New Insights Into the Pharmacological Management of Postoperative Pain: A Narrative Review

Postoperative pain is prevalent and often undertreated. There is a risk that untreated or suboptimally treated postoperative pain may transition into chronic postoperative pain, which can be challenging to treat. Clinical guidelines recommend the use of multimodal analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and, in some cases, opioids. NSAIDs are a broad class of drugs with different attributes such as cyclo-oxygenase (COX)-1 or COX-2 selectivity, onset of action, and analgesic potency. NSAIDs are associated with gastrointestinal and cardiovascular side effects and should be administered at the lowest effective dose for the shortest effective duration but can be effective in postoperative pain. The role of opioids in postoperative analgesia is long-standing but has recently come under scrutiny. Opioids are often used in multimodal analgesic combinations in such a way as to minimize the total consumption of opioids without sacrificing analgesic benefit. Special clinical considerations are required for surgical patients already on opioid regimens or with opioid use disorder. A particularly useful fixed-dose combination product for postoperative analgesia is dexketoprofen-tramadol, which confers safe and effective postoperative pain control and reduces the risk of persistent postoperative pain

A New Technique for Inferior Hypogastric Plexus Block: A Coccygeal Transverse Approach -A Case Report-

Chronic pelvic pain is a common problem with variable etiology. The sympathetic nervous system plays an important role in the transmission of visceral pain regardless of its etiology. Sympathetic nerve block is effective and safe for treatment of pelvic visceral pain. One of them, the inferior hypogastric plexus, is not easily assessable to blockade by local anesthetics and neurolytic agents. Inferior hypogastric plexus block is not commonly used in chronic pelvic pain patients due to pre-sacral location. Therefore, inferior hypogastric plexus is not readily blocked using paravertebral or transdiscal approaches. There is only one report of inferior hypogastric plexus block via transsacral approach. This approach has several disadvantages. In this case a favorable outcome was obtained by using coccygeal transverse approach of inferior hypogastric plexus. Thus, we report a patient who was successfully given inferior hypogastric plexus block via coccygeal transverse approach to treat chronic pelvic pain conditions involving the lower pelvic viscera

A Case of Propofol-Induced Oropharyngeal Angioedema and Bronchospasm

Propofol (2,6-diisopropylphenol) is an ultrashort-acting sedative agent with sedative and amnestic effects that is used not only for anesthesia but also for sedation during minor outpatient procedures and endoscopic examinations. Rare cases of anaphylaxis following propofol administration have been reported in the medical literature. Documentation of anaphylaxis is often lacking because the cause and effect relationship is often hard to prove. Only a minority of patients get referred for allergy testing to confirm the offending drug. Here we report a 74-year-old woman who had an anaphylactic reaction with severe oropharyngeal edema and bronchospasm for a few minutes after receiving propofol during endoscopic examination. An allergy skin test was positive for both propofol and soybean. Soybean in the intralipid is one component of propofol, and we concluded that this anaphylaxis was caused by soybean

Infection rates associated with epidural indwelling catheters for seven days or longer: systematic review and meta-analysis

BACKGROUND: To determine infection rate with use of epidural catheters in place for seven days or more. METHODS: Systematic review and pooled analysis of observational studies. RESULTS: Twelve studies with 4,628 patients (median 197 patients) provided information, of which nine (4,334 patients) were published after 1990. Eight studies (3,893 patients) were retrospective, and four studies (735 patients) prospective. Electronic searches identified three studies and searching reference lists nine. There were 257 catheter-related infections in total, of which 211 were superficial and 57 deep, giving rates of 6.1%, 4.6% and 1.2% respectively. Ten of the 12 studies had deep infection rates of 2% or less. The incidence of deep infection was 1 per 2391 days of treatment, or 0.4 per 1000 catheter treatment days. In nine studies (1503 patients), predominantly in cancer, and with average catheter duration of 74 days, the deep infection rate was 2.8%. The proportion of patients with infection of any type was higher in cancer patients with longer catheter duration. Limited numbers of events meant that no reliable estimate of the impact of prospective and retrospective design could be made. There appeared to be a relationship between catheter duration and infection rate from this and other recent estimates. Four of 57 (7%) patients with deep infection died. CONCLUSION: The best estimate is that one person in 35 with an epidural catheter in place for 74 days for relief of cancer pain can be expected to have a deep epidural infection, and that about 1 in 500 may die of infection-related causes. This is a most uncertain estimate given the limited nature of the evidence

Lack of Antinociceptive Cross-Tolerance With Co-Administration of Morphine and Fentanyl Into the Periaqueductal Gray of Male Sprague-Dawley Rats

Tolerance to the antinociceptive effect of mu-opioid receptor (MOPr) agonists, such as morphine and fentanyl, greatly limits their effectiveness for long-term use to treat pain. Clinical studies have shown that combination therapy and opioid rotation can be used to enhance opioid-induced antinociception once tolerance has developed. The mechanism and brain regions involved in these processes are unknown. The purpose of this study was to evaluate the contribution of the ventrolateral periaqueductal gray (vlPAG) to antinociceptive tolerance and cross-tolerance between administration and co- administration of morphine and fentanyl. Tolerance was induced by pretreating rats with morphine or fentanyl or low-dose combination of morphine and fentanyl into the vlPAG followed by assessment of cross-tolerance to the other opioid. In addition, tolerance to the combined treatment was assessed. Cross-tolerance did not develop between repeated vlPAG microinjections of morphine and fentanyl. Likewise, there was no evidence of cross-tolerance from morphine or fentanyl to co-administration of morphine and fentanyl. Co-administration did not cause cross-tolerance to fentanyl. Cross- tolerance was only evident to morphine or morphine and fentanyl combined in rats pretreated with co-administration of low-doses of morphine and fentanyl. In conclusion, cross-tolerance does not develop between morphine and fentanyl within the vlPAG. This finding is consistent with the functionally selective signaling that has been reported for antinociception and tolerance following morphine and fentanyl binding to the MOPr. This research supports the notion that combination therapy and opioid rotation may be useful clinical practices to reduce opioid tolerance and other side effects. Perspective: This preclinical study shows that there is a reduction in cross tolerance between morphine and fentanyl within the periaqueductal gray which is key brain region in opioid antinociception and tolerance

A randomized, double-blind comparison of OROS® hydromorphone and controlled-release morphine for the control of chronic cancer pain

<p>Abstract</p> <p>Background</p> <p>Long-acting opioid formulations are advocated for maintaining pain control in chronic cancer pain. OROS^®hydromorphone is a sustained-release formulation of hydromorphone that requires dosing once daily to maintain therapeutic concentrations. The objective of this study was to demonstrate the clinical equivalence of immediate-release and sustained-release formulations of hydromorphone and morphine for chronic cancer pain.</p> <p>Methods</p> <p>200 patients with cancer pain (requiring ≤ 540 mg/d of oral morphine) participated in this double-blind, parallel-group trial. Patients were randomized to receive hydromorphone or morphine (immediate-release for 2–9 days, sustained-release for 10–15 days). Efficacy was assessed with the Brief Pain Inventory (BPI), investigator and patient global evaluations, Eastern Cooperative Oncology Group performance status, and the Mini-Mental State Examination. The primary endpoint was the 'worst pain in the past 24 hours' item of the BPI, in both the immediate-release and sustained-release study phases, with treatments deemed equivalent if the 95% confidence intervals (CI) of the between-group differences at endpoint were between -1.5 and 1.5. No equivalence limits were defined for secondary endpoints.</p> <p>Results</p> <p>Least-squares mean differences (95% CI) between groups were 0.2 (-0.4, 0.9) in the immediate-release phase and -0.8 (-1.6, -0.01) in the sustained-release phase (intent-to-treat population), indicating that the immediate-release formulations met the pre-specified equivalence criteria, but that the lower limit of the 95% CI (-1.6) was outside the boundary (-1.5) for the sustained-release formulations. BPI 'pain now PM' was significantly lower with OROS^®hydromorphone compared with controlled-release morphine (least-squares mean difference [95% CI], -0.77 [-1.49, -0.05]; <it>p </it>= 0.0372). Scores for other secondary efficacy variables were similar between the two sustained-release treatments. At endpoint, > 70% of investigators and patients rated both treatments as good to excellent. The safety profiles of hydromorphone and morphine were similar and typical of opioid analgesics.</p> <p>Conclusion</p> <p>Equivalence was demonstrated for immediate-release formulations of hydromorphone and morphine, but not for the sustained-release formulations of OROS^®hydromorphone and controlled-release morphine. The direction of the mean difference between the treatments (-0.8) and the out-of-range lower limit of the 95% CI (-1.6) were in favor of OROS^®hydromorphone.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: NCT0041054</p

An Overview of the 2014 ALMA Long Baseline Campaign

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation