A Dose-response Study Of Dexmedetomidine Combined With Sufentanil On Patient Controlled Intravenous Analgesia In Elderly Patients After Hip Fracture Surgery

BackgroundThe old people prone to hip fractures.According to the statistics, hip fractures accounting for 23.79% of body fractures in 65 years or elderly people. Elderly hip fracture is expected to more than 700,000 cases per year in China.20% of patients died within 1 year,20% will fracture again within one year. With the aging population became social issues, surgery such as femoral neck fracture fixation、 intertrochanteric fracture fixation、hemiarthroplasty、total hip replacement in elderly patients continue to increase.The elderly patients early exercise can cause severe pain after hip fracture surgery,these increased the cardiovascular and respiratory complications, increasde the incidence of thrombosis, caused the digestive and urinary system dysfunction. Pain and bad environment can cause patient cardiac diseases such as anxiety, fear, depression, sleep disorders. In addition, the patient will protectively limit hip motion because the acute pain not timely and effective relief after the hip fracture surgery. These affects the recovery of limb function early, leading to limb joint stiffness, muscle disuse atrophy, bone loss in braking and other serious complications.Postoperative analgesia has many species. Patient controlled intravenous analgesia(PCIA) which is clinical used earliest and widely, accepted highest by patients. PCIA provides a stable plasma concentration of analgesic drugs, can reduce pharmacokinetic, pharmacodynamic individual differences. During PCIA,patients can control their own dosage according to their own pain, avoid obvious excessive postoperative pain or analgesic,which improved the comfort and safety of patients.Sufentanil was currently used in PCIA. Sufentanil is strong analgesic effect, and low toxicity, a wide range of security. Sufentanil can be antagonized by naloxone, widely affirmed in PCIA.But Sufentanil also has other adverse effects of opioids,such as respiratory depression, bradycardia, hypotension, nausea, vomiting,etal. In order to reduce the adverse effects of sufentanil, there are clinical research about sufentanil combined with dexmedetomidine.Dexmedetomidine is a highly selective α2-adrenergic receptor agonist, which not only have a calming, moderate analgesic effect, but also inhibit sympathetic activity, reduce stress, stable hemodynamic. Dexmedetomidine combined with sufentanil which have a synergistic sedative, analgesic effect, but on the respiratory depression caused by opioids no synergy, while reducing the side effects caused by opioid overdose. So Dexmedetomidine can optimize the effect of sufentanil PCIA. The most common adverse reactions of dexmedetomidine are hypotension and bradycardia. Currently, the effective safety and appropriate dosage of dexmedetomidine given in elderly patients with hip fracture surgery PCIA, has no Clinical Studies.ObjectiveDuring the use of 3 different dosage of dexmedetomidine combined with sufentanil on PCIA in elderly patients after hip fracture surgery, observed the amount of dexmedetomidine and sufentanil, PCIA analgesia, sedation, postoperative hemodynamic and respiratory changes, adverse reactions,etal. And discussed the doses and effect relationshipand of dexmedetomidine and this PCIA, the security and appropriate dose of dexmedetomidine in this PCIAMethods1. Patients selection:This test is approved by the ethics committee of the hospital. Chose 120 cases of partial hip arthroplasty, total hip arthroplasty, intertrochanteric fracture fixation, internal fixation of femoral neck fracture, in our hospital from January 2014 to January 2016. All Patients willingly to use PCI A, who aged 65 to 80 years, the American Society of Anesthesiologists (ASA) grade Ⅱ～Ⅲ, the patient’s body mass index (BMI) 18～25kg/m2.Both patients and their families understand and sign an informed consent form.2. Anesthesia:All patients had no premedication. After entering the operating room, patients were monitorde electrocardiogram (ECG), noninvasive blood pressure (BP), heart rate (HR), respiratory rate (RR) and pulse oximetry (SpO2) by Multi-function monitor (Infinity Delta, Drager, USA),established upper extremity venous access,injected ringer lactate 10～20ml/kg and/or hydroxyethyl starch 130/0.4 sodium chloride injection (6% HES 130/0.4) 5～10ml/kg,in order to add volume and maintain hemodynamic stability. Patients were rowed radial artery catheterization continuous monitoring of arterial blood pressure (ABP), central venous (under the right internal jugular vein or right subclavian vein) catheterization continuous monitoring of central venous pressure (CVP). Using spinal anesthesia, puncture L2-3 or L3-4, in subarachnoid injected ropivacaine hydrochloride 0.2～0.4mg/kg (with cerebrospinal fluid was diluted from 1% to 0.5% ropivacaine). Operated after patient no pain, anesthesia is fixed to the chest 10 (T10) or less, and hemodynamic stability. Patients undergone sedation by dexmedetomidine 0.1～0.5μg/kg (diluted with 0.9% saline 100ml) intravenous infusion (time 15～20min). Had no use of the other analgesic drugs during operation. 10min before the end of surgery accessed intravenous electronic controlled analgesia (BCDB-200, Haibo create medical devices).3. PCIA program:3.1 Test grouping:Anesthesiologist according to the standard selected patients (inclusion criteria and exclusion criteria) configured to patients intravenous analgesia pump.Anesthesiologist divided into three teams:Team I formulated group S or D1 analgesic liquid; team II formulated group S or D2 analgesic liquid; teamⅢ formulated group S or D3 analgesic liquid. According to which the patients used analgesic drug solution, patients divided into 4 groups, group S (control group), group D1, D2, D3 (experimental group).Each group PCIA analgesia liquid follows: (1) Group S:sufentanil 100 μg plus 0.9% normal saline (NS) dubbed 100ml; (2) Group D1:dexmedetomidine 0.5μg/kg and sufentanil100μg plus 0.9% NS dubbed 100ml; (3) Group D2:dexmedetomidine 1.0μg/kg and sufentanil 100μg plus 0.9% NS dubbed 100ml; (4) Group D3:dexmedetomidine 1.5μg/kg and sufentanil 100μg plus 0.9% NS dubbed 100ml;3.2 Parameter settings of the electronic self controlled analgesia pump:The first dose is 1ml, background dose is 1ml/h, PC A dose is 1ml, lock time 15min, limit dose is 5ml/h, quantitative dose is 100ml. Cleared the records data of the former fluence (total usage), PC A number (Pressing times).3.3 PCIA implementation methods:lOmin before the end of the surgery , in the internal jugular vein anesthesiologist gave the first dose of 1ml, accessed electronic analgesia pump, started PCIA, which continuoused 48h.All patients were used the same electronic controlled analgesia pump, cared by multi-function monitor, gave nasal cannula low-flow oxygen 1～2L/min in 48h. Ward nurse noticed anesthetist if patients had related adverse reactions of PCIA treatment.Anesthetist nurse follow-up regularly, record data of outcome measures, treatment of adverse reactions on PCIA. After PCIA48h, anesthetist nurse retrieved electronic analgesia bump,recorded fluence (total usage), PCA number (Pressing times), patients satisfaction with PCIA3.4 The handles of the poor analgesia and adverse reactions during the PCIA:If poor analgesic, tramadol 100mg given intramuscularly. If nausea and vomiting, intravenous tropisetron 5mg or metoclopramide 20mg. If sustained hypotension, appropriate to add volume and use of vasoactive drugs such as dopamine sustain, and suspension of analgesia. If severe bradycardia, use atropine and suspension of analgesia. If respiratory depression, use naloxone and suspension of analgesia. If sedation(Ramsay score>4), treat symptomatic and suspension of analgesia.4. Observed indicators:4.1 The patients’ condition:(1)General situation of patients:age, sex, BMI, ASA. Complications: hypertension (grade 1-2), anemia (mild to moderate), chronic obstructive pulmonary disease (stable), type Ⅱ diabetes.(2)Preoperative patients’hemodynamic and respiratory conditions:systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate(RR), pulse oximetry (SpOa).(3)Intraoperative conditions of patients:operative time, blood loss, fluid type and fluid volume, urine.4.2 The total dosage of dexmedetomidine and sufentanil,PCA times in PCIA:After PCIA 48h, nurse recovered PCIA pump, recorded the PCA times, the total amount of dexmedetomidine and sufentanil, whether or not to use analgesic drugs and the frequency.4.3 Analgesic effect in PCIA:Numerical rating score (NRS) combined with Wong-Baker Faces Pain Rating Scale obtain Pain assessment picture, Figure 1.According to pain assessment picture obtained dynamic NRS and static NRS (0～10), after 4h,8h,24h,48h.4.4 Sedative effect in PCIA:Ramsay score standard:1 score:anxiety and restlessness or restless or both.2score:quiet cooperation, orientation accurately.3score:drowsiness, after awakening to the instruction responsive.4score:sleep, but can wake up.5score: Slow response and call.6score:deeply sleep, cann’t wake up call.According to Ramsay score standard, recorded Ramsay score (1-6) after 4h, 8h,24h,48h.4.5 The other observed indicator in PCIA:Hemodynamic and respiratory changes, adverse reactions, patients satisfaction of PCIA treatment.The same nurse investigated and documented visits.5. Statistical method:Use SPSS13.0 statistical software for statistical analysis. Measurement data were expressed as mean ± standard deviation (x±s) represent, t test was used to compare the group. Single factor analysis of variance was used to compare among groups. The count data is expressed as a percentage, comparison between groups using x2 test, P<0.05 was considered statistically significant, P>0.05 was no significant difference. The relationship between the amount of dexmedetomidine dose sufentanil given by linear regression analysis, the correlation coefficient of the regression is r(-1≤r≤1). If r is positive,it is a positive correlation;if r is negative, it is a negative correlation;if r is zero, it is no correlation.Results1. The patients’ condition:(1)General situation of patients:age, sex, BMI, ASA. Complications: hypertension (grade 1-2), anemia (mild to moderate), chronic obstructive pulmonary disease (stable), type Ⅱ diabetes. Theire difference were not statistically significant(P>0.05).(2)Preoperative patients’hemodynamic and respiratory conditions:systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate (RR), pulse oximetry (SpO2). Theire difference were not statistically significant(P>0.05).(3)Intraoperative conditions of patients:operative time, blood loss, fluid type and fluid volume, urine. Theire difference were not statistically significant(P>0.05).2. The amount of dexmedetomidine and sufentanil, PCA times in PCI A:(1) The amount of dexmedetomidine:Group D1 the amount of dexmedetomidine was (18.1 ± 4.3) μg, Group D2 the amount of dexmedetomidine was (31.3±3.5)μg, Group D3 the amount of dexmedetomidine was (45.2±3.8)μg.Compared with the group D1, group D2 and group D3 were increaser (P <0.05).Compared with the group D1, group D3 was increaser (P<0.05).(2)The amount of sufentanil in PCIA:Group S the amount of sufentanil was (84.8 ± 3.5) μg, Group D1 the amount of sufentanil was (72.0±4.1)μg, Group D2 the amount of sufentanil was (62.9±3.2) μg, Group D3 the amount of sufentanil was (60.3±4.3) μg.Compared with group S, group D1, group D2 and group D3 were lower (P <0.05). Compared with group D1, group D2 and D3 were lower (P<0.05). Compared with group D2, group D3 was no significant difference (P>0.05).(3)The correlation analysis of different dosage of dexmedetomidine and the amount of sufentanil in PCIA:Linear regression analysis of different dosage of dexmedetomidine and the amount of sufentanil in PCIA, When Dexmedetomidine 0.5ug/kg～1.0μg/kg, the correlation coefficient (r) was -0.9879, was negatively correlated,its linear regression equation was Y=81.13-18.24X, Y was the amout of sufentanil (μg), X was the dosage of dexmedetomidine (μg/kg). When the dosage of Dexmedetomidine 1.5μg/ kg,it reduced the amount of sufentanil no longer significant.(4)PCA times:Group S the PCA times were (32.1 ± 3.5) times, Group Di the PCA times were (23.2±4.1) times, Group D2 the PCA times were (13.5±3.4) times, Group D3 the PCA times were (11.3±4.3) times.Compared with group S, group D1, D2 and D3 were lower (P<0.05). Compared with group D1, group D2and D3 were lower (P<0.05). Compared with group D2, group D3 was no significant difference (P>0.05).(5) 4 groups PCIA course did not use the remedy tramadol.3. Analgesic effect in PCIA:(1)In the same group:Compared with the static NRS score, the dynamic NRS of group S and D1 were all higher(P<0.05), group D2 and D3 were no significant difference (P>0.05).(2)Static NRS score:Compared with group S, group D1, D2 and D3 static NRS were lower (P <0.05)after 4h,8h,24h. Each static NRS compared with Group S after 48h, the difference was not statistically significant (P>0.05). Compared with the Group D1, D2 and D3 after surgery 4h,8h,24h static NRS were lower (P<0.05), Each static NRS compared with group D1 after 48h, the difference was not statistically significant(P>0.05). Compared with the group D2, group D3 was no significant difference in static NRS(P>0.05).(3)Dynamic NRS score:Compared with group S, group D1, D2 and D3 dynamic NRS were lower (P <0.05)after 4h,8h,24h. The dynamic NRS of group D3 and D2 were all lower after 48h(P<0.05); dynamic NRS of group D1 compared with group S after 48h, the difference was not statistically significant(P>0.05). Compared with group D1, The dynamic NRS of group D3 and D2 were all lower after 48h(P<0.05). Compared with the group D2, The dynamic NRS of group D3 was no significant difference(P>0.05).(4)The dynamic and static NRS score of 4 groups after 4h,8h,24h,48h of surgery were lower then 6, and no severe pain.4. Sedative effect in PCI A:(1)Compared with group S, the ramsay score of group D1, D2 and D3 were higher (P<0.05). Compared with group D1, the ramsay score of group D2 and D3 were higher (P<0.05). Compared with group D2, the ramsay score of group D3 were higher (P <0.05).(2)the ramsay score of 4 groups were lower then 4, no excessive sedation.5. The other observed indicator in PCIA:(1) Comparison of hemodynamic and respiratory changes:Comparison of SBP/DBP change:Compared with group S, The SBP of group D2 after 8h,12h,24h, group D3 after 8h,12h,24h,48h decreased (P<0.05); The DBP of group D2 after 8h,12h,24h, group D38h,24h,48h decreased (P<0.05). Compared with the group D,, The SBP of group D3 after 8h,12h,24h decreased (P<0.05). Compared with the group D2, The SBP of group D3 after 8h,12h,24h were decreased (P<0.05); The DBP of group D3 declined after 12h,48h (P<0.05).Comparison of HR change:Compared with group S, The HR of group Di after 8h,12h decreased (P<0.05); group D2, D3 after 4h,8h,12h,24h,48h decreased (P <0.05). Compared with the group D1, The HR of group D2 decreased (P<0.05) after 24h,48h. and D3 decreased (P<0.05) after 4h,8h,12h,24h,48h. Compared with the group D2, The HR of group D3 after 12h,48h decreased (P<0.05).Comparison of RR change:Compared with group S, The RR of group D1, D2, D3 were no significant difference (P> 0.05).Comparison of SpO2 change:Compared with group S, The SpO2 of group D1, D2, D3 were no significant difference (P> 0.05).In 4 groups RR> 10 times/min, SpO2> 95%, no respiratory depression.(2) Adverse reactions:In PCIA 48h,in group S dizziness, nausea and vomiting were 6.7%(2/30), 23.3%(7/30), in group D1 nausea and vomiting were 3.3%(1/30), in group D2 did not show any adverse reactions, in group D3 hypotension, bradycardia were 16.7%(5/30), 10%(3/30).Compared with group S, group D1> D2 were lower (P<0.05). Group D3 hypotension were 16.7%, bradycardia were 10%, were higher (P<0.05).All groups were no Itching, no Respiratory depression, no Excessive sedation.(3) The satisfaction of PCIA:The satisfaction of group S, D1, D2, D3 were 56.7%、83.3%,100%,93.3%.Compared with group S, the satisfaction of group D1, D2 and D3 were higher (P <0.05). Compared with group D1, the satisfaction of group D2 and D3 were higher (P <0.05).Conclusions1. In PCI A of elderly patients after hip fracture surgery, when Dexmedetomidine 0.5μg/kg～1.0μg/kg combined with Sufentanil, the dosage of Dexmedetomidine and the amount of Sufentanil were negative correlation (r=-0.9879), and Dexmedetomidine reduced the amount of Sufentanil significantly. But Dexmedetomidine 1.5μg/kg reduced the amount of Sufentanil no longer evident.2. The PCIA of Dexmedetomidine 0.5μg/kg～1.5μg/kg combined with Sufentanil, used in elderly patients after hip fracture surgery, had exact analgesic effect, a low incidence of adverse reactions, and improved the patients’ satisfaction. When combined with Dexmedetomidine 1.0μg/kg, It had the lowest incidence of adverse reactions, the highest patients’ satisfaction. The safe and appropriate dosage of dexmedetomidine is 1.0μg/kg.