Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

BACKGROUND: The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). METHODS: Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg(-1)) or S-ketamine (1.1 mg kg(-1)) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine enantiomer plasma concentrations were determined by capillary electrophoresis. Individual R-ketamine and S-ketamine concentration vs time curves were analysed by non-linear least square regression two-compartment model analysis using PCNonlin. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating AUC, C(max), and T(max). Pulse rate (PR), respiratory rate (R(f)), tidal volume (V(T)), minute volume ventilation (V(E)), end-tidal partial pressure of carbon dioxide (PE'(CO(2))), and mean arterial blood pressure (MAP) were also evaluated. RESULTS: The pharmacokinetic parameters of S- and R-ketamine administered in the racemic mixture or S-ketamine administered separately did not differ significantly. Statistically significant higher AUC and C(max) were found for S-norketamine compared with R-norketamine in the racemic group. Overall, R(f), V(E), PE'(CO(2)), and MAP were significantly higher in the racemic group, whereas PR was higher in the S-ketamine group. CONCLUSIONS: Norketamine enantiomers showed different pharmacokinetic profiles after single i.v. administration of racemic ketamine in ponies anaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonary variables require further investigation.

Subcutaneous oxygen pressure in spontaneously breathing lean and obese volunteers: a pilot study

BACKGROUND: Oxidative killing is the primary defense against surgical pathogens; risk of infection is inversely related to tissue oxygenation. Subcutaneous tissue oxygenation in obese patients is significantly less than in lean patients during general anesthesia. However, it remains unknown whether reduced intraoperative tissue oxygenation in obese patients results from obesity per se or from a combination of anesthesia and surgery. In a pilot study, we tested the hypothesis that tissue oxygenation is reduced in spontaneously breathing, unanesthetized obese volunteers. METHODS: Seven lean volunteers with a body mass index (BMI) of 22 +/- 2 kg/m(2) were compared to seven volunteers with a BMI of 46 +/- 4 kg/m(2). Volunteers were subjected to the following oxygen challenges: (1) room air; (2) 2 l/min oxygen via nasal prongs, (3) 6 l/min oxygen through a rebreathing face mask; (4) oxygen as needed to achieve an arterial oxygen pressure (arterial pO(2)) of 200 mmHg; and (5) oxygen as needed to achieve an arterial pO(2) of 300 mmHg. The oxygen challenges were randomized. Arterial pO(2) was measured with a continuous intraarterial blood gas analyzer (Paratrend 7); deltoid subcutaneous tissue oxygenation was measured with a polarographic microoxygen sensor (Licox). RESULTS: Subcutaneous tissue oxygenation was similar in lean and obese volunteers: (1) room air, 52 +/- 10 vs 58 +/- 8 mmHg; (2) 2 l/min, 77 +/- 25 vs 79 +/- 24 mmHg; (3) 6 l/min, 125 +/- 43 vs 121 +/- 25 mmHg; (4) arterial pO(2) = 200 mmHg, 115 +/- 42 vs 144 +/- 23 mmHg; (5) arterial pO(2) = 300 mmHg, 145 +/- 41 vs 154 +/- 32 mmHg. CONCLUSION: In this pilot study, we could not identify significant differences in deltoid subcutaneous tissue oxygen pressure between lean and morbidly obese volunteers.

Relative impact of respiratory muscle activity on tidal flow and end expiratory volume in healthy neonates

INTRODUCTION: It has been suggested that infants dynamically regulate their tidal flow and end-expiratory volume level. The interaction between muscle activity, flow and lung volume in spontaneously sleeping neonates is poorly studied, since it requires the assessment of transcutaneous electromyography of respiratory muscles (rEMG) in matched comparison to lung function measurements. METHODS: After determining feasibility and repeatability of rEMG in 20 spontaneously sleeping healthy neonates, we measured the relative impact of intercostal and diaphragmatic EMG activity in direct comparison to the resulting tidal flow and FRC. RESULTS: We found good feasibility, repeatability and correlation of timing indices between rEMG activity and flow. The rEMG amplitude was significantly dependent on the resistive load of the face mask. Diaphragm and intercostal muscle activity commenced prior to the onset of flow and remained active during the expiratory cycle. The relative contribution of intercostal and diaphragmatic activity to flow was variable and changed dynamically. CONCLUSION: Using matched rEMG, air flow and lung volume measurements, we have found good feasibility and repeatability of intercostal and diaphragm rEMG measurements and provide the first quantitative measures of the temporal relationship between muscle activity and flow in spontaneously sleeping healthy neonates. Lung mechanical function is dynamically regulated and adapts on a breath to breath basis. So, non-invasive rEMG measurements alone or in combination with lung function might provide a more comprehensive picture of pulmonary mechanics in future studies. The data describing the timing of EMG and flow may be important for future studies of EMG triggered mechanical ventilation.

Accuracy of tidal breathing measurement of FloRight compared to an ultrasonic flowmeter in infants.

INTRODUCTION Monitoring breathing pattern is especially relevant in infants with lung disease. Recently, a vest-based inductive plethysmograph system (FloRight®) has been developed for tidal breathing measurement in infants. We investigated the accuracy of tidal breathing flow volume loop (TBFVL) measurements in healthy term-born infants and infants with lung disease by the vest-based system in comparison to an ultrasonic flowmeter (USFM) with a face mask. We also investigated whether the system discriminates between healthy infants and those with lung disease. METHODS Floright® measures changes in thoracoabdominal volume during tidal breathing through magnetic field changes generated by current-carrying conductor coils in an elastic vest. Simultaneous TBFVL measurements by the vest-based system and the USFM were performed at 44 weeks corrected postmenstrual age during quiet unsedated sleep. TBFVL parameters derived by both techniques and within both groups were compared. RESULTS We included 19 healthy infants and 18 infants with lung disease. Tidal volume per body weight derived by the vest-based system was significantly lower with a mean difference (95% CI) of -1.33 ml/kg (-1.73; -0.92), P < 0.001. Respiratory rate and ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF/tE) did not differ between the two techniques. Both systems were able to discriminate between healthy infants and those with lung disease using tPTEF/tE. CONCLUSION FloRight® accurately measures time indices and may discriminate between healthy infants and those with lung disease, but demonstrates differences in tidal volume measurements. It may be better suited to monitor breathing pattern than for TBFVL measurements.