Ultrasound-guided Paravertebral Block Combined With General Anesthesia For Retroperitoneoscopic Nephrectomy

BACKGROUND & OBJECTIVEProper management of acute postoperative pain is important not only for patient satisfaction but also for patient outcome. On the contrary, poorly controlled acute postoperative pain may predispose patients to chronic post-surgical pain and influence the function recovery of multiple organs such as respiratory system and circulation system after operation, which may bring difficulties to perioperative treatment. The mechanism of postoperative pain include two aspects:on the one hand, the process of surgery raise the noxious stimulation of the tissue cells, which lead to multiple of inflammatory pain-producing substances produced by injuried tissue and raise inflammation reaction such as tissue edema. On the the other hand, a series of noxious stimulation result in the increased sensitivity of neurone, which would improve the intensity of reaction to the pain stimulus and induce the pain threshold decline.Patient controlled intravenous analgesia(PCIA) using opioids is one of the most widely used methods, but a single method with IV PCA is insufficient for managing postoperative pain in some patients with severe pain. In such cases, a multimodal approach is helpful, and a perioperative nerve block is a good choice. A paravertebral block(PVB) provides good-quality analgesia or anesthesia to patients undergoing the racic, abdominal, or pelvic procedures. Therefore, PVB is widely used and researched in clinical treatment. For example, a thoracic paravertebral block(TPVB) can be used in the perioperative analgesia or anesthesia in racic operation include breast surgery, cardiac surgery and thoracic surgery, and upper abdomen operation. In addition, TPVB can be used in the treatment of chronic chest wall pain, radiculitis pain and cancer pain. Recent studies show that TPVB using during perioperation can reduce the rate of postoperative pain and chronic pain in one year after surgery. Thoracic paravertebral space is formed by loose connective tissue between the spine and the parietal pleura, connected with the epidural space via intervertebral foramen. The local anaesthetics injecting to a certain paravertebral space can easily spread to the neighbouring paravertebral space, producing multiple segments of anesthesia scope. Spinal nerve root travels along paravertebral space in the anterior inferior part of thoracic transverse pass through intervertebral foramen, which anterior is pleura and the lungs. So the spinal transverse is the important anatomic landmark in PVB performent. A series of retrospective study found that thoracic paravertebral block could provide the same analgesia effect with the thoracic epidural block, but in contrast to maintain better oxygenation index ventilation and reduce complications include hypotension and urinary retention.Early thoracic paravertebral block was located by the anatomical landmarks and the puncture needle’s location was estimated by the feeling of loss resistance or pressure monitor, but its success rate was not ideal, and it easily damaged nerve and blood vessels, which would induce the severe complications. As the rapidly development of ultrasound technology, ultrasound technology used in nerve block is hot in recent years. Compared with other imaging techniques, ultrasound has advantages of no X-ray exposure, convenient, fast and accuracy at the same time. To require the high-quality nerve ultrasound images, on the one hand, high frequency probe of ultrasound should be used, on the other hand, the nerve anatomical position should be superficial. High frequency probe has high resolution but low penetrability. On the contrary, low frequency probe has high penetrability but low resolution. We should choose different kinds of probe(5-14 MHz) according to different puncture points and different somatotype. The early paravertebral block may lead to complications include pneumothorax, total spina anesthesia, local anesthetic intoxication, nerve injury and so on. Studies showed that the failure rate of nerve block in patients whose anatomical landmarks unclear or variant is up to 20%. Ultrasound technology can let us visualize in real time, minimize complications and improve puncture success ratio.PVB is widely used in clinical anesthesia, especially in the racic procedures. Recently, some studies showed that PVB could provide the same analgesia efficacy compare to the thoracic epidural block, but in contrast to maintain more stable hemodynamics and better analgesia effect than PCIA. However, the study of PVB in patients undergoing retroperitoneoscopic nephrectomy, which is accompanied by relatively severe postoperative pain resulting from the long incision is rare. Moreover, CO2 pneumoperitoneum pulls abdominal muscle and diaphragm result in severe pain. Hypercapnia which is caused by CO2 absorb indirectly increases the neuroendocrine hormone such as catecholamine relief and enhances emergency reaction. Recently, there was a report showing that PVB provided safe and effective perioperative analgesia for open renal operative procedures, but no randomized, controlled trials could be found, and no retroperitoneoscopic surgery application studies. In this study, by comparison with placebo group, we compared the dosage of opioids, VAS score, emergency reaction, hemodynamics and the incidence of adverse events perioperation. Combined with analgesia satisfaction rate by surgeons and patients, we evaluated the perioperative analgesia effect of PVB in unilateral retroperitoneoscopic nephrectomy and studied the emergency reaction impact of combined anesthesia in this kind of surgery.[METHODS]1.The inclusion criteria, exclusion criteria and rejection criteria of study objectInclusion criteria: ①Age between 18～75 years ②18<BMI<28 kg/m2 ③SA status I-II ④atients without severe visual and auditory disorder or patients who are able to read.Exclusion criteria: ①atients with severe cardiac, liver, pulmonary and renal functions insufficient, requiring postoperative management in the ICU ②oagulation abnormalities or patients who are expected to be on therapeutic ③ Allergy to any of the drugs/agents used in study protocol ④atients with painful conditions or chronic use of opioid or antineuropathic medications ⑤atients with scar, infection and tumor on the site of piercing ⑥ersonal or family history of malignant hyperthermia ⑦atients who can not cooperate with the follow-up or with poor compliance ⑧regnant and lactant women.Rejection criteria:patients enrollment who conform to one of the following conditions, should be removed:①Misdiagnosis ②onform to the exclusion criteria ③Serious violation of protocol and affect the observation of the study ④The important data lost or inaccessible ⑤Investigator considered the study continuing would be harmful to patients’health ⑥Subjects could exit because of any reasons.2.Study object and groupingThis study chose 60 cases of patients(ASA I-II) undergoing elective retroperitoneoscopic nephrectomy between June 2014 and October 2015 in our hospital. There were 32 males and 28 females age between 25-75 years and BMI 19-28 kg/m2 among these cases.Randomization:we used SPSS 13.0 statistical package to generate random numbers, then patients were divided into three groups(20 patients per group) according to 1:1:1 ratio:the group using ropivacaine paravertebral block combined with general anesthesia(Group A); the group using ropivacaine and morphine paravertebral block combined with general anesthesia(Group B); the placebo group(Group C). PCIA with the same fomula was used for postoperative analgesia in all patients of the three groups.3.Blinding and unblindingBlinding:double blind, all the liquor used in paravertebral block was colorless and tasteless transparency liquid. Neither the subjects nor the researchers were told the grouping situation, which eliminated their biases.Unblinding:twice unblinding. After collecting the data, the first unblinding would be performed by the person who kept the blinding codes. This unblinding would announce that subjects belong to which groups(such as Group A, GroupB or Group C) but not mark which group was treatment groups or control groups..When the statistic analysis finished, the second unblinding would be performed to mark which group was the group using ropivacaine paravertebral block combined with general anesthesia, which was the group using ropivacaine and morphine paravertebral block combined with general anesthesia or the placebo group.4. ProtocolAll the patients were prohibited eating and drinking for 8 hours before operation and without premedication. Entered the operation room, patients were established the conventional periphery vein passage and infused the compound sodium chloride solution with 8ml/kg/h velocity to supple the lost body fluid because of eating and drinking prohibition. Then patients were connected with the multi parameter monitor to monitor the heart rate (HR), blood pressure(BP), electrocardiogram(ECG) and pulse oxygen saturation(SPO2). The catheterization through transradial artery was performed under 1% lidocaine local anesthesia to monitor the continuous invasive arterial pressure and connected with the continuous cardiac output monitor Vigileo. All the three groups of patients would be performed general anethesia. Before the general anesthesia, patients were performed the ultrasound-guided paravertebral block on the affected side of paravertebral space. First of all, make sure the thoracic spinous process of puncture location(T9 and T11 double puncture points). Then sufficient local infiltration anesthesia was performed with 1% lidocaine after disinfection. After that, inserted the needle with 10 cm long 22G lumbar puncture needle from the lateral side of ultrasonic probe, alongside the lateral edge of vertebral plate, through the intertransverse ligament into the thoracic paravertebral space. After the needle tip into expected position and withdrawing without blood or cerebrospinal fluid, the solution was injected slowly.15 minutes after injection. we can confirm the block level and determine the block effect.After 20 minutes the paravertebral block finished, the general anesthesia induction began:intravenous propofol 1.5-2.5 mg/kg, fentanyl 2-4 ug/kg and rocuronium 0.6mg/kg to proceed anesthesia induction. Assistant respiration was performed with mask oxygen inhalation after patients’eyelash reflexes disappeared. Three to five minutes later tracheal intubation was given, followed by artificial ventilation. The tidal volume, inspiration and expiration ratio and respiratory rate was adjusted as required and the ETCO2 was maintained about 35 to 45 mmHg during operation. Besides, anesthesia depth was maintained with sevoflurane inhalation and remifentanil continuous intravenous infusion and muscle relaxant maintain with rocuronium intravenous as required. Stoped sevoflurane inhalation and remifentanil infusion, increased the oxygen flow rate and then connected with patient controlled intravenous analgesia(PCIA) immediately when surgery finished. After spontaneous breathing recovering, all the patients were given atropine and neostigmine to antagonist muscle relaxant residual effect. Tracheal extubation was performed when VT> 6 ml/kg.5. Observed indicatorTotal usage of remifentanil during operation and cumulant of morphine 1h,6h, 12h,24h and 48h postoperation were recorded. During the operation, we record the SBP、MAP、HR、CI、CO and SVV when resting(TO),15 minutes after PVB(Tl), 15 minutes after the beginning of the operation(T2),30 minutes after the beginning of the operation (T3),1 hour after the beginning of the operation(T4) and at the end of surgery (T5). Record the dosage and frequency of vasoactive drugs in the operation; monitor the MAP, HR and SPO21 h,6 h,12 h,24 h and 48 h postoperation. Draw arterial blood 1 ml in the radial artery for blood-gas analysis to determine the blood glucose level and lactic acid level, respectively in 30 minutes before skin incision and 30 minutes after skin incision. Pain was evaluated using a visual analogue scale (VAS), which required wide-awake patients to accept evaluation in quiet and cough state respectively 1h,6h,12h,24h and 48h postoperation. Zero:painless; score 1-2:occasionally mild pain; score 3-4:frequently mild pain; score 5-6:occasionally obvious pain but endurable; score 7-8:frequently obvious pain but still endurable; score 9～10:unbearable pain, need to inject analgesic drugs. When VAS>5, press the patient controlled analgesia bolus once. Record the PACU residence time, analgesia duration and postoperative hospital stays. Analgesia satisfaction rated by surgeons and patients, including 0～10 points,0 is not satisfied and 10 is very satisfied. Keep the record of adverse event rate of three groups. Record the incidence of adverse events in patients of three groups.6. Statistical analysisData analysis was performed by SPSS 13.0 software. Data was expressed as mean ± standard deviation(x±s). The comparison among groups of measurement data used One-Way ANOVA, Two-Way ANOVA, There-Way ANOVA and t-test. The multiple comparisons used LSD test(equal variance) or Durmett’S T3 test(heterogeneity of variance). The rate comparison used x2-test. P<0.05 was considered statistically significant.[RESULTS]1. General conditions comparison:the age, gender, body mass index, ASA status and operation time respectively showed no significant differences among three groups(P>0.05).2. Remifentanil usage intraoperation comparison:remifentanil usage showed significant differences among three groups(p＜0.05). Compare to Group C (1310.0±240.39ug), Group A (441.5±204.77ug) and Group B (344.0± 191.46ug) showed significant differences(P＜0.001), however, no significant differences among Group A and Group B(P=0.154).Morphine cumulant postoperation comparison:morphine cumulant showed significant differences among three groups 1h,6h,12h and 48h postoperation (P＜0.001). Group C (0.85±0.81mg,3.6±1.19mg,5.8±1.48mg,7.10±1.29mg, 7.25±1.55mg) was apparently higher than Group A (0.10±0.45mg,0.65±0.49mg, 2.0±0.86mg,3.4±1.67mg,3.5±1.67mg) and Group B(0.00±0.00 mg,0.25±0.44mg, 0.6±0.88mg,1.0±1.17mg,1.0±1.17mg) (P<0.001). In addition, Group A was higher than Group B. The difference between these two groups was statistically significant, especially in 12h,24h and 48h postoperation (P＜0.001)3. Intraoperative hemodynamic index comparison:compare to Group C, SBP, MAP and HR in Group A and Group B intraoperation showed significant differences in T2, T3, T4 and T5(P<0.05), however, CI, CO and SVV showed no significant differences(P>0.05). Extent to vasoactive drugs usage in the operation, Group A used atropine three times(0.9mg total) and ephedrine four times(24mg total); Group B used atropine twice(0.6mg total) and ephedrine three times(18mg total); Group C used atropine three times(0.9mg total) and ephedrine three times(18mg total), showing no significant differences among three groups(P>0.05).Postoperative hemodynamic index comparison:MAP showed significant differences among three groups (F= 18.065,P＜0.001), but no significant differences in 1h、6h、12h、24h and 48h postoperation (F=2.144, P=0.075). HR showed no significant differences among three groups (F=2.203, P=0.112), but significant differences in various time points postoperation (.F=3.041, P=0.018) and HR in 12h and 24h after operation was apparently faster than other time points’. However, SPO2 showed no significant differences among three groups and various times points(P>0.05).4. Lactic acid and blood glucose level comparison 30 minutes before and after skin incision comparison:lactic acid level showed no significant differences among three groups(F=0.053, P=0.948). Blood glucose level showed significant differences among three groups before and after skin incision and it was higher after skin incision than that before skin incision (F=3.109,P=0.048).5. Postoperative VAS score comparison:VAS score showed significant differences among three groups in 1h、6h、12h、24h and 48h postoperation,no matter in quiet state or in cough state(P<0.001). In quiet state, Group A (0.10±0.31, 0.65±0.67,1.80.±1.01,1.00±0.79,0.40±0.68) and Group B(0.00±0.00,0.35±0.59, 1.75±0.97,0.75±0.72,0.30±0.57) were apparently lower than Group C (4.20±1.67, 4.85±0.99,5.20±1.06,0.90±0.85,0.65±0.93). In cough state, Group C (5.65±1.93, 6.75±1.37,7.30±1.03,3.35±1.23,1.50±1.61) was much higher than Group A (0.18±0.79,2.65±1.42,4.45±1.28,3.10±0.97,1.30±1.26) and Group B(0.10±0.31, 1.25±1.52,3.70±1.34,2.50±1.57,1.25±1.25).6. Other observed indicators comparison:the PACU residence time and postoperative hospital stays showed significant differences among three groups(P<0.05), and Group C was much longer than Group A and Group B, but no significant differences between Group A and Group B(P>0.05). About the analgesia duration, Group B was apparently longer than Group A, which showed significant differences(t=-5.056, P<0.001). Extent to the analgesia satisfaction rate, it showed significant differences among three groups both by patients(P<0.05), and scores in Group A and Group B were much higher than Group C, but no significant differences between Group A and Group B (P=0.573). In addition, no significant differences among three groups by surgeons(P=0.343).7. The incidence of adverse events comparison:the complications include analgesia insufficient, blood vessels injury, pneumothorax, total spinal anesthesia, toxicity of local anaesthetics nerve injury etc. and postoperative adverse reactions include nausea, emesis, chill, hypotension, respiratory depression, pruritus, rash etc. showed no significant differences among three groups(.P>0.05).[CONCLUSION]1. Ultrasound-guided paravertebral block combined with general anesthesia for retroperitoneoscopic nephrectomy can reduce perioperative analgesics usage effectively, which make perioperative hemodynamics more stable.2. Ultrasound-guided paravertebral block combined with general anesthesia for retroperitoneoscopic nephrectomy can relieve intraoperative emergency reaction and ease postoperative pain, which is beneficial to patients’recovery.As a consequence, ultrasound-guided paravertebral block combined with general anesthesia can be considered a safety and effective anesthesia procotol for retroperitoneoscopic nephrectomy.