Anna Fijałkowska

The role of human lungs in the biotransformation of propofol.

BackgroundThe metabolism of propofol is very rapid, and its transformation takes place mainly in the liver. There are reports indicating extrahepatic metabolism of the drug, and the alimentary canal, kidneys, and lungs are mentioned as the most probable places where the process occurs. The aim of this study was to determine whether the human lungs really take part in the process of propofol biotransformation. MethodsBlood samples were taken from 55 patients of American Society of Anesthesiologists grade 1–3 scheduled for elective intracranial procedures (n = 47) or for pulmonectomy (n = 8). All patients were premedicated with diazepam (10 mg) administered orally 2 h before anesthesia. Propofol total intravenous anesthesia was performed at the following infusion rates: 12 mg · kg−1 · h−1, 9 mg · kg−1 · h−1, and 6 mg · kg−1 · h−1. Fentanyl and pancuronium bromide were also administered intermittently. After tracheal intubation, the lungs were ventilated to normocapnia with an oxygen–air mixture (fraction of inspired oxygen = 0.33). Blood samples for propofol and 2,6-diisopropyl-1,4-quinol analysis were taken simultaneously from the right atrium and the radial artery, or the pulmonary artery and the radial artery. The concentration of both substances were measured with high-performance liquid chromatography and gas chromatography–mass spectroscopy. ResultsThe concentration of propofol in the central venous system (right atrium or pulmonary artery) is greater than in the radial artery, whereas the opposite is observed for propofol’s metabolite, 2,6-diisopropyl-1,4-quinol. Higher propofol concentrations are found in blood taken from the pulmonary artery than in the blood collected from the radial artery. ConclusionsHuman lungs take part in the elimination of propofol by transforming the drug into 2,6-diisopropyl-1,4-quinol.

Emotional sequelae among survivors of critical illness: a long-term retrospective study.

Context Treatment in an ICU can be stressful and traumatic for patients, and can lead to various physical, psychological and cognitive sequelae. Objectives The aim of the study was to assess the influence of the social, economic and working status of individuals in regard to long-term anxiety and depression among ICU convalescents. Design Retrospective, cross-sectional, 5-year survey between 2005 and 2009. Setting The general ICUs of two hospitals in Lublin (Poland): the Teaching Hospital, Medical University of Lublin and the District Hospital. Patients All adults surviving an ICU stay of more than 24 h were eligible. In December 2010, 533 questionnaires were sent to discharged ICU survivors, and 195 (36.6%) were returned. One hundred and eighty-six patients were enrolled in the study. Patients with brain injuries were excluded. Main outcome measures The questionnaire consisted of the Hospital Anxiety and Depression Scale (HADS); questions defining social, economic and working status before and after intensive care stay, health status before intensive care stay, as well as questions about memories and readmissions to intensive care were included. Results According to HADS, 34.4% patients had an anxiety disorder and 27.4% were depressed. There was a strong positive correlation between anxiety and depression (r = +0.726, P < 0.001). Better material and housing conditions correlated with lower anxiety and depression rates. Acute Physiology and Chronic Health Evaluation II scores on admission positively correlated with both anxiety (r = +0.187; P = 0.011) and depression (r = +0.239; P = 0.001). A negative correlation between health status before intensive care admission and HADS scores was observed (anxiety rs = −0.193; P = 0.008; depression rs = −0.227; P = 0.002); better health resulted in less anxiety and depression disorders. Conclusion Adverse social and economic status is associated with higher rates of anxiety and depression following ICU stay.

Determining the influence of storage time on the level of propofol in blood samples by means of chromatography.

Due to unsatisfactory equipment efficiency and the time consuming manual procedures of sample preparation, drug analyses in physiological fluids and tissues frequently have to be carried out a few days after the sample collection. This is especially the case with investigations which require the examination of materials for which a large number of samples is necessary. The paper deals with the influence of storing blood samples on the level of propofol in blood and plasma. Propofol (2,6-diisopropylphenol, Diprivan) is a very popular intravenous agent used both for the induction and the maintenance of anaesthesia in human and veterinary patients as well as in laboratory animals. The results obtained show that, due to distinct losses of propofol in samples during their storage, the comparison of data estimated for subsequent days after sampling can lead to misleading or even wrong conclusions. The speed of drug diminution depends both on the type of blood and the anticoagulant used. The established interdependencies between the change in the level of propofol in blood and plasma samples and their storage time show that analogous investigations of other pharmaceutical agents are necessary.

Possibilities of Propofol Analysis in Various Blood Components by Means of HPLC

Abstract Propofol (2,6 disopropylphenol) is a short-acting hypnotic agent, effective for the maintenance of anaesthesia when given intravenously as repeated bolus injections or as a continuous infusion. The present paper deals with the analysis of this drug in different parts of the blood. The results obtained by means of HPLC show that propofol not only variously bonds with plasma or solid blood elements, but also penetrates into the interior of blood cells. The investigations carried out with whole blood, plasma, non-washed or washed cells and washed and lysed cells suggest a different behaviour of thymol (used in chromatographic analysis as internal standard) in relation to propofol.

Changes of Propofol Concentration in Cerebrospinal Fluid During Continuous Infusion

We studied the changes in the propofol concentration in the cerebrospinal fluid (CSF) in 14 patients, undergoing elective intracranial procedures, who were anesthetized with propofol administered by target-controlled infusion. During anesthesia, fentanyl and cisatracurium were administered as required. After intubation of the trachea, the lungs of the patients were ventilated to normocapnia with an oxygen-air mixture (Fio2 = 0.33). Arterial blood and CSF samples (from an intraventricular drain) were collected between 90–180 min after the induction of anesthesia. Blood propofol concentrations were stable, between 5.0 ± 1.89 and 4.5 ± 1.7 &mgr;g/mL (mean ± sd). There was a significant decrease in the CSF propofol concentration, from 52.2 ± 35.01 ng/mL at 90 min to 28.6 ± 21.9 ng/mL at 150 min (P < 0.05). The CSF propofol concentration at 180 min (21.4 ± 14.0 ng/mL) was not significantly different from the concentration at 150 min. Some possible reasons for this decrease after commencing continuous intraventricular drainage are discussed.

Relationships between total and unbound propofol in plasma and CSF during continuous drug infusion

Background:Propofol is one of the most frequently applied intravenous anesthetics. Although it has been used for a long period, its pharmacokinetics, especially central nervous system pharmacokinetics, are not fully recognized. Objective:Investigation of the relationships between total propofol concentration in blood, total propofol concentration in cerebrospinal fluid (CSF), free propofol concentration in blood, and free anesthetic concentration in CSF in patients undergoing elective neurosurgery and anesthetized with propofol. Methods:Eleven patients scheduled for elective intracranial procedures were studied. Propofol was applied in the form of target control infusion. During anesthesia, fractional doses of fentanyl and cisatracurium were administered as necessary. After tracheal intubation the lungs were ventilated to achieve normocapnia with an oxygen-air mixture (Fi O2 = 0.33). CSF and blood were taken at the moment of intraventricular drainage application. Results:The unbound propofol concentration in plasma is 1.12% (SD 0.61%; SEM 0.18%) of the total concentration in plasma, and the free propofol concentration in plasma is 71.6% (SD 61.0%; SEM 18.4%) of the total CSF propofol concentration. The free anesthetic concentration in CSF is 30.9% (SD 15.7%; SEM 4.7%) of the total CSF propofol concentration, and 61.8% (SD 34.9%; SEM 10.5%) of the free propofol concentration in plasma. Conclusion:The relationship between unbound drug concentrations in plasma and in CSF determined in this study leads to the postulate that propofol is transported from blood to CSF by passive diffusion.

New generation pulse oximetry in the assessment of peripheral perfusion during general anaesthesia — a comparison between propofol and desflurane

BACKGROUND A pulse oximeter is a standard device for perioperative monitoring. It is well known that the early detection of tissue hypoxia is of great importance. It has been made easier due to a new generation pulse oximetry device from Masimo. This enables measurements of the peripheral perfusion index (PI) in real time. It has been found that volatile anaesthetics such as sevoflurane and desflurane increase the perfusion index. As we know, no data is available about perfusion index during propofol/remifentanil total intravenous anaesthesia. METHODS ASA I and II class women scheduled for elective gynaecological surgery were eligible for the study. Patients were divided into two groups: group P receiving propofol/remifentanil intravenous anaesthesia and group D receiving desflurane/fentanyl general anaesthesia. PI was noted before anaesthesia, after remifentanil/fentanyl injection, after endotracheal intubation, at the beginning of surgery, during the procedure at ten minute intervals, at the end of the procedure, after awakening, after extubation and before discharge to the ward. RESULTS Eighty-three patients were enrolled to the study. In both groups, PI increased significantly from the start to the end of surgery. There was a significant correlation between PI and end-tidal desflurane concentration (r = 0.807; P = 0.001). No correlation was found between propofol or remifentanil concentrations and PI. CONCLUSION Both intravenous propofol/remifentanil and desflurane/fentanyl general anaesthesia increase peripheral perfusion. An increase in end-tidal desflurane concentration raises peripheral perfusion.

Intraoperative awareness – comparison of its incidence in women undergoing general anaesthesia for Caesarean section and for gynaecological procedures

BACKGROUND Intraoperative awareness (IA) is diagnosed when patients can recall their surroundings or an event related to the surgery that occurred while they were under general anaesthesia. The female gender and Caesarean section are considered to be contributing factors. The aim of the present study was to analyse the frequency of IA in patients undergoing general anaesthesia either for Caesarean section or gynaecological procedures. METHODS ASA I and II women were included into the study. Patients were randomly allocated to 4 groups: A, B and C included patients qualified for elective gynaecological surgery, and group D comprised Caesarean section patients. Premedication was not given. Group A received total intravenous anaesthesia with TCI, and groups B, C and D received balanced anaesthesia. The depth of anaesthesia was monitored with an AEP monitor. Blinded structured interviews were conducted 2 hours after anaesthesia and on postoperative days 7 and 30. RESULTS 337 patients were enrolled into the study. 45 patients reported diverse sensations connected to the anaesthesia (Group A - 7 patients, B - 9 patients, C - 2 patients, D - 28 patients). There were mainly dream sensations, but IA was present in 3 cases. In all of the cases, IA was recognised during the first interview. One episode of awareness appeared in group B, and the other two appeared in group D. One Caesarean section was complicated by intraoperative haemorrhage. The patient from group B had similar sensations during previous anaesthesia. Two women enrolled in the study reported awareness in the past, which did not occur this time. CONCLUSION Awareness during general anaesthesia occurs occasionally. The frequency of occurrence in a group of patients undergoing general anaesthesia for uncomplicated Caesarean section is not higher than for other procedures. The anaesthesia for Caesarean section, as well as for other procedures, may be accompanied by pleasant dreams.

Myasthenia gravis: a careful perioperative anesthetic management of coronary artery bypass grafting.

Nowadays, even hazardous cardiac surgery can be performed on patients with autoimmune diseases like myasthenia gravis. It requires a sensitive perioperative anesthetic approach especially in relation to nondepolarizing muscle relaxant administration. Myasthenic patients produce antibodies against the end-plate acetylcholine receptors causing muscle weakness and sensitivity to nondepolarizing muscle relaxants that could lead to respiratory failure. Perioperative nurse care is critical for uncomplicated course of treatment; therefore, apprehension of surgical procedure should be helpful on an everyday basis. We describe successful management without any pulmonary complications of two patients with myasthenia gravis undergoing coronary artery bypass grafting. In addition, antiacetylcholine receptor antibodies concentrations were evaluated during treatment time. In conclusion, we have found that reduced titrated doses of cisatracurium may be safely used in patients with myasthenia gravis undergoing cardiac surgery without anesthesia and respiratory-related complications.