The analgesic effect of total intravenous anaesthesia with propofol versus inhalational anaesthesia for acute postoperative pain after hepatectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain control can be challenging in patients undergoing hepatectomy. A previous retrospective study on hepatobiliary/ pancreatic surgeries showed better postoperative pain control in patients who received propofol TIVA. The aim of this study was to determine the analgesic effect of propofol TIVA for hepatectomy. This clinical study has been registered at ClinicalTrials.gov (NCT03597997). METHODS: A prospective randomized controlled trial was performed to compare the analgesic effect of propofol TIVA versus inhalational anaesthesia. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy were recruited. Ninety patients were randomly allocated to receive either propofol TIVA (TIVA group) or inhalational anaesthesia with sevoflurane (SEVO group). Perioperative anaesthetic/analgesic management was the same for both groups. Numerical rating scale (NRS) pain scores, postoperative morphine consumption, quality of recovery, patient satisfaction and adverse effects were evaluated during the acute postoperative period and at 3 and 6 months after surgery. RESULTS: No significant differences were found for acute postoperative pain scores (both at rest and during coughing) and postoperative morphine consumption between TIVA and SEVO groups. Patients given TIVA had lower pain scores with coughing at 3 months after surgery (p = 0.014, and FDR < 0.1). TIVA group was associated with better quality of recovery on postoperative day (POD) 3 (p = 0.038, and FDR < 0.1), less nausea (p = 0.011, and FDR < 0.1 on POD 2; p = 0.013, and FDR < 0.1 on POD 3) and constipation (p = 0.013, and FDR < 0.1 on POD 3). CONCLUSION: Propofol TIVA did not improve acute postoperative pain control compared to inhalational anaesthesia in patients who underwent hepatectomy. Our results do not support the use of propofol TIVA for reducing acute postoperative pain after hepatectomy.

Adiponectin regulates thermal nociception in a mouse model of neuropathic pain.

BACKGROUND: Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising adiponectin knockout (KO) mice. METHODS: Wild type (WT) and adiponectin KO mice were subjected to partial sciatic nerve ligation (pSNL) or sham operation. Pain-like behavioural tests, including thermal allodynia, hyperalgesia, and mechanical allodynia, were performed before and after pSNL from Day 3-21. Dorsal root ganglions (DRGs), lumbar spinal segments at L3-5, and somatosensory cortex were collected for protein measurement via western blotting and immunofluorescence staining. RESULTS: Compared with WT mice, KO mice had significantly lower (40-50%) paw withdrawal latency to innocuous and noxious stimuli before and after pSNL. In DRG neurones from KO mice, where adiponectin receptor (AdipoR) 2 is located, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and heat-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) were significantly higher (by two- to three-fold) than from WT mice. In spinal microglia and somatosensory cortical neurones, where AdipoR1 is mainly located, p-p38 MAPK and TRPV1 were also higher (by two- to three-fold) in KO compared with WT mice, and altered signalling of these molecules was exacerbated (1.2- to 1.3-fold) by pSNL. CONCLUSIONS: Our results show that adiponectin regulates thermal nociceptive sensitivity by inhibiting activation of DRG neurones, spinal microglia, and somatosensory cortical neurones in physiological and neuropathic pain states. This study has relevance for patients with adiponectin disorders, such as obesity and diabetes.

Spinal cord stimulation for chronic non-cancer pain: a review of current evidence and practice.

Spinal cord stimulation provides analgesia through electrical stimulation of the dorsal column of the spinal cord via electrode leads placed into the epidural space. In traditional tonic stimulation, a painful sensation is replaced with paraesthesia. Spinal cord stimulation is effective in reducing neuropathic pain, enhancing function, and improving quality of life in different chronic pain conditions. Currently, there is most evidence to support its use for failed back surgery syndrome when multidisciplinary conventional management is unsuccessful. Temporary trial leads are inserted in carefully selected patients to test their responsiveness prior to permanent implantation. Newer neuromodulation modalities are now available. These include burst stimulation, high-frequency stimulation, and dorsal root ganglion stimulation. Results are encouraging to date, and they may provide superior analgesia and cover for deficiencies of traditional tonic stimulation. Although complications are not uncommon, they are rarely life threatening or permanently disabling. Nonetheless, device removal is occasionally needed.

Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

Effects of intra-operative maintenance of general anaesthesia with propofol on postoperative pain outcomes - a systematic review and meta-analysis.

Propofol is used both for induction and maintenance of anaesthesia. Recent evidence shows that propofol has analgesic properties. This meta-analysis evaluated differences in postoperative analgesia between general anaesthetic maintenance with intravenous propofol and inhalational anaesthetics. Fourteen trials met inclusion criteria and were included. Our outcomes were pain scores 2 and 24 h after surgery. No significant difference in pain scores was found at 2 h after surgery (Hedge's g (95% CI) -0.120 (-0.415-0.175) (p = 0.425). Propofol was associated with a statistically significant, albeit marginal, reduction in pain scores 24 h after surgery (Hedge's g (95% CI) -0.134 (-0.248 to -0.021) (p = 0.021). Data were insufficient to allow a meaningful analysis regarding 24-h morphine-equivalent consumption. Propofol was associated with reduced postoperative nausea and vomiting (relative risk (95%CI) 0.446 (0.304-0.656) (p < 0.0001). In conclusion, this meta-analysis suggests that propofol improves postoperative analgesia compared with inhalational anaesthesia 24 h after surgery, with a lower incidence of nausea and vomiting.

Predictive factors and clinical biomarkers for treatment in patients with chronic pain caused by osteoarthritis with a central sensitisation component.

AIMS: The aim of this non-systematic review was to provide a practical guide for clinicians on the evidence for central sensitisation in chronic osteoarthritis (OA) pain and how this pain mechanism can be addressed in terms of clinical diagnosis, investigation and treatment. METHODS: The authors undertook a non-systematic review of the literature including a MEDLINE search (search terms included central sensitisation, osteoarthritis, osteoarthrosis) for relevant and current clinical studies, systematic reviews and narrative reviews. Case reports, letters to the editor and similar literature sources were excluded. Information was organised to allow a pragmatic approach to the discussion of the evidence and generation of practical recommendations. RESULTS: There is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients. Clinically, a central sensitisation component in chronic OA pain can be suspected based on characteristic pain features and non-pain features seen in other conditions involving central sensitisation. However, there are currently no diagnostic inventories for central sensitisation specific to OA. Biomarkers may be helpful for confirming the presence of central sensitisation, especially when there is diagnostic uncertainty. Several non-pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features. Multimodal therapy may be required to achieve control of symptoms. DISCUSSION: Clinicians should be aware of central sensitisation in patients with chronic OA pain, especially in patients presenting with severe pain with unusual features.

Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong.

Opioids are increasingly used to control chronic non-cancer pain globally. International opioid guidelines have been issued in many different countries but a similar document is not generally available in Hong Kong. Chronic opioid therapy has a role in multidisciplinary management of chronic non-cancer pain despite insufficient evidence for its effectiveness and safety for long-term use. This document reviews the current literature to inform Hong Kong practitioners about the rational use of chronic opioid therapy in chronic non-cancer pain. It also aims to provide useful recommendations for the appropriate, effective, and safe use of such therapy in the management of chronic non-cancer pain in adults. Physicians should conduct a comprehensive biopsychosocial evaluation of patients prior to the commencement of opioid therapy. When opioid use is deemed appropriate, the patient should provide informed consent within an agreement that specifies treatment goals and expectations. A trial of opioid can be commenced and, provided there is progress towards treatment goals, then chronic therapy can be considered at a dose that minimises harm. Monitoring of effectiveness, safety, and drug misuse should be continued. Treatment should be stopped when opioids become ineffective, intolerable, or misused. The driving principles for opioid prescription in chronic pain management should be: start with a low dose, titrate slowly, and maintain within the shortest possible time.

Intranasal dexmedetomidine in combination with patient-controlled sedation during upper gastrointestinal endoscopy: a randomised trial.

BACKGROUND: Sedation using intranasal dexmedetomidine is a convenient and well-tolerated technique. This study evaluated the sedative efficacy of intranasal dexmedetomidine in combination with patient-controlled sedation (PCS) for upper gastrointestinal endoscopy. METHODS: In this double-blind, randomised, controlled trial, 50 patients received either intranasal dexmedetomidine 1.5 µg/kg (dexmedetomidine group) or intranasal saline (placebo group) 1 h before the procedure. PCS with propofol and alfentanil was provided for rescue sedation. Additional sedative consumption, perioperative sedation scores using Observer's Assessment of Alertness/Sedation (OAA/S) scale, recovery, vital signs, adverse events and patient satisfaction were assessed. RESULTS: Total consumption of PCS propofol and alfentanil was significantly less in the dexmedetomidine than placebo group with a mean difference of -13.8 mg propofol (95% confidence interval -27.3 to -0.3) and -34.5 µg alfentanil (95% confidence interval -68.2 to -0.7) at the completion of the procedure (P = 0.044). Weighted areas under the curve (AUCw ) of OAA/S scores were significantly lower in the dexmedetomidine group before, during and after procedures (P < 0.001, P = 0.024 and P = 0.041 respectively). AUCw of heart rate and systolic blood pressure were also significantly lower during the procedure (P = 0.007 and P = 0.022 respectively) with dexmedetomidine. There was no difference in recovery, side effects or satisfaction. CONCLUSION: Intranasal dexmedetomidine with PCS propofol and alfentanil confers deeper perioperative clinical sedation with significantly less use of additional sedatives during upper gastrointestinal endoscopy.

Over-expression of astrocytic ET-1 attenuates neuropathic pain by inhibition of ERK1/2 and Akt(s) via activation of ETA receptor.

A differential role of endothelin-1 (ET-1) in pain processing has recently been suggested. However, the function of central ET-1 in neuropathic pain (NP) has not been fully elucidated to date. We report here the action of endogenous central ET-1 in sciatic nerve ligation-induced NP (SNL-NP) in a transgenic animal model that over-expresses ET-1 in the astrocytes (GET-1 mice). We hypothesized that the over-expression of astrocytic ET-1 would exert anti-allodynic and anti-hyperalgesic effects in NP, as demonstrated by mechanical threshold and plantar withdrawal latency using the von Frey filament and heat stimuli. In our animal model, GET-1 mice showed an increase in the withdrawal threshold and latency in response to the mechanical and thermal stimuli, respectively, in pain behavior tests after SNL. ET-1 and endothelin type A receptor (ETA-R) levels were increased significantly in L4-L6 segments of the spinal cord (ipsilateral to SNL) of GET-1 mice at 7 and 21days after surgery. Moreover, intrathecal administration of a specific ETA-R antagonist, BQ-123, attenuated the anti-allodynic and anti-hyperalgesic phenotype in GET-1 mice. The effects of BQ-123 on the mRNA expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase B/serine protein kinase (Akt(s)) were assessed in the ipsilateral L4-L6 segments harvested 30min after BQ-123 administration on day 7 after surgery. Phosphorylation of ERK1/2 and Akt(s) in the ipsilateral spinal cord of GET-1 mice was reduced following SNL, whereas no reduction was observed after intrathecal injection of BQ-123. In conclusion, our results showed that the xover-expression of astrocytic ET-1 reduced SNL-induced allodynia and hyperalgesia by inhibiting the activation of ERK1/2 and Akt(s) via the ETA-R-mediated pathway.

The effects of intra-operative dexmedetomidine on postoperative pain, side-effects and recovery in colorectal surgery.

In this double-blind, randomised study, 100 patients undergoing open or conventional laparoscopic colorectal surgery received an intra-operative loading dose of dexmedetomidine 1 µg.kg(-1) followed by an infusion of 0.5 µg.kg(-1) .h(-1) , or a bolus and infusion of saline 0.9% of equivalent volume. Forty-six patients in the dexmedetomidine group and 50 in the saline group completed the study. The area under the curve of numerical rating scores for pain at rest for 1-48 h postoperatively was significantly lower in the patients receiving dexmedetomidine (p = 0.041). There was no difference in morphine consumption, duration of recovery ward or hospital stay. From the data obtained in this study, we calculated a number needed to treat for effective pain relief of 4. Intra-operative dexmedetomidine in colorectal surgery resulted in a reduction in resting pain scores, but there was no morphine-sparing effect or improvement in patients' recovery outcome measures.

Pain Relief After Total Knee Arthroplasty with Intravenous and Periarticular Corticosteroid: A Randomized Controlled Trial.

BACKGROUND: Total knee arthroplasty (TKA) is a cost-effective procedure, but it is also associated with substantial postoperative pain. The present study aimed to compare pain relief and functional recovery after TKA among groups that received intravenous corticosteroids, periarticular corticosteroids, or a combination of both. METHODS: This randomized, double-blinded clinical trial in a local institution in Hong Kong recruited 178 patients who underwent primary unilateral TKA. Six of these patients were excluded because of changes in surgical technique; 4, because of their hepatitis B status; 2, because of a history of peptic ulcer; and 2, because they declined to participate in the study. Patients were randomized 1:1:1:1 to receive placebo (P), intravenous corticosteroids (IVS), periarticular corticosteroids (PAS), or a combination of intravenous and periarticular corticosteroids (IVSPAS). RESULTS: The pain scores at rest were significantly lower in the IVSPAS group than in the P group over the first 48 hours (p = 0.034) and 72 hours (p = 0.043) postoperatively. The pain scores during movement were also significantly lower in the IVS and IVSPAS groups than in the P group over the first 24, 48, and 72 hours (p ≤ 0.023 for all). The flexion range of the operatively treated knee was significantly better in the IVSPAS group than in the P group on postoperative day 3 (p = 0.027). Quadriceps power was also greater in the IVSPAS group than in the P group on postoperative days 2 (p = 0.005) and 3 (p = 0.007). Patients in the IVSPAS group were able to walk significantly further than patients in the P group in the first 3 postoperative days (p ≤ 0.003). Patients in the IVSPAS group also had a higher score on the Elderly Mobility Scale than those in the P group (p = 0.036). CONCLUSIONS: IVS and IVSPAS yielded similar pain relief, but IVSPAS yielded a larger number of rehabilitation parameters that were significantly better than those in the P group. This study provides new insights into pain management and postoperative rehabilitation following TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Simulation of survivorship bias in observational studies on plasma to red blood cell ratios in massive transfusion for trauma.

BACKGROUND: Observational studies on injured patients requiring massive transfusion have found a survival advantage associated with use of equivalent number of units of fresh frozen plasma (FFP) and packed red blood cells (RBCs) compared with use of FFP based on conventional guidelines. However, a survivorship bias might have favoured the higher use of FFP because patients who died early never had the chance to receive sufficient FFP to match the number of RBC units transfused. METHODS: A Markov model using trauma data from local hospitals was constructed and various FFP transfusion scenarios were applied in Monte Carlo simulations in which the relative risk of death associated with exposure to high FFP transfusion was set at 1.00, so that the FFP : RBC ratio had no influence on mortality outcome. RESULTS: Simulation results showed that the relative risk associated with exposure to high FFP transfusion was less than 1.00 (0.33-0.56 based on programmed delays in achieving an FFP : RBC ratio of 1 : 1-2), thus demonstrating a survivorship bias in favour of FFP : RBC equal to or more than 1 : 1-2 in certain observational trauma studies. This bias was directly proportional to the delay in achieving a FFP : RBC ratio of 1 : 1-2 during resuscitation. CONCLUSION: Some observational studies comparing low and high FFP administration in injured patients requiring massive transfusion probably involve survivorship bias that inflates or creates a survival advantage in favour of a higher FFP : RBC ratio.

Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia.

BACKGROUND: Dexmedetomidine (DEX) is an alpha 2-adrenoreceptor agonist, which induces sedation and analgesia. This study aimed to determine whether intranasal DEX offered perioperative sedation and better postoperative analgesia. METHODS: Patients having unilateral third molar surgery under local anaesthesia were recruited and allocated to receive either intranasal DEX 1 µg kg(-1) (Group D) or same volume of saline (Group P) 45 min before surgery. Patient-controlled sedation with propofol was offered as a rescue sedative. Perioperative sedation, postoperative pain relief and analgesic consumption, vital signs, adverse events, postoperative recovery, and satisfaction in sedation and analgesia were assessed. RESULTS: Thirty patients from each group were studied. Areas under curve (AUC) of postoperative numerical rating scale (NRS) pain scores 1-12 h at rest and during mouth opening were significantly lower in Group D (P=0.003 and 0.009, respectively). AUC BIS values and OAA/S sedation scores were significantly lower before surgery and at the recovery area (all P<0.01) with significantly less intra-operative propofol used in group D (P<0.01). In group D, heart rate was significantly lower at recovery period (P=0.005) while systolic blood pressure in different periods of the study (all P<0.01), but the decreases did not require treatment. More patients from placebo group experienced dizziness (P=0.026) but no serious adverse event was found. No difference was found in postoperative psychomotor recovery and satisfaction in pain relief and sedation. CONCLUSIONS: Patients receiving intranasal DEX for unilateral third molar surgery with local anaesthesia were more sedated perioperatively with better postoperative pain relief. No delay in psychomotor recovery was seen.

Low-dose desmopressin improves hypothermia-induced impairment of primary haemostasis in healthy volunteers.

Mild hypothermia (34-35 °C) increases peri-operative blood loss. We have previously demonstrated the beneficial effect of in vitro desmopressin on impairment of primary haemostasis associated with hypothermia. This study evaluated subcutaneous desmopressin in 52 healthy volunteers, randomly assigned to receive either normal saline or desmopressin 1.5, 5 or 15 µg (with 13 in each group). Blood samples were collected before and 2 h after drug administration and incubated at 32 and 37 °C. Platelet function analyser PFA-100(®) closure times were measured. Hypothermia at 32 °C prolonged mean (95% CI) closure times (for adenosine diphosphate/collagen by 11.3% (7.5-15.2%) and for adrenaline/collagen by 16.2% (11.3-21.2%); these changes were reversed by desmopressin. A very small dose was found to be effective (1.5 µg); this dose did not significantly change closure times at 37 °C, but fully prevented its prolongation at 32 °C. Subcutaneous desmopressin prevents the development of hypothermia-induced impairment of primary haemostasis.

Additive Effects of Environmental Enrichment and Ketamine on Neuropathic Pain Relief by Reducing Glutamatergic Activation in Spinal Cord Injury in Rats.

Spinal cord injury (SCI) impairs mobility and often results in complications like intractable neuropathic pain. A multi-approach management of this chronic pain condition has been encouraged, but little has been explored of the field. Here, we focus on the effect and underlying mechanism of environmental enrichment (EE), which promotes voluntary social and physical activities, combined with a clinical analgesic, ketamine, on SCI-induced neuropathic pain as well as motor dysfunction. We performed T13 spinal hemisection in rats, which induced unilateral motor impairment and neuropathic pain-like behaviors in the hindlimb. Treatment regimen started a week after SCI, which consists of ketamine administration (30 mg kg-1 day-1; intramuscular) for 10 days, or EE housing for 20 days, or their combination. Paw withdrawal response to mechanical and thermal stimuli, motor function, burrowing behaviors, and body weight was monitored. Spinal segments at T13 lesion and L4-L6 were collected for histopathological and protein analyses. The joint treatment of EE and ketamine provided greater relief of pain-like behaviors and locomotor recovery than did either paradigm alone. These improvements were associated with reduced cavitation area, astrogliosis, and perilesional phosphorylation of glutamate N-methyl-D-aspartate receptor (NMDAR). Concurrently, lumbar spinal analysis of NMDAR-linked excitatory markers in hypersensitization showed reduced activation of NMDAR, mitogen-activated protein kinase (MAPK) family, nuclear factor (NF)-κB, interleukin (IL)-1ß signaling, and restored excitatory amino acid transporter 2 level. Our data support a better therapeutic efficacy of the combination, EE, and ketamine, in the attenuation of neuropathic pain and motor recovery by reducing spinal glutamatergic activation, signifying a potential multifaceted neurorehabilitation strategy to improve SCI patient outcome.