Sunday, October 7, 2012

Compounding Pharmacies & Drug Shortage: the case of Fungal Meningitis

Epidural steroid injections have been an option in the treatment of pain due to spinal disc herniation for many years, and their safety record has been acceptable until now! As we hear in the media, contaminated steroid preparations that were purchased from a non-accredited compounding pharmacy have led to the death of 7 people and the serious illness of at least 47 individuals who were afflicted with fungal meningitis. Many more might show-up over the next days or weeks. By far, this is the worst trend of complications and bad outcomes related to the treatment of epidural steroid injections for painful spinal conditions, which in my opinion will hold back this form of therapy for many years to come, even if the root cause of this tragic development is eradicated.

Our medical history is a living proof of this: a case in point is the landmark Woolley and Roe case that occurred in Britain in 1947. Two patients who received spinal anesthesia on the same day in the same hospital who became permanently paralyzed because of contaminated ampules. Their tragic loss led to the "death" of spinal anesthesia for many years afterwards, particularly in Britain. It took a long while for the practice of spinal anesthesia to recover afterwards, particularly with modern sterilization techniques, better drugs and needles, and improved understanding of the science.

Below is an extract from an article in the Guardian regarding this story (full article here):

An outbreak of meningitis linked to contaminated steroid shots prepared by a Massachusetts pharmacy has now resulted in seven deaths, officials said Saturday as they confirmed that the illness had spread to more states. 
The total number of cases of the rare form of fungal meningitis is now 64, with Minnesota and Ohio added to the list of states affected. 
Since the outbreak was traced to products sent out by an unaccredited pharmaceutical compounding company with a history of health violations, medical clinics across the eastern USA have been making contact with patients given the injection. 
In the past 24 hours, Centers for Disease Control and Prevention (CDC) has added two people to the number of fatalities. The total number of cases has jumped by 17 from Friday's figure of 47. 
The updated figures comes amid growing concern over why clinics from as far away as Florida and Tennessee chose to buy in bulk from a pharmacy that had not applied for accreditation form a professional body and had a checkered health and safety record. 
The outbreak has been traced to the New England Compounding Center, which from premises in Framingham, Massachusetts sent out as many as 17,000 doses of contaminated steroid injections. 
Investigators from the Food and Drug Administration (FDA) who were sent to the company found a fungal contaminate in a sealed vial of the steroid methylprednisolone acetate. They also found a "foreign material" in another, opened container. Tests are being conducted to determine if the contaminants match the one that has led to recent cases of meningitis....

Wednesday, January 27, 2010

More on Haiti

On January 25, 2009, PBS NewsHour Ray Suarez talks with Dr. Paul Farmer (Partners in Health co-founder and the United Nations' deputy special envoy to Haiti) about the obstacles facing aid workers in Port-au-Prince, where thousands require urgent care:

Tuesday, January 19, 2010

Haiti: Beyond the Surface of Catastrophe

This is an outstanding interview that, not only examines the Haiti disaster, but goes way beyond the apparent surface of the country's catastrophic state.

Katie Couric of CBS News "speaks with Mark Schneider from the International Crisis Group, and Ophelia Dahl, Executive Director of Partners in Health about the disastrous earthquake in Haiti and the relief efforts to help Haitians in need." A must watch!

Watch CBS News Videos Online

Friday, September 7, 2007

A Tribute to a Loved Giant: Luciano Pavarotti

The New York Times wrote: "Luciano Pavarotti, the Italian singer whose ringing, pristine sound set a standard for operatic tenors of the postwar era, died Thursday at his home near Modena, in northern Italy. He was 71."

Read more here....

Credit: David Henderson

Thursday, August 16, 2007

Pain Treatment Can Become Lethal!

The following is information on the dangers of using transdermal fentanyl system (DURAGESIC) in the treatment of pain. Fentanyl is a very powerful synthetic narcotic that has been safely used intravenously in anesthesia under tight control for several decades. Its use was extended to external application as a patch, and lollypops as well, in the treatment of chronic and acute pain. It has been safely used for about two decades in the treatment of pain due to cancer, but its use has been advocated recently for the treatment of chronic non-cancer pain, and on occasions, in acute pain. The following information from the Institute for Safe Medication Practices (ISMP) is about its dangers when used in these latter applications, particularly in narcotic-naïve patients.

Ongoing, Preventable Fatal Events With Fentanyl Transdermal Patches Are Alarming

ISMP Medication Safety Alert!
June 28, 2007 Vol. 12, Issue 13

Despite warnings from the FDA, manufacturers, and various patient safety agencies, fentanyl transdermal patches continue to be prescribed inappropriately to treat acute pain in opiate-naive patients, sometimes in large doses or in combination with oral or intravenous opiates. Some of these prescribing errors have occurred in hospitals; others have originated in physician offices or ambulatory surgery centers, where well-meaning but misinformed primary care physicians or surgeons have prescribed the drug for opiate-naïve patients under contraindicated circumstances such as acute post-operative pain. Unfortunately, pharmacists have often filled these prescriptions without question, and nurses caring for patients have applied the patches without recognizing the prescribing error. The databases to which ISMP has access bear proof of this ongoing safety issue, and numerous case reports have already appeared in previous editions of ISMP newsletters (May 31, 2007; June 29, 2006; May 4, 2006; August 11, 2005; May 20, 2004; September 19, 2001).

Two years ago in our August 11, 2005 newsletter (New fentanyl warnings: more needed to protect patients), Ortho-McNeil (Janssen), maker of DURAGESIC (fentanyl transdermal), issued a “Dear Health Professional” letter to bring attention to new boxed warnings in the product label related to improper prescribing ( Likewise, FDA issued a Public Health Advisory ( to alert healthcare providers that deaths and overdoses had occurred in patients using both the brand name product Duragesic and the generic product. Despite these warnings, label changes, and publication of prescribing problems in ISMP newsletters and elsewhere, some practitioners still seem unaware of the dangers with this potent narcotic and the proper prescribing guidelines (see “Excerpts from product labeling for fentanyl transdermal” at the end of the article).

In our May 31, 2007 newsletter, we reported that an elderly patient had several fentanyl patches totaling 125 mcg/hour applied to her skin, which caused delirium and led to her transfer to a critical care step-down unit for close observation. In the past few weeks, we received two more reports of prescribing errors—one of which was fatal.

In the first case, the person reporting the event described a post-operative patient with a morphine infusion running immediately after surgery, who was discharged the same day. According to the reporter, a nurse applied a prescribed fentanyl patch, 75 mcg/hour, to the patient’s skin before discharge, and gave the patient three patches to take home as well as a prescription for oxycodone prn every 4-6 hours. Sadly, the patient died within 12 hours of discharge. We were told that the coroner attributed the patient’s death to application of the fentanyl patch and use of oxycodone–both found in the patient’s blood. Not only was this patient opiate naïve, and his pain not chronic, he was also being treated for sleep apnea and bronchopneumonia at the time of his surgery. Depending on its severity, existing respiratory compromise is another contra-indication to administering the drug.

In another event reported this month, an elderly patient was admitted to a hospital after application of a 100 mcg/hour patch to the skin. A family member had called the clinic where the patient had been receiving periodic epidural injections for back pain and asked a nurse to arrange an ambulance for transport for his next visit. This represented a significant change in the patient’s status, so the nurse questioned the family and learned that a fentanyl patch had been prescribed, and that the patient had continued taking PERCOCET 5/325 (oxycodone 5 mg and acetaminophen 325 mg), two tablets, three or four times a day. After calling the patient’s pharmacist to confirm his prescribed medications, the nurse called the family and told them to remove the patch immediately and take the patient to the emergency department (ED). The patient was admitted to the step-down unit. During the call to the patient’s family, the nurse also confirmed that the patient and family had not been counseled when picking up the prescription. They had no awareness of the potency of the drug. Fortunately, this patient did not suffer any permanent adverse consequences.

Safe Practice Recommendations: The examples of errors described above are closely associated with a knowledge deficit about proper prescribing of fentanyl patches. These examples and others help substantiate the fact that reliance on product labeling and practitioner education alone will not do enough to solve this life-threatening problem. Yes, healthcare practitioners should be educated about safe prescribing, and the potency of fentanyl patches should be stressed. (You can view a free FDA Patient Safety Video [created in cooperation with ISMP] on this subject at: But there will always be those who are unaware of the great risks they take when prescribing fentanyl patches to opiate-naïve patients to treat acute pain. Thus, prescribing guidelines along with checkpoints as described below must be established for this high-alert medication to help avoid the risk of patient harm.

Create guidelines. Specific prescribing and dispensing guidelines for fentanyl patches that are congruent with the product labeling should be developed and referenced during order entry of the medication in inpatient and outpatient settings. Fentanyl patches should only be used by patients who are opiate-tolerant with chronic pain that is not well controlled with shorter-acting analgesics. Equianalgesic conversion tables should also be included in the guidelines to help prescribers convert patients to an appropriate fentanyl transdermal dose based on preexisting opiate doses the patient has been taking.

Determine the indication. Pharmacists should determine the indication and ensure that the patient is opiate-tolerant and suffering from chronic pain before dispensing the medication. In inpatient settings, this information may come from the admission data set or nursing staff. In outpatient settings such as community pharmacies, the information must come from the patient profile, the prescriber, or from the patient (or patient’s family) when the prescription is dropped off, ideally, or when providing counseling, if necessary. (See recommendation for mandatory counseling below.) If a new prescription is received for an opiate-naïve patient or the drug is intended to treat short-term pain, intermittent pain, or post-operative pain, the prescriber should be called to question the order. Verification of the indication and any conversations with the prescriber regarding the patient and the prescribed medication should be documented in a consistent place (e.g., pharmacy computer system, progress notes, order form, outpatient prescription).

Set dosing limits. The fentanyl patch should always be prescribed at the lowest dose needed for pain relief. Inpatient and outpatient pharmacy computer systems as well as computerized prescriber order entry systems should be designed to flash an alert on the screen and create a hard stop if more than 25 mcg/hour has been prescribed as a first-time dose. For patients who are admitted to the hospital and using fentanyl patches at home, the dose should be verified during medication reconciliation, and the verified drug list should be sent to the pharmacy. Healthcare providers should remain cautious about orders for a 125 mcg/hour strength because the decimal point has been overlooked at times with orders for 12.5 mcg/hour patches.

Assess concomitant use of opiates. To reduce the risk of an overdose, take into consideration any other opiates pre-scribed for the patient when evaluating the appropriateness of the patient’s dose.

Limit prescribing privileges. In inpatient settings, consider limiting the prescribing of fentanyl patches to certain categories of prescribers who have been educated about the drug and privileged to prescribe it. Alternatively, orders for patches in doses greater than 25 mcg/hour could be limited to privileged prescribers, or the organization could require a review by a pain management specialist within a specified timeframe.

Mandatory patient education. Patients who are using a fentanyl patch and their caregivers should be educated about how to use the patch safely. In both inpatient and outpatient settings, this education should be mandatory and scripted for pharmacists and nurses to promote consistent discussions about: indications; potency; dose; safety precautions (e.g., avoid heating pads or hot tubs, remove old patch before application of a new patch); application, removal, and disposal processes; and signs of fentanyl toxicity. The patient package insert (or medication guide if one becomes available) should also be provided to the patient. In outpatient settings, pharmacists should use this counseling opportunity to verify that the patient is opiate-tolerant and being treated for ongoing chronic pain. All patient education should be documented in the patient record.

Know the signs of overdose. Healthcare practitioners who prescribe fentanyl patches, and nurses, patients, and caregivers who place the patches on the skin, should be aware of the signs of fentanyl overdoses, including: respiratory distress; shallow breathing; tiredness, extreme sleepiness, or sedation; inability to think, talk, or walk normally; and feeling faint, dizzy, or confused. If these signs occur, patients (or their caregivers) should seek medical attention immediately. Patients (and caregivers) should also know that they may have a sudden and possibly dangerous rise in their blood level of fentanyl or have a stronger effect from fentanyl if they: use other drugs that affect brain function; drink alcohol; have an increase in body temperature or are exposed to heat; or use other medications that affect how fentanyl is broken down in the body (e.g., ritonavir, ketoconazole).

ISMP has communicated with Ortho-McNeil and will also be contacting other manufacturers of fentanyl patches to alert them to the latest reports we have received about overdoses in opiate-naïve patients. We learned that Ortho-McNeil, maker of Duragesic, has filed an updated risk management plan for FDA approval that calls for ongoing surveillance to determine the scope of opiate-naïve patients who have been prescribed a fentanyl patch. They have also developed a patient medication guide, which healthcare providers will be required to give to patients, and indicated that the guide would be freely available on its website soon. We suggested that fentanyl transdermal sales forces provide targeted education to physician groups, perhaps standardizing the educational program and making it easily accessible to all healthcare practitioners. As an additional measure, ISMP will continue pursuing a collaborative effort with community pharmacy chains and independent pharmacies to further develop the mandatory education (counseling) process for patients, including scripted topics that detail the information that should be provided and documented.

Excerpts from product labeling for fentanyl transdermal**

Indication. Fentanyl patches should ONLY be used to manage persistent, moderate to severe chronic pain that requires continuous, around-the-clock opiate administration for an extended period of time, and when the pain cannot be managed by other means such as non-steroidal analgesics, opiate combination products, or immediate-release opiates. Transdermal fentanyl should ONLY be used in patients who are already tolerant to opiate therapy, and who require a total daily dose of other opiates at least equivalent to a 25 mcg per hour fentanyl patch. Patients who are considered opiate-tolerant are those who have been taking, for a week or longer, at least 60 mg of morphine daily, at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily (or an equianalgesic dose of another opiate).

Initial dose. In selecting an initial dose, attention should be given to 1) the daily dose, potency, and characteristics of the opiate the patient has been taking previously, 2) the reliability of dose conversion guidelines featured in the package insert to predict the potency of the fentanyl dose needed, 3) the degree of opiate tolerance, and 4) the patient’s medical status. Equianalgesic dosing tables are available in the package insert for assistance. Overestimating the dose when converting patients from another opiate can result in a fatal overdose with the first dose.

Dose titration. During the initial patch application, patients should use short-acting analgesics as needed until efficacy with fentanyl is attained. There-after, some patients may still require short-acting analgesics for “breakthrough” pain. The starting doses listed in the equianalgesic tables are conservative to reduce the risk of overdosing patients on the first dose; 50% of patients may require a dose increase. The dose may be titrated upwards on the basis of the average daily use of a supplemental analgesic, but no more frequently than 3 days after the initial dose or every 6 days (after 2 patch applications) thereafter.

**The information provided is incomplete and should not be relied upon for prescribing.
Full prescribing information can be found at this link.

[From the the June 28, 2007 issue, Institute for Safe Medication Practices]

The above message comes from "Institute for Safe Medication Practices", who is solely responsible for its content.

Thursday, June 14, 2007

Prevention of Herpes Zoster [Shingles]

In a previous post, we talked about a dreadful disease--"Herpes Zoster" or "Shingles"--that can lead to severe and intractable pain, particularly in the elderly population. In order to refresh your memory, it might help if you refer to the post, linked here.

Vaccination against this condition is now being promoted as an important preventive measure. The article below will shed some light on the question of vaccination and its value for the aging population.

Who should receive zoster vaccine?

In this review, the authors consider the nature of herpes zoster and the preventive value of the herpes zoster vaccine. Herpes zoster will occur in approximately one third of the population during a lifetime. Because immunity conferred by the childhood varicella vaccination wanes over time, reactivation of the virus in older adults becomes increasingly likely with increasing age. Half of those aged 85 will experience at least one zoster outbreak. Postherpetic neuralgia is one troublesome complication of this condition, particularly in the elderly.

Can herpes zoster be prevented? In a large efficacy study, more than 38,000 subjects were randomized to receive live attenuated zoster vaccine or placebo (see Journal Watch Dermatology Jun 14 2005). Compared with placebo recipients, vaccine recipients had a 51% lower incidence of herpes zoster, and less frequent, less painful, and shorter-course postherpetic neuralgia.

The authors, therefore, recommend a single dose of vaccine for everyone over the age of 60, barring contraindications, to decrease the incidence of zoster and postherpetic neuralgia. Whether to vaccinate immunocompromised persons is an open issue that is important to resolve because of increased risk for herpes zoster in this population.

— Lowell A. Goldsmith, MD, MPH

Published in Journal Watch Dermatology March 30, 2007

Kimberlin DW and Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 2007 Mar 29; 356:1338-43. [PubMed® abstract]

Copyright © 2007. Massachusetts Medical Society. All rights reserved.

The above message comes from "Journal Watch", who is solely responsible for its content.

Friday, June 1, 2007

Choosing Non-Opioid Analgesics for Osteoarthritis

The following are the most recent guidelines for treatment of pain caused by osteoarthritis. This information is provided by the United States Department of Health & Human Services, Agency for Healthcare Research and Quality.

This guide summarizes clinical evidence on the effectiveness and safety of non-opioid analgesics for osteoarthritis. It covers most available over-the-counter (OTC) medications and prescription non-steroidal anti-inflammatory drugs (NSAIDs). The reviewed drugs are listed on the back page. This guide does not address non-pharmacologic therapies such as diet, exercise, acupuncture, or surgical interventions.

Clinical Issue Twenty-one million Americans have osteoarthritis. It is a chronic condition associated with pain and substantial disability. Managing pain can assist in maintaining mobility and improving quality of life. Choosing among the available prescription and over-the-counter medications requires careful consideration of benefits, risks, and cost.

The categories of non-opioid drug treatments for osteoarthritis are:

- Acetaminophen.
- NSAIDs, including aspirin and celecoxib.
- Glucosamine and chondroitin.
- Topical medications (including capsaicin, topical salicylates, and topical NSAIDs).


Acetaminophen relieves mild pain but is inferior to NSAIDs for reducing moderate or severe pain. Acetaminophen has fewer systemic side effects than NSAIDs. Level of confidence: HIGH. There are consistent results from good quality studies.

All non-aspirin NSAIDs work equally well for pain reduction. Level of confidence: HIGH. There are consistent results from good quality studies.

NSAIDs increase the risk of GI bleeding. The risk increases with higher doses and with age. People over 75 years old have the highest risk. Level of confidence: HIGH. There are consistent results from good quality studies.

Celecoxib, high dose ibuprofen, and high dose diclofenac increase the risk of myocardial infarction. Naproxen does not increase the risk of myocardial infarction. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

Capsaicin cream relieves chronic osteoarthritic pain, but about half of the people using it will experience local burning sensations. The burning diminishes over time. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

Topical salicylates do not reduce osteoarthritic pain. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.


The most frequent serious complication is gastrointestinal (GI) bleeding due to gastric irritation. Age is one important factor that affects a person's risk, as shown in the box below.

Risk of NSAID-Associated GI Bleeding Increases with Age

- For people age 16-44:
5 of 10,000 people on NSAIDs will have a serious GI bleed
1 of 10,000 people on NSAIDs will die from a GI bleed
- For people age 45-64:
15 of 10,000 people taking NSAIDs will have a serious GI bleed
2 of 10,000 people taking NSAIDs will die from a GI bleed
- For people age 65-74:
17 of 10,000 people taking NSAIDs will have a serious GI bleed
3 of 10,000 people taking NSAIDs will die from a GI bleed
- For people age 75 or older:
91 of 10,000 people taking NSAIDs will have a serious GI bleed
15 of 10,000 people taking NSAIDs will die from a GI bleed

Strategies to Lower the Risk of GI Bleeding

- Avoid NSAIDs for people with a history of GI bleeding. Level of confidence: HIGH. There are consistent results from good quality studies.

- Avoid NSAIDs for people on anticoagulant therapy. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Consider acetaminophen. It is associated with a lower risk of GI bleeding than NSAIDs. Level of confidence: HIGH. There are consistent results from good quality studies.

- Consider co-prescribing proton pump inhibitors (PPIs) or misoprostol. These drugs are effective in reducing GI bleeding for people on NSAIDs. Misoprostol is poorly tolerated by many individuals due to its GI side effects. Level of confidence: HIGH. There are consistent results from good quality studies.

- Consider celecoxib. Results from short-term trials indicate it has a lower risk of GI bleeding than other NSAIDs. Concomitant use of aspirin (even low dose) reduces or negates the benefit of using celecoxib. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.


The cardiovascular risk of NSAIDs has received considerable attention. In general, the increased risk of myocardial infarction for any of the NSAIDs other than naproxen is about 30 per 10,000 people taking NSAIDs per year.

- Celecoxib, ibuprofen at high doses (800 mg three times a day), and diclofenac at high doses (75 mg twice a day) have a higher risk of myocardial infarction compared to not taking these medications. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Naproxen, even at high doses (500 mg twice a day), does not increase the risk of myocardial infarction. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- For other oral NSAIDs, we do not have enough data on cardiovascular risks to make reliable judgments.


- Clinically significant hepatotoxicity is rare for all the NSAIDs in this guide. Level of confidence: HIGH. There are consistent results from good quality studies.

- Diclofenac is associated with higher rates of aminotransferase elevations (compared to other NSAIDs) but not with a higher incidence of serious liver disease. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.


- All NSAIDs, including COX-2 inhibitors, can cause or aggravate hypertension, congestive heart failure, edema, and kidney problems. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- 5 mm Hg is the average increase in mean blood pressure for nonselective NSAIDs. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- 2 out of 1,000 people stop taking an NSAID because of renal problems. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Long-term, regular acetaminophen use is associated with a small decrease in renal function in women but not in men. In people without underlying renal disease, this decrease is unlikely to progress to clinically significant renal failure. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.


- Consider glucosamine and chondroitin. Pharmaceutical grade glucosamine hydrochloride (1500 mg a day) plus chondroitin sulfate (1200 mg a day) reduces moderate to severe pain without serious side effects, but this combination has no effect on mild pain. The Food and Drug Administration (FDA) does not regulate these supplements as drugs, so the purity may vary. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Consider acetaminophen. For mild pain, it is an effective alternative to NSAIDs. Level of confidence: HIGH. There are consistent results from good quality studies.

- Consider capsaicin cream. It relieves chronic osteoarthritic pain, but about half of the people using it will experience local burning sensations. The burning diminishes over time. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Consider topical NSAIDs. They work as well as oral NSAIDs for osteoarthritic pain relief and have fewer systemic side effects. Topical diclofenac and topical ibuprofen are the best studied topicals. The FDA has not approved any topical NSAID formulations, but compounding is widely available. Level of confidence: HIGH. There are consistent results from good quality studies.


- There have been few studies comparing aspirin or salsalate to other NSAIDs for the treatment of osteoarthritis.
- We do not have enough data to make reliable judgments about the cardiovascular risks of many oral NSAIDs. The drugs most studied are celecoxib, ibuprofen, diclofenac, and naproxen.
- There is insufficient evidence to assess whether therapeutic doses (up to 4 gm a day) of acetaminophen lead to liver abnormalities in people without underlying liver disease.
- Results from recent observational studies suggest an increased cardiovascular risk with heavy use of acetaminophen, but large, long-term trials of acetaminophen and associated cardiovascular safety are lacking.
- It is not known whether using celecoxib is a better strategy than adding a PPI or misoprostol to a conventional NSAID for lowering the risk of GI bleeding.

[Please refer to table on line at this link for price information.]

Consumer Guide: Choosing Pain Medicine for Osteoarthritis: A Guide for Consumers is a companion to this Clinician's Guide. It can help people talk with their health care professional about pain relief options. It provides information about:
- Types of over-the-counter and prescription pain relievers.
- Benefits, risks, and price of pain relievers.

The source material for this guide is a systematic review of 351 research publications, Comparative Effectiveness and Safety of Analgesics for Osteoarthritis (2006). The Agency for Healthcare Research and Quality (AHRQ) funded the systematic review and this guide. AHRQ's John M. Eisenberg Center at Oregon Health and Science University developed this guide using feedback from clinicians who reviewed preliminary drafts.

[Osteoarthritis Clinician Guide PDF version] [Osteoarthritis Clinician Guide on-line html version]

The above message comes from "AHRQ", who is solely responsible for its content.

Monday, April 16, 2007

NSAID and Musculoskeletal Pain: Most Recent Guidelines

The following is the latest set of guidelines from the American Heart Association (AHA) regarding the use of non-steroidal anti-inflammatory drugs (NSAID) in the treatment musculoskeletal pain:

A Stepwise Approach to NSAID Use

Given their cardiovascular risks, COX-2 inhibitors should be a last resort for managing musculoskeletal pain.

Sponsoring Organization
American Heart Association


Evidence that selective COX-2 inhibitors, a type of nonsteroidal anti-inflammatory drug (NSAID), increase the risk for serious cardiovascular events has led to a cascade of drug warnings, safety advisories, and even withdrawals from the market. The lingering issue for practitioners has been to pinpoint the appropriate clinical roles for specific NSAIDs and other pain relievers. Now, the AHA has issued a scientific statement on NSAID use for patients with, or at high risk for, heart disease. The statement places management of musculoskeletal pain in a broader context, synthesizes recent evidence on pharmacologic treatment options, and proposes a stepwise approach to treatment.

Key Contextual Points

1. The risks and benefits of any pain-management approach must be understood in light of current evidence, applied appropriately to the individual patient with musculoskeletal pain.

2. Musculoskeletal symptoms should be considered those from tendonitis/bursitis, degenerative joint problems (e.g., osteoarthritis), or inflammatory joint problems (e.g., rheumatoid arthritis).

3. Initial treatment should focus on nonpharmacologic approaches such as physical therapy, heat or cold therapy, and orthotics.

Stepwise Approach to Drug Therapy, If Needed


Step 1 (short-term use): Use acetaminophen, aspirin, tramadol, or a narcotic analgesic at the lowest safe and efficacious dose. Bear in mind the potential for abuse of narcotics by some patients. Also, for low-dose aspirin users with histories of or risk for gastrointestinal bleeding, a concomitant proton-pump inhibitor may reduce that risk.

Step 2: Use a nonacetylated salicylate such as salsalate, sodium salicylate, or choline magnesium trisalicylate.


Step 3: Use a non–COX-2 selective NSAID such as naproxen, ibuprofen, or indomethacin. Naproxen is the widely preferred choice from a cardiovascular standpoint.

Step 4: Use an NSAID with some COX-2 activity such as diclofenac. Diclofenac carries a black box warning against use for perioperative pain in coronary artery bypass graft (CABG) surgery.

Step 5 (the last resort): Use a COX-2–selective NSAID. The only one currently on the market is celecoxib (Celebrex), which carries a broad black box warning about risks for very serious cardiovascular events.

Comment: The authors are clear in saying that COX-2 inhibitor use has been associated with increased risks for MI, stroke, hypertension, and heart failure. They warn that "even a relative lack of COX-2 selectivity does not completely eliminate the risk of cardiovascular events . . . all drugs in the NSAID spectrum should only be prescribed after thorough consideration of the risk/benefit balance." Patients with recent CABG, unstable angina, MI, or ischemic stroke need to be especially cautious. COX-inhibitor use can lead to impaired renal perfusion, sodium retention, and increased blood pressure, thereby increasing the risk for adverse cardiovascular events.

New evidence on the cardiovascular effects of drug therapy for musculoskeletal pain will continue to emerge (e.g., from the forthcoming PRECISION trial comparing celecoxib, ibuprofen, and naproxen). Clinicians should stay abreast of these developments. For now, the AHA’s stepwise approach is a practical one to follow.

— Joel M. Gore, MD

Published in Journal Watch Cardiology March 28, 2007

Antman EM et al. Use of nonsteroidal antiinflammatory drugs: An update for clinicians. A scientific statement from the American Heart Association. Circulation 2007 Mar 27; 115:1634-42.

[Original Circulation article (free pdf)] [Medline® abstract]

Copyright © 2007. Massachusetts Medical Society. All rights reserved.

The above message comes from "Journal Watch", who is solely responsible for its content.

Tuesday, April 3, 2007

Neck Pain

The following is an informative article from the British Medical Journal on cervical spondylosis which can cause neck and arm pain. For full text, click on the link below.

Cervical Spondylosis and Neck Pain

BMJ 2007;334:527-531 (10 March), doi:10.1136/bmj.39127.608299.80
[Free full-text BMJ article (pdf)] [BMJ abstract]

Clinical Review

Allan I Binder, consultant rheumatologist
Lister Hospital, East and North Hertfordshire NHS Trust, Stevenage, Hertfordshire SG1 4AB.
Correspondence to:

Most patients who present with neck pain have "non-specific (simple) neck pain," where symptoms have a postural or mechanical basis. Aetiological factors are poorly understoodw1 and are usually multifactorial, including poor posture, anxiety, depression, neck strain, and sporting or occupational activities.w2 Neck pain after whiplash injury also fits into this category, provided no bony injury or neurological deficit is present.w3 When mechanical factors are prominent, the condition is often referred to as "cervical spondylosis," although the term is often applied to all non-specific neck pain. Mechanical and degenerative factors are more likely to be present in chronic neck pain.

In cervical spondylosis, degenerative changes start in the intervertebral discs with osteophyte formation and involvement of adjacent soft tissue structures. Many people over 30 show similar abnormalities on plain radiographs of the cervical spine, however, so the boundary between normal ageing and disease is difficult to define.w4 Even severe degenerative changes are often asymptomatic, but can lead to neck pain, stiffness, or neurological complications.

I will concentrate on the diagnosis of cervical spondylosis and the evidence available for the different treatments. I will also mention some practical measures that are thought to be important but have not yet been studied. Specific conditions like fibromyalgia, disc prolapse, and whiplash will not be considered, although some patients with these conditions may have been included in therapeutic studies.

Summary points

--The diagnosis of cervical spondylosis is usually based on clinical symptoms.
--Patients need detailed neurological assessment of upper and lower limbs as cervical degeneration is often asymptomatic, but can lead to pain, myelopathy, or radiculopathy.
--"Red flag" symptoms identify the small number of patients who need magnetic resonance imaging, blood tests, and other investigations.
--The best treatments are exercise, manipulation, and mobilisation, or combinations thereof.
--Radiculopathy has a good prognosis and may respond to conservative measures.
--Results of neck surgery for myelopathy or intractable pain are often disappointing.

Box 1 Presenting features of cervical spondylosis


--Cervical pain aggravated by movement.
--Referred pain (occiput, between the shoulder blades, upper limbs).
--Retro-orbital or temporal pain (from C1 to C2).
--Cervical stiffness—reversible or irreversible.
--Vague numbness, tingling, or weakness in upper limbs.
--Dizziness or vertigo.
--Poor balance.
--Rarely, syncope, triggers migraine, "pseudo-angina"w15.


--Poorly localised tenderness.
--Limited range of movement (forward flexion, backward extension, lateral flexion, and rotation to both sides).
--Minor neurological changes like inverted supinator jerks (unless complicated by myelopathy or radiculopathy).

Box 3 "Red flag" features and the conditions they may suggest

Malignancy, infection, or inflammation

--Fever, night sweats.
--Unexpected weight loss.
--History of inflammatory arthritis, malignancy, infection, tuberculosis, HIV infection, drug dependency, or immunosuppression.
--Excruciating pain.
--Intractable night pain.
--Cervical lymphadenopathy.
--Exquisite tenderness over a vertebral body.


--Gait disturbance or clumsy hands, or both.
--Objective neurological deficit—upper motor neurone signs in the legs and lower motor neurone signs in the arms.
--Sudden onset in a young patient suggests disc prolapse.


--History of severe osteoporosis.
--History of neck surgery.
--Drop attacks, especially when moving the neck, suggest vascular disease.
--Intractable or increasing pain.

[References available in the free full-text pdf version]

© 2007 BMJ Publishing Group Ltd.

The above message comes from "BMJ", who is solely responsible for its content.

Wednesday, March 7, 2007

Important FDA Public Health Advisory

Here is an important FDA Public Health Advisory:

Dolophine (Methadone Hydrochloride) - Reports of Death, Narcotic Overdose, and Cardiac Arrhythmias
MedWatch - The FDA Safety Information and Adverse Event Reporting Program

FDA notified healthcare professionals of reports of death and life-threatening adverse events such as respiratory depression and cardiac arrhythmias in patients receiving methadone. These adverse events are the possible result of unintentional methadone overdoses, drug interactions, and methadone's cardiac toxicities (QT prolongation and Torsades de Pointes).

The reports underscore the importance of knowing methadone's toxicities and unique pharmacologic properties, including dosing and monitoring recommendations.

FDA has reviewed reports of death and life-threatening adverse events such as respiratory depression and cardiac arrhythmias in patients receiving methadone. These adverse events are the possible result of unintentional methadone overdoses, drug interactions, and methadone’s cardiac toxicities (QT prolongation and Torsades de Pointes). Physicians prescribing methadone should be familiar with methadone’s toxicities and unique pharmacologic properties. Methadone’s elimination half-life (8-59 hours) is longer than its duration of analgesic action (4-8 hours). Methadone doses for pain should be carefully selected and slowly titrated to analgesic effect even in patients who are opioid-tolerant. Physicians should closely monitor patients when converting them from other opioids and changing the methadone dose, and thoroughly instruct patients how to take methadone. Healthcare professionals should tell patients to take no more methadone than has been prescribed without first talking to their physician.

This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

Read the complete MedWatch 2006 Safety summary, including links to the FDA Healthcare Professional Sheet, Patient Information Sheet, and new prescribing information for Dolophine regarding this issue at this link.
Excerpt from the FDA Healthcare Professional Sheet [November 27, 2006 - Healthcare Professional Sheet - FDA]


Methadone is an effective analgesic and may provide pain relief when other analgesics are ineffective. However, methadone can cause significant toxicities. We are highlighting important safety information from the new label about using methadone for pain. See the methadone label (Dolophine) for more details.

Methadone’s elimination half-life (8-59 hours) is longer than its duration of analgesic action (4-8 hours). Methadone’s peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects. During treatment initiation, methadone’s full analgesic effect is usually not attained until 3-5 days of dosing. Initiation and titration to analgesic effect and dose adjustments should be done cautiously and in consideration of these properties. In chronic use, methadone may be retained in the liver and then slowly released, prolonging the duration of action despite low plasma concentrations.

Cross-tolerance between methadone and other opioids is incomplete. This incomplete cross-tolerance makes the conversion of patients on other opioids to methadone complex and does not eliminate the possibility of methadone overdose, even in patients tolerant to other opioids. Deaths have been reported during conversion from chronic, high-dose treatment with other opioid agonists to methadone. It is critical to understand the pharmacokinetics of methadone when converting patients from other opioids to methadone. Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose adjustments.

Methadone can cause serious cardiac conduction effects, including QT interval prolongation and Torsades de Pointes.

There are pharmacokinetic and pharmacodynamic drug interactions between methadone and many other drugs. Drugs administered concomitantly with methadone should be evaluated for interaction potential.

FDA homepage

Thursday, December 14, 2006

Hot Air Balloons

As I have been quite busy with my other blog, I feel that I owe something to the readers of this one. Before going on with more medical information subjects, here is a bit of entertainment which is a bit faster than the last one, but fun to watch. It is showing the famous annual Albuquerque Balloon Fiesta, hosting over 1000 balloons from allover the world. For an informative post on it, you will find this brand new blog, named The Land of Enchantment, a joy to read....

Friday, December 8, 2006

Relax in the Forest

This post is to relax the mind & the body by showing the beauty of nature in the Redwood National Forest near the Pacific ocean, between California and Oregon.

Tuesday, December 5, 2006

Epidural (Cont-2)

What are the contraindications of epidural anaesthesia?

1) Patient refusal of the procedure.
2) Inability to communicate with the patient.
3) Severe psychiatric disease.
4) Allergy to the drugs used for epidural anaesthesia.
5) Low blood pressure due to hemorrhage or shock state.
6) Anatomical deformity of the spine.
7) Acute neurological disease.
8) Infection at the insertion site of the intended epidural.
9) Systemic infection and septic state.
10) Coagulation disorders.
11) Anticoagulant therapy (blood thinners).
12) Very high blood pressure.
13) Very high blood sugar.
14) Inexperience of the medical practitioner.

Some of the above contraindications are absolute and some are relative. The final decision normally rests after careful consideration of all the factors involved, and after open consultation between the patient and the physician.

Thursday, November 23, 2006

Happy Thanksgiving!

Getting ready for Thanksgiving meal....

A good laugh is worth a thousand shots!

Wednesday, November 22, 2006

Epidural (Cont-1)

What are the indications for epidural anaesthesia?

For the sake of clarity, indications will be classified systematically as shown below.

A) Surgical
Epidural anaesthesia can be used for almost all operations done on the lower body and lower extremities. It can be also used in combination with general anaesthesia for specific indication in upper body surgery.

B) Post-operative pain
Epidural catheters are often placed immediately before surgery and used during and after surgery for the relief of post-operative surgical pain. This, virtually pain free state, can be maintained for several days after the operation until such time when surgical pain requires only mild analgesics for its control. Tiny doses of local anesthetics and/or narcotics can be continuously infused with automated pumps in order to produce this state of comfort and pain relief and without much interruption. Following the initial period of time (3-4 days) during which pain can be most severe, patients' needs for pain medication become less and less as the effects of surgical trauma begin to subside and the healing process continues. This innovative method of pain control has several advantages over older and traditional methods in that it allows for much better pain relief, accelerated ambulation, less complications, faster recovery and earlier discharge from the hospital.

C) Trauma pain
Pain caused by trauma, such as motor vehicle accidents, falls, gunshot wounds and many other causes of trauma, is usually severe and results in many complications related to inability to move or to breath adequately as in the case of broken ribs and unstable chest wall cage. If untreated, it can result in severe disabilities and complications. Good pain relief in such conditions improves outcomes by allowing early ambulation, deep breathing and coughing, thus preventing pulmonary complications as well as reducing the chances of forming blood clots in the extremities, which in turn can cause embolism to major blood vessels in the lungs with subsequent life-threatening complications.

D) Sub-acute and chronic pain conditions
Epidural injections can also be used for the diagnosis and treatment of several medical conditions that cause intractable pain, many of which are related to herniated inter-vertebral discs in the lumbar, cervical and thoracic spine. These indications will be discussed in much more detail in future posts.

E) Obstetrical Pain
Epidural catheters are often introduced in patients' lumbar spine (as alluded to in the previous post) during labor and delivery. Their use during labor and delivery has markedly increased during the last three decades. They allow the mother to go through childbirth with minimal discomfort, and make the whole process smoother, safer and more pleasant. Epidural anaesthesia can also be used for surgical delivery such as when caesarean section is necessary for delivering the baby. More will be written on this in future posts.

(Intrathecal means inside the spinal fluid)

F) Cancer related pain

Epidural catheters can be implanted and tunneled under the skin for long term use in the treatment of intractable, severe cancer pain. These catheters can be left in place for months and even years if necessary. They facilitate the ability to continuously infuse small amounts of pain relieving medications, such as morphine, directly into the spine, thus allowing the drug to be infused as close as possible to the central nervous system. Normally when narcotics are administered orally or by injection (intramuscular, under the skin or intravenous), they will have to cross a barrier between the blood and the brain in order to reach their target receptors in the central nervous system. By injecting these drugs directly into the spinal canal, close to the nerves and the spinal fluid, much smaller doses are required in order to accomplish the degree of pain relief that is possible with much higher doses of the drug when given systemically. The quality of pain relief is also far more superior when the drugs are delivered closer to the sites of their action. In other words, this method of administration allows us to get to the receptors in the central nervous system "by the back door." There will be more details on this particular subject in future posts.

To be Continued....

Saturday, November 18, 2006


What is an epidural?

An epidural is a procedure done to either provide a painless state in order to perform surgery and to have childbirth without significant pain, or is used for the diagnosis & treatment of certain chronic pain conditions.

Anatomy: there is a potential space (epi- or extra-dural) located outside the dura which is a thick membrane surrounding the spinal cord and its terminal nerve structures that are called cauda equina. The spinal cord and all these nerve structures are bathed in a watery fluid medium called cerebrospinal fluid which provides the central nervous system with protection, pressure balance, suspension and nutrition. The spinal fluid is contained in between an internal membrane called pia mater and two external coverings (membranes), the first of which is called arachnoid mater and the second and outermost layer is called dura mater.

Just outside the dura mater there is a narrow space containing veins, fat, lymphatics, and through which the nerves travel on their way exiting the spinal canal towards their target sites in the body. This narrow space is termed Epidural Space, and is surrounded on the outside with strong ligaments, periosteum (a strong layer of tissue on the surface of bone) and bony structures that form the spine.

When a person receives an "epidural" it implies the placement of a needle into that space (epidural space), and through that needle a catheter is introduced into the epidural space, then the needle is removed and the catheter is secured in place so that medications can be delivered over extended periods of time. For other specific indications, the medications can be injected directly through the needle as a "one shot" technique, and the needle is then removed.

To be continued....

Wednesday, November 8, 2006

Acute & Chronic Pain


What are the main differences between acute and chronic pain?


Acute pain, even though is not a pleasant sensation, serves a useful function. Without the sensation of pain we could easily injure or burn ourselves without knowing it. Another example: if we do not feel the pain caused by a disease condition, such as acute appendicitis, we would not know that we suffer from a serious medical condition and neglect to seek medical help; so in this case pain acts as a warning signal telling us that something is wrong with our body. Acute pain is usually associated with other signs of increased sympathetic nervous system activity, such as increase in blood pressure, rise in heart rate, sweating, pallor, anxiety, fear and restlessness.

On the other hand, chronic pain is the sensation of pain that continues after the complete healing of the initial cause of pain and might last for months, weeks or years. It no longer serves a useful function, and becomes a disease on its own. It is not associated with rise in blood pressure or heart rate, but is rather accompanied with significant changes in personality and behavior. It leads to depression, anxiety and anger. In some cases it can be accompanied with manifestations of hypochondriasis and hysteria as well as certain personality disorders. it leads to employment difficulties, job loss, socio-economic consequences, drug dependence and abuse, as well as family difficulties and divorce. In severe and intractable cases, it can even lead to suicide.

One of the examples of chronic pain conditions is shingles (herpes zoster), an extremely painful condition caused by the reactivation of a dormant varicella-zoster virus which infects young people--mostly children--causing the disease known as chickenpox. After the resolution of this disease, the virus becomes dormant (goes to sleep) and remains in the body hidden in the brain and the spinal cord in certain nerve tissue relay structures called ganglia.

Later on in life the virus can reactivate as a result of a variety of factors, such as decreased immunity, cancer, HIV infection, trauma to the nervous system, toxic exposure, severe illness and many other conditions. When the virus reactivates (wakes up) it spreads along the individual nerves connected to these ganglia. causing severe nerve pain and rash. The older the person the more likelihood of continuation of pain after the complete healing of the rash, which is the result of permanent nerve damage.

This is a perfect example of differences between acute and chronic pain and it illustrates how an acute condition could turn into a chronic disease.

Sunday, November 5, 2006

Purpose Of This Blog & Disclaimer

The main purpose of this blog, as a public service, is to provide the readers with information regarding all questions related to anaesthesia and resuscitation for surgical operations, including pre-operative preparation, intra-operative care and post-operative management. It will also address issues related to pain management in the acute setting--such as in trauma and obstetrics--as well as in chronic pain conditions, with special emphasis on cancer-related pain.

In order to assess the needs of the readers, questions and comments are strongly encouraged.

The content of this blog is not intended as a substitution for advice you receive from your personal physician, and is provided to help improve awareness and education of the public. Therefore the blog's author does not assume any legal responsibility for any content, information or advice given on this blog.

This blog does not represent or imply the practice of medicine in any form.