Study of free opioid anesthesia for laparoscopic cholecystectomy

To assess of qualities of free opioid anesthesia, the effects on circulation, respiration and its side effects. Subjects and methods: Prospective free opioid anesthesia study, 30 patients were treated by laparoscopic cholecystectomy at 103 Millitary Hospital from May, 2018 to February, 2019.

Journal of military pharmaco-medicine no8-2019 STUDY OF FREE OPIOID ANESTHESIA FOR LAPAROSCOPIC CHOLECYSTECTOMY Nguyen Luu Phuong Thuy1; Nguyen Truong Giang2 Hoang Van Chuong1; Vu Thi Thanh Nga3; Nguyen Trung Kien1 SUMMARY Objectives: To assess of qualities of free opioid anesthesia, the effects on circulation, respiration and its side effects Subjects and methods: Prospective free opioid anesthesia study, 30 patients were treated by laparoscopic cholecystectomy at 103 Millitary Hospital from May, 2018 to February, 2019 Before induction: Slow injection intravenous lidocaine mg/kg; magnesium 30 mg/kg Induction: propofol - 2.5 mg/kg; ketogesic 30 mg; rocuronium 0.8 mg/kg, intubation when train of four is 0, respond entropy and state entrop ≤ 60 After induction: Injection ketamine 0.5 mg/kg, local trocar anesthesia: ropivacaine 0.5% Maintaining: Adjust propofol dose to keep respond entropy, state entropy within 40 - 60 Monitoring heart rate, blood pressure, drug consumption, side effects Results: All patients had an excellent quality of anesthesia with respond entropy, state entrop ≤ 60 and respond entropy - state entrop ≤ after anesthesia to closed incision without electromyography - in frontal lobe There was no case of awareness and the memory of the operation, hemodynamic stability during the operation; 100% of patients were extubated immediately after surgery finished Non-complications of circulation and respiration occurred during operation The rate of hypersalivation was 26.67%, which was limited by using suction; only patient felt postoperative nausea but no vomiting 100% of patients had a good recovery Conclusion: Free opioid anesthesia provided good anesthesia quality for laparoscopic cholecystectomy Side effects were mild and transient * Keywords: Free opioid anesthesia; Laparoscopic cholecystectomy INTRODUCTION Balanced anesthesia using anesthetic drugs, opioid and neuromuscular blockade was often applied for laparoscopic cholecystectomy Fentanyl is a potent drug used to control pain, reduce the dose of sympathomimetic inhibitors and remain hemodynamic stability [3] However, most common side effects of fentanyl are well known: nausea and vomiting, constipation, urinary retention, headache, pruritus, rash, histamine release, biliary spasm especially respiratory depression the most severe negative impact The proportion of opioid-related side effects in postoperative patients using opioids was reported at 2.67% in a study and was associated with an increase in length of hospital stay as well as health care costs [2] Vietnam Military Medical University 103 Military Hospital Viet Tiep Hospital Corresponding author: Nguyen Luu Phuong Thuy (cattuong2209@gmail.com) Date received: 23/08/2019 Date accepted: 10/10/2019 198 Journal of military pharmaco-medicine no8-2019 Patients taking high doses of fentanyl during surgery always require higher doses of opioids in the postoperative period than those in lower doses [5] Free opioid anesthesia (FOA) is used in many countries around the world, including multimodal pain therapy: Local anesthesia combined with NSAIDs and sympathetic block in surgery contribute to enhanced recovery after surgery (ERAS) [3] The use of long-acting local anesthetics also enhances postoperative pain relief As a result, the concept of balanced anesthesia now has a change of three basic components: sleeping pills, muscle relaxants and sympathomimetics inhibitors [6] This research purposes were: To evaluate the anesthetic quality, effects on circulation, respiratory and side effects in laparoscopic cholecystectomy SUBJECTS AND METHODS Subjects 30 patients were treated by laparoscopic cholecystectomy at 103 Military Hospital from May 2018 to February 2019 * Included criteria: - Patients aged ≥ 18 - Agreed to enroll in the study - General anesthesia by endotracheal intubation was indicated - Laparoscopic cholecystectomy - Early extubation may be predicted after general anesthesia * Excluded criteria: - Patients did not agree to enroll in the study - Patients had history of epilepsy, mental illness, communication difficulties - Patients were damage in the head, face, neck, mouth, and tongue; a history of intracranial pressure increase; heart disease, hypertension; slow heart rate - Patients had liver failure, kidney failure - Pregnant women or nursing mother * Taken out criteria: - Patients had complications during surgery - Patients did not collect enough data - Patients had an allergy to drugs used Methods Prospective studies, free opioid anesthesia * Technical process: Patients had preoperative examination the day before surgery Patient was admitted to the endoscopic surgery room, intravenous infusion of NaCl 0.9%, set up monitoring system in monitor Nihon Kohden: Electrocardiogram, SpO2, blood pressure, train of four (TOF) scan monitor to stimulate the nerve at the position of the thumb muscles closed * Study protocol: - Before just induction: Lidocaine mg/kg; magnesium 30 mg/kg - Induction: Propofol - 2.5 mg/kg; ketogesic 30 mg; rocuronium 0.8 mg/ kg Artificial ventilation, when TOF = "0" and respond entropy (RE), state entrop (SE) ≤ 60 to insert intubation - After induction: Ketamine 0.5 mg/kg Local trocar anesthesia: ropivacaine 0.5% 199 Journal of military pharmaco-medicine no8-2019 - Maintenance: Tidal volume - 10 mL/kg mode ventilation-control volume, frequency 12 - 14 times/minute, maintain peak airway pressure 12 - 16 cm H2O; EtCO2 25 - 35 mmHg; fresh gas flow (FGF) 1.2 liters/minute When the CO2 insufflation, keeping EtCO2 < 40 mmHg and peak airway pressure < 30 cm H2O Maintenance by propofol, adjust dose to maintain RE, SE within 40 - 60, intravenous infusion injection by lidocaine 1.5 mg/kg/h; intravenous infusion by magnesium 1.5 g Rocuronium was repeated 0.5 mg/kg when TOF ≥ twitch (no last injection when the estimated time from the estimated time of injection to the time of abdominal closure was less than 20 minutes), intravenous infusion paracetamol g when the gallbladder was excised During and after surgery, the patient was warmed up by Warm Touch 6,000 Covidien machine Reversal of neuromuscular blockade: Followed by follow-up TOF every 15 seconds Reversing neuromuscular blockade with sugammadex mg/kg - Standard endotracheal extubation: + Normal mental + Normal skin and mucous + Cough reflex recovery + Respiratory: Self breathing 10 30 times/minute; Vt > mL/kg + Circulatory: Systolic blood pressure ≥ 90 mmHg; heart rate ≥ 60 beats per minute + Body temperature ≥ 35°C + TOF index ≥ 0.9; no complications after surgery - Variables: 200 + Age, gender, BMI, surgical duration (from incision to the end of surgery), general anesthesia duration (from induction to the end of surgery), induction duration (from induction to intubation) + Total drug dosages: Propofol (mg), lidocaine (mg), magnesium (mg), ketamine (mg), rocuronium (mg), sugammadex (mg), atropin (mg); prostigmin (mg) + Evaluating effectiveness on circulation and respiratory: Heart rate, blood pressure, SpO2, EtCO2 at times from T1 to T9: in operating room, pre-induction, after induction, pre-incision, after incision, before close incision, after close incision, before extubation, after extubation, respectively + Indicators for evaluating the sedation: Entropy, surgical memories and surgical awareness + Indicators for evaluating muscle relaxation: Duration from reversing neuromuscular blockade to TOF > 0.5; TOF > 0.7; TOF > 0.9; duration of endotracheal tube withdrawal (from the reversing neuromuscular blockade to the endotracheal extubation) + Side effects: Vomiting, nausea, bradycardia, shivering, allergies, hypersalivation + Visual analog scale (VAS) at the times: after surgery, after 10 mins, after 20 mins, after hour, after hours, after hours The data were collected, analyzed and processed by medical statistics using SPSS 20.0 software Quantitative variables were described as the means ± standard deviations Journal of military pharmaco-medicine no8-2019 RESULTS General characteristics - Gender: Male 10 patients; female 20 patients - Aged average: 49,67 ± 14,21 years; min: 24 years, max: 73 years - Body mass index (BMI): 20,4 ± 2,4 kg/m2; 15,78 kg/m2, max 25,39 kg/m2 - ASA I: 26 patients; ASA II: patients General anesthesia and surgical characteristics Table 1: Characteristics Induction duration (minutes) Results 9.30 ± 2.30 [5 - 12] General anesthesia duration (minutes) 86.17 ± 41.04 [35 - 195] Surgical duration (minutes) 83.50 ± 44.22 [40 - 205] TOF index (minutes) TOF = 0.5 1.15 ± 0.24 [0.43 - 2.04] TOF = 0.7 1.47 ± 0.23 [1.04 - 2.52] TOF = 0.9 2.15 ± 0.42 [1.16 - 3.67] Extubated duration (minutes) 3.46 ± 0.53 [2.17 - 4.32] Table 2: Dosage of drugs Propofol (mg) Rocuronium (mg) 421.30 ± 134 [250 - 710] 43.83 ± 9.79 [30 - 70] Lidocaine (mg) 170.20 ± 42.89 [120 - 296] Magiesium (g) 2.85 ± 0.27 [2 - 3.1] Ketamine (mg) 25.67 ± 4.69 [20 - 35] Suggamadex (mg) 95 ± 10 [80 - 100] Figure 1: Change of Entropy during surgery 201 Journal of military pharmaco-medicine no8-2019 Other characteristics: SpO2 99 - 100%, heart rate, blood pressure were stable Figure 2: Change of heart rate and blood pressure during surgery EtCO2, peak fluctuated within normal limits Side effects Nausea: patient (3,33%); hypersalivation: patients (26,67) Pain after surgery Figure 3: VAS score during rest and cough DISCUSSION Enhanced recovery after surgery is the most concern of anesthesiologists and the surgeons to enhance the quality of taking care for patients The use of opioid replacement drugs and NSAIDs contribute to reduce treatment costs and improve patient,s recovery [7] However, the clinical fact shows that patients with 202 general anesthesia use high doses of fentanyl - a potent opioid in surgery that always require higher doses of opioid in the postoperative period causing opioid induced hyperalgesia (OIH) compared to those in lower doses [5] Therefore, free-opioid anesthesia (FOA) has being applied in many countries around the world Journal of military pharmaco-medicine no8-2019 According to Mulier et al (2017), combining multimodal sympathetic nervous system stabilizers including α2-adrenoreceptor agonists (clonidine, dexmidetomidine), intravenous local anesthetic (lidocaine, procaine), magiesium can completely avoid opioid using in surgery which causes long-term sedation and OIH after surgery [6] The author also confirmed the possibility of significant opioid complication decrease, especially postoperative nausea and vomiting and respiratory depression [7, 8] In another study of 5,061 patients in laparoscopic gastrectomy, Mulier found that free-opioid anesthesia for 2,337 patients combined between clonidine, dexmidetomidine, lidocaine, magiesium and small doses below 50 mg ketamine had the same effectiveness but decreased significantly the rate of complications and postoperative analgesic morphine doses in comparison with 264 patients using low opioid anesthesia (LOA) and 2,451 patients using opioid [7] In our study, free-opioid anesthesia was performed by using intravenous anesthetic (lidocaine), magnesium, low doses of ketamine and intravenous NSAIDs (ketogesic) and local anesthetic with 0.5% ropivacaine Paracetamol g was rapidly infused before the end of surgery for sympathetic stability The heart rate and blood pressure were stable Both RE and SE were always under 60 and RE - SE ≤ from after anesthesia to closed incision without electromyography in frontal lobe [8], there was no case of awareness and the memory of the operation Intravenous lidocaine has been shown to be analgesia - mediated by suppression of spontaneous impulses generated from injured nerve fibers and proximal dorsal root ganglion and occured by inhibition of NA-channels, NMDA (N-methyl-D-aspartat) and G-protein coupled receptors It was useful during abdominal surgeries reduction in opioid consumption, opioid-related side clinical effects and pain intensity and decreased incidence of postoperative ileus [10] Magnesium acts as noncompetitive antagonist of NMDA glutamate receptors and prevents depolarization and transmission of pain signals Intraoperative used magnesium during surgery could also reduce opioid consumption in the first postoperative 24 hours [11] Ketamine is a NMDA antagonist, with a low dose (< 0.5 mg/kg) reducing postoperative analgesic needs, reducing up to 25% in pain intensity and in analgesic consumption up to 48 hours after surgery [12] Javier confirmed that free-opioid anesthesia is better choice in some cases such as narcotic abuse history, morbidly obese patients with obstructive sleep apnea, opioid intolerance and history of chronic diseases (immunodeficiency, cancer) [12] In another study by Mansour et al (2013), 28 obese patients (BMI > 50 kg/m2) undergoing laparoscopic sleeve gastrectomies were received either opioid or non-opioid based general anesthesia The results showed that non-opioid general anesthesia is as effective as opioid one and trends to less pain for postoperative analgesia in non-opioid general anesthesia However, Mansour used only ketamine in relatively high doses (0.5 mg/kg for induction of general anesthesia and 203 Journal of military pharmaco-medicine no8-2019 0.5 mg/kg/h for maintenance anesthesia), the hallucinations appeared higher in this group than the opioid group [13] The other studies by Feld (2003) and Yalcin Cok (2017) in obese patients also showed similar results, confirming the free-opioid anesthesia effectiveness The difference among these studies was the combination of sympathomimetic stabilizers, intravenous anesthesia, ketorolac, low dose of ketamine, limit the hallucinations [14, 15] Side effects in our study on 30 patients were low, no dangerous circulation and respiratory complications, extubation immediately after surgery finished 8/30 patients (26.67%) had hypersalivatiom which were limited by suction; only patient (3.33%) suffered from nausea but did not vomit; no patient with hallucination The Bakan’s study (2015) on 80 patients undergoing laparoscopic cholecystectomy following two different methods had side effects rates such as vomiting, nausea, hypotension, tremor in the opioidremifentanyl (RF) group higher than the non-opioid anesthesia group (DL), particularly the rate of ephedrine and ondansetron and fentanyl hours after surgery on the RF group was significantly higher than the DL group [16] In our study, we made intravenous infusion of propofol TIVA mg/kg/h for induction and maintenance general anesthesia, which is a safe anesthetic, no airway irritation, rapid recovery, little effect on the liver and kidneys, enhancing the quality of postoperative recovery Our result was similar to the Nguyen Van Chung’s study (2004) [2] After surgery, the patients in our study group were used suggamadex mg/kg to muscle relaxation reversal, 204 extubation when TOF ≥ 0.9 and other standard endotracheal extubation demanded [17] The results showed that recovery durations to TOF = 0.5; 0.7; 0.9 and the extubated duration in patients using suggamadex were significant, which were similar to the result of the rocuronium blockade quality using sugammadex after total anesthesia in all researches [18] Postoperative pain was followed during hours after surgery basing on VAS VAS at the cough was higher at rest CONCLUSION Free-opioid anesthesia provided good and safe quality of general anesthesia for cholecystectomy Both RE and SE were always under 60 and RE - SE ≤ from after anesthesia to closed incision, there was no case of awareness and memory of the operation There were no circulation and respiratory complications, 100% of patients were made endotracheal extubation soon after surgery in the operating room, 8/30 patients (26.67%) had hypersalivation which was limited by suction, only one patient suffered from nausea but did not vomit REFERENCES Nguyễn Thụ Triệu chứng gây mê theo dõi độ mê Gây mê hồi sức Trường Đại học Y Hà Nội 2014, tr.163-175 Nguyễn Văn Chừng, Nguyễn Thu Chung Đánh giá tác dụng propofol gây mê phẫu thuật nội soi cắt túi mật Tạp chí Y học TP Hồ Chí Minh 2005, tập 9, tr.76-82 Jan P Mulier Perioperative opioids aggravate obstructive breathing in sleep apnea syndrome: Mechanisms and alternative anesthesia strategies Current Opinion in Anesthesiology 2016, 29 (1), pp.129-133 Journal of military pharmaco-medicine no8-2019 Gary M Oderda et al Cost of opioidrelated adverse drug events in surgical patients Journal of Pain and Symptom Management 2003, 25 (3), pp.276-283 Yuan-Yi Chia et al Intraoperative high dose fentanyl induces postoperative fentanyl tolerance Canadian Journal of Anesthesia 1999, 46 (9), pp.872 Jan Paul Mulier New anesthesia concepts opioid free anesthesia, we need it? https://www.researchgate.net/publication/2844 04080_New_concepts_in_anesthesia_Do_we _need_opioid_free_anesthesia_Basel_lecture 2015 P Ziemann-Gimmel et al Opioid-free total intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple prophylaxis British Journal of Anaesthesia 2014, 112 (5), pp.906-911 J Mulier Opioid free general anesthesia: A paradigm shift? 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Javier Opioid - free anesthesia (OFA) for thought, https://fr.scribd.com/ document/381448498 /Opioid -Free- Anesthesia- Ja 13 Mohamed Ahmed Mansour, Ahmed Abdelaal Ahmed Mahmoud, Mohammed Geddawy Non -opioid. .. Journal of Anesthesiology (English edition) 2015, 65 (3), pp.191-199 J Mulier, B Dillemans, P Van Lancker Opioid free (OFA) versus opioid (OA) and low opioid anesthesia (LOA) for the laparoscopic. .. Paul Mulier New anesthesia concepts opioid free anesthesia, we need it? https://www.researchgate.net/publication/2844 04080_New_concepts_in _anesthesia_ Do_we _need _opioid _free_ anesthesia_ Basel_lecture