Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats

Background: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.

Methods: In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.

Results: Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.

Discussion: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.

Conclusion: Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.     

Impact of an enhanced recovery program for cesarean delivery on postoperative opioid use

BackgroundCesarean delivery is one of the most common surgeries performed worldwide and the adoption of enhanced recovery programs for cesarean delivery is gaining popularity. We tested the hypothesis that implementation of an enhanced recovery program for cesarean delivery would be associated with a decrease in postoperative opioid consumption.MethodsWe compared a retrospective cohort of women delivered by elective cesarean delivery (January 1, 2017 to June 30, 2018) to a prospective cohort exposed to the enhanced recovery protocol (July 1, 2018 to December 31, 2018). The primary outcome was inpatient maternal opioid use, measured as total oral morphine equivalents. Secondary outcomes included postoperative 0–10 pain scores, length of stay, 30-day postoperative complication rates, and hospital re-admissions.ResultsData from 541 patients were analyzed. The enhanced recovery cohort used significantly less oral morphine equivalents compared with the pre-enhanced recovery cohort (60.3 mg vs 104.3 mg, P <0.001). The number of patients who required opioid medication within 24 h of discharge was significantly reduced in the enhanced recovery cohort (41.1% vs 74.6%, P <0.001). There were no significant differences in average pain scores (1.6 vs 1.9, P=0.037).ConclusionsThe implementation of an enhanced recovery program for cesarean delivery was associated with a significant reduction in postoperative opioid consumption throughout hospitalization, with average pain scores remaining <2. Implementation of this program was also associated with an increase in the number of patients who were opioid-free 24 h prior to discharge.     

Opioid use frequency in early axial spondyloarthritis in Finland – a pharmacoepidemic register study

ObjectivesTo evaluate opioid use among incident axial spondyloarthritis (axSpA) patients compared to general population.MethodsFrom the national register, we identified all adult patients with axSpA (ICD-10 codes M45-46), who between 2010 and 2014 (index date, ID) were for the first time granted special reimbursement for any disease-modifying antirheumatic drugs (DMARDs). Three matched population controls were identified for each patient. Drug purchases were evaluated between 2009–2015, and opioid use was analyzed for one year before and after the ID. The Defined Daily Dose (DDD) was used as a tool to assess the opioid consumption before and after the biological (b) DMARD initiation.ResultsWe identified 3577 axSpA patients and 10,573 controls. Of these patients, 97.2% started a conventional synthetic (cs) DMARD during a year after ID and 23.4% switched later to a self-injected bDMARD between the ID and 31 Dec 2015 (median follow-up 3.4 years). Opioids were purchased at least once by 29.8% and 21.7% of the patients in the years before and after the ID, respectively, compared to 8.1% and 7.8% of the controls. The proportion of opioid-using patients was greatest during the last quarter before the ID [relative risk (RR) 4.72 (95% CI 4.14 to 5.39)] compared to controls, and it remained higher [RR 2.84 (2.59 to 3.11)] also after the start of csDMARDs. DDD of opioid consumption decreased from 7.7 to 1.6/1000 inhabitants after bDMARD initiation.ConclusionConsiderably more axSpA patients than population controls used opioids. The opioid consumption by dose decreased clearly after bDMARD initiation.     

Opioid consumption in patients undergoing Roux-en-Y bariatric surgery compared with population controls with and without obesity

BackgroundPatients with obesity are prescribed more opioids than the general population.ObjectivesTo compare opioid consumption in patients with obesity who underwent Roux-en-Y bariatric surgery (RYGB) with population controls with and without obesity, not undergoing bariatric surgery, and to identify characteristics associated with opioid use.SettingThis study included all patients with a principal diagnosis of obesity, aged 18–72 years, with a RYGB surgical code in the Swedish Patient Register between 2007 and 2013.MethodsRYGB patients (n = 23,898) were age- and sex-matched with 1 control patient with obesity (n = 23,898) and 2 population controls without obesity (n = 46,064). Participants were classified as nonconsumers and consumers based on their opioid dispensations during the 12 months before baseline. Opioid consumption was assessed for 24 months.ResultsNonconsumers. Within 24 months, a significantly higher proportion of RYGB patients (16.6%) started using opioids compared with the controls with obesity (14.3%, P < .0001) and population controls (5.4%, P < .0001). RYGB patients and controls with obesity had higher median daily intake of opioid morphine equivalent (MEQ) (2.8 mg/d) than population controls (2.5 mg/d, P < .0001). Consumers. Within 24 months, the proportion of RYGB patients and controls with obesity that was using opioids were similar (53.1% and 53.4%), but higher compared to population controls (38.0%, P < .0001). The median daily opioid MEQ was higher among RYGB patients than in population controls (10.5 versus 7.8 mg/d, P < .0001). RYGB patients, overall, had higher incidence of bowel surgery and cholecystectomy compared with controls with obesity and population controls, leading to prolonged opioid use in this group. Opioid consumption in general was associated with chronic pain and psychiatric disorder, which were more common in patients with obesity than in the population controls.ConclusionRYGB surgery increased the risk of prolonged opioid use in patients with obesity who were nonconsumers before surgery but had no effect on overall opioid use among prior consumers. RYGB-associated complications requiring surgery influenced opioid use for both nonconsumers and consumers. Regular reassessments of pain mechanisms and specific treatment owing to type of pain could prevent unnecessary opioid use in this patient group.     

Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized,double-blind,prospective trial

BACKGROUND: Codeine is frequently added to paracetamol to treat post-operative dento-alveolar pain; studies have shown effectiveness in relief of post-operative pain at high doses but at the expense of central nervous and gastrointestinal side effects. There has been no trial to compare the efficacy and safety of paracetamol 1000 mg with paracetamol 1000 mg combined with codeine 30 mg. METHOD: A randomized, single centre, double-blind prospective parallel group trial was performed to compare paracetamol 1000 mg with paracetamol 1000 mg with codeine 30 mg for the relief of pain following surgical removal of impacted third molars, and analysed on an intention-to-treat (ITT) basis. Eighty-two patients were assigned randomly to receive either drug for a maximum of three doses. Patients recorded their pain intensity one hour after surgery and hourly thereafter for 12 hours. RESULTS: The average increase in pain intensity over 12 hours was significantly less in patients receiving paracetamol plus codeine than in those receiving paracetamol alone (p=0.03) -1.81 cm/h compared with 0.45 cm/h - a difference of 1.13 cm/h (95 per cent CI: 0.18 to 2.08). Of the patients who received the paracetamol codeine combination, 62 per cent used escape medication compared with 75 per cent of those on paracetamol alone (p=0.20). There was no significant difference between the two groups in the proportion of patients experiencing adverse events (p=0.5). CONCLUSION: A combination of 1000 mg paracetamol and 30 mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal, with no significant difference of side effects during the 12 hour period studied.     

Medication of the dental pulp: a review and proposals

Abstract For years, dentists have desired to treat the intact dental pulp. Since it is well-known that many substances, including some drugs, arc capable of permeating dentin, we believe it is possible to treat certain types of pulpitis by applying drugs at the base of cavity preparations. Useful drugs include local anesthetics to block pain transmission, glucocorticoids or non-steroidal anti-inflammatory agents (NSAIA) to treat inflammation. NSA1A or narcotic analgesics for pain control, and antibiotics to treat infection. The literature is reviewed and proposals are presented to study medication of the dental pulp.     

Drugs for pain management in dentistry

Pain is one of the most common reasons patients seek dental treatment. It may be due to many different diseases/conditions or it may occur after treatment. Dentists must be able to diagnose the source of pain and have strategies for its management. The ‘3‐D’ principle — diagnosis, dental treatment and drugs — should be used to manage pain. The first, and most important, step is to diagnose the condition causing the pain and identify what caused that condition. Appropriate dental treatment should then be undertaken to remove the cause of the condition as this usually provides rapid resolution of the symptoms. Drugs should only be used as an adjunct to the dental treatment. Most painful problems that require analgesics will be due to inflammation. Pain management drugs include non‐narcotic analgesics (e.g., non‐steroidal anti‐inflammatory drugs, paracetamol, etc) or opioids (i.e., narcotics). Non‐steroidal anti‐inflammatory drugs (NSAIDs) provide excellent pain relief due to their anti‐inflammatory and analgesic action. The most common NSAIDs are aspirin and ibuprofen. Paracetamol gives very effective analgesia but has little anti‐inflammatory action. The opioids are powerful analgesics but have significant side effects and therefore they should be reserved for severe pain only. The most commonly‐used opioid is codeine, usually in combination with paracetamol. Corticosteroids can also be used for managing inflammation but their use in dentistry is limited to a few very specific situations.