Maternal and preterm fetal sheep responses to dexmedetomidine.

BACKGROUND: The α(2) adrenergic receptor agonist dexmedetomidine has some unique pharmacologic properties that could benefit pregnant patients (and their fetuses) when they require sedation, analgesia, and/or anesthesia during pregnancy. The purpose of the present study was to delineate maternal and fetal responses to an intravenous infusion of dexmedetomidine. METHODS: This study was conducted on surgically-recovered preterm sheep instrumented for physiologic recording and blood sampling. Maternal and fetal cardiovascular and blood gas parameters and fetal cerebral oxygenation levels were recorded before, during, and after 3h of dexmedetomidine infusion to the ewe at a rate of 1 µg/kg/h. RESULTS: Drug infusion produced overt sedation but no apparent respiratory depression as evidenced by stable maternal arterial blood gases; fetal blood gases were also stable. The one blood parameter to change was serum glucose, By the end of the 3-h infusion, glucose increased from 49±10 to 104±33mg/dL in the ewe and from 22±3 to 48±16mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63±12mg/dL, P=0.0497; and fetal, 24±4mg/dL, P=0.012). With respect to cardiovascular status, dexmedetomidine produced a decrease in maternal blood pressure and heart rate with fluctuations in uterine blood flow but had no discernable effect on fetal heart rate or mean arterial pressure. Likewise, maternal drug infusion had no effect on fetal cerebral oxygenation, as measured by in utero near-infrared spectroscopy. CONCLUSIONS: Using a clinically-relevant dosing regimen, intravenous infusion of dexmedetomidine produced significant maternal sedation without altering fetal physiologic status. Results from this initial acute assessment support the conduct of further studies to determine if dexmedetomidine has clinical utility for sedation and pain control during pregnancy.

Mathematical model for describing cerebral oxygen desaturation in patients undergoing deep hypothermic circulatory arrest.

BACKGROUND: Surgical treatment for aortic arch disease requiring periods of circulatory arrest is associated with a spectrum of neurological sequelae. Cerebral oximetry can non-invasively monitor patients for cerebral ischaemia even during periods of circulatory arrest. We hypothesized that cerebral desaturation during circulatory arrest could be described by a mathematical relationship that is time-dependent. METHODS: Cerebral desaturation curves obtained from 36 patients undergoing aortic surgery with deep hypothermic circulatory arrest (DHCA) were used to create a non-linear mixed model. The model assumes that the rate of oxygen decline is greatest at the beginning before steadily transitioning to a constant. Leave-one-out cross-validation and jackknife methods were used to evaluate the validity of the predictive model. RESULTS: The average rate of cerebral desaturation during DHCA can be described as: Sct(o(2))[t]=81.4-(11.53+0.37 x t) (1-0.88 x exp (-0.17 x t)). Higher starting Sct(o(2)) values and taller patient height were also associated with a greater decline rate of Sct(o(2)). Additionally, a predictive model was derived after the functional form of a x log (b+c x delta), where delta is the degree of Sct(o(2)) decline after 15 min of DHCA. The model enables the estimation of a maximal acceptable arrest time before reaching an ischaemic threshold. Validation tests showed that, for the majority, the prediction error is no more than +/-3 min. CONCLUSIONS: We were able to create two mathematical models, which can accurately describe the rate of cerebral desaturation during circulatory arrest at 12-15 degrees C as a function of time and predict the length of arrest time until a threshold value is reached.

NIRS: dose dependency of local changes of cerebral HbO2 and Hb with pCO2 in parietal cortex.

Regional cerebral oxygenated hemoglobin and total hemoglobin increased systematically with increasing depth of hypercapnia, but the concentration of deoxygenated hemoglobin remained relatively constant. Relative mean changes of oxygenated and total hemoglobin increased nearly linearly, corresponding to the characteristic increase of the cerebral vascular dilation with increasing depth of hypercapnia.

Regional cerebral oxygenation during cardiopulmonary bypass.

A significant number of patients suffer transient neuropsychological dysfunction after coronary artery bypass graft (CABG) surgery. Recent studies have implicated reduced levels of O2 supply/demand ratio during the rewarming phase of cardiopulmonary bypass (CPB). Using a near infrared spectroscopy (NIRS) system that permits continuous noninvasive monitoring of regional cerebral O2 saturation (rSO2), we investigated rSO2 during CPB. Following Institution Review Board approval and informed consent, 10 patients undergoing elective CABG were studied. Nonpulsatile CPB with a membrane oxygenator, haemodilution and alpha-state pH management was used. The NIRS system consisting of two low-power laser diode sources (780 nm and 810 nm) with a photodetector placed on the frontal cortex was used to measure continuously haemoglobin, oxyhaemoglobin and cerebral blood volume. Continuous rSO2 measurements were obtained before, during moderate hypothermia, and during the rewarming phase of CPB. A rSO2 < 50% was defined as abnormal. Onset of rSO2 < 50% was at 32 degrees C, and the highest incidence occurred during the late stages of rewarming (35-37 degrees C). On rewarming from hypothermic CPB, 70% of our patients sustained a rSO2 < 50% for an average total duration of 9.3 minutes, primarily at the end of the rewarming period. This suggests a transient global imbalance in cerebral O2 supply and demand in a large percentage of patients during the rewarming phase of CPB. However, it has not been determined how long a rSO2 < 50% can be permitted before neuropsychological dysfunction is induced. Additional studies correlating psychometric testing with rSO2 measurements should prove useful in detecting episodes of impaired cerebral oxygenation, and help define rewarming protocols.