(ICG)), and gastric intramucosal to arterial PCO2 difference (Pi-aCO2). DESIGN AND SETTING: Prospective randomized study in the intensive care unit of a university hospital. PATIENTS: 12 mechanically ventilated, hemodynamically stable patients with acute lung injury. INTERVENTION: Positioning supine and prone for 3 h in random order. MEASUREMENTS: Systemic hemodynamics were determined by transpulmonary double-indicator dilution technique using an integrating fiberoptic monitoring system. The same monitoring system was used to measure PDR(ICG). IAP was measured in the urinary bladder and gastric intramucosal PCO2 was evaluated by automated recirculation gas tonometry. RESULTS: IAP increased from 10 +/-3 in the supine to 13+/-4 mmHg in the prone position. Cardiac index increased from 3.8+/-0.9 (supine) to 4.2+/-0.6 l/m(2) per minute (prone), mean arterial pressure from 75+/-10 (supine) to 81+/-11 mmHg (prone), PaO2/FIO2 from 194+/-66 (supine) to 269+/-68 mmHg (prone), and oxygen delivery from 558+/-122 (supine) to 620+/-74 ml/m(2) per minute (prone). No other parameters, including PDR(ICG) and Pi-aCO2, differed between the two positions. CONCLUSIONS: Prone positioning in mechanically ventilated patients with acute lung injury, despite a small increase in IAP, does not negatively affect the hepatic capacity to eliminate ICG and gastric intramucosal energy balance when systemic blood flow and oxygenation are improved.
APACHE↗