The impact of prophylactic intravenous lidocaine on opioid-induced cough: a meta-analysis of randomized controlled trials

Background

Opioids are commonly used for general anesthesia, but reflex cough can occur after an intravenous injection. We have performed a meta-analysis of randomized controlled trials (RCTs) that evaluated the effectiveness and safety of prophylactic lidocaine administered intravenously (IV) on opioid-induced cough (OIC) during induction in patients undergoing general anesthesia.

Methods

We searched three bibliographic databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) to identify studies meeting a priori inclusion criteria and also conducted a secondary reference review. The information used to calculate the relationship between lidocaine prophylaxis and the risk and severity of OIC was extracted by two principal investigators, respectively.

Results

Six RCTs with a total of 1,740 participants were included in this meta-analysis. Overall, prophylactic lidocaine administered IV reduced both the risk of OIC [pooled risk ratio (RR) 0.471; 95 % confidence interval (CI) 0.355–0.625; P = 0.074; heterogeneity test, I ² = 50.3 %] and its severity (weighed mean difference ?0.316; 95 % CI ?0.480 to ?0.151; P = 0.038; heterogeneity test, I ² = 60.5 %). Sub-group analysis indicated a significant reduction in the incidence of both fentanyl-induced cough (FIC) and remifentanil-induced cough (RIC), but it appeared that lidocaine only alleviated the severity of FIC. Further sub-group analysis indicated that the lowest effect dose of lidocaine for preventing the prevalence of OIC was 0.5 mg/kg. No severe adverse effects were reported.

Conclusions

Our meta-analysis establishes the effectiveness of prophylactic lidocaine administered IV for the prevention of OIC during induction. The lowest effective dose of lidocaine on the risk of OIC appeared to be 0.5 mg/kg.     

Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial

BACKGROUND: Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains. METHODS: The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects' self-reported pain relief and satisfaction were assessed at the end of each infusion. RESULTS: Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01) when compared with placebo (9.6 +/- 21.0). CONCLUSIONS: Stump pain was diminished both by morphine and lidocaine, while phantom pain was diminished only by morphine, suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different.     

Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial

BACKGROUND: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine. METHODS: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing. RESULTS: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction > or = 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick. CONCLUSIONS: Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain. Results are consistent with a central-acting effect of sodium channel blockers acting on neuronal hyperexcitability. Agents (such as anticonvulsants or antiarrhythmics) with sodium channel-blocking properties may be a treatment option for spinal cord injury pain.     

Analgesic effects of a 5% lidocaine patch after cesarean section: A randomized placebo-controlled double-blind clinical trial

Study objectiveThis study aimed to evaluate the analgesic effects of a 5% lidocaine patch in acute postoperative pain after cesarean section.DesignThis is a prospective, randomized, double-blind study.SettingAfter surgery, active and placebo patches were applied in the operating room, and patients were evaluated during their stay at the postoperative recovery room and at the hospital ward.PatientsSeventy-two women (18 years of age or older and American Society of Anesthesiologists status II) scheduled for cesarean section under spinal anesthesia were enrolled in the study.InterventionsPatients were randomly assigned to an intervention or placebo group. According to the assigned group, a 5% lidocaine patch or a placebo patch was applied 1 cm above and below the Pfannenstiel incision after the surgery.MeasurementsThe primary outcome was the pain score, evaluated using an 11-point numerical verbal scale in the first 36 h postoperatively. Secondary outcomes were the quality of recovery 24 h after surgery, consumption of rescue opioids, and the presence of adverse effects.Main resultsSixty-five women completed the study. The pain score was lower in the lidocaine group at 6 h (lidocaine group: 2.16 ± 1.71, placebo group: 3.21 ± 2.25; p = 0.031), 12 h (lidocaine: 1.58 ± 0.81, placebo: 2.24 ± 0.74; p = 0.001), 24 h (lidocaine: 0.74 ± 0.89, placebo: 1.94 ± 1.39; p < 0.0001), and 36 h (lidocaine: 0.48 ± 1.03, placebo: 1.68 ± 0.94; p = 0.001) after surgery. There were no differences in secondary outcomes during the follow-up period.ConclusionThe lidocaine patch reduced pain scores compared to placebo in the first 36 h after the surgery, despite no influence over opioid consumption, quality of recovery, or incidence of side effects.     

Effect of labetalol or lidocaine on the hemodynamic response to intubation: a controlled randomized double-blind study

Labetalol, a combined alpha 1- and nonselective beta-adrenergic blocking drug, was compared to lidocaine or saline to minimize the hypertensive and tachycardic response to intubation in a controlled randomized double-blind study in patients undergoing surgical procedures under general anesthesia. Forty adult patients were divided into four groups of 10 each: placebo (saline), lidocaine 100 mg, labetalol 5 mg, or labetalol 10 mg. The double-blind preparation was administered as an IV bolus just prior to induction and 2 min before the stimulus of laryngoscopy and intubation. Heart rate and blood pressure were measured at 1-min intervals for 2 min prior to induction of anesthesia and through 6 min following induction of anesthesia. Labetalol 10 mg prevented a rise in heart rate after intubation compared to patients who received placebo, lidocaine 100 mg, or labetalol 5 mg. The hypertensive response to intubation was similar in all four groups. Labetalol 10 mg IV just prior to induction of anesthesia is a safe and cost-effective means of preventing tachycardia but not hypertension in response to laryngoscopy and intubation.     

Intrapleural bupivacaine analgesia in chest trauma: a randomized double-blind controlled trial

A randomized double-blind study was undertaken to investigate whether 0.25 per cent bupivacaine administered intrapleurally is an effective and reasonably safe method of obtaining analgesia in patients with thoracic injuries. A total of 120 patients complaining of pain after chest injury were entered into the trial. All had thoracostomy tubes already in situ. Of 60 patients who were given the test dose of bupivacaine intrapleurally, 37 obtained satisfactory pain relief for 2 or more hours compared with only 9 of 60 patients who received saline P less than 0.000001). Duration of analgesia in the test group (mean 3.9 h) was significantly longer than that in the control group (mean 0.9 h) P less than 0.005). There were no important side-effects attributable to the bupivacaine administered. We conclude that intrapleural bupivacaine is an effective and reasonably safe method for obtaining analgesia in patients who have chest drain tubes inserted.     

The effects of intracuff lidocaine on endotracheal-tube-induced emergence phenomena after general anesthesia

Coughing during emergence from general anesthesia is a common clinical problem. We sought to determine whether inflating the endotracheal tube cuff with lidocaine would create a reservoir of local anesthetic, which might diffuse across the cuff membrane to anesthetize the mucosa, thus attenuating stimulation during extubation of the trachea. A total of 63 patients undergoing elective surgery were enrolled in a prospective, randomized, double-blinded study. After intubation of the trachea with an endotracheal tube, the cuff of the tube was inflated with either lidocaine 4%, saline, or air. After extubation, a blinded observer noted heart rate, blood pressure, oxygen saturation, end-tidal isoflurane concentration, and the incidence of coughing. Data were analyzed by using analysis of variance, Student's t-test, and the chi(2) test for multiple variables. The groups were demographically comparable. There was no difference in hemodynamic or oxygen saturation data between either group. The incidence of coughing was decreased in the lidocaine group for the time period of 4-8 min postextubation (P < 0.05). We conclude that inflation of the cuff of the endotracheal tube can reduce the incidence of coughing in the initial postextubation period, a finding that may benefit certain patient groups in which this is particularly desirable. IMPLICATIONS: Tracheal intubation with an endotracheal tube is often necessary during anesthesia. After intubation, inflating a cuff around the endotracheal tube maintains a seal. This can result in coughing during emergence from anesthesia. Our study shows that inflating the cuff of an endotracheal tube with lidocaine rather than air can reduce the incidence of postextubation coughing.     

Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery: a randomized, double-blind, controlled trial

BACKGROUND: Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study. METHODS: In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 microg/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil. RESULTS: The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, -17 to 31] mmHg) compared with the control group (42 [6-73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23-45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23). CONCLUSIONS: A single bolus of 1 microg/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.     

Effects of preemptive analgesia in laparoscopic cholecystectomy: a double-blind randomized controlled trial

Background  

This study aimed to investigate the effect of preemptive etoricoxib compared with placebo in laparoscopic cholecystectomy.     

Effect of tramadol on fentanyl induced cough: A double-blind,randomized, controlled study

BackgroundTramadol has NMDA antagonist effect and reported to have antitussive effect. The aim of this study to assess the effect of preoperative i.v. tramadol compared to placebo on the incidence and severity of fentanyl induced cough.MethodIn a prospective, randomized, double-blind study, 100 patients ASA I, age 18–50 years old, scheduled for elective laparoscopic surgeries under general anesthesia. Patients were randomly allocated to one of two groups: Tramadol group received i.v. tramadol 1 mg/kg in 100 ml saline and control group received 100 ml saline over 15 min before induction of anesthesia. The incidence and severity of cough was assessed following injection of fentanyl 2 μg/kg. The postoperative analgesic requirements, nausea, and vomiting were also recorded.ResultsThe incidence of FIC was significantly less in tramadol treated group being [10 (20%)], compared to control group being [19 (38%)] (p < 0.05). Regarding the grade of FIC; 7 out of 10 in tramadol group and 12 out of 19 in control group showed mild form, 3 out of 10 in tramadol group and 4 out of 19 in control group showed moderate form and 3 out of 19 in control group with no patients in tramadol group showed severe form. The postoperative analgesic requirements was significantly less in tramadol group (p < 0.05) with no significant difference in postoperative nausea and vomiting between the two groups.ConclusionTramadol 1 mg/kg i.v. infusion 15 min before induction of anesthesia reduced the incidence and severity of cough after fentanyl injection 2 μg/kg with reduction of postoperative analgesic requirements and without changes in postoperative nausea and vomiting compared to placebo.     

Effect of narcotic pretreatment on pain after rocuronium injection: a randomized,double-blind controlled comparison with lidocaine

Various strategies have been studied to reduce the discomfort of rocuronium pain. These studies have shown fentanyl and lidocaine to be effective in reducing the incidence of pain on rocuronium injection. This prospective, randomized, and double-blind study was carried out on 80 neurosurgical patients for whom pain on rocuronium injection was assessed after pretreatment with lidocaine, fentanyl, sufentanil, or normal saline. The 80 neurosurgical patients were randomly allocated to anyone of the groups to receive lidocaine, fentanyl, sufentanil, or normal saline prior to being given rocuronium. The patients were asked about any discomfort in the hand, and also to rank that discomfort on a 5-point scale. In the normal saline group, the incidence of pain was 95%, of which 90% had very severe pain. In the lidocaine group, only 10% of patients reported pain, which was mild in nature. In the fentanyl group, 95% of patients had pain, of whom 25% had severe to very severe pain. In the sufentanil group, 85% of patients reported pain, of whom 25% fell into the severe to very severe group. We found that lidocaine was best at decreasing the incidence of pain on intravenous (i.v.) injection of rocuronium. Although the incidence of pain on injection of rocuronium with both fentanyl and sufentanil was high, the intensity was definitely reduced, with most patients falling in the mild pain group.     

Effect of intravenous lidocaine on ischemia-reperfusion injury in DIEP microsurgical breast reconstruction. A prospective double-blind randomized controlled clinical trial

BackgroundIschemia-reperfusion injury in free flaps is associated with tissue damage and is one of the main factors causing flap failure in reconstructive microsurgery. The aim of this study is to assess whether any ischemia-reperfusion injury takes place during a microsurgical flap reconstruction as seen through the levels of malondialdehyde (MDA) and superoxide dismutase, biomarkers of oxidative stress, and to analyze the effect of lidocaine in this process.MethodsTwenty-four patients operated for immediate breast reconstruction using the Deep Inferior Epigastric Perforator free flap technique were divided into two groups: one group was treated with a lidocaine intravenous perfusion and the other group with a saline perfusion. MDA and superoxide dismutase (SOD) levels were measured at several points before, during, and after surgery.ResultsThere was an increase in MDA levels in both groups, but the lidocaine group experienced a decrease during reperfusion. On the other hand, we observed a rise in SOD levels in both groups, but a decrease during reperfusion in the placebo group. However, these differences between groups were not statistically significant.ConclusionsThe decreased SOD activity and increased MDA content in our research prove a redox imbalance and high reactive oxygen species levels in flaps, indicating that tissues experience ischemia-reperfusion injury during microsurgical reconstruction. Lidocaine may have a protective effect in free flap surgery, but our results were not statistically significant, so further studies will be required.     

Prophylactic ilioinguinal neurectomy in open inguinal hernia repair: a double-blind randomized controlled trial

OBJECTIVE: We conducted a double-blinded randomized controlled trial to investigate the short- to mid-term neurosensory effect of prophylactic ilioinguinal neurectomy during Lichtenstein repair of inguinal hernia. METHOD: One hundred male patients between the age of 18 and 80 years with unilateral inguinal hernia undergoing Lichtenstein hernia repair were randomized to receive either prophylactic ilioinguinal neurectomy (group A) or ilioinguinal nerve preservation (group B) during operation. All operations were performed by surgeons specialized in hernia repair under local anesthesia or general anesthesia. The primary outcome was the incidence of chronic groin pain at 6 months. Secondary outcomes included incidence of groin numbness, postoperative sensory loss or change at the groin region, and quality of life measurement assessed by SF-36 questionnaire at 6 months. All follow-up and outcome measures were carried out by a designated occupational therapist at 1 and 6 months following surgery in a double-blinded manner. RESULTS: The incidence of chronic groin pain at 6 months was significantly lower in group A than group B (8% vs. 28.6%; P = 0.008). No significant intergroup differences were found regarding the incidence of groin numbness, postoperative sensory loss or changes at the groin region, and quality of life measurement at 6 months after the operation. CONCLUSIONS: Prophylactic ilioinguinal neurectomy significantly decreases the incidence of chronic groin pain after Lichtenstein hernia repair without added morbidities. It should be considered as a routine surgical step during the operation.     

Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used after coronary artery bypass surgery (CABG), yet their effects have seldom been evaluated in randomized controlled settings. The aim of this study was to examine the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that naproxen would reduce postoperative pain following CABG without increasing complications. METHODS: Patients (N=98) undergoing primary CABG were randomized to receive naproxen (500 mg q12hX5 doses via suppository started 1h after operation, followed by oral 250 mg q8hX6 doses) or placebo. Standard analgesic and anti-emetic regimens were available to both patient groups. Interventions were double-blinded. Primary end-points were postoperative pain measured before and after chest physiotherapy by visual analog scale and pulmonary slow vital capacity (SVC). RESULTS: Baseline characteristics were equivalent between the two groups. Over the first 4 postoperative days, naproxen decreased pain by 47+/-17% on average before chest physiotherapy (P=0.034), and 44+/-13% after chest physiotherapy (P=0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who received naproxen had more chest tube drainage after 4h postoperatively, but there was no difference in the incidence or amount of transfusions. There was no difference in medication use, length of stay, or in the incidence of atrial fibrillation, azotemia, and other complications. CONCLUSIONS: Naproxen is an effective and low-cost adjunct for optimization of pain control and lung recovery after CABG. Its use may result in increased chest tube drainage, but no apparent increase in other complications.