Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery

Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids. However, because opioids have numerous side effects, coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose. In this prospective, randomized, double-blinded study, we evaluated the efficacy of propacetamol, an IV administered prodrug of acetaminophen (paracetamol), as an adjunctive analgesic after cardiac surgery. Seventy-nine patients scheduled for elective coronary artery bypass grafting were randomized to receive either propacetamol 2 g (n = 40) or placebo (n = 39) IV in 6-h intervals for 72 h. From the time of extubation, patients had access to an opioid (oxycodone) via a patient-controlled analgesia device. Pain was evaluated on a visual analog scale four times daily, whereas respiratory function tests (forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and arterial blood gas measurements) were performed once a day. The prespecified primary efficacy variable (cumulative oxycodone consumption at the end of the 72-h postoperative period) was 123.5 mg (51.3 mg) (mean [SD]) in the propacetamol group and 141.8 mg (57.5 mg) in the placebo group (difference in mean, 18.3 mg = 13%; 95% confidence interval, 6.1-42.7 mg; P = 0.15). Pain scores did not differ between the groups at rest (P = 0.65) or during a deep breath (P = 0.72). The groups were also similar in terms of pulmonary function tests, postoperative bleeding, and hepatic function tests, and no significant differences were noted in the incidences of adverse effects. After completion of the study, apost hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals. This analysis showed a significantly (P = 0.036) smaller consumption of oxycodone in the propacetamol group at 24 h (47.1 mg [20.7 mg] versus 57.9 mg [23.9 mg]; difference in mean, 10.8 mg; 95% confidence interval, 0.7-20.9 mg). In conclusion, propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients, nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery. However, post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group. IMPLICATIONS: This is the first placebo-controlled study to investigate the efficacy of propacetamol as a complementary analgesic to opioids after cardiac surgery. Propacetamol did not enhance analgesia, nor did it decrease cumulative opioid consumption or reduce adverse effects in a dose of 2 g given every sixth hour for 3 days after surgery.     

Reduction of pain following laparoscopic surgery: a double blind prospective randomised controlled trial

The following abstracts won prizes at the 153rd East Midlands Surgical Society meeting held on 9 November 2012 at Leicester General Hospital. First prize was won by George et al. The paper by Ogunbiyi et al was placed second and the paper by Khanna et al was placed third.     

Parasternal intercostal block with ropivacaine for pain management after cardiac surgery: a double-blind, randomized, controlled trial

OBJECTIVE: The purpose of this study was to test the hypothesis that administration of a parasternal intercostal block using ropivacaine 0.75% improved analgesia in postoperative cardiac surgical patients. DESIGN: Randomized, controlled, double-blinded trial. SETTING: Teaching hospital. PARTICIPANTS: Eighty-eight cardiac surgery patients. INTERVENTIONS: Ropivacaine 0.75% with 5 doses each side, total dosage 40 mL (300 mg), via parasternal intercostal injection or saline before insertion of the sternal wires and closure of the sternal wound. MEASUREMENTS AND MAIN RESULTS: At extubation, patients who had a parasternal intercostal block with ropivacaine had visual analog and numerical rating pain scores approximately 50% less than those in the saline group (29.5 [standard deviation (SD) = 24.3] v 53.2 [SD = 24.1], ropivacaine v saline, respectively, p < 0.001). Patients who received ropivacaine used approximately 50% less PCA morphine (12.0 [SD = 5.4] v 23.2 [SD = 8.3] total morphine equivalents in milligrams, ropivacaine v saline, respectively; p < 0.001) in the first 12 hours postoperatively, with a continued reduction in dosages for the ensuing 12 to 24 hours (18.8 [SD = 9.6] v 23.7 [SD = 10.0] total morphine equivalents in milligrams, ropivacaine v saline; p = 0.028). CONCLUSIONS: A ropivacaine parasternal intercostal block is a safe, simple, and effective adjunct for optimizing of pain control and reducing opioid analgesics after adult cardiac surgery. This study provides clinicians with an effective treatment for sternal wound pain.     

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.     

A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery

Purpose  

We hypothesized that patients who received ketamine during thoracic surgery would benefit from suppression of the inflammatory cascade, represented by lower interleukin (IL)-6 and C-reactive protein (CRP) plasma levels.     

Cerebral oximetry and postoperative delirium after cardiac surgery: a randomised,controlled trial

Postoperative delirium is associated with increased morbidity and mortality. We hypothesised that restoration of regional cerebral oxygen desaturation would reduce the incidence of postoperative delirium in elderly patients after cardiac surgery. After institutional ethics review board approval and informed consent, a double‐blinded, prospective, randomised, controlled trial was conducted in patients ≥ 60 years of age undergoing cardiac surgery with cardiopulmonary bypass. In the intervention group, an algorithm was commenced if regional cerebral oxygen saturation decreased below 75% of baseline value for 1 min or longer. In the control group, the cerebral oximetry monitor screen was electronically blinded. Assessment of delirium was performed with confusion assessment method for intensive care unit or confusion assessment method after discharge from intensive care unit at 12‐h intervals for seven postoperative days. Postoperative delirium was present in 30 out of 123 (24.4%) and 31 out of 126 (24.6%) patients in the intervention and control groups, respectively, odds ratio 0.98 (95%CI 0.55–1.76), p = 0.97. Postoperative delirium was present in 20 (71%) out of 28 and in 41 (18%) out of 221 patients with baseline regional cerebral oxygen saturation ≤ 50, or > 50%, respectively, p = 0.0001. Higher baseline regional cerebral oxygen saturation and body mass index were protective against postoperative delirium. Restoration of regional cerebral oxygen desaturation did not result in lower postoperative delirium after cardiac surgery. Pre‐operative regional cerebral oxygen saturation ≤ 50% was associated with increased postoperative delirium rates in elderly patients following cardiac surgery.     

Preemptive analgesia for postoperative pain relief in lumbosacral spine surgeries: a randomized controlled trial.

BACKGROUND CONTEXT: Administration of analgesic medication, before the actual onset of painful stimulus, is more effective than that after the onset of painful stimulus. This is the principle of preemptive analgesia. Although it is often considered superior to other forms of analgesia, its role in postoperative pain relief after lumbosacral spinal surgery has not been fully investigated. PURPOSE: To analyze the efficacy of preemptive analgesia with a single caudal epidural injection for patients undergoing surgeries on the lumbosacral spine by the posterior approach. STUDY DESIGN/SETTING: Randomized, double-blinded and controlled clinical trial. PATIENT SAMPLE: Eighty-two patients who underwent discectomy in the lumbosacral spine by the posterior approach, with or without instrumentation, were randomized to the control group (n=40) and to the study group (n=42). METHODS: Patients in control group received a single caudal epidural injection of 20 ml of normal saline. Patients in study group received a single caudal epidural injection of 20 ml containing bupivacaine and tramadol as the active agents. The time interval between this injection and the surgical incision was never less than 20 minutes in either of the groups. This facilitated enough time for the drug to get fixed to the nerve roots, leading to effective preemptive analgesia. OUTCOME MEASURES: Patients were monitored for postoperative pain immediately after surgery when they had completely recovered and regained consciousness from general anesthesia, and subsequently 4, 8, 12 and 24 hours thereafter. Pain was quantified using the visual analog scale (VAS) and the verbal rating scale (VRS). The time at which supplemental analgesic medication was first demanded in the postoperative period by the patient was also noted. RESULTS: The two groups were comparable for age, sex, body weight and the type of surgery they underwent. Because the data did not have a normal Gaussian distribution, the one-tailed Mann-Whitney test, being a nonparametric test, was adopted for statistical analysis. Accordingly, VAS and VRS values at all time intervals were significantly lower (p<.0001) in the study group as compared with the control group. This indicated significantly better pain relief in the study group. There was also a significant delay (p=.0041) in the first demand for supplemental analgesic medication in the postoperative period in the study group. No complication specific to the procedure was noted except for the development of postoperative urinary retention, which was transient and appropriately managed with urinary catheterization. CONCLUSIONS: Preemptive analgesia with a single caudal epidural injection of bupivacaine and tramadol is a safe, simple and effective method for postoperative pain relief.     

Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial

ObjectiveTo determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery.MethodsAdult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed.ResultsSixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P = .84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P < .0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P = .033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P = .046).ConclusionsCommencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials.     

Remifentanil compared with morphine for postoperative patient-controlled analgesia after major abdominal surgery: a randomized controlled trial

BACKGROUND AND OBJECTIVE: This randomized, double-blinded clinical study was designed to compare the efficacy and safety of remifentanil and morphine administered using intravenous (i.v.) patient-controlled analgesia (PCA) for postoperative analgesia after major abdominal surgery during the first 24 postoperative hours. METHODS: Sixty-nine patients were randomly allocated into two groups, each receiving remifentanil or morphine. The first group received i.v. remifentanil PCA with a loading dose of 45 microg, a maintenance dose of 1 microg min(-1), a bolus dose of 15 microg and a lockout interval of 10 min during the first 24 postoperative hours. The second group received i.v. morphine PCA with a loading dose of 5 mg, a maintenance dose of 0.3 mg h(-1), a bolus dose of 1 mg and a lockout interval of 15 min. Age, weight, sex, history of general anaesthesia, duration of surgery and time spent in the post-anaesthesia care unit were recorded. Preoperative pulse rate, systolic and diastolic blood pressures (BP), respiration rate and arterial blood gases were collected. Pulmonary function was tested before induction of anaesthesia, as well as at 4 and 26 h after operation. Pulse rate, systolic and diastolic BP, respiration rate, arterial blood gases, sedation and visual analogue scores, and presence of side-effects in the recovery room and on the ward for 24 h were recorded at 0, 1, 2, 4, 6, 12, 18 and 24 h after operation. Total drug use, number of boluses delivered, number of boluses demanded and delivery/demand ratio were collected. RESULTS: Sixty patients were evaluated. The groups did not differ in age, weight, sex, history of general anaesthesia, duration of surgery or time spent in the recovery unit. There were also no clinically relevant differences between the groups with regard to haemodynamic and respiratory parameters as well as sedation and visual analogue scores (P > 0.05). More bolus doses were demanded and delivered and the delivery/demand ratio was significantly higher in the remifentanil group (P < 0.05). There was no finding suggesting acute opioid tolerance during remifentanil or morphine PCA. CONCLUSION: The i.v. remifentanil PCA with the chosen dosage regimen after abdominal surgery produces postoperative analgesia and has cardiovascular side-effects similar to those achieved with i.v. morphine. Special attention must be given to respiratory depression during establishment of PCA with remifentanil.     

Pain and nausea after bariatric surgery with total intravenous anesthesia versus desflurane anesthesia: a double blind,randomized, controlled trial

BackgroundThere is limited evidence-based knowledge regarding optimal anesthesia in obese patients.ObjectiveTo evaluate optimal anesthetic approach for patients undergoing bariatric surgery by determining and comparing peri- and postoperative outcomes in patients receiving intravenous anesthesia with propofol versus desflurane anesthesia.SettingNonacademic primary referral center.MethodsPatients who underwent laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass between 2016 and 2017 were randomized into 1 of the following 2 types of anesthesia: intravenous anesthesia with propofol, or desflurane. Perioperative outcomes were registered by the operation staff. A form based on visual analog scale estimating the patient’s intensity of pain and nausea was completed postoperatively at the postoperative unit, surgical ward, and 24 to 48 hours postsurgery. The primary outcome was postoperative nausea and vomiting or postoperative pain between treatment groups. The secondary outcome was to evaluate the “time of awakening,” peritoneal stretch, and use of perioperative muscle relaxants.ResultsOne hundred eighty-three patients were randomized to receive intravenous anesthesia (n = 90) or desflurane anesthesia (n = 93). Mean time ± standard deviation of surgery for both procedures was 41 ± 17 minutes, whereas mean time of awakening was 2 ± 2 minutes for both the intravenous anesthesia and desflurane group. There was no significant difference in visual analog scale for pain or for nausea and vomiting postoperatively, nor in the number of patients receiving muscle relaxants for peritoneal stretch between the 2 groups.ConclusionsWe found no significant differences between the 2 anesthetic regimens regarding postoperative nausea and pain, awakening time, peritoneal stretch, or the use of perioperative muscle relaxants.     

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial

Background: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy.
Methods: One hundred and sixteen patients were randomly assigned to either group A (paracetamol+placebo × 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg × 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation, dizziness, number of vomits and consumption of ondansetron were recorded 2, 4 and 24 h after the operation. P <0.05 was considered statistically significant.
Results: The 24-h morphine consumption and pain score, both at rest and during mobilization, were not significantly different between treatment groups. The mean nausea score ( P =0.002) was reduced in group C vs. A. The number of vomits was significantly reduced in both group B ( P =0.041) and C ( P =0.001) vs. A. Consumption of ondansetron was reduced in group C vs. A and B ( P <0.001). Other side effects were not different between groups.
Conclusion: Combinations of paracetamol and pregabalin, or paracetamol, pregabalin and dexamethasone did not reduce morphine consumption and pain score compared with paracetamol alone for patients undergoing abdominal hysterectomy. Dexamethasone reduced nausea, vomiting and use of ondansetron.     

Pulmonary recruitment maneuver reduces pain after laparoscopic bariatric surgery: a randomized controlled clinical trial

Background

Pulmonary recruitment maneuver (PRM) at the end of laparoscopic gynecologic surgery has been shown to reduce postoperative pain. This prospective, randomized, controlled clinical trial aimed to investigate postoperative pain (primary endpoint) and nausea when performing a ventilator-piloted PRM at the end of laparoscopic bariatric surgery.