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10 Articles in Volume 13, Issue #10
Poor Adherence to Opioid Pain Management Regimens
A Practical Approach to Discontinuing NSAID Therapy Prior to a Procedure
Opioid-induced Osteoporosis: Assessing Causes and Treatments
Persistent Acute Lower Back Pain: The Importance of Psychosocial Evaluation
Research Advance Of The Year
A Day of Consulting in Rural America
Ask the Expert: Should You Test For and Treat Opioid-induced Hypogonadism?
Ask the Expert: Do NSAIDs Cause More Deaths Than Opioids?
News Briefs
Letters to the Editor

News Briefs

November/December 2013

The Dilemma of Delirium in Older Patients

Ill and hospitalized older people sometimes experience episodes of delirium, confusion, and disorientation. Often considered a transient and reversible condition, delirium in older people is still viewed by many to be a normal consequence of surgery, chronic disease, or infections.

There is mounting evidence, however, that delirium may be associated with increased risk for dementia and may contribute to morbidity and death. A recent study of 553 patients (85 years and older) found that those with a history of delirium had an 8-fold increase in the risk for developing dementia.1 The researchers also found that among the participants with dementia, delirium was associated with an acceleration of dementia severity, loss of independent functioning, and higher mortality. These findings showed that delirium is a strong risk factor for dementia and cognitive decline in the oldest patients.

Growing Momentum, Awareness

At the National Institute of Aging (NIA), and throughout the geriatric research community, momentum is building to better understand the mechanisms involved in delirium and to improve ways to recognize and treat the condition.NIA supports several clinical trials focused on finding effective drugs and protocols to prevent or reduce the impact of delirium in hospitalized older people. The goal is to identify a variety of interventions that reduce delirium for patients receiving intensive care, including the testing of supplements, pain medications, and sedatives that may alleviate delirium in pre- and post-operative patients.

“The research and medical communities are becoming more aware and interested in the impact delirium may have on the long-term cognitive health of older patients,” said Molly Wagster, MD, Chief of the NIA’s Behavioral and Systems Neuroscience Branch. “At this stage, unfortunately, there are more questions than answers. In order to treat or prevent delirium, it will be important to determine why some older people are more susceptible to developing it during hospital stays or as a result of trauma or illness.”

Attitudes About Delirium Changing

Attitudes about delirium are slowly evolving among medical practitioners, noted Joseph Flaherty, MD, of the Division of Geriatrics at Saint Louis University, who is a leading member of American Delirium Society. “As a medical student 20 years ago, I was taught delirium was completely reversible. That’s simply not the case for many older patients,” he said. “Over the past 15 years, interest has grown in identifying ways not only to reverse the condition but to prevent it from occurring in the first place.”

Dr. Flaherty said that he applauds NIA funding of delirium drug trials, but he also suggested that changes in nursing and hospital protocols today could help prevent the onset and/or reduce the severity of delirium. “Changing the hospital environment and culture to match [the needs of] the older patients with delirium or at risk for delirium is critical,” Dr. Flaherty said.

Examples of such changes include allowing hospitalized older people to sleep undisturbed between 10 p.m. and 6 a.m. so that their normal sleep cycle is less disrupted, not using physical restraints, and giving staff concrete nonpharmacologic methods to deal with agitation that may occur with delirium.2

“There are very promising, nonpharmacological methods being tested that may enable hospitals and nursing facilities to prevent, treat, and manage delirium,” he said. “For example, the new standard in ICUs is to get patients up and out of their beds within 1 to 2 days, even if they are connected to a ventilator. This reduces the number of days with delirium and time spent in intensive care.”

Dr. Flaherty said these new methods also might improve the odds that patients regain normal cognitive and physical function.3


Is the Brain Hard-Wired for Chronic Pain?

A new study has identified a potential anatomical marker for predicting who will develop chronic pain. White matter structural anomalies were discovered in the area of the brain connecting the nucleus accumbens and the medial prefrontal cortex, two areas thought to be involved with pain. The study suggests that “the structure of a person’s brain may predispose one to chronic pain,” noted Vania Apkarian, PhD, a senior author of the study, which was recently published in Pain.4 These concepts might lead to better ways to diagnose and treat chronic pain.

Dr. Apkarian and researchers at Northwestern University Feinberg School of Medicine, Chicago, conducted a study of 24 people who had recently been diagnosed with low back pain (3 months duration). The investigators conducted brain scans using a technique called diffusion tensor imaging (DTI), physical examinations, and questionnaires quarterly over the course of one year. About half of the subjects recovered at some time during the year-long study, while the other half developed chronic pain, which the researchers categorized as “persistent.”

To test the diagnostic value of the scan, the researchers asked whether the white matter differences they saw during the initial brain scans predicted whether the subjects would recover or continue to experience pain. The DTI scans were highly effective in predicting whether a patient will suffer from chronic low back pain, noted the researchers. “There was a consistent difference in white matter between the subjects who recovered and the subjects who experiences pain throughout the year,” wrote Dr. Apkarian. The team also found that the white matter of subjects who had persistent pain looked similar to patients’ known to suffer from chronic pain. They found white matter brain scans predicated at least 80% of the outcomes.

“We were surprised how robust the results were and amazed at how well the brain scans predicted persistence of low back pain,” noted Dr. Apkarian. “Prediction is the name of the game for treating chronic pain.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke, a wing of the National Institutes of Health.


Opioid Use After Spine and Bariatric Surgery Examined

Two new studies raise concerns about the increased use of opioids long-term following surgery. Both studies found that opioid use was common up to 1 year after both spine surgery and bariatric surgery.

In the first study, researchers from the Medical College of Wisconsin reviewed data from 172 patients who underwent elective surgery for repair of the cervical spine. The investigators found that 55 patients (32%) were using opioid a year after surgery, noted Marjorie Wang, MD, MPH, who presented the team’s findings at the North American Spine Society Meeting, held in New Orleans.

The results surprised the researchers, who found that more than 70% of patients reported being satisfied with the result of their surgery. When the authors compared pre- and post-surgical use of opioids, they found that 51% of patients who were prescribed opioids prior to surgery were still taking the medications 1 year later. Moreover, among non-users prior to surgery, 18% were using opioids at the end of the study period.

Chronic opioid use post-surgery was also seen in the second study. In that study, led by Marsha A. Raebel, PharmD, of Kaiser Permanente Colorado in Denver, 11,719 adults underwent weight-loss bariatric surgery for the management of obesity. Before surgery, only 8% of bariatric patients were chronic opioid users. “Among the 933 patients on the opioids before surgery, 77% [723] continued chronic opioid use in the year following surgery, and the dosage of opioid was greater postoperatively than preoperatively,” noted the investigators in an article in JAMA.5  The mean daily morphine equivalents rose 13% in the first year (from 45.0 mg to 51.9 mg) and 18% across 3 years after surgery.

These findings suggest the need for better pain management, including use of non-opioids, in patients perioperatively and postoperatively. Researchers also noted that it is the doctor’s responsibility to properly screen patients prior to prescribing opioids, including performing risk assessment, as well as informing patients of the risk-versus-benefits of opioid therapy.


New Surgical Techniques Improves Prosthesis Performance

EMG-derived signaling has improved the control of robotic leg prostheses, allowing for seamless transitions between walking on level ground, stars, and ramps. However, the technology is not perfect, and tweaks still need to be made in order to eliminate the risk of falling, according to the results of a study published in The New England Journal of Medicine.6

Tremendous advances have been made in the development of prosthetic limbs. In the current study, the research team evaluated a new advance, the use of electromyographic (EMG) signals from the patient’s own muscles, to help improve the control of a robotic leg prosthesis.

The study included a 31-year-old man who lost his limb in a motorcycle accident. During the amputation surgery, two nerve transfers were performed to prevent neuroma formation. The tibial nerve branch and the common peroneal nerve branch were then transferred to reinnervate the hamstring muscles, noted lead investigators Levi J. Hargrove, PhD, from the Center for Bionic Medicine, Rehabilitation Institute of Chicago.

Dr. Hargrove and his team followed the progress of the patient for 2 years after surgery.  Previous studies have shown that targeted muscle innervation has improved the control of motorized arm prostheses. And, indeed, a few months after surgery, the study patient showed “discrete contractions in reinnervated muscles,” noted Dr. Hargrove. The EMG signals from the natively and surgically reinnervated thigh muscles improved control of the robotic prosthesis “The patient was able to ambulate freely outside, climb stairs, and descend ramps” without difficulty—transitions that previously caused problems for patients wearing prostheses.

Remaining challenges include keeping full contact between the EMG signal electrodes and the residual limb during walking without become uncomfortable for the user (ie, avoiding chafing or pressure sores at contact points). The investigators also noted that the robotic leg should be made quieter, smaller, and lighter to benefit a larger number of amputees.


Role of Epigenetics in Pain Pathway

Histone modification is an important epigenetic mechanism that regulates surgical incision pain, according to a study in the November issue of Anesthesiology.7 “Postoperative pain is an incompletely understood and only partially controllable condition that can result in suffering, medical complications, unplanned hospital admissions and disappointing surgery outcomes,” said David J. Clark, MD, PhD, Professor of Anesthesia at Stanford University and Director of Pain Management at the VA Palo Alto Health Care System. “We know that histone acetylation and deacetylation modifies many cellular processes and produces distinct outcomes. In this study we found that histones can epigenetically activate or silence gene expression to either increase or decrease incision pain.”

In this study, groups of mice had small surgical incisions made in their hind paws after being anesthetized. These mice were then regularly injected with suberoylanilide hydroxamic acid (SAHA), which prevents deacetylation (thus promoting gene transcription), or anacardic acid, which prevents acetylation (thus reducing gene transcription). The authors tested the animals daily for the degree of pain sensitivity in their hind paws.

The study found that regulation of histone acetylation can control pain sensitization after an incision. Specifically, maintaining histone in a relatively deacetylated state reduced hypersensitivity after incision. This is due, in part, to the epigenetic regulation of a specific gene chemokine CC motif receptor 2 (CXCR2) and one of its chemokine ligands (KC). The authors also found that these epigenetic changes far outlasted the recovery of animals from their incisions, a property that might help explain why some patients suffer from chronic postoperative pain. Study authors suggest that looking into the roles of these epigenetic mechanisms may help scientists find new ways to treat or prevent acute and chronic postoperative pain in the future.

“Epigenetics is a relatively underappreciated area of science, but the discoveries yet to be made in this field will be many,” Dr. Clark said. “While fascinating information has been found by studying specific genes, we need to bridge the gap in science and focus on groups or systems of many genes simultaneously, which could be give us clues to greater breakthroughs in pain control and other areas of medicine.”




Last updated on: November 5, 2020
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