Małgorzata Grześkowiak

Assessing circadian rhythms during prolonged midazolam infusion in the pediatric intensive care unit (PICU) children

BACKGROUND This study evaluates possible circadian rhythms during prolonged midazolam infusion in 27 pediatric intensive care unit (PICU) children under mechanical ventilation. METHODS Blood samples for midazolam and 1-OH-midazolam assay were collected throughout the infusion at different times of the day. The blood pressure, heart rate and body temperature were recorded every hour for the rhythms analysis. Population nonlinear mixed-effect modeling with NONMEM was used for data analysis. RESULTS A two-compartment model for midazolam pharmacokinetics and a one-compartment model for midazolam metabolite adequately described the data. The 24 h profiles of all monitored physiological parameters were greatly disturbed/abolished in comparison with the well-known 24 h rhythmic patterns in healthy subjects. There was no significant circadian rhythm detected with respect to midazolam pharmacokinetics, its active metabolite pharmacokinetics and all monitored parameters. CONCLUSIONS We concluded that the light-dark cycle did not influence midazolam pharmacokinetics in intensive care units children. Also, endogenous rhythms in critically ill and sedated children are severely disturbed and desynchronized. Our results confirmed that it is necessary to adjust the dose of midazolam to the patients body weight. The low value of midazolam clearances observed in our study was probably caused by mechanical ventilation, which was shown to decrease the cardiac output.

Evaluation of the Trail Making Test and interval timing as measures of cognition in healthy adults: comparisons by age, education, and gender.

Background Human cognitive functioning can be assessed using different methods of testing. Age, level of education, and gender may influence the results of cognitive tests. Material/Methods The well-known Trail Making Test (TMT), which is often used to measure the frontal lobe function, and the experimental test of Interval Timing (IT) were compared. The methods used in IT included reproduction of auditory and visual stimuli, with the subsequent production of the time intervals of 1-, 2-, 5-, and 7-seconds durations with no pattern. Subjects included 64 healthy adult volunteers aged 18–63 (33 women, 31 men). Comparisons were made based on age, education, and gender. Results TMT was performed quickly and was influenced by age, education, and gender. All reproduced visual and produced intervals were shortened and the reproduction of auditory stimuli was more complex. Age, education, and gender have more pronounced impact on the cognitive test than on the interval timing test. The reproduction of the short auditory stimuli was more accurate in comparison to other modalities used in the IT test. Conclusions The interval timing, when compared to the TMT, offers an interesting possibility of testing. Further studies are necessary to confirm the initial observation.

Pharmacokinetics and pharmacodynamics of propofol in children undergoing different types of surgeries

BACKGROUND Propofol is a commonly used agent in total intravenous anesthesia (TIVA). However, the link between its pharmacokinetics and pharmacodynamics has not been fully characterized in children yet. Our aim was to determine the quantitative relationship between the venous plasma concentration and bispectral index (BIS) effect in a heterogeneous group of pediatric patients undergoing various surgical procedures (ASA status I-III). METHODS Nine male and nine female patients were anesthetized with propofol-fentanyl TIVA. Sparse venous samples for propofol concentrations assay and dense BIS measurements were collected during and after the end of infusion. Nonlinear mixed-effect modeling in NONMEM was used for data analysis. RESULTS A three-compartment model was linked with a classical Emax model through a biophase compartment to describe the available data. All clearance and volume terms were allometrically scaled to account for the body mass difference among the patients under study. A typical patient had their PK parameters observed within the range of literature values for children. The pharmacodynamic parameters were highly variable. The EC50 of 2.80 mg/L and the biophase distribution rate constant of 3.33 min(-1) were found for a typical patient. CONCLUSIONS The BIS values in children are highly correlated with the propofol effect compartment concentrations according to the classical Emax concentration-response relationship. Children had slightly lower sensitivity to propofol and slightly higher clearance, as compared with the adult data available in literature. The intra-patient variations in the BIS require the anesthesiologists attention in using BIS values alone to evaluate the depth of anesthesia in children.

Psychomotor Functions and Interval Timing in Patients Receiving Intravenous Anesthesia for Endoscopic Procedures: The Pilot Study

Introduction. The aim of this study was to evaluate two measures in a cognitive examination: psychomotor function and the perception of time (PT) in patients after intravenous anesthesia for endoscopic procedures. Material and Methods. We tested 23 anesthetized patients (Anesthesia Group, AG) and 17 not anesthetized patients (Control Group, CG). The Dufour Cross-Shaped Apparatus (DA) was used to assess quick reactions. Perception of time (PT) was measured for 1-, 2-, 5-, and 7-second intervals. The tests were performed before the anesthesia was administered and 1.5, 3, and 6 hours after the procedure was completed. Results. The intervals that were generated and the reproduced visual stimuli were shorter than the patterns. The reproduced 1- and 2-second auditory stimuli were longer than the patterns. The remaining reproduced auditory impulses were shorter than the patterns. Conclusions. In anesthetized patients, quick psychomotor reactions and the ability to time intervals are preserved 1.5 h and later after intravenous anesthesia for endoscopy.

Carbon dioxide as a potential danger to medical rescue teams at work – A case study

Medical rescue teams might be exposed to the risk of accidental poisoning while performing rescue procedures. Exposure to the risk of lethal carbon dioxide (CO2) concentrations is a rare situation. This case study describes rescuing a patient who suffered from sudden cardiac arrest due to accidental CO2 poisoning. The victim was finally evacuated and resuscitated, but the circumstances of the rescue operation point to the need to equip ambulances with carbon dioxide detectors and hermetic oxygen masks. Med Pr 2017;68(1):135-138.

Procedural sedation and analgesia in children undergoing digestive endoscopic procedures – paediatrician or anaesthesiologist?

Endoscopic procedures of the gastrointestinal tract were successfully introduced into paediatric practice in the 1970s. Recent expansive development has become useful for improvement of both diagnosis and treatment in many children with gastrointestinal diseases. Most of these procedures are performed under procedural sedation (PSA) knowing anatomical, physiological and psychological differences and requiring good experience from the paediatrician and anaesthesiologist. These principles help to provide the procedure safely and minimise adverse events, which are greater the smaller the child is. Procedural sedation and analgesia in healthy children can be performed by a paediatrician, but children with congenital defects and serious coexisting diseases (ASA ≥ III) and also during the usage of anaesthetics (e.g. propofol), should be managed by an anaesthesiologist.