Objective To assess the effects of different doses of oxycodone hydrochloride on spontaneous breathing and consciousness level of patients,so as to provide theoretical basis for its clinical application.Sixty patients undergoing elective surgery were randomly divided into 3 groups:0.05 mg·kg-1 oxycodone group (group P1),0.1 mg·kg-1 oxycodone group (group P2),0.2 mg·kg-1 oxycodone group (group P3).Changes of respiratory rate (RR),end tidal carbon dioxide partial pressure (PETCO2),saturation of blood oxygen (SpO2) and bispectral index (BIS) were recorded in patients before injection (t0) and 1-15 min after injection (once per min);the Observer's Assessment of Alertness/Sedation Scale (OAA /S) were recorded.At the same time,the adverse reactions were observed after drug injection in each group. Results In 10 min after injection there were no significant differences in the RR,SpO2,PETCO2,BIS and OAA/S in group P1 as compared with those before injection (P>0.05).The patients had no respiratory depression in group P1.In group P2,RR had a significant decrease (P<0.05),BIS had decreased but were greater than 85;there were no significant differences in the SpO2,PETCO2 and OAA/S (P>0.05).The P2 group had 3 cases with respiratory frequency<10 per min,but SpO2 were all greater than 94%.In group P3,There were significant differences in the RR,SpO2,PETCO2,BIS and OAA/S (P<0.05).The P3 group had 12 cases of respiratory frequency <10 per min,at the same time there were 8 patients with SpO2 less than 94%.With the increasing dose,the frequency of respiratory inhibition increased,and there were statistical differences (P<0.05).In 15 min after injection,RR,SpO2,PETCO2,BIS and OAA/S were not significantly different in group P1 and P2 as compared with those before injection (P>0.05).In group P3,RR was significantly different after injection (P<0.05).There were no significant differences in the SpO2,PETCO2,BIS and OAA/S in group P3 after injection (P>0.05).No patients complained with chest wall stiffness,nausea and vomiting,cough and other adverse reactions in group P1 and P2.In group P3,three patients had nausea 5 min after injection,two patients complained of chest skin itching but no skin flushing. Conclusion With the increasing dose,effect of oxycodone hydrochloride on breathing and consciousness level of patients gradually increased.Injection of oxycodone hydrochloride 0.05 mg·kg-1 had no obvious effect on breathing and consciousness.After injection of oxycodone hydrochloride 0.1 and 0.2 mg·kg-1 for 5 to 10 min,respiration inhibition and sedative effect were the most obvious.Fifteen min after injection,the 0.1 mg·kg-1 dose group recovered to the level before,the respiratory rate of the 0.2 mg·kg-1 dose group was still lower than that before the injection.
表2
3组患者注药前后不同时间点RR、SpO2 及PETCO2的比较
Tab.2
Comparison of RR,SpO2 and PETCO2 among three groups of patients at different time points before and after drug injection x¯±s,n=20
组别与时间
RR/ (次·min-1)
SpO2/ %
PETCO2/ kPa
P1组
t0
17.6±1.2
98.8±1.2
5.12±0.33
t1
16.2±2.1
97.3±2.3
5.25±0.43
t2
16.6±2.4
97.8±2.6
5.13±0.40
P2组
t0
17.8±1.6
98.6±1.8
5.20±0.24
t1
13.1±2.6*1
94.7±5.5
5.55±0.47
t2
15.7±2.2
95.6±6.9
5.40±0.36
P3组
t0
17.1±1.3
98.4±1.9
5.13±0.25
t1
11.6±3.1*1
86.1±5.6*1
6.13±0.61*1
t2
13.8±2.5*1*2
92.1±3.5*1*2
5.49±0.49*2
Compared with t0 at the same group, *1P<0.05;compared with P1 group at the same time group, *2P<0.05
与同组t0比较,*1P<0.05;与P1组同时间点比较,*2P<0.05
表2
3组患者注药前后不同时间点RR、SpO2 及PETCO2的比较
Tab.2
Comparison of RR,SpO2 and PETCO2 among three groups of patients at different time points before and after drug injection x¯±s,n=20
CHANGS,MANEYK,PHILLPSJ,et al.A comparison of the respiratory effects of oxycodone versus morphine:a randomised,double-blind,placebo-controlled investigation[J].Anaesthesia,2010,65(10):1007-1012.
Oxycodone's respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri-operative period. We randomly assigned ASA 1-2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg6301, or oxycodone 0.05 mg.kg6301, 0.1 mg.kg6301, or 0.2 mg.kg(-1) . Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg6301, oxycodone 0.05 mg.kg6301 and 0.1 mg.kg6301, and from 10 patients who received oxycodone 0.2 mg.kg6301. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine.
DERRODEN,LEBRUNF,LEVRON JC,et al.Influence of peroperative post operative pain after major abdominal surgery:sufentanil TCI versus remifentanil TCI.A randominzed,controlled study[J].Br J Anaesth,2003,91(6):842-849.
Sufentanil and remifentanil are characterized by two different pharmacokinetic profiles. The aim of this study was to compare the effects of sufentanil and remifentanil administered using target-controlled infusion (TCI) on recovery and postoperative analgesia after major abdominal surgery.Thirty adult patients scheduled for open colorectal surgery were included in a prospective, randomized study. Sufentanil TCI (sufentanil group) or remifentanil TCI (remifentanil group) was administered during surgery. In the remifentanil group, 30 min before the anticipated end of surgery, morphine 0.15 mg x kg(-1) was administered i.v. In the sufentanil group, an effect-site concentration of 0.25 ng x ml(-1) was targeted at extubation. In both groups, postoperative pain was controlled by titration of i.v. morphine and then patient-controlled analgesia with morphine.The extubation time was similar in the two groups (mean (SD) 13 (6) and 14 (6) min in the sufentanil and remifentanil groups respectively). Visual analogue scale scores were significantly greater during the first 2 h after tracheal extubation in the remifentanil group than in the sufentanil group. The time to first analgesic request in the postanaesthesia care unit was significantly longer in the sufentanil group than in the remifentanil group (55 (64) (range 2-240) vs 11 (7) (1-29) min; P<0.001). The cumulative morphine dose for titration was significantly greater in the remifentanil group (P<0.01). The cumulative morphine dose used during titration and patient-controlled analgesia was significantly greater in the remifentanil group 4, 12 and 24 h after extubation (P<0.05).TCI sufentanil (0.25 ng ml(-1) effect-site concentration at extubation) is more effective than the intraoperative combination of remifentanil TCI infusion with morphine bolus (0.15 mg x kg(-1)) for postoperative pain relief after major abdominal surgery and does not compromise extubation and recovery.
KALSOE,POYHIAR,ONNELAP,et al.Intravenous mor-phine and oxycodone for pain after abdominal surgery[J].Acta Anaesthesiol Scand,1991,35(7):642-646.
Intravenous morphine and oxycodone were given double blind in doses of 0.05 mg/kg after major abdominal surgery to 39 patients. The dosing interval was 5 min, until the patient did not want any further analgesics. Less oxycodone was needed than morphine, both to achieve the "first state of pain relief" (13.2 mg vs. 24.9 mg) and during the whole 2-h study period (21.8 mg vs. 34.2 mg). The "first state of pain relief" was achieved faster (28 min vs. 46 min) and lasted longer (39 min vs. 27 min) with oxycodone than morphine. Morphine caused more sedation and a greater decrease in the mean arterial blood pressure than oxycodone. In other respects the two opioids were comparable.
OLKKOLA KT,HAMUNENK,SEPPALAT,et al.Pharma-cokinetics and ventilatory effects of intravenous oxycodone in postoperative children(see comments)[J].Brit J Clin Pharm,1994,38(1):71-76.
1. Oxycodone hydrochloride (0.1 mg kg-1) was given by intravenous bolus to 18 children after ophthalmic surgery. Plasma was sampled for up to 8 h. Blood pressure, heart rate, peripheral arteriolar oxygen saturation, end-tidal carbon dioxide and halothane concentrations and ventilatory rate were also recorded. 2. Mean (+/- s.d.) values of drug clearance and volume of distribution (Vss) were 15.2 +/- 4.2 ml min-1 kg-1 and 2.1 +/- 0.8 l kg-1. Maximum mean end-tidal carbon dioxide concentration and minimum mean ventilatory rate occurred 8 min after administration of oxycodone but the minimum mean peripheral arteriolar oxygen saturation occurred at 4 min. 3. Oxycodone (0.1 mg kg-1) appears to cause greater ventilatory depression than comparable analgesic doses of other opioids.
GAJRAJ RJ,DOIM,MANTZARIDISH,et al.Analysis of the EEG bispectrum,auditory evoked potentials and th eEEG powers pectrum during repeated transitions from consciousness to unconsdousness[J].Br J Anaesth,1998,80:46-52.
We have compared the auditory evoked potential (AEP) index (a numerical index derived from the AEP), 95% spectral edge frequency (SEF), median frequency (MF) and the bispectral index (BIS) during alternating periods of consciousness and unconsciousness produced by target-controlled infusions of propofol. We studied 12 patients undergoing hip or knee replacement under spinal anaesthesia. During periods of consciousness and unconsciousness, respective mean values for the four measurements were: AEP index, 60.8 (SD 13.7) and 37.6 (6.5); BIS, 85.1 (8.2) and 66.8 (10.5); SEF, 24.2 (2.2) and 18.7 (2.1); and MF, 10.9 (3.3) and 8.8 (2.0). Threshold values with a specificity of 100% for a state of unconsciousness were: AEP index, 37 (sensitivity 52%); BIS, 55 (sensitivity 15%); and SEF, 16.0 (sensitivity 9%). There was no recorded value for MF that was 100% specific for unconsciousness. Of the four measurements, only AEP index demonstrated a significant difference (P < 0.05) between all mean values 1 min before recovery of consciousness and all mean values 1 min after recovery of consciousness. Our findings suggest that of the four electrophysiological variables, AEP index was best at distinguishing the transition from unconsciousness to consciousness.
HAO GT,ZHOU HY,GAO HZ,et al.Pharmaco-kinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain[J].Pharm Rep,2014,66(1):153-158.
The aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese patients with pain.Forty-two subjects were assigned to receive intravenous administration of oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were collected for up to 24 h after intravenous administration of oxycodone hydrochloride.Pharmacokinetic parameters showed that mean values of C(max), AUC(0-t) and AUC(0- ) of oxycodone were dose dependent, whereas Tmax and t(1/2) were not. The mean AUC(0-t) ratio of noroxycodone to oxycodone ranged from 0.35 to 0.42 over three doses, and those of noroxymorphone, or oxymorphone, to oxycodone were ranging of 0.06-0.08 and 0.007-0.008, respectively. Oxycodone and its three metabolites were excreted from urine. Approximately 10% of unchanged oxycodone was recovered in 24 h. Most adverse events (AEs) reported were mild to moderate. The frequently occurred AEs were dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were found.Our pharmacokinetics of oxycodone injection in Chinese patients with pain strongly support continued development of oxycodone as an effective analgesic drug in China.
, 范婷
