Effectiveness And Safety Of Dexmedetomidine Mixed With Ropivacaine Used In Continuous Thoracic Paravertebral Blocks For Thoracotomy

BackgroundThe surgical incision of thoracotomy is a kind of deep-level pain. Patients can’t cough and sputum effectively which will occur lung inflammation, infection and pulmonary atelectasis, if the pain is out of control in postoperative 72 hours. Patients suffer from pain that influence the postoperative quality of life. The acute pain of surgical incision will develop into chronic post-thoracotomy pain which is also called post-thoracotomy pain syndrome(PTPS) when the pain is unhealed. Patients are led to sleep disorders, anorexia, even mental abnormality. The subsequent reports that the incidence rate of PTPS took up 50% of thoracotomy,5%～25% of the patients with severe symptoms. Study reports that the PTPS’s mechanism is associated with the following:direct or indirect intercostals nerve injury during operation and incomplete healing postoperatively, inflammatory response, tumor recurrence, incision type and nerve sensitization, et al. In addition, opioid abuse during anesthesia and analgesia will result in opioid tolerance and hyperpathia that aggravate the chronic post-thoracotomy pain. Studies have pointed out that opioid abuse can lead to tumor recurrence and metastasis. Therefore, to formulate a reasonable perioperative analgesic plan is meaningful to relief the acute pain, meanwhile, cutting off the root causes of chronicity of acute pain. At present, most of the local hospital will choose patient-controlled intravenous analgesia(PCIA) as postoperative analgesia for thoracotomy. However, PCIA can’t avoid the abuse of perioperative opioid. Epidural analgesia with satisfactory anesthesia has been widely used, but it could cause bradycardia and hypotension during perioperative period. Thoracic paravertebral nerve block(TPVB) is a newly-developing analgesic method. It can produce several adjacent segments of truck and sympathetic nerve block at the homolateral injection site through injecting the local anesthetics into the thoracic paravertebral space. TPVB can effectively cut off the transmission of sexual stimulation signals to central nervous system from the surgical incision, also, it can control the amplification of sexual stimulation signals and formation of formation, so as to achieve the goal of satisfying analgesia. Dexmedetomidine(Dex) isα2 adrenergic((α2 AR) agonists with highly effect. Clinical practices prove that combination of Dex and local anesthetics applying to brachial plexus or lumbar plexus blocks can enhance the curative effect of local anesthetics significantly. There are seldom domestic research related to the effectiveness of Dex mixed with local anesthetics using in TPVB.ObjectiveThrough for using TPVB under ultrasound guidance, injecting Dex mixed with ropivacaine into thoracic paravertebral space, to compare the analgesic effect with PCIA and patient-controlled epidural analgesia(PCEA). To analyze the effectiveness and safety of Dex used in continuous TPVB for post-thoracotomy acute pain, than to further explore the control efficacy of analgesic strategy above for PTPS.Methods(1)Thirty patients, including male 20 and female 10, received single-port VATS were randomly and equally divided into two groups:group C received general anesthesia only, and group T received ultrasound-guided thoracic paravertebral nerve block combined with general anesthesia. Both groups did not use the PCA, if insufficient analgesia happened(VAS scores> 4), than used dezocine intravenously as additional analgesia(a single-dose 5-20 mg, no more than 120 mg a day). The ramsay scores at 1,4,8,12 h after the surgery and the mechanical withdrawal threshold on one day before the surgery, at 4,8,12,24 h after the surgery were recorded. The first time of post-operation pain feedback, the consumption of dezocine in the first 24 h after surgery, the incidence rates of side effects, the first time off-bed and the hospital stays were also recorded.(2) Sixty patients undergoing thoracotomy were divided into four groups based on randomized complete-block grouping method:group I(n=13) received intravenous analgesia only, group E(n=14) received postoperative continuous epidural analgesia, group T(n=16) received continuous thoracic paravertebral nerve block patient-controlled analgesia, anesthesia and postoperative analgesic methods of group TD(n=17) were the same as group T, but with Dex added to ropivacaine in thoracic paravertebral space as an adjuvant. Postoperative self-control analgesia lasting time was 48 h. If insufficient analgesia happened(VAS scores>4), than used dezocine intravenously as additional analgesia. The mechanical withdrawal threshold on 1 day before the surgery,12,24,48,72h, 1w after the surgery were recorded. The consumption of opioid during perioperative period and general anesthetics during the operation were also recorded(the consumption of sufentanil was converted to the consumption of remifentanil producing the equivalent effect by 1:10). To compare the incidence rates of side effects related to anesthesia procedure and drugs in the first 3 days after operation. Venous blood was sampled at pre-operation, postoperative 6,24, 72h. Plasma IL-6, IL-10 and TNF-a were detected with liquid chip technology.(3) The patients came from group T (named group R in this part) and group TD (named group RD in this part) in program (2), all the anesthesia and analgesia methods were the same as above. Testing and recording the onset time of sensory block, the upper and lower bound of sensory, the total segments of blocks when 30 min after blocking(Ta),24 h postoperatively(Tb),12 h after finishing PCA(Tc). Mean arterial pressure (MAP) and heart rate (HR) were recorded respectively when the patient was brought to the operation room rest (TO),15 min after paravertebral administration (T1), after intubation (T2), after skin incision (T3), before extubation (T4). The VAS scores on 6、24、48 and 72 h after operation when patients in quiet were recorded. The Ramsay scores on 1、6、24 h after operation were recorded. To record the times of using dizocine. To compare the incidence rates of side effects related to anesthesia procedure and drugs in the first 3 days after operation.(4)Brief pain inventory(BPI) was administered to the patients in program(2) on one and three months postoperatively which aimed of pain status for incision of thoracotomy, also drug therapy about pain, and the influence of pain toward to the quality of life. Quantification scores were gotten from the BPI, than to compare and analyze the data, summarizing the most effective analgesic method for decreasing the incidence rate of PTPS.Results(1)Compare with group C, the ramsay scores at 8,12 h postoperatively in group T significantly decreased (P<0.05), and the mechanical withdrawal threshold at 4,8 h postoperatively significantly increased (P< 0.05). The first time of post-operation pain feedback in group T was significantly longer than group C (P< 0.05). The consumption of dezocine in the first 24h after surgery significantly decreased in group T (P<0.05). Also, the incidence rates of nausea, vomiting in the first 24 h postoperatively were lower in group T(P<0.05). The first time off-bed and the hospital stays in group T were shorter than group C(P<0.05).(2) To compare with group Ⅰ, the mechanical withdrawal threshold at 12,24h postoperatively in group E, T and TD significantly increased(P<0.05). Compared with group Ⅰ, the consumption of propofol and remifentanil in unit time during anesthesia maintenance and opioid for three days after surgery significantly decreased in the other three groups(P<0.01), especially in group TD(P<0.05). To compare with T0, the concentrations of IL-6 at T1～T3 were significantly decreased in four groups(P<0.05), reached peak at T2 than demonstrated downward trends at T2 to T3. Both concentrations of IL-10 in group Ⅰ and group T at T1 and T2 were higher than T0(P<0.05) as well as those in group E and group TD at T1 to T3(P<0.05). The concentrations of IL-10 reached peak at T1 in four groups. Comparing to T0, the concentrations of TNF-αat T1～T3 in both group Ⅰ and group E were significantly increased(P<0.05), at T2, T3 in group T were increased(P<0.05). To compare with group Ⅰ, the concentrations of IL-6 at T1-T3 were significantly decreased in the other groups(P<0.05), IL-10 were lower than the others at T1, and lower than group E and TD at T2, T3(P<0.05), TNF-α was higher than group TD(P<0.05). To compare with group E, IL-6 was lower in group TD at T2, T3(P<0.05), and IL-10 is lower in group T at T2, T3(P<0.05). Compared with group T, IL-6 in group TD at T2, T3 was lower, IL-10 in group E and TD were higher at that time(P<0.05). There were no significant between the concentrations of IL-6 and TNF-α in group E and T when in different time point(P>0.05). Also, in the first 3 days after operation, the incidence rates of nausea, vomiting and dizziness were lower in group E, T and TD. The incidence rate of hypotension in group E was higher than group I and TD(P< 0.05).(3) The spreading range of cranial segment was smaller than caudal(P<0.01). To compare with group R, the range of sensory block was smaller than group RD at both Ta and Tc(P<0.05), so did the spreading range of cranial and caudal segment(P <0.05). At Tb, the number of caudal segments were increased in group RD(P<0.05). In group R, compared with T0, the MAP and HR were increased in T2 to T4(P< 0.05). Compared with Tl, the MAP and HR were increased in T3 and T4CP<0.05). In group RD, compared with T0, the MAP was increased in Tl and T4(P<0.05). Compared with T2, the HR was increased in T3 (P<0.05). The MAP and HR in group RD were lower than group R (P<0.05). The grouping factors interacted with time factors (P<0.05). To compare with group R, the Ramsay sedation score was higher in group RD when postoperative 6 h(P<0.05), and VAS score was lower in group RD when postoperative 48h,72 h(P<0.05). And frequency of using the dizocine as remedial analgesia was less in group RD than group R(P<0.05). To compare with group R, the incident rate of hypotension was higher in group RD(P=0.025), and the incident rate of shivering was lower in group RD(P=0.028).(4) One month after the operation, the incidence of chronic pain:group I was 92%, group E was 85%, group T was 86%, group TD was 79%. And after three months, the chronic incidence of pain:group I was 83%, group E was 62%, group T was 57%, group TD was 31%. According to the most dramatic pain in the past 24 h when questioned in postoperative one month, the incident rate of mild pain in group TD was higher than group E(P<0.05), moderate pain and severe pain were lower than group E(P<0.05). For the average degree of pain in the past 24 h when questioned in postoperative three months, the incident rate of mild pain in group I was lower than other three groups(P<0.05), moderate pain and severe pain were higher than others(P<0.05). The remnant pain took less influence to the life quality in postoperative three months than that in postoperative one month. As time goes by, pain relieved, the seven targets getting lower. The follow up in postoperative one month showed that, compared with group I, chronic pain took more serious influence on everyday life, emotions, ability to walk, daily work and life interest than other three groups(P<0.05). Compared with group E, chronic pain took more serious influence on everyday life, emotions, ability to walk, daily work and life interest than group T and group TD(P<0.05). The influence extent of pain on sleep was more serious in group T than group TD(P<0.05). In postoperative one month, the follow up showed that, chronic pain took more serious influence on everyday life and emotions than other three groups (P<0.05), and on ability to walk, daily work, sleep, interpersonal relationship, it had less influence in group TD than group I(O<0.05). Compared with group E, chronic pain took more serious influence on everyday life, ability to walk and daily work than group T and group TD(P<0.05). The influence extent of pain on sleep and life interest were more serious in group T than group TD(P<0.05).Conclusion(1) Single-port VATS is a kind of minimally invasive surgery, however, patients with less pain during postoperative period can recover more rapidly. Preemptive analgesia with ultrasound guided single-injected thoracic paravertebral never block can relieve the postoperative acute pain in patients undergoing single-port VATS, improve the quality of postoperative revival, reduce the consumption of opioids, cutting down the occurring rates of adverse reactions, which was beneficial to early ambulate and shortened the hospital stays.(2) Dexmedetomidine as an adjunctive analgesic mixed with ropivacaine used in continuous thoracic paravertebral block can improve the qualiy and the duration of analgesia in patients undergoing thoracotomy, reduce the consumption of opioid and general anesthetics, prevent the postoperative hyperalgesia and paralgesia. Otherwise, dexmedetomidine can inhibite the postoperative inflammatory response, control the development of SIRS, accelerate to be restored to health the process.(3) Dexmedetomidine mixed with ropivacaine used in continuous thoracic paravertebral block is safety. Patients with more steady blood flow dynamics, more effectiveness sensory block, lower incident rate of adverse response related to anesthesia procedure and anesthetic, can recover in rapid and efficient.(4) Dexmedetomidine mixed with ropivacaine used in continuous thoracic paravertebral block for post-thoracotomy can decrease the incident rate of long-term complication——PTPS, enhance the life quality of patients.