Pavel Suk

Quantitative analysis of drug losses administered via nasogastric tube - In vitro study

PURPOSE Drug administration through nasogastric tube (NGT) is a standard practice but the real amount of the delivered drug is unknown. Therefore, we designed a study to determine the losses of various dosage forms administered by different methods through NGT. METHODS In vitro model was used. Five different administration methods (A-E) and six dosage forms (simple compressed tablets - T/S; film coated tablets - T/FC; enteric coated tablets - T/EC; capsules with powder filling - C/P; capsules containing extended release pellets - C/ER; capsules containing gastro-resistant pellets - C/GR) were investigated. Measurement was repeated six times for each drug-method combination. The overall losses were determined by gravimetry. In method A partial losses associated with each step of drug administration were also determined. RESULTS Significant drug losses were measured (4-38%). Only methods A (crushing-beaker-syringe-water-NGT) and B (crushing-water-syringe-NGT) were suitable for administration of all tested dosage forms. Method B proved the most effective for all kinds of tablets and C/GR (p<0.05) and tended to be more effective also for C/ER (p=0.052) compared to method A. C/P showed minimal losses for both tested methods (B and E). Flushing of the drug through NGT causes major losses during drug administration compared to crushing and transfer (p<0.05). All methods for intact pellets (C-E) were found inappropriate for clinical practice due to NGT clogging. CONCLUSIONS Choosing a suitable administration method can significantly affect the amount of drugs delivered through NGT.

Temperature corrected thromboelastography in hypothermia: is it necessary?

Context Hypothermia is known to influence thromboelastography (TEG). TEG reproducibility is generally low. Objective The aim of this study was to evaluate the rationale of TEG temperature adjustment in patients during hypothermia. We hypothesised that temperature adjustment would not be important because of low TEG reproducibility. Design Prospective observational study. Setting Single-centre, secondary care study performed 01/2009 to 07/2010. Patients Survivors of cardiopulmonary resuscitation in whom therapeutic hypothermia (32 to 34°C) was indicated for 24 h were recruited to the study which lasted 36 h. Four hundred samples from 30 patients (22 men and eight women) were obtained. No specific exclusion criteria were defined. Main outcome measures Temperature adjusted and non-adjusted Kaolin–Heparinase and Rapid-TEG were done at 12-h intervals during the first 36 h. Results Bland–Altman plots were used for analysis. During hypothermia, the bias of adjusted measurements was greater in clot formation variables for both Kaolin–Heparinase-TEG (from −15 to −19%) and Rapid-TEG (−9 to −25%) compared to normothermia (from −3 to 3% for Kaolin–Heparinase-TEG and −10 to 2% for Rapid-TEG). Bias of clot strength variables was not influenced by temperature adjustment (median −1%). The 95% limits of agreement were wide for clot formation variables and independent of temperature. In Kaolin–Heparinase-TEG (R −42 to 40% normothermia, −47 to 18% hypothermia) and in Rapid-TEG (R −117 to 97% normothermia, −114 to 95% hypothermia). Limits of agreement of clot strength variables were narrower and independent of temperature in Kaolin–Heparinase-TEG (MA −16 to 13% normothermia, −9 to 10% hypothermia) and also in Rapid-TEG (MA −27 to 24% normothermia, −18 to 20% hypothermia). Conclusion Although TEG analysis with temperature adjusted to the in-vivo value during hypothermia yields results with small systematic bias, the importance of temperature adjustment in clinical routine is low because of the precision limits of TEG measurement itself. Therefore, we see no need to perform TEG analysis at the in-vivo temperature.

The impact of sedation on pulse pressure variation.

OBJECTIVE Pulse pressure variations (PPV) are mainly influenced by ventilation. The impact of sedation on PPV is not known. The aim of the study was to test the influence of sedation on pulse pressure variation in mechanically ventilated critically ill patients and to compare PPV in critically ill and brain dead patients. Beside the absolute value of PPV, the adjusted values of pulse pressure were used to eliminate influence of ventilation. DESIGN AND INTERVENTION Mechanically ventilated patients received four different breath frequencies. At each frequency airway pressure was adjusted to keep the end-tidal CO2 stable. In critically ill patients the frequencies were applied at basal (bispectral index - BIS median 38) and deeper sedation (BIS 29). MAIN OUTCOME MEASURES Simultaneous haemodynamic and respiratory data including oesophageal pressure were recorded, adjusted PPV were calculated as PPV/VT, PPV/dPair, PPV/dPes where VT is tidal volume, dPair and dPes are airway and oesophageal driving pressures. SETTING University Hospital, ICU. PARTICIPANTS 30 critically ill and 23 patients with a diagnosis of brain death. RESULTS The pulse pressure variation did not change significantly during deep sedation compared to basal sedation (median 10.3 vs 10.9%) whereas PPV/dPair increased from 0.7 to 0.8%/cmH2O and PPV/dPes from 1.9%/cmH2O to 2.4%/cmH2O (p=0.04). Patients with a diagnosis of brain death had higher PPV and adjusted PPV than critically ill patients. CONCLUSION Deeper sedation increases values of adjusted pulse pressure variation.

Early resuscitation of septic shock to defferent level ofarterial pressure

TOWARDS RESOLVING THE CHALLENGE OF SEPSIS DIAGNOSTIC. Thomas Herget* and Thomas Joos . *Merck KGaA, Darmstadt, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany Biomarkers have proven to be very useful in clinical conditions such as heart attack, stroke and cancer. There are characteristics linked to sepsis like in blood pressure, body temperature and heart rate. Efforts over the last decade to improve diagnosis for infectious inflammation have been unsuccessful in identifying a single and universal biomarker that provides sufficiently high sensitivity and specificity. In gramnegative septicemia and following major abdominal trauma, the determination of endotoxin continues to be a leading candidate which could become adopted into clinical practice. The importance of endotoxin measurement continues to grow as more clinicians recognize the added value of measuring endotoxin in critically ill patients and with the emergence of major pharmaceutical trials directly targeting endotoxin in the bloodstream. However, hundreds of other candidates potentially serving as biomarker for sepsis have been recently described, e.g. cysteinyl-leukotriene (LTC4) generation, procalcitonin (PCT) and C-reactive protein (CRP). However, none of them fulfils the criteria requested by clinicians, namely being specific and sensitive. The presentation will discuss criteria for a sepsis biomarker, will give an overview of obtaining samples from appropriate cell systems and from patients. Furthermore, tools will be described to identify marker candidates on genetic-, proteinand metabolite level. The integration of these data sets covering e.g. signal transduction, protein : protein interaction, gene expression with the help of bioinformatics and systems biology will help to validate such candidates. The final goal is manufacturing a robust diagnostic device for clinical routine work. A solid sepsis diagnostics method will be beneficial for patients, but also for the healthcare systems and will open challenges for the pharmaceutical industry.

Impact of abdominal banding on splanchnic organ perfusion

Abdominal banding is still recommended by some surgeons to prevent eventeration after abdominal surgery. We assessed the impact of increased abdominal pressure (IAP) caused by abdominal banding on perfusion of splanchnic organs, ventilation and hemodynamics.

Intra-abdominal pressure (IAP) and hypoperfusion of splanchnic organs after major abdominal surgery.

In patients after major elective uncomplicated abdominal surgery clinically significant increase of intraabdominal pressure and markers of splanchic hypoperfusion are very rare.