Caring for patients with pain during the COVID-19 pandemic: consensus recommendations from an international expert panel.

Chronic pain causes significant suffering, limitation of daily activities and reduced quality of life. Infection from COVID-19 is responsible for an ongoing pandemic that causes severe acute respiratory syndrome, leading to systemic complications and death. Led by the World Health Organization, healthcare systems across the world are engaged in limiting the spread of infection. As a result, all elective surgical procedures, outpatient procedures and patient visits, including pain management services, have been postponed or cancelled. This has affected the care of chronic pain patients. Most are elderly with multiple comorbidities, which puts them at risk of COVID-19 infection. Important considerations that need to be recognised during this pandemic for chronic pain patients include: ensuring continuity of care and pain medications, especially opioids; use of telemedicine; maintaining biopsychosocial management; use of anti-inflammatory drugs; use of steroids; and prioritising necessary procedural visits. There are no guidelines to inform physicians and healthcare providers engaged in caring for patients with pain during this period of crisis. We assembled an expert panel of pain physicians, psychologists and researchers from North America and Europe to formulate recommendations to guide practice. As the COVID-19 situation continues to evolve rapidly, these recommendations are based on the best available evidence and expert opinion at this present time and may need adapting to local workplace policies.

Epidural adhesiolysis: an evidence-based review.

First described over 25 years ago, epidural lysis of adhesions (LOA) involves the mechanical dissolution of epidural scar tissue, which may directly alleviate pain and facilitate the spread of analgesic substances to area(s) of pain generation. Although it most commonly performed for lumbar failed back surgery syndrome, there is a growing body of evidence that suggests it may be effective for spinal stenosis and radicular pain stemming from a herniated disc. There is weak positive evidence that LOA is more effective than conventional caudal epidural steroid injections for failed back surgery syndrome and spinal stenosis, and that LOA is more effective than sham adhesiolysis and conservative management for lumbosacral radiculopathy. For cervical disc herniation and spinal stenosis, there is only anecdotal evidence suggesting effectiveness and safety. Factors that may contribute to the enhanced efficacy compared to traditional epidural steroid administration include the high volume administered, the use of hypertonic saline, and to a lesser extent the use of hyaluronidase and a navigable catheter to mechanically disrupt scar tissue and guide medication administration. Although LOA is widely considered a safe intervention, the complication rates are higher than for conventional epidural steroid injection.

Corticosteroid injections for trochanteric bursitis: is fluoroscopy necessary? A pilot study.

BACKGROUND: Numerous studies have demonstrated that therapeutic injections carried out to treat a variety of different pain conditions should ideally be performed under radiological guidance because of the propensity for blinded injections to be inaccurate. Although trochanteric bursa injections are commonly performed to treat hip pain, they have never been described using fluoroscopy. METHODS: The authors reviewed recorded data on 40 patients who underwent trochanteric bursa injections for hip pain with or without low back pain. The initial needle placement was done blindly, with all subsequent attempts done using fluoroscopic guidance. After bone contact, imaging was used to determine if the needle was positioned on the lateral edge of the greater trochanter (GT). Once this occurred, 1 ml of radiopaque contrast was injected to assess bursa spread. RESULTS: The GT was contacted in 78% of cases and a bursagram obtained in 45% of patients on the first needle placement. In 23% of patients a bursagram was obtained on the second attempt and in another 23% on the third attempt. Four patients (10%) required four or more needle placements before a bursagram was appreciated. Attending physicians obtained a bursagram on the first attempt 53% of the time vs 46% for fellows and 36% for residents (P=0.64). Older patients were more likely to require multiple injections than younger patients. CONCLUSIONS: Radiological confirmation of bursal spread is necessary to ensure that the injectate reaches the area of pathology during trochanteric bursa injections.

Ketamine patient-controlled analgesia for dysesthetic central pain.

STUDY DESIGN: Case report. OBJECTIVES: To describe the first use of intravenous (IV) ketamine as the sole agent in a patient-controlled analgesic delivery system (ie PCA) in a patient with cervical syringomyelia. SETTING: A tertiary-care university teaching hospital in New York City. METHODS: A 41-year-old tetraplegic female on high-dose opioids suffering from intractable dysesthetic central pain received her best pain relief from a low-dose ketamine infusion after failing trials with multiple neuropathic medications. After several weeks of titrating her infusion rate up and down, she was switched to an IV ketamine PCA device. RESULTS: The patient was maintained on an IV ketamine PCA for almost 1 year under the following settings: 2.7 mg/h basal rate; 2.7 mg/h demand dose; 15 min lockout period. Although she continues to report some pain, it has dramatically decreased since the ketamine PCA was instituted, enabling us to significantly reduce her opioid dosage. CONCLUSIONS: Ketamine PCA may be a viable treatment option in patients suffering from intractable central pain. The rationale for this treatment, along with dosing guidelines and possible drawbacks, is discussed.

Prostate cancer Tx. Therapeutic options based on tumor grade, life expectancy, and patient preferences.

Cancer of the prostate is the most common malignancy in American men. Its incidence is associated with age, race, family history, and life style factors, such as high-fat diets. Some men develop prostate cancer before age 55, but 80% of tumors occur in men older than age 65. For organ-confined prostate cancers, treatment options include observation, radical prostatectomy, external beam or interstitial radiation, and cryoablation. The appropriate therapeutic decision is based on analysis of multiple factors by the physician and the individual patient. Advanced prostate cancer remains incurable, but hormonal manipulation and newer chemotherapeutic regimens offer palliation in later stages of the disease.

New developments in the use of tricyclic antidepressants for the management of pain.

In recent years, tricyclic antidepressant drugs have experienced a resurgence in their use as valuable pharmacological tools in the treatment of pain. Along with the evolution in our understanding of their analgesic mechanisms of action, there have been concurrent breakthroughs regarding their indications for use and modes of administration. This review focuses on recent advances in our understanding of how antidepressant drugs exert their antinociceptive effects, and new developments regarding their clinical application.

Intravenous lidocaine in the treatment of hiccup.

The word "hiccup" refers to an involuntary, spasmodic contraction of the diaphragm that is followed by the abrupt closure of the glottis to produce the characteristic sound. Among the many documented causes of this occurrence are those due to neurogenic dysfunction. In the past few decades, lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms, including seizures, chronic pain, and arrhythmias. We describe a postsurgical patient in whom two successive intravenous infusions of lidocaine, 1.5 mg/kg followed the next day by 0.75 mg/kg, terminated his hiccup twice, whereas multiple other treatments failed to alleviate the problem. Various causes of this phenomenon are discussed, as well as a possible mechanism for the successful treatment.

Elicitation of the oculocardiac reflex during endoscopic forehead lift surgery.

Elicitation of the oculocardiac reflex is a well-documented phenomenon encountered during ophthalmologic surgical procedures. Familiarity with and prompt recognition of this entity has significantly reduced the morbidity associated with it; however, potentially lethal arrhythmias and cardiac arrest still occur. We report elicitation of the reflex during manipulation of the supraorbital nerve during endoscopic forehead lift surgery. To our knowledge this is the first case of elicitation of the oculocardiac reflex reported during endoscopic forehead lift surgery.

Effects of priming with pancuronium or rocuronium on intubation with rocuronium in children.

Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset and intermediate duration of action. The goal of this study was to compare the neuromuscular blocking actions of rocuronium with and without a priming dose of pancuronium or rocuronium in children. Thirty patients were randomly allocated into 3 groups. Ten patients received a single dose of 0.6 mg/kg rocuronium (Group I). The others received either 0.015 mg/kg pancuronium (Group II) or 0.06 mg/kg rocuronium (Group III) 3 minutes before an intubating dose of 0.54 mg/kg rocuronium was given. Neuromuscular blockade was measured via accelerographic response to single stimulations (1 Hz) of the ulnar nerve until maximal twitch depression was reached followed by train-of-four (TOF) stimuli (2 Hz) at 15 second intervals for the remainder of recovery. Groups were compared with regard to onset time, duration and recovery indices. The onset time and duration of block did not differ significantly between groups. However, the time to recovery in group II (24.5 +/- 9.9 min) was significantly prolonged compared to that in group I (12.7 +/- 3.1 min) or group III (12.7 +/- 3.9 min). We concluded that the use of rocuronium with a preceding dose of either pancuronium or rocuronium provided no advantage for intubation in children.

Mucoid impaction following nasal intubation in a child with an upper respiratory infection.

We describe a case of mucoid impaction following nasotracheal intubation in a child with an upper respiratory infection that was successfully treated with a fiberoptic bronchoscope too large to pass through the endotracheal tube lumen. To the best of our knowledge, it is the first report in the anesthesia literature in which the placement of a nasal tracheal tube is implicated as the cause of the mucous obstruction. The physiologic changes that occur with anesthesia and that place patients at increased risk for this phenomenon, as well as the differential diagnosis, treatment, and prevention of this entity, are discussed.

Detection of rRNA from four respiratory pathogens using an automated Q beta replicase assay.

Ribosomal RNA targets from Mycobacterium avium complex (23S), Mycoplasma pneumoniae (16S), Pneumocystis carinii (18S) and Legionella pneumophila (16S) were detected in four separate assays on a model automated Q-beta amplification instrument. Sandwich hybridization, reversible target capture, detector probe amplification and fluorescent signal detection occurred in closed, disposable packs at 38 degrees C. Packs were injected with 0.5 ml samples in 3.06 M guanidine thiocyanate. Ten samples per run were read after 7 h, requiring only 4 min loading time. Synthetic RNA transcripts and purified, natural RNAs from up to four different strains per assay were diluted to 10(6) or fewer molecules per sample (approximately 100 cells for prokaryotes, 10 cells for Pneumocystis). All analytes were detected at 10(6) targets. The limits of detection were found at 10(5) to 10(4). Discrimination against competitor RNA was tested using up to 10(9) molecules (1000 X excess) of appropriate test strains. Samples containing either zero targets or 10(7) competitors produced negative results in 95 to 100% of the samples, depending on the assay. Closely related Legionella and Mycoplasma species cross-reacted at high challenge levels of 10(9) molecules as a result of sequence similarities in the target regions. These results demonstrate the utility and versatility of an automated, high sensitivity, closed system for amplified analysis of direct-from-sample testing of respiratory pathogens.

Untranslated sequence upstream of MarA in the multiple antibiotic resistance locus of Escherichia coli is related to the effector-binding domain of the XylS transcriptional activator.

MarA, the 129-amino-acid (aa) protein which plays a crucial role in the multiple antibiotic resistance (Mar) phenotype in Escherichia coli, shows homology to members of the XylS/AraC family of transcriptional regulators. Although these proteins vary in size from around 100 to 350 aa they all contain a DNA-binding domain with a helix-turn-helix motif. The larger ones, e.g., XylS, AraC, and Rob, contain an additional domain either at their amino- or at their carboxyterminus. This domain is important for effector-binding or dimerization or of unknown function. MarA consists only of the DNA-binding component. Nevertheless, a sequence with a coding potential of 141 aa upstream of its ATG start-codon showed 20.5-26.9% aa identity with the corresponding section within the effector-binding domain of XylS from the TOL plasmid of Pseudomonas putida when translated in the same reading frame as MarA. However, the reading frame was interrupted by 11 translational stops. In another frame, this upstream sequence actually codes for a real protein, MarR, that is completely unrelated to XylS. Implications for the putative evolution of regulatory proteins through translocation of domains followed by adaptation are discussed.

Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli.

Resistance to multiple antibiotics and certain oxidative stress compounds was conferred by three independently selected mutations (marR1, soxQ1, and cfxB1) that mapped to 34 min on the Escherichia coli chromosome. Mutations at this locus can activate the marRAB operon, in which marR encodes a putative repressor of mar transcription and marA encodes a putative transcriptional activator of defense genes against antibiotics and oxidants. Overexpression of the wild-type MarR protein reversed the phenotypes (antibiotic resistance and increased antioxidant enzyme synthesis) of all three mutants. DNA sequence analysis showed that, like marR1, the other two mutations were alterations of marR: a 285-bp deletion in cfxB1 and a GC-->AT transition at codon 70 (Ala-->Thr) in soxQ1. All three mutations cause increased amounts of mar-specific RNA, which supports the hypothesis that MarR has a repressor function in the expression of the marRAB operon. The level of mar RNA was further induced by tetracycline in both the marR1 and soxQ1 strains but not in the cfxB1 deletion mutant. In the cfxB1 strain, the level of expression of a truncated RNA, with or without tetracycline exposure, was the same as the fully induced level in the other two mutants. Overproduction of MarR in the cfxB1 strain repressed the transcription of the truncated RNA and restored transcriptional inducibility by tetracycline. Thus, induction of the marRAB operon results from the relief of the repression exerted by MarR. The marRAB operon evidently activates both antibiotic resistance and oxidative stress genes.

Salicylate induction of antibiotic resistance in Escherichia coli: activation of the mar operon and a mar-independent pathway.

Since the growth of wild-type Escherichia coli in salicylate results in a multiple antibiotic resistance phenotype similar to that of constitutive mutants (Mar) of the chromosomal mar locus, the effect of salicylate on the expression of the marRAB operon was investigated. The amount of RNA hybridizing with a mar-specific DNA probe was 5 to 10 times higher in wild-type cells grown with sodium salicylate (5.0 mM) than in untreated controls. Untreated Mar mutants had three to five times more mar-specific RNA than wild-type cells did. When a Mar mutant was treated with salicylate, a 30- to 50-fold increase of mar-specific RNA was seen. In wild-type cells bearing a mar promoter-lacZ fusion on the chromosome, salicylate increased beta-galactosidase activity by sixfold. Thus, salicylate induces transcription of the marRAB operon. Other inducers of phenotypic multiple antibiotic resistance, e.g., benzoate, salicyl alcohol, and acetaminophen, but not acetate, also increased transcription from the mar promoter but to a lesser extent than did salicylate. Both in wild-type and mar-deficient strains, growth in salicylate resulted in increased antibiotic resistance, decreased permeation of the outer membrane to cephaloridine, increased micF transcription, and decreased amounts of OmpF. However, the magnitude of these changes was generally greater in wild-type (mar-containing) cells. Thus, salicylate and other compounds can induce transcription of the mar operon and, presumably, give rise to multiple antibiotic resistance via this pathway. However, salicylate can also activate an unidentified, mar-independent pathway(s) which engenders multiple antibiotic resistance.

A multidrug resistance regulatory chromosomal locus is widespread among enteric bacteria.

Constitutive expression of the mar operon (marRAB) in Escherichia coli produces a multiple antibiotic resistance phenotype mediated by the expression of multiple genetic loci in response to regulatory proteins in the operon. A mar-specific DNA probe was used to search for the operon in bacterial strains representing 53 species and 27 genera. Among these, 6 other Enterobacteriaceae, Salmonella, Shigella, Klebsiella, Citrobacter, Hafnia, and Enterobacter species, contained DNA sequences that hybridized to the probe under high-stringency conditions. By use of a selection protocol developed to obtain multiple antibiotic resistant mutants of E. coli, multiply resistant mutants that showed increased expression of mar-specific RNA were obtained from Enterobacter agglomerans and Salmonella species.

Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli.

A 7.8-kbp fragment of chromosomal DNA from a region controlling multiple antibiotic resistance (Mar) in Escherichia coli has been sequenced. Within the fragment is a potential divergent promoter region including marO, which contains two pairs of direct repeats, suggesting possible operator-regulatory sites. To the left of marO (region I) are one or two transcriptional units with three putative open reading frames (ORFs) encoding 64, 157, and 70 amino acids. To the right (region II) is a transcriptional unit containing three putative ORFs (ORF125/144, ORF129, and ORF72). Of six independent Mar mutants, four had mutations within the ORF encoding the first putative protein (ORF125/144) downstream of marO, including three different single-point mutations and an IS2 insertion. One of the other mutations occurred in marO (20-bp duplication), and the other occurred in a site in marO or ORF144 (a 1-bp change). All six mutations led to increased transcription of the region II transcript. High-copy-number plasmids containing marO and the adjacent ORF125/144 region from a wild-type source but not from a Mar mutant reduced the antibiotic resistance of a Mar mutant to levels comparable to those of wild-type cells. High-copy-number plasmids containing wild-type marO alone caused an increase in resistance to tetracycline, chloramphenicol, and norfloxacin in a wild-type strain. The nature of the Mar mutations and the results of the complementation studies suggest that ORF125/144 encodes a repressor (designated MarR) which acts at marO. The second ORF (ORF129), designated marA, would encode a protein, MarA, whose sequence shows strong similarity to those of a family of positive transcriptional regulators. A Tn5 insertion in marA inactivated the multiresistance phenotype of Mar mutants. The function of ORF72, designated marB, encoding the third putative protein in the operon, and that of other ORFs detected within the 7.8-kb fragment have not yet been determined.