Category Archives: Complications

The Impact Of NSAIDs On Fracture Healing

In my last post I discussed some of the basic effects of NSAIDs on bone healing. Now let’s see if theory applies to practice.

In 2003, several papers brought to light possible interactions between these drugs and fracture healing. Specifically, there were questions about these drugs interfering with the healing process and of increasing the number of delayed unions or nonunions. But once again, how convincing were these papers, really?

It would seem to make sense that NSAIDs could interfere with bone healing. The healing process relies heavily on the regulation of osteoblast and osteoclast function, which itself is regulated by prostaglandins. Since prostaglandins are synthesized by the COX enzymes, COX inhibitors like the NSAIDs should have the potential to impair this process. Indeed, animal studies in rats and rabbits seem to bear this out.

But as we have seen before, good animal studies don’t always translate well into human experience. Although a study from 2005 suggested that NSAID administration in older patients within 90 days of injury had a higher incidence of fracture nonunion, the study design was not a very good one. It was equally likely that patients who required these drugs in this age group may have been at higher risk for nonunion in the first place.

A meta-analysis of human studies was performed in 2011. Out of 558 potential studies, only 5 met criteria review. (This is yet another reminder of the sheer amount of sub-par research out there.) The authors found that short-term use (< 14 days) of normal dose NSAIDS was not associated with non-union. High doses of ketorolac (> 120mg/day) and diclofenac sodium (> 300mg total) did have an association. But remember, this does not show causation. There are many other factors that can impede healing (smoking, diabetes, etc).

A study from 2016 examined the effect of ketorolac administration on fracture healing in patients undergoing repairs of femoral and tibial fractures. It did not find an association between non-union and ketorolac, but did find one with smoking. Unfortunately, the study was small (85 patients given ketorolac, 243 controls without it). It probably does not have the statistical power to detect any difference with the NSAID. A power analysis was not provided in the methods section.

Bottom line: Once again, the animal data is clear and the human data less so. Although there are theoretical concerns about NSAID use and fracture healing, there is still not enough solid risk:benefit information to abandon short-term NSAID use in patients who really need them. NSAIDs can and should be prescribed in patients with short-term needs and simple fractures, and consider COX-1 specific drugs like ketorolac while your patient is in the hospital. And we do have some evidence that high-dose NSAIDs may have some impact, so stick to the usual doses for just as long as they are needed for pain management.

References:

  1. Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing. J AM Acad Orthop Surg 12:139-43, 2004.
  2. Effect of COX-2 on fracture-healing in the rat femur. J Bone Joint Surg Am 86:116-123, 2004.
  3. Effects of perioperative anti-inflammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy 25:1566-1591, 2005.
  4. Pharmacological agents and impairment of fracture healing: what is the evidence? Injury 39:384-394, 2008.
  5. High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion. Can J Anaesth 52:506-512, 2005.
  6. Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality. JBJS Rev 4(3), 2016.
  7. High-dose ketorolac affects adult spinal fusion. Spine 36(7):E461-E468, 2011.
  8. Ketorolac administered in the recovery room for acute pain management does not affect healing rates of femoral and tibial fractures. J Orthop Trauma 30(9):479-482, 2016.
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NSAIDs And Bone Healing: How Do They Impact It?

The arguments about whether NSAID administration has any effect on bone healing continues to be argued by our orthopedic and spine surgery colleagues. In the early days of research in this area (about 20 years ago) there were concerns in animal models that there might be a problem. Apparently lots of rats and bunnies were suffering from fractures in those days.

But physiologically, how could NSAIDS do this? Here’s a simplified diagram of how the bone healing process works.

First, an acute injury occurs and macrophages and other cells move into the area to start the inflammatory process. COX-2 receptors are highly expressed on these cells, resulting in an increase in prostaglandin E2 (PGE2) production.

PGE2 then promotes proliferation of stem cells that differentiate into osteoblasts, which in turn begin forming bone to repair the injury.  In theory, if PGE2 is reduced in the healing area there is the possibility that bone formation may be impaired, leading to non- or malunion or refracturing.

Administration of NSAIDs can block COX-1 and COX-2 receptors throughout the body. This serves to decrease prostaglandin production and hence reduces inflammation and pain. Doesn’t it follow that giving these drugs should be bad for bone formation in patients with fractures?

Not so fast! There are a number problems with this argument. First, not all NSAIDs are created alike. Here is a chart that shows where the primary focus of COX inhibition is with some common NSAIDs.

Note how the common over-the-counter drugs affect both COX-1 and COX-2, yet there are some that are more selective. So the choice of drug may be relevant.

And we can’t assume that an in vitro effect in a Petri dish of cells actually carries over into the in vivo world. Many researchers rely initially on animal models to study drug effects in vivo. Predictions based on studies of rats and bunnies frequently do not pan out in humans.

We are left with only a theory based on an understanding of the basic mechanism of bone healing. Tune in to my next post where I discuss the research that’s been done in this field and whether it actually translates into human bone healing or not.

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The Tertiary Survey For Trauma: Residents vs APPs

This is the final installment of my series on the tertiary survey for trauma.  For years, this exam was performed by trauma surgeons or residents. However, over the years advanced practice providers (APPs) such as physician assistants and nurse practitioners have become more common in trauma. It is now commonplace for these providers to participate on the trauma service, perform procedures, and document examinations such as the tertiary survey.

But until now, no one has compared the accuracy of this exam when performed by a physician vs an APP. One would assume that the results should be the same, but as we’ve seen time and time again, common sense doesn’t always pan out. A group at the Royal Brisbane and Women’s Hospital in Queensland, Australia tried to answer this question using a retrospective review of their experience.

This busy trauma center admits about 2,250 patients per year, and began to employ clinical nurse consultants on the trauma service nearly ten years ago. Since there was no formal trauma curriculum for these nurses, they were required to complete the Trauma Nursing Core Curriculum (TNCC) or an equivalent prior to hire. The nurses were supervised by one of the trauma / emergency physicians.

For this study, 165 patients who underwent a tertiary survey by both an emergency medicine resident and a trauma nurse over a three year period were reviewed. The surveys were typically performed within 24 hours of admission to a ward bed or 24 hours before transfer from ICU to the ward. Typically, the resident and nurse tertiary surveys were performed within 30 minutes of each other to avoid any effects from injury progression.

All missed injuries were graded for severity by an attending physician using the Clavien-Dindo system. Here’s what it looks like:

And here are the factoids:

  • A total of 3,065 patients had a tertiary survey performed during the study period, but only 165 had it performed by both a resident and an APP
  • Based on their surveys, additional investigations were ordered in 35 patients, 14 by the trauma nurse, 11 by the resident, and 10 by both
  • Eight of 14 studies ordered by the nurse identified a missed injury, two of 11 studies ordered by the resident did, and two were identified in the studies ordered by both
  • Of the 12 identified missed injuries, the Clavien-Dindo (C-D) score was 0 in one, I in ten patients, and III (required surgery) in one
  • The nurses identified a higher number of missed injuries (10 of 24) than the residents (4 of 21) without significantly increasing the number of tests ordered

The authors concluded that performance of the nurses was similar to that of the house officers.

Bottom line: Maybe the authors were trying to be gentle on their residents. But it looks to me like the trauma nurses did a much better job of finding occult injuries. I wish the authors had broken down the C-D scores to see which group identified the score III patient.

To be fair, this study has some significant limitations. Out of more than 3,000 eligible patients, only 165 had a dual tertiary survey. So the sample may not be representative. But the results were impressive enough that I would speculate the results of a larger group may be similar.

So I think it is safe to assume that APPs (specifically nurse practitioners, but this can probably be generalized to physician assistants as well) can do a tertiary survey just as well as a resident. And possibly better!

Reference: Trauma tertiary survey: trauma service medical officers and trauma nurses detect similar rates of missed injuries. J Trauma Nursing 28(3):166-172, 2021.

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The Tertiary Survey For Trauma: Does It Work?

Here’s the second part in my series on the tertiary survey for trauma. In my last post I discussed the basics, and in the next and final one I’ll review who can do it.

Delayed diagnoses / missed injuries are with us to stay. The typical trauma activation is a fast-paced process, with lots of things going on at once. Trauma professionals are very good about doing a thorough exam and selecting pertinent diagnostic tests to seek out the obvious and not so obvious injuries.

But we will always miss a few. The incidence varies from 1% to about 40%, depending on who your read. Most of the time, they are subtle and have little clinical impact. But some are not so subtle, and some of the rare ones can be life-threatening.

The trauma tertiary survey has been around for at least 30 years, and is executed a little differently everywhere you go. But the concept is the same. Do another exam and check all the diagnostic tests after 24 to 48 hours to make sure you are not missing the obvious.

Does it actually work? There have been a few studies over the years that have tried to find the answer. A paper was published that used meta-analysis to figure this out. The authors defined two types of missed injury:

  • Type I – an injury that was missed during the initial evaluation but was detected by the tertiary survey.
  • Type II – an injury missed by both the initial exam and the tertiary survey

Here are the factoids:

  • Only 10 observational studies were identified, and only 3 were suitable for meta-analysis
  • The average Type I missed injury rate was 4.3%. The number tended to be lower in large studies and higher in small studies.
  • Only 1 study looked at the Type II missed injury rate – 1.5%
  • Three studies looked at the change in missed injury rates before and after implementation of a tertiary survey process. Type I increased from 3% to 7%, and Type II decreased from 2.4% to 1.5%, both highly significant.
  • 10% to 30% of missed injuries were significant enough to require operative management

Bottom line: In the complex dance of a trauma activation, injuries will be missed. The good news is that the tertiary survey does work at picking up many, but not all, of the “occult” injuries. And with proper attention to your patient, nearly all will be found by the time of discharge. Develop your process, adopt a form, and crush missed injuries!

Reference: The effect of tertiary surveys on missed injuries in trauma: a systematic review. Scand J Trauma Resusc Emerg Med 20:77, 2012.

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The Tertiary Survey for Trauma: The Basics

After a recent request, I’m re-posting a three part series on the trauma tertiary survey. Today, I’ll cover the basics. In the next two posts I’ll dig into how well it works and who can do it.

Major trauma victims are evaluated by a team to rapidly identify life and limb threatening injuries. This is accomplished during the primary and secondary surveys done in the ED. The ATLS course states that it is more important for the team to identify that the patient has a problem (e.g. significant abdominal pain) than the exact diagnosis (spleen laceration). However, once the patient is ready for admission to the trauma center, it is desirable to know all the diagnoses.

This is harder than it sounds. Physical examination tends to direct diagnostic testing, and some patients may not be feeling pain, or be awake enough to complain of it. Injuries that are painful enough may distract the patient’s attention away from other significant injuries. Overall, somewhere between 7-13% of patients have injuries that are missed during the initial evaluation.

A well-designed tertiary survey helps identify these occult injuries before they are truly “missed.” This survey consists of a structured and comprehensive re-examination that takes place within 48-72 hours, and includes a review of every diagnostic study performed. Ideally, it should be carried out by two people: one familiar with the patient, and the other not. It is desirable that the examiners have some experience with trauma (sorry, medical students).

Why 48-72 hours? Why not just do it when the patient leaves the ED, or when they arrive on the floor? Many occult injuries take time to show themselves. Swelling or bruising takes many hours to become obvious. And the patient may have distracting injuries and just won’t notice a sore finger or wrist that early.

And you can’t wait too long either! Otherwise the issue becomes a clearly delayed injury. A best practice is to require the tertiary survey be done within a specific window (24-48 hours, 48-72 hours, whatever works for your trauma team. Any injuries found in that time interval are not delayed diagnoses, since this process is designed to identify those pesky injuries. Any found after the time interval expires must go through a formal PI review at the primary and/or secondary levels.

The patients at highest risk for a missed injury are those with severe injuries (ISS>15) and/or impaired mental status (GCS<15). These patients are more likely to be unable to participate in their exam, so a few injuries may still go undetected despite a good exam.

I recommend that any patient who triggers a trauma team activation should receive a tertiary survey. Those who have an ISS>15 should also undergo the survey. Good documentation is essential, so an easy to use form should be used. Click here to get a copy of our original paper form. We have changed over to an electronic record, and have created a dot phrase template, which you can download here.

In my next post: Does the tertiary survey actually work?

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