Research | Rogue Medic

We are there for the good of the patient, not for the good of the protocol, not for the good of the medical director, and not for the good of the company.

- Rogue Medic

Intramuscular Midazolam for Seizures – Part I

Fri, 17 Feb 2012 12:10:30 +0000 By Rogue Medic 4 Comments

A study of IM (IntraMuscular) midazolam for EMS to treat seizures. The study looks at status epilepticus, but any seizure still present when EMS arrives should be treated. The terminology does not help. The only time I use the term status epilepticus is when teaching/writing about seizures; not when describing what I treated; not when thinking about what to do.

Many emergency medical services (EMS) systems, however, have begun to use intramuscular midazolam rather than an intravenous agent, largely because intramuscular administration is faster and is consistently achievable. ² This practice has become increasingly common despite the lack of clinical-trial data regarding the efficacy and safety of intramuscular midazolam.^[1]

Really?

In about an hour, using PubMed and Google, I found these. All of them examine the use of IM midazolam. Only one is not on humans.

1988

IM midazolam for status epilepticus in the emergency department.
Mayhue FE.
Ann Emerg Med. 1988 Jun;17(6):643-5.
PMID: 3377295 [PubMed - indexed for MEDLINE]

A 71-year-old man presented with a continuous generalized tonic-clonic seizure of 80 minutes duration. Multiple attempts to establish an IV line failed. Ten milligrams of midazolam hydrochloride was administered IM and was followed by prompt termination of seizure activity. This report discusses the pharmacokinetic and anticonvulsant properties of midazolam as an alternative to diazepam for the initial treatment of status epilepticus.

1991

A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy.
Bell DM, Richards G, Dhillon S, Oxley JR, Cromarty J, Sander JW, Patsalos PN.
Epilepsy Res. 1991 Nov-Dec;10(2-3):183-90.
PMID: 1817958 [PubMed - indexed for MEDLINE]

Since intravenous administration of AEDs including diazepam is not always feasible in status epilepticus there are obvious advantages in having an effective intramuscular formulation. Our data suggest that midazolam may be such a drug.

1992

Midazolam in treatment of epileptic seizures.
Lahat E, Aladjem M, Eshel G, Bistritzer T, Katz Y.
Pediatr Neurol. 1992 May-Jun;8(3):215-6.
PMID: 1622519 [PubMed - indexed for MEDLINE]

Midazolam (Versed), the first water-soluble benzodiazepine, has had widespread acceptance as a parenteral anxiolitic agent. Its antiepileptic properties were studied in adult patients with good results. Midazolam was administered intramuscularly to 48 children, ages 4 months to 14 years, with 69 epileptic episodes of various types. In all but 5 epileptic episodes, seizures stopped 1-10 min after injection. These results suggest that midazolam administered intramuscularly may be useful in a variety of epileptic seizures during childhood, specifically when attempts to introduce an intravenous line in convulsing children are unsuccessful.

1994

Intravenous versus intramuscular midazolam in treatment of chemically induced generalized seizures in swine.
Orebaugh SL, Bradford SM.
Am J Emerg Med. 1994 May;12(3):284-7.
PMID: 8179731 [PubMed - indexed for MEDLINE]

It is concluded that midazolam is effective in the control of tonic-clonic manifestations of generalized seizures when administered by the IV or the IM route

1997

Midazolam in treatment of various types of seizures in children.
Yakinci C, Müngen B, Sahin S, Karabiber H, Durmaz Y.
Brain Dev. 1997 Dec;19(8):571-2.
PMID: 9440805 [PubMed - indexed for MEDLINE]

No side effects were observed. These results suggest that i.m. administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (i.v.) line problem.

A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children.
Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y.
Pediatr Emerg Care. 1997 Apr;13(2):92-4.
PMID: 9127414 [PubMed - indexed for MEDLINE]

CONCLUSIONS:
IM midazolam is an effective anticonvulsant for children with motor seizures. Compared to IV diazepam, IM midazolam results in more rapid cessation of seizures because of more rapid administration. The IM route of administration may be particularly useful in physicians’ offices, in the prehospital setting, and for children with difficult IV access.

1999

Use of intramuscular midazolam for status epilepticus.
Towne AR, DeLorenzo RJ.
J Emerg Med. 1999 Mar-Apr;17(2):323-8. Review.
PMID: 10195494 [PubMed - indexed for MEDLINE]

The pharmacodynamic effects of midazolam can be seen within seconds of its administration, and seizure arrest is usually attained within 5 to 10 min. Case reports and a recent randomized trial that demonstrate the successful use of i.m. midazolam in the termination of epileptic seizures are reviewed.

2002

Midazolam for the treatment of out-of-hospital pediatric seizures.
Vilke GM, Sharieff GQ, Marino A, Gerhart AE, Chan TC.
Prehosp Emerg Care. 2002 Apr-Jun;6(2):215-7.
PMID: 11962570 [PubMed - indexed for MEDLINE]

CONCLUSION:
Prehospital IV midazolam is an effective intervention for pediatric seizures, while IM midazolam was associated with a 20% failure rate, with both having minimal risk of respiratory compromise.

This was the only study of midazolam cited as a midazolam study by the authors.

Controlling seizures in the prehospital setting: diazepam or midazolam?
Rainbow J, Browne GJ, Lam LT.
J Paediatr Child Health. 2002 Dec;38(6):582-6.
PMID: 12410871 [PubMed - indexed for MEDLINE]

CONCLUSION:
Midazolam controls seizures as effectively as diazepam in the prehospital setting. Furthermore, midazolam potentially reduces respiratory depression and time to treatment.

2005

Status epilepticus: an evidence based guide.
Walker M.
BMJ. 2005 Sep 24;331(7518):673-7. Review. No abstract available.
PMID: 16179702 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central.

Intramuscular midazolam vs intravenous diazepam for acute seizures.
Shah I, Deshmukh CT.
Indian J Pediatr. 2005 Aug;72(8):667-70.
PMID: 16131771 [PubMed - indexed for MEDLINE]

CONCLUSION:
i.m. midazolam is an effective agent for controlling acute convulsions in children especially in children with febrile convulsions. It has relatively no side effects as compared to Intravenous diazepam and can be used as a first line agent for treatment of acute convulsions in patients with difficult intravenous access.

2010

Human safety and pharmacokinetic study of intramuscular midazolam administered by autoinjector.
Reichard DW, Atkinson AJ, Hong SP, Burback BL, Corwin MJ, Johnson JD.
J Clin Pharmacol. 2010 Oct;50(10):1128-35. Epub 2010 May 13.
PMID: 20466872 [PubMed - indexed for MEDLINE]

Midazolam in an autoinjector was evaluated in an open-label dose escalation study involving 39 healthy participants. Safety and pharmacokinetic parameters were determined for doses ranging from 5 to 30 mg. No serious adverse events were noted during the study.

2011

RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics.
Silbergleit R, Lowenstein D, Durkalski V, Conwit R; Neurological Emergency Treatment Trials (NETT) Investigators.
Epilepsia. 2011 Oct;52 Suppl 8:45-7. doi: 10.1111/j.1528-1167.2011.03235.x.
PMID: 21967361 [PubMed - indexed for MEDLINE]

That is a preliminary release of information from the study that was just published in NEJM.

This practice has become increasingly common despite the lack of clinical-trial data regarding the efficacy and safety of intramuscular midazolam.^[1]

I haven’t looked at the rest of the study, but I hope that more thought went into the study design than went into the search for other research.

To be continued in Part II, Part III, and Part IV.

Footnotes:

^[1] Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus
Robert Silbergleit, M.D., Valerie Durkalski, Ph.D., Daniel Lowenstein, M.D., Robin Conwit, M.D., Arthur Pancioli, M.D., Yuko Palesch, Ph.D., and William Barsan, M.D. for the NETT Investigators
N Engl J Med 2012; 366:591-600February 16, 2012
Preview from NEJM

Apparently, there is no PubMed abstract, yet.

Late entry 02/18/2012 22:27 – Correction, there is a PubMed abstract for this study –

Intramuscular versus intravenous therapy for prehospital status epilepticus.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators.
N Engl J Med. 2012 Feb 16;366(7):591-600.
PMID: 22335736 [PubMed - in process]

Filed Under: Heresy, Midazolam, Pharmacology, Research, Sedation

Happy Darwin Day

Sun, 12 Feb 2012 17:30:28 +0000 By Rogue Medic 2 Comments

Opposition to evolution may be the gateway drug of conspiracy theorists. Maybe other conspiracy theories have evolved from Creationism. Only some religions claim that evolution conflicts with their religion. Their problem is that there is no objective evidence to support their claim, but they claim that their world does not require evidence, only belief.

Why do they not have a problem with gravity? They do not see any conflict with their beliefs. But the better question is – How do they explain obvious examples of confirmation of evolution?

What do they have in common?

A desire for an explanation that ignores facts, but relies on belief in things that not only cannot be demonstrated, but can be demonstrated to be not true. A need to attribute coincidences to some sort of conspiracy (Intelligent Design).

1859 – Charles Darwin’s On the Origin of Species is published. This transforms how we look at medicine.

1869 – Friedrich Miescher identifies DNA (DeoxyriboNucleic Acid). This continues to confirm the work of Darwin, which while not perfect, has been as revolutionary as the science of Newton in explaining how the world works.

1963 – John Fitzgerald Kennedy is assassinated. Conspiracy theorists claim that there must be a large conspiracy (Intelligent Design) behind this murder. Exaggerations of the difficulty of things happening as they did with just a lone gunman are important parts of this theory. Sounds that might be gunshots that are too close together for just one rifle, but is there a good reason to assume that they are all gunshots; a shooter of average ability could not make this almost impossible shot, but the reality is that it is a very easy shot; the pristine bullet could not have passed through 2 bodies without damage, but the bullet is not undamaged and test firing into cadavers produces bullets with similar damage; and on and on with the claims of things that conspiracy theorists could only have been explained by a conspiracy (an Intelligent Design) – except that they are not proof of anything except the desperation of conspiracy theorists.

1969 – Apollo 11 lands on the Moon and 2 people get out and walk on the surface of the Moon. Conspiracy theorists claim that this is faked based on a belief that something they believe must be true. Mythbusters does a better job of deconstructing these myths than I do –

Part 1

Part 2

Part 3

Part 4

Part 5

What about 9/11?

The most perfectly coordinated demolition ever? Twice? And miraculously, none of the explosives were affected by the impact of the planes. What about the collapse of the undamaged (pristine?) Building 7?

Or just the result of an itty-bitty airliner flying into a building, weakening the building, burning the building, and eventually causing so much damage that it collapses?

Obviously, President Bush was behind 9/11!

Image credit.

The History Channel covered the debunking done by Popular Mechanics.

Part 1

Part 2

Part 3

Part 4

Part 5
Part 5 is missing. Conspiracy?

Part 6

Part 7

Part 8

Part 9

What about all of the evidence for Intelligent Design?

Almost all of the species that have existed are extinct. This is not an example of Intelligent Design.

The evidence for Intelligent Design requires ignoring evidence that does not support Intelligent Design and claiming that there is more evidence for Intelligent Design than against. This is not honest. There are thousands of research papers on evolution published each year. The research is done by people all over the world. The researchers do not find evidence that evolution does not work, but they provide more information about how evolution does work.

When we limit ourselves to looking at only what confirms our beliefs, we limit our understanding.

This cannot be good science, cannot be good reasoning, and cannot be good religion.

How do so many people come to such different conclusions about what is written in the same book? By listening to different preachers.

Sacramento-area churches participate in Evolution Weekend

Filed Under: Critical Judgment, Heresy, Research, Science

This is the Way to Bad Medicine – II

Thu, 02 Feb 2012 06:30:32 +0000 By Rogue Medic Leave a Comment

A post at EM Literature of Note provides another example of bad research. Not just bad, but deadly.

The benefit of tPA in acute stroke is linked to the speed and degree of clot lysis and artery recanalization. ^{16 –18} ^[1]

Speed does appear to be most important. The debate about the efficacy of tPA (tissue-type plasminogen activator) for stroke is not that tPA will not be a good treatment when given within 90 minutes (1 1/2 hours). The debate is about the whether there is benefit when tPA is given between 90 minutes and 180 minutes (between 1 1/2 hours and 3 hours). The AHA (American Heart Association) quickly made it part of the guidelines to give tPA to as many patients with embolic stroke within 3 hours as possible. Some places have even expanded the fibrinolytic window to 270 minutes (4 1/2 hours).

If the AHA does the same with this proposed treatment, our stroke patients might be better off if we took them to hospitals NOT equipped to treat strokes.

Why?

Let’s look at the study –

Purpose
The primary purpose of this study was to assess the safety of combined Argatroban and tPA in ischemic stroke as measured by the incidence of significant intracerebral hemorrhage (ICH). The secondary objective was to evaluate drug activity by determining the speed and completeness of arterial recanalization and reocclusion.^[1]

The primary purpose of this study is to determine safety.

Safety was defined as a rate of symptomatic ICH or Parenchymal Hematoma Type 2 intracranial hemorrhage not exceeding 10%. We hypothesized that a hemorrhage rate of 10% might be acceptable only in the setting of significant increases in arterial recanalization, which is highly associated with improved clinical outcomes. ^[1]

Highly associated with?

I love treatments that are highly associated with some surrogate endpoint, because that is what matters to the patient.

We achieved the surrogate endpoint. That surrogate endpoint is highly associated with improved outcome. Therefore, you’re cured. Don’t try to speak to thank us. Just trust us.

You are cured.

Your inability to speak is probably just a conversion disorder – and don’t try to get up. You are cured, but your inability to walk is probably just psychological. It’s all in your head.

Too much sarcasm? Am I being unfair? Keep reading.

All patients received intravenous tPA (0.9 mg/kg). There was no delay in starting intravenous tPA as a result of participation in this study. Informed consent and other qualifying activities for the study took place after the intravenous recombinant tPA bolus was given.^[1]

This is good. There is no change that affects the initiation of the standard treatment.

(3) baseline NIHSS score 17 (modified to 15 after the first 15 patients) for right hemisphere and 22 (modified to 20) for left hemisphere strokes;^[1]

Why modified?

The first 2 significant hemorrhages occurred with NIHSS scores of 15 and 21 (both right MCA strokes), prompting the data and safety monitoring board to reduce the upper limit of the NIHSS score to 15 (right hemisphere) and 20 (left hemisphere).^[1]

The lower the NIHSS (National Institutes of Health Stroke Scale^[2]) number, the less serious the stroke. Scores range from 0 to 42, with higher being worse, so these are not severe strokes. How much improvement is worth to each patient vs. the risk of worse neurological injury, or death, is difficult to state. Looking through the grading, very intoxicated might score around the 13 average for the patients in this trial. I would not classify that as mild.

A total of 32 serious adverse events occurred in 22 patients (see Table 3).^[1]

I do not know why they calculated these as percentages of the serious adverse events, rather than according to patients treated.

If you develop a serious adverse event, you have a 21% chance of death.

They appear to be assuming that this ratio will persist across serious adverse events, which is not a reasonable conclusion. This is just a derivative of what I want to know. What I want to know is –

If I receive the treatment, what are my odds of death, disability, et cetera.

Their categorization of only 3 (out of 32) serious adverse events as Probably related to treatment and none as Definitely related to treatment suggests that they are not being objective. How do they explain this in the discussion? They don’t. Maybe they aren’t referring to the serious adverse events, but are referring to deaths. I don’t know and since they do not explain, I can only speculate.

We know that tPA increases the risk of bleeding. We expect that giving an anticoagulant (argatroban is a thrombin inhibitor) with tPA increases that risk of bleeding. We conclude that the bleeding in our patients is just a coincidence, because that’s the way we roll, Yo!

You had a thrombotic stroke, but now you have so much bleeding that your brain is squeezing out through any orifice possible. This is just one of the improbably large number of coincidences during this study.

On discharge, 76% of patients went either home or to acute rehabilitation, and 7 patients died (10.8%). Five of the 7 deaths resulted from large hemispheric infarction with herniation, whereas the other 2 died from respiratory failure. Six of the 7 deaths occurred after the family requested withdraw of care.^[1]

Six of the 7 deaths occurred after the family requested withdraw of care.

I don’t know if they are just providing complete information or suggesting that the deaths are the fault of the families for not trying to keep their family members alive in nursing homes with zero quality of life.

long enough to prevent any reocclusion. ¹² However, 3 of our 4 significant hemorrhages occurred 18 hours into the infusion. A 12- to 18-hour infusion might produce even safer and equally effective results.^[1]

However, shortening the infusion to zero hours might produce even safer and equally effective results.

What does Dr. Radecki say about this trial?

Because NIHSS score predicts bleeding, we can compare to the NINDS trial TPA group, whose median NIHSS score of 14 compared with this trial’s median of 13. The NINDS trial showed a 10.8% rate of ICH and about 4% mortality at 7 days.^[3]

3 dead patients would have been 4.6%.

There were 7 dead – 10.8%.

Is it safe?

I guess that depends on how much life insurance you have on the person being treated and how much you dislike them.

These rates of bleeding are of the same order of magnitude seen with intravenous recombinant tPA alone and therefore low enough to justify further evaluation in more patients to arrive at a more confident assessment of the true risks of bleeding.^[1]

What is their point?

What if . . . ?

What if this really is beneficial? We wouldn’t want to miss out on this potentially useful, although potentially very dangerous, treatment.

They are ignoring the risks. The question, What if . . . ? can also be reversed –

What if the adverse events in this group are statistically much lower than what we should expect if we were to treat a large number of patients?

Do the authors understand the risks they are subjecting patients to?

Higher doses of Argatroban might also be safe and even more effective, but this will require careful evaluation.^[1]

Maybe the patients had all of these bleeds because we gave too much of our study drug that causes bleeding, but we aren’t going to rule out the possibility that we did not give enough.

Is this really that much different from presuming that blood-letting is not working because of not taking enough blood?^[4]

Further study of this treatment combination appears warranted.^[1]

No.

I hope that no IRB (Institutional Review Board) is ever impaired enough to come to the conclusion that this should be expanded to harm more patients.

Earlier, I asked if I was using too much sarcasm, but now I think I may have been too subtle. What do you think.

Footnotes:

^[1] The Argatroban and Tissue-Type Plasminogen Activator Stroke Study: Final Results of a Pilot Safety Study.
Barreto AD, Alexandrov AV, Lyden P, Lee J, Martin-Schild S, Shen L, Wu TC, Sisson A, Pandurengan R, Chen Z, Rahbar MH, Balucani C, Barlinn K, Sugg RM, Garami Z, Tsivgoulis G, Gonzales NR, Savitz SI, Mikulik R, Demchuk AM, Grotta JC.
Stroke. 2012 Jan 5. [Epub ahead of print]
PMID: 22223235 [PubMed - as supplied by publisher]

^[2] NIH Stroke Scale
NINDS
PDF Download of Stroke Scale with explanations of scoring

^[3] Helping TPA Help Patients Bleed
Wednesday, January 25, 2012
EM Literature of Note
Article

^[4] Answer to What is this Dangerous Treatment and How Long Did it Take to Stop Using it
Wed, 01 Feb 2012
Rogue Medic
Article

Barreto, A., Alexandrov, A., Lyden, P., Lee, J., Martin-Schild, S., Shen, L., Wu, T., Sisson, A., Pandurengan, R., Chen, Z., Rahbar, M., Balucani, C., Barlinn, K., Sugg, R., Garami, Z., Tsivgoulis, G., Gonzales, N., Savitz, S., Mikulik, R., Demchuk, A., & Grotta, J. (2012). The Argatroban and Tissue-Type Plasminogen Activator Stroke Study: Final Results of a Pilot Safety Study Stroke DOI: 10.1161/STROKEAHA.111.625574

Filed Under: Ethics, Heresy, Pharmacology, Research, Research Blogging, Science

NIH launches trials to evaluate CPR and drugs after sudden cardiac arrest

Sun, 29 Jan 2012 06:30:21 +0000 By Rogue Medic 3 Comments

The NIH (National Institutes of Health) announced two new resuscitation studies. This is not the kind of research to find any private sponsorship, but it is important – well, one study is.

The CCC trial will compare survival-to-hospital-discharge rates for two CPR approaches delivered by paramedics and fire fighters. Persons experiencing cardiac arrest will be randomly assigned to receive continuous chest compressions, or standard CPR by emergency responders. Standard CPR, the approach recommended by the American Heart Association (AHA) for use by emergency responders, includes chest compressions with short pauses for assisted breathing. This approach has been called into question by emerging data suggesting that stopping chest compressions to provide assisted breathing interrupts overall blood flow, thereby lowering survival.^[1]

The AHA wants to find some evidence to justify their preferred method of combining chest compressions with ventilations.

There is no evidence that ventilations improve survival from adult cardiac arrest of cardiac origin.

There is evidence that any interruption to compressions decreases survival.

The only known interruption that does not decrease survival is defibrillation.

Not for ventilation.

Not for intubation.

Not for any medication.

Not for application of any CPR machine.

Not for transport.

Not for acupuncture.

Trained emergency personnel will give all participants in the CCC trial three cycles of CPR followed by heart rhythm analysis and, if needed, an electrical shock (defibrillation), applied to the chest. Half will be randomly assigned to receive continuous compressions combined with pause-free rescue breathing and half will receive standard professional CPR.^[1]

Why only three cycles?

This suggests that the hypothesis presumes some benefit from ventilations.

Based on what?

Apparently based on tradition and wishful thinking – a deadly combination.

Tradition and wishful thinking have been a deadly combination for thousands of years.

The Amiodarone, Lidocaine, or neither (Placebo) for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia study (ALPS) will determine whether amiodarone or lidocaine improves survival-to-hospital-discharge rates for participants with shock-resistant ventricular fibrillation. Participants will receive one or the other drug or a placebo.^[1]

We already know that these drugs do not improve survival from V Fib (Ventricular Fibrillation). The only questions are

Image modified from Paramedicine 101 – 2010 AHA Updates.

How many resuscitations does lidocaine prevent?

How many resuscitations does amiodarone prevent?

The CCC trial will enroll up to 23,600 participants at eight major regional locations across the U.S. and Canada.^[1]

That number of patients should be enough for clear results.

The ALPS trial will enroll up to 3,000 participants at nine locations across the U.S. and Canada.^[1]

That ridiculously small number of patients should allow those who base treatment on tradition and wishful thinking to continue to pretend that their treatments do not make things worse.

Almost 60 fire and EMS organizations will participate in the ALPS trial, and approximately 125 EMS organizations will participate in the CCC trial.^[1]

Maybe the number 3,000 is a misprint. That would be only 50 V Fib (Ventricular Fibrillation) cardiac arrests per EMS organization.

Estimated Enrollment: 3000 ^[2]

How will that produce statistically significant results, while the CPR study requires 8 times as many patients?

Footnotes:

^[1] NIH launches trials to evaluate CPR and drugs after sudden cardiac arrest
Embargoed for Release
Thursday, January 26, 2012
11 a.m. EST Contact:
NHLBI Communications Office
(301) 496-4236
NIH
Press Release

^[2] Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia (ALPS)
ClinicalTrials.Gov
Last Updated on September 21, 2011
ClinicalTrials.gov Identifier: NCT01401647
Trial data

Filed Under: ACLS, Heresy, Research

This is the Way to Bad Medicine

Tue, 24 Jan 2012 16:30:51 +0000 By Rogue Medic 1 Comment

Dr. Radecki at EM Literature of Note has a nice analysis of a study that promises to try to change medicine for the worse. Of course, that is not the intent of the study’s authors, but they have too much confidence in their results. The study is only looking at patients with minor head injury and minor symptoms, but taking warfarin (Coumadin).

Patient ﬂow is shown in the Figure, with 97 patients observed according to our protocol. Ten of these patients declined the second CT scan; all remained asymptomatic and none were readmitted within 30 days because of symptoms related to the head injury.^[1]

These 10 patients – patients with no signs of any complications for 30 days – were excluded because they did not complete the protocol.

I admire the authors’ attempts at adherence to their protocol, but there is a problem with their placing more emphasis on a flawed protocol, than they place on the patient outcomes.

Was the purpose of the study to evaluate the ability of the protocol to predict something?

Outcome Measures
Two investigators (V.G.M. and M.L.) reviewed the electronic medical record (Sistema Informatico Ospedaliero, Fly Tecnologie e Servizi, Perugia, Italy) to identify the presence or absence of the following outcomes: acute traumatic intracranial lesion (deﬁned earlier) on the second CT scan, death, admission for any CT abnormality, operative neurosurgery, or readmission within 30 days because of symptoms related to the head injury.^[1]

The ability of a second CT scan to identify problems was only one of the outcomes being measured. The authors should not have excluded these 10 patients from the other outcomes.

How do we come up with 6% bad outcomes?

It all depends on how we define our outcomes.

Is there a big difference between 1/87 having neurosurgery and 1/97 having neurosurgery?

Not really, but it does allow the authors to turn 5/97 (5%) into 5/87 and it becomes 6%. The bigger the number, the more ~~significant~~ impressive the result. This would suggest that their 24 hour observation period for minor head injury is a good idea, but how good was their protocol at identifying admission for signs of intracranial bleeding?

Two additional patients (2%; 95% CI 0.5% to 5%) who were discharged after a negative second CT scan result were readmitted 2 and 8 days later, one with confusion and the second with headache. Their initial presentations were accidental trauma and syncope, respectively; however, both had an initial international normalized ratio of greater than 3.0 (Table 2). Both had subdural hematomas without mass effect; neither required neurosurgery (Table 2).^[1]

We will look at Table 2, but first let’s look at Table 3 –

I already provided you with a quote that contradicts what is shown in Table 3.

It is true that 5/7 is 71%, but . . .

the second CT was negative for 2 of these patients. It was only after the two patients returned complaining of symptoms suggestive of head injury that each had a third CT scan.

The correct calculation would be quite a bit different.

Out of 87 patients, 5 patients had positive second CTs, but 2 were discharged because the bleeding was not considered significant.

3/5 were admitted based on a second CT.

The math is easy on that one – 60% – not 71%.

Of the patients admitted for head injury, 2 had negative second CT scans and only had third CT scans because of symptoms that caused the patients to return to the hospital.

In other words 2/82 had false negative second CT scans – if admission is the criterion being examined. 82 because we cannot include the 10 who refused a second CT, nor can we include the 5 who had positive CT scans.

How useful is this protocol?

2 patients with positive CTs discharged with no sequelae.

2 patients with positive CTs admitted with no sequelae.

1 patient with positive CT admitted and treated with neurosurgery.

2 patients with negative CTs discharged, but returned with sequelae and admitted.

Is the 24 hour observation and second CT scan able to predict admission?

After the second CT scan, only 60% were admitted, but 60% is just barely better than flipping a coin. that might be worth paying attention to, but they only found 60% of total admissions by this method.

The protocol completely missed 40% of the total admissions. These patients stayed for 24 hours of observation; these patients agreed to the second CT scan; these patients had negative second CT scans; these patients were discharged after completely following the protocol and having no positive findings. These patients returned with symptoms of head injuries.

One patient returned after 2 days and the other patient returned after 8 days. Neither patient ended up having neurosurgery.

Accordingly, our ﬁndings support both the advisability of initial CT scanning and the 24-hour observation and repeated CT protocol advocated by the European guidelines.⁴ ^[1]

Absolutely not.

However, because both of our patients with delayed hemorrhage had an initial international normalized ratio of greater than 3.0, longer observation may be warranted in this subset.^[1]

Maybe.

Maybe not.

What kind of treatment did these patients receive?

Nothing is specified in the paper. They might have received medication. they might just have been observed. We do not know.

The only patient who ended up having neurosurgery had an INR of 2.4. Although 8 of the 87 patients receiving a second CT scan had INRs over 3, we do not know how many of the patients, who were admitted, but refused the second CT scan might have had INRs over 3.

How many of the neurosurgery patients had an INR of over 3?

Zero.

Is the 24 hour observation and second CT scan able to predict neurosurgery?

Maybe.

Maybe not.

The most important flaw in this study is presuming that we can use fewer than 100 patients to identify the incidence of a rare condition.

We need to expect that the number of patients studied will not be representative, when the incidence of what is being studied is so uncommon. When each patient makes up more than 1 percent of the total and the total number of patients having surgery is just one, how can we conclude that we are learning anything from the research.

This is an example of research that is only going to confirm biases.

Confirmation of biases is not the purpose of research.

Supervising editor: Steven M. Green, MD^[1]

With all of his experience, Dr. Green should know better than to accept this.

However, we simply cannot expose all anticoagulated patients with minor head trauma to the harms and costs of hospitalization. Better studies are required to prospectively determine the risk profile of patients who require further observation in a hospital setting, rather than a watchful discharge home.^[2]

Absolutely.

Go read Dr. Radecki’s analysis and especially the comment of steve, who might need to get his own blog.

Footnotes:

^[1] Management of Minor Head Injury in Patients Receiving Oral Anticoagulant Therapy: A Prospective Study of a 24-Hour Observation Protocol.
Menditto VG, Lucci M, Polonara S, Pomponio G, Gabrielli A.
Ann Emerg Med. 2012 Jan 13. [Epub ahead of print]
PMID: 22244878 [PubMed - as supplied by publisher]

^[2] Observation For Anticoagulated Head Trauma
EM Literature of Note
Radecki
Article

Menditto, V., Lucci, M., Polonara, S., Pomponio, G., & Gabrielli, A. (2012). Management of Minor Head Injury in Patients Receiving Oral Anticoagulant Therapy: A Prospective Study of a 24-Hour Observation Protocol Annals of Emergency Medicine DOI: 10.1016/j.annemergmed.2011.12.003

Filed Under: Critical Judgment, Heresy, Legal Medicine, Research, Research Blogging, Spinal Immobilization

How Should EMS Courses Be Taught – Part II

Mon, 16 Jan 2012 13:00:01 +0000 By Rogue Medic 3 Comments

In response to Part I (How Should EMS Courses Be Taught) there are some valid questions about how to teach the interpretation of research to paramedics.

I would not start with paramedic school. Paramedic school is too late.

How much dogma, blind faith, and indoctrination in the EMS old wives’ tales club has already taken place by the time that we reach paramedic school?

Dewayne wrote –

While maybe not along the same line as your intended meaning, I would love to see a mandatory associates degree for the paramedic level. To reach that goal of an AS degree, I would like to see more classes such as A&P, pathophysiology, medical terminology, and the like as opposed to large credit hour classes labeled Paramedic I, Paramedic II, etc. From looking over my local community college’s course catalog, the classes I feel are important are already being taught, they just need to be filled with future paramedics.

We could have the same prerequisites as nursing students, but include a basic medical research course, too.

However, I would rather see paramedics taking a medical research course, than Anatomy & Physiology. Too much of A&P is used to justify assumptions about the necessity of ventilations in cardiac arrest, because the theory has not yet caught up with the research.

Can you go to an A&P textbook and find explanations of the necessity of ventilation and oxygenation for human life?

Absolutely!

Can you find resuscitation research on real people that demonstrates the necessity of ventilation and oxygenation for human life?

Absolutely NOT!

Our theorists have gotten too far ahead of the research on which we base our theories.

We took a good idea. We ran with it, but we ran the wrong way. Now we find ourselves trying to defend a lie. We find ourselves pleading with people to ignore the evidence. We find that we have to cheat in our presentations of the evidence and give an unfair advantage to the intervention.

In medicine, the ethical approach is to give the advantage to benign neglect – not to unproven intervention.

We are giving the advantage to wishful thinking.

This is indoctrination – not education.

We need to educate people in EMS to see the fraud of this indoctrination.

As long as we are a dogma-based industry, we do NOT deserve to be treated as professionals.

It rubs the lotion on its skin. It does this whenever it’s told.

Too much of EMS is rubbing the lotion on its skin whenever it can to avoid getting the hose.

Skinner’s pigeons would have excelled in EMS..

We need to stop applying lotion and start applying real medicine.

We need to get rid of the people with the hoses.

Filed Under: Critical Judgment, Education, Heresy, Mythology, Research

Intravenous Access During Out-of-Hospital Emergency Care of Noninjured Patients – Part I

Mon, 09 Jan 2012 06:30:05 +0000 By Rogue Medic Leave a Comment

Does EMS provide any benefit to patients by starting an IV (IntraVenous) line?^[1]

I think that it helps to start by looking at some of the results. The distribution of the vital signs gives us a bit of information about the patients receiving EMS IVs.

The numbers appear to be mean averages, except where noted to be median. The red lines are under the SD (Standard Deviation) for each vital sign with the wider SD. All of these are in the IV group. The overall numbers are almost identical. Usually a wider SD indicates a smaller sample, which suggests less reliability of the data. This sample is large and split close to 50/50 IV vs. No IV. The wider SDs indicate that the vital signs are much more diverse in the IV group. To look at it from the other perspective, the No IV group has much more stable looking vital signs.

For blood pressure, the mean is 140 for both. The SD ranges from 106 to 176 for one SD of the No IV group, but from 100 to 180 for the IV group.

For pulse, the mean is 90 for the No IV group and 94 for the IV group. The SD ranges from 67 to 113 for one SD of the No IV group, but from 63 to 125 for the IV group. The mean pulse is higher and the SD is wider, resulting in a pulse that is only 4 beats lower at the low end of the SD, but 12 beats higher at the upper end.

For the GCS (Glasgow Coma Score^[2]), the mean is 14.2 for the No IV group and 14.0 for the IV group. The SD ranges from 12.1 to 15 (upper limit of measurement) for one SD of the No IV group, but from 11.5 to 15 for the IV group. The mean GCS is lower and the SD is wider, resulting in a GCS that is the same at the high end of the SD (it cannot go any higher), but 0.6 points lower at the lower end. Since GCS is not measured in fractions, that means that about two thirds of the IV patients were a full point lower than the No IV group, on average for those with the most normal GCS. One standard deviation around the mean average is the most normal group of patients.

As the numbers become less normal, we should expect that the differences between the groups will increase, rather than decrease, unless there is something affecting the distribution that has not been accounted for. There is no guarantee of this. With the GCS, 15 is the highest number that can be recorded, so the GCS numbers will not continue to deviate in that direction, but the number of patients with a GCS of 15 will probably be what changes.

If we want to look at this from the perspective of those not receiving EMS IVs, we only need to flip the results. More of the vital signs in the No IV group will appear to be stable, while in the IV group, more will appear to be unstable. This will become more important to consider when looking at the outcome that matters – mortality, or to flip that around – survival.

Another place where we can see some dramatic differences between the groups. The difference in the presumed disease by whether an IV was started.

The biggest difference is in the patients with the potential cardiovascular complaints. Almost three times as many received IVs as did not. The only other category that had a higher percentage receiving IVs than not receiving IVs was the metabolic/endocrine group.

After cardiovascular, the next largest medical condition is respiratory, but these are about one and a half times as likely to have No IV. Why? I think a lot of this has to do with two different conditions. Asthma often responds to a nebulized treatment, so an IV may not be seen as important outside of the hospital. The other respiratory condition may be anxiety-induced hyperventilation.

There does appear to be discrimination among patients according to medical condition. The question is whether this discrimination is beneficial to the patients.

One look at the outcomes produces a mixed picture.

The length of stay is the same, but the IQR (InterQuartile Range) is shorter for the IV group – 1-4 vs. 2-5. It would be interesting to see the distribution, because this suggests that a graph of one group is not just a bit more/less than the other, but that the pattern of distribution looks different.

Mechanical ventilation is 3% with IV vs. 2% without IV. The need for ICU admission is 18% with IV vs. 8% without IV.

In spite of this, the in-hospital mortality is 3% each and the 28 day survival is 4% each.

In Part II, I will look at the probable explanation for this.

Footnotes:

^[1] Intravenous Access During Out-of-Hospital Emergency Care of Noninjured Patients: A Population-Based Outcome Study.
Seymour CW, Cooke CR, Hebert PL, Rea TD.
Ann Emerg Med. 2011 Aug 26. [Epub ahead of print]
PMID: 21872970 [PubMed - as supplied by publisher]

^[2] Glasgow Coma Scale
Wikipedia
Article

Filed Under: Critical Judgment, Heresy, Research

How Should EMS Courses Be Taught

Tue, 03 Jan 2012 06:30:21 +0000 By Rogue Medic 8 Comments

First, I will assume that there is a simple way to get all of the required EMS dogma delayed until the end, when students will be able to figure out what is true, what is partially true, and what is completely false.

Then, where do we begin?

The first subject, the most important subject, is the interpretation of research. If there is no research basis for our treatments, we are practicing witchcraft, not medicine.

If we cannot use a treatment to predictably produce a good result, then we should not endanger patients with that treatment.

The only way we can show that a treatment will predictably produce a good result is with research.

An RCT (Randomized Controlled Trial) is not always the goal, or appropriate, but –

If we do not collect and evaluate evidence, we hurt our patients.

If we do not understand research, we hurt our patients.

Go ahead. Disagree.

Now, prove it.

Without evidence, we are only basing what we do on wishful guessing.

In several recent posts, I have pointed out that there is no evidence to justify the use of ventilations during CPR. We still have plenty of people, including doctors, who insist that because we were taught that Airway comes before Breathing and both come before Circulation – that airway and breathing are important to a person who has a primary problem of heart not beating. Maybe it is because we used to insist that at least 1 liter of air be delivered with each breath, that we do not realize that passive oxygen insufflation is adequate oxygenation during chest compressions.

That’s the way we’ve always done it.

Vs.

Evidence that the way we have always done it is wrong – again.

We don’t care about evidence.

VS.

The reason I do not put my hand in a fire and leave it there is evidence that this is painful. Ignoring evidence is a great way to experience pain – over and over and over . . . .

Research changes all of the time.

Vs.

Research changes as we learn more about what works. If we want to keep improving the care we provide to our patients, we need to learn. Learning is change.

Change is bad.

Life requires change.

Death is when change no longer matters.