The Effect Of Intravenous Injection Of Different Doses Of Dexmedetomidine On Respiratory Mechanics And The Depth Of Sedation In Patients

BACKGROUND:Dexmedetomidine (Dex) is a highly selective alpha2-receptor agonist, whichcan inhibit sympathetic nerve and reduce the norepinephrine release so that result tosedation, analgesia and cut down on use of anesthetic drugs. The affinity of Dextargering to the alpha2adrenergic receptor is7times bigger than clonidine, and theelimination half-life about2hours which shorter than clonidine. Dex has beenapproved by American food and Drug Administration (FDA) in1999, which couldapply to adult sedation and analgesia in intensive care unit (ICU). During to itsadvantages of decreasing sympathetic nerve excitability, prevention of stress reaction,effects of sedation and analgesia, the stability of hemodynamics, reduction dossageof anesthetic and opioid analgesic, and anti shivering effect, which is widely used inclinical anesthesia and ICU sedation. Respiratory depression is a concern when usingpotent analgesics or sedatives. Routine use of sedatives such as midazolam can leadto a fatal outcome when overdosed. Dex, a highly selective alpha!2-adrenoceptoragonist, is currently used for short-term sedation of initially intubated andmechanically ventilated patients. A high concentration of alpha!2receptors isfound in the locus ceruleus,which is involved in regulating sleep and may beinvolved in the modulation of the respiratory controls. Dex, through its actions onthe alpha!2-adrenoceptors, imparts sedative and analgesic effects while havingminimal ventilatory effects.The respiratory safety of Dex has been suggested by four studies. Although Ebert et al. investigated Dex infusions over a wide range of concentrations(8ng/ml,5-8times than the dose of intravenous injection), their respiratory data are limited torespiratory rate and blood gases, and the SpO2maintain over （96±0.7）%. Bellevilleet al. presented a more elaborate respiratory analysis, but their study was limited torelatively small boluses of Dex, and the plasma concentrations were not measured.Intravenous injection of Dex2μg/kg, MV decrease from8.7±0.7L/min to6.3±1.5L/min；and RR from17.0±3.5bpm to14.2±2.1bpm；but PETCO2increase to10mmHg(45~55mmHg), SpO2decrease from98.3±0.8%to95.4±1.2%. Venn et al.performed a retrospective analysis of the respiratory rate and blood gas data fromsurgical patients in the surgical intensive care unit, Before extubation given a loadingdose of intravenous infusion of Dex, in order to maintain the Ramsay sedation scoreof3points or more to after extubation, they found that compared to the placebogroup, no difference in effect of Dex on RR, SpO2, arterial blood pH, PaO2andPaCO2, but PaO2and FIO2were increased, suggesting that Dex on respiration is notthere are adverse effects. Hsu founded that compared with Dex and remifentanil onnormal adult volunteers breathing, target controlled infusion of remifentanil resultedin decreased RR, MV, respiratory acidosis and apnea, resulting in oxygen saturationdecreased respiratory inhibition; however, target controlled infusion of Dex inducedRR significantly increased, the total apnea/hypopnea index decreased, inspiratorytime/ventilation cycle distribution showed a peak increases, conclusion that Dexdoes not cause clinically significant respiratory inhibition, but exhibit similar tonatural sleep state.So far, the effect of dexmedetomidine on respiratory mainly in slightly lowerresting minute ventilation (MV), slightly elevated arterial partial pressure of carbondioxide (PaCO2), but there were not data that reported in the literature whichreseasing the influence of different concentrations of dexmedetomidine onrespiratory mechanics (breathing mechanics), such as the forced expiratory volumein one second (FEV1%) and the pressure-volume loop(PV loop). This study is toobserve the effect of a single intravenous injection of different doses ofdexmedetomidine on respiratory mechanics and the depth of sedation, which providing the reference for the clinical application of Dex.ObjectiveTo observe the effect of intravenous injection of different doses of Dex onrespiratory mechanics and the degree of sedation, provides the reference for theclinical application of Dex.MethodEighty undergoing general anesthesia operation patients of ASA physical statusI~II, randomly divided into four groups, Dex0.5μg/kg group (D1),1μg/kg group(D2),1.5μg/kg group (D3) and control group (D0),20patients in each group. Allpatients were monitored by the arterial pressure, electrocardiogram (ECG), heart rate(HR), pulse oxygen saturation (SpO2) and bispectral index (BIS). The respiratorymechanics index determined by Datex-Ultima monitor. Intravenous infusion of0.5,1.0, or1.5μg/kg Dex within10min, beginning35min induction of anesthesia.The respiratory mechanics index including Tidal volume (VT), minute ventilation(MV), end tidal carbon dioxide (PETCO2), respiratory rate (RR), the forcedexpiratory volume in one second (FEV1%)、the pressure-volume loop(PV loop),pulse oxygen saturation (SpO2), heart rate (HR) and mean arterial pressure (MAP),Bispectral analysis index (BIS) and the Observer’s Assessment of Alertness/SedationScale(OAA/S). Record the monitor index at the time of0min(T0),5min(T1),10min(T2),15min(T3),20min(T4),25min(T5)and30min(T6). The alveolar arterialcarbon dioxide tension (PaCO2),alveolar arterial oxygen tension(PaO2) and potentialof hydrogen(pH) recorded at0min(T0),5min(T1),15min(T3) and30min(T6).ResultsFour groups of patients all did not appear obvious respiratory depression andapnea phenomenon. Compared with the control group, D1group, VT, RR, MV,PETCO2, FEV1%, PaCO2and SpO2had no significant change (P>0.05), PV loopshape was normal; group D2and D3, MV was decreased by16.9%and27%respectively, compared with the control group, the difference was statisticallysignificant (P<0.05); PaCO2was increased by11%and19.9%respectively,compared with the control group, the difference was statistically significant (P<0.05); FEV1%were decreased by11%and14.9%respectively, compared with the controlgroup, the difference has statistical significance. Four groups of patients are noapnea, and all patients with SpO2are at98%or above. The PV loop area of D3groupautonomous respiration was significantly reduced (P<0.05).In group D1, BIS values were more than85,65%patients with OAA/S4,satisfactory sedation rate is low, only20%patients with OAA/S3; group D2with thehighest rate of satisfactory sedation,70%patients with OAA/S3, and no excessivesedation; in group D3,60%patients with a OAA/S score of less than or equal to2.In group D3, there were four cases (20%) in patients with hypertension, theother groups were free of hypertension and hypotension. The bradycardia incidencerates of groups D2and D3were30%and70%respectively, compared with thecontrol group was statistically significant (P<0.05).ConclusionThe effect on respiratory mechanics and sedation of Dex related withdoses.With the infusion of Dex’s dose increased, the degree of sedation depth, whileSpO2is still in the normal range, but respiration was inhibited. Dex0.5μg/kg effectson respiratory function in patients with mild; intravenous infusion of Dex1μg/kgreduce RR,VTand MV, PETCO2and PaCO2increased. The RR, VT, MV andFEV1%significantly decreased and the PETCO2, PaCO2increased with reduced ofthe PV loop area while intravenous infusion of Dex1.5μg/kg, and70%patients withbradycardia,60%with excessive sedation.Clinical recommend intravenous infusionof Dex at a dose of0.5μg/kg~1μg/kg for safety.