All posts by TheTraumaPro

Calcitonin Nasal Spray And Osteoporosis

Osteoporosis is a major risk factor for fractures in our elderly patients, particularly postmenopausal females. A number of treatment modalities have been introduced, primarily medications. One of the less expensive of these is salmon calcitonin nasal spray. This drug has been used sporadically in the spine surgery community and I’ve always been curious about the supporting data. So I finally looked into it and wanted to share my findings.

The earliest research that most tend to hang their hat on is the Prevent Recurrence of Osteoporotic Fractures (PROOF),  a five-year study from the early 90’s published in 2000. It was a double-blind placebo controlled study involving 47 centers in the US and UK. All subjects received supplemental calcium and Vitamin D daily. They also received one of three different doses of nasal calcitonin or a placebo daily.

Completion rates were dreadful. A total of 1,255 women with established osteoporosis started the study. Only 783 made it to 3 years and 511 to 5 years. Partly, this was due to the fact that the patients’ repeat bone density results were unblinded to the investigators, and the “statistically significant” increase in this value was only about 1.5%. I don’t believe that this is even close to clinically significant. Thus, the investigators and patients may have seen this as ineffective, dropped out of the study, and switched to some newer treatment.

As I mentioned, the study used a placebo dose of nasal spray, as well as 100, 200, or 400 unit doses daily. It is puzzling that only the 200 unit dose showed any statistically significant decline in recurrent spine fracture rate. Since the numbers in each analysis group were low due to patient attrition (about 275 in each group), this raises the question of whether this is a statistical anomaly. One would expect to see some sort of dose-response curve, not just a result only for the middle of the road dose.

The authors concluded that the 200 unit dose significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis. And unfortunately, multiple authors and clinicians have taken this to heart without questioning the real results in the paper.

A newer study, Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL), published in 2012, compared oral vs nasal calcitonin in 565 women. Their endpoints were changes in bone density and markers of bone turnover. The oral group had a whopping increase (haha) in lumbar bone density of 1.5%, while nasal and placebo dosing were the same at about 0.5-0.8%. This is in no way clinically significant. And paradoxically this bone density increase appeared to peak by week 24 and then slowly decline.

Similarly, bone turnover markers decreased. Interestingly, of the three markers measured, some were statistically significant for oral, nasal, and even placebo. There was no consistent pattern. And furthermore, there is no way to translate these lab tests into risk for fracture.

Bottom line: Although nasal calcitonin spray is cheap (about $1 per day), there is no valid literature that supports that it decreases the risk of future vertebral fractures. Always remember that there is a difference between what is significant to the statisticians, and what is clinically significant to your patient. Incidentally, between 10% and 40% of these patients had adverse effects from the medication, usually GI in nature. So if a drug has a measurable risk but little actual benefit, is it worth even a buck?

Osteoporosis takes decades to develop and become clinically significant. It is unlikely that a quick fix like a drug, sprayed, swallowed, or injected will make a difference in the short term. The best treatments are free (diet and exercise) but must be adopted long before it becomes a problem.

References:

  1. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med 109(4):267-276, 2000.
  2. A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: The oral calcitonin in postmenopausal osteoporosis (ORACAL) trial. J Bone Mineral Res 27(8):1821-1829, 2012.

The Post-Crunch Debriefing

Trauma centers generally design their trauma teams around the type and volume of injured patients they receive. There must be sufficient depth of coverage to handle multiple “hits” at once. But even the best planning can be overwhelmed by the occasional confluence of the planets where multiple, multiple patients arrive during a relatively short period of time (the “crunch”).

As the reserve of available trauma professionals to see new, incoming patients dwindles, it sometimes even becomes necessary to close the center to new patients. Once those who have already arrived have been processed, the trauma center can open again.

This scenario, while hopefully rare, unfortunately introduces a huge opportunity for errors and omissions in care. There is much more clinical activity, lots of patient information to be gathered and processed, and many decisions to be made. How can you reduce the opportunity for these potential problems?

Consider a “post-crunch” debriefing! Once things have quieted down, assemble all team members in one room. Systematically review each patient involved in the “crunch”, going through physical exam, imaging, lab results, and the final plan. It’s helpful to have access to the electronic medical record during this process so everything that is known can be reviewed. Make sure that all clinical questions are answered, and that solid plans are in place and specific people are assigned to implement them. And most importantly, make sure everything is properly documented. Remember:

“Work not documented is work not done!”

Once you’ve reviewed all of the incoming, don’t forget your patients already in the hospital. Significant issues may have occurred while you were busy, so quickly review their status as well. Chat with their nurses for updates. Make sure they are doing okay.

Then prepare yourself for the next “crunch”!

Related post:

Time for some more philosophy! After providing trauma care for decades, one begins to see the common threads and underlying principles of their area of expertise. I’ve been trying to crystallize these for years, and today I’m going to share one of the most basic laws of trauma care.

The First Law of Trauma: Any anomaly in your trauma patient is due to trauma, no matter how unlikely it may seem.

Some examples:

  • An elderly patient who crashes his car and presents with arrhythmias and chest pain is not having a heart attack. Nor does he need a cardiologist or a trip to the cath lab.
  • A spot in the liver after blunt trauma is not a cyst or hemangioma; it is a laceration until proven otherwise.
  • A patient found at the bottom of a flight of stairs with blood in their head did not have a stroke and then fall down.

Bottom line: The possibility of trauma always comes first! It is your job to rule it out. Only consider non-traumatic problems as a last resort. Don’t let your non-trauma colleagues try to steer you down the wrong path, only to have your patient suffer.

What’s The Best Trigger For Your Massive Transfusion Protocol?

Every trauma center verified by the American College of Surgeons Committee on Trauma (ACS-COT) must have a massive transfusion protocol (MTP). The details and logistics of the protocol are up to the individual center. The difficult question is: how is a trauma professional to know that the MTP should be activated?

Sometimes it’s extremely obvious. The patient is very hypotensive. Blood is spurting all over the room. But sometimes it’s more subtle and the need just seems to creep up on you. And frequently, this delays activation and the actual arrival of the blood that is so desperately needed.

I’ve previously written about common triggers for the MTP, including psychic powers, shock index, and ABC index. See the links below to read my MTP week posts. But is one better than the other? The group at Vancouver General Hospital in British Columbia, Canada performed a systematic review of the literature to try to answer this question.

A total of 45 pertinent articles were identified in the literature up to 2017. Fifteen different scoring systems were evaluated involving combinations of clinical assessment, laboratory tests, and ultrasound evaluation.

Here are the factoids:

  • The best validated score using clinical assessment plus ultrasound was the Assessment of Blood Consumption score (click here for my post). This was the easiest to score compared to other systems using ultrasound.
  • Shock index (SI) was the only validated system using just the clinical exam
  • Some other studies were promising, with excellent areas under the receiver operating characteristic curve (AUROC), but had not been validated. The best of the bunch was one from Mina et al, but it is complicated enough to require a smartphone tool for calculation.
  • Other promising studies required laboratory evaluations which preclude their use at the time of patient arrival
  • Scoring systems that used more variables generally showed better correlation with actual need for MTP, but were more less likely to provide suficiently early predictions
  • Most validation studies involved single centers
  • No studies were designed to or able to show improved outcomes

Bottom line: There are many, many systems out there for predicting need for activation of the MTP (at least 15 to date)! This review concludes that the system used should be tailored to the center implementing it.

Simpler is better. I still recommend either Shock Index (SI) or ABC. Shock index is quickly calculated based on physical exam as heart rate divided by systolic blood pressure. The normal range is 0.5 to 0.7. The likelihood of MTP escalates 2x with SI > 0.9, 4x if SI > 1.1, and 7x with SI > 1.3. The ratio can easily be calculated based on numbers available from EMS providers prior to arrival. Basically, pick your threshold.

The Assessment of Blood Consumption (ABC) uses four parameters, three of which could be reported prior to patient arrival:

  • Heart rate > 120
  • Systolic blood pressure < 90
  • FAST positive
  • Penetrating mechanism

If two or more criteria are met, the patient has a 41% likelihood of needing MTP.

So basically, use a system that works for you. From my experience, centers that use a system tend to use ABC. But definitely pick a system, don’t leave it up to chance with the trauma surgeon. And use your trauma PI program to assess utilization to see if it’s the best tool for your center.

Related posts:

Reference: Systematic Reviews of Scores and Predictors to Trigger Activation of Massive Transfusion Protocols. Accepted ahead of print, J Trauma, 2019.

NFTI Scoring Revisited – Not Just For Triage Calculations?

Earlier this week, I wrote about a new tool for monitoring over- and under-triage for trauma programs. In place of using ISS as the metric for triggering review, the Need For Trauma Intervention (NFTI) is based on resource utilization during the initial portion of the hospital stay.

The original study was performed at a single Level I trauma center in Dallas. The authors then rolled it out as a multicenter study to test its overall reliability. However, the authors changed the focus in this work. The original paper focused on the development of a new tool to improve upon the evaluation of proper decisions to activate the trauma team. The authors have now extrapolated that their system predicts when a patient’s physiologic reserve is depleted. In turn, this should be the indicator that a trauma activation is needed.

The authors performed a convenience sample of 38 trauma centers around the US. Of these, 25 were adult only, 3, pediatric only, and 10 were combined adult/peds centers. Two years of data were collected from each. Injury severity score (ISS) and revised trauma score (RTS) were calculated for all patients. Outcomes analyzed were discharge location (home vs ongoing care), complications, and length of stay.

A complicated statistical model was adopted that evaluated the associations between higher ISS (> 15), lower RTS (< 7.84) and any positive NFTI factor. To refresh your memory, here’s the list of NFTI factors:

  • blood transfusion within 4 hours of arrival
  • discharge from ED to OR within 90 minutes of arrival
  • discharge from ED to interventional radiology (IR)
  • discharge from ED to ICU AND ICU length of stay at least 3 days
  • require mechanical ventilation during the first 3 days, excluding anesthesia
  • death within 60 hours of arrival

Here are the factoids regarding the new study:

  • Nearly 90,000 patient encounters were submitted over a 2 year period
  • The risk of experiencing a complication increased by 9x if NFTI+, 6x for ISS>15, and 5x for RTS<7.84
  • Odds of discharge to a continuing care facility was about 2.5x more likely if any of the three thresholds were met
  • Length of stay was significantly better predicted by NFTI

The authors conclude that NFTI was a better indicator of major trauma when compared to ISS and RTS. They claim that it is the best single definition because the model fit is better and that it has stronger associations with complications, discharge location, and length of stay.

Bottom line: Hmm, I’m not so sure. It’s a great idea and does allow us to drill down on those patients most in need of high-level trauma center resources. The authors admit that each tool (ISS, RTS, and NFTI) identifies some important patients that the others do not. It just seems that more of them tend to be identified by NFTI.

I always worry when complicated statistical models are needed to show these differences. This is a complex concept, so more sophisticated models may indeed be needed by virtue of the data that needs to be analyzed. Overtriage can be easily identified in many cases when NFTI- patients trigger a full trauma activation. Obvious undertriage occurs in NFTI+ patients with no activation.

But NFTI still does not obviate the need to search harder for undertriage. What about the case of a stab to the chest in the “box” region, who does not end up with a cardiac injury or hemo/pneumothorax? They would be NFTI- but mechanism positive.

How do we learn from NFTI+ patients who did not have a trauma activation. Just like using the Cribari grid, we must look at each individual chart and ask two questions:

  1. Did this patient meet any of our highest level activation criteria? If so, it is frank undertriage.
  2. If not, do we need a new criterion to catch this in the future?

So NFTI is a somewhat improved version of the Cribari grid. Sure, it can predict complications better, as well as length of stay (which may be related). But not discharge location, as claimed. As for being an indicator of depleted patient reserve, I think that’s just speculation at this point. Both tools can be used to automatically generate data for review from the trauma registry. And both will have some false negatives and positives.

My recommendation: This paper provides an academic argument that NFTI is somewhat better than the Cribari method. Now it’s time to get practical. Some enterprising trauma centers need to do a study where they use both systems side by side. How many charts for review are generated by each? How many false negatives and positives are there? How much work (abstractor / registrar time) is needed to analyze and act on the results? This is the only way we can answer the question of which one is better in the real world.

Reference: Rethinking the definition of major trauma: The Need For Trauma Intervention outperforms Injury Severity Score and Revised Trauma Score in 38 adult and pediatric trauma centers. J Trauma publish ahead of print, 2019.