If you have a BVM (Bag Valve Mask resuscitator), you should not need naloxone. The problem is inadequate respiration, not inadequate naloxonation.

- Rogue Medic

Safety of Intranasal Fentanyl in the Out-of-Hospital Setting – A Prospective Observational Study

ResearchBlogging.org
 
I have been very critical of plans to have first responders treat people they suspect of having a heroin (or other) opioid overdose with naloxone.

Would first responders be safer with fentanyl?

It is not really the same question, but it does highlight the differences and why I think fentanyl is safer. The patient will be seen by someone more likely to recognize when the treatment is inappropriate. This study looked at IN (IntraNasal) fentanyl given by basic EMTs prior to transport to the ED (Emergency Department).
 


Image credit.
 

Previous studies demonstrate adverse effects in 3.3% to 39% of patients treated with intranasal fentanyl,3, 4 and 5 providing an ambiguous safety profile.[1]

 

The concentration of fentanyl (Instanyl in this study) is different from what I have available. They use 500 µg/ml, while I only have fentanyl in a concentration of 50 µg/ml. Ten times the volume does make measurement easier, but ten times the volume may impair absorption.
 

The atomizer contains a single dose with a prefixed quantity of either 50 μg (500 μg/mL) or 100 μg (1,000 μg/mL) fentanyl and has a dose volume of 0.1 mL (lower than the 0.15 mL limit necessary to avoid pharyngeal runoff7). The Instanyl preparation contains fentanyl in no other recipients than purified water and a phosphate buffer to match the physiologic environment of the nasal cavity and to increase bioavailability.9 [1]

 

Patients were not limited to healthy trauma patients, so these results can be generalized to a variety of patients.
 

We administered 50 μg to patients younger than 18 years, older than 65 years, with chronic obstructive pulmonary disease, or who were considered generally weakened or malnourished by the attending paramedic/EMT. All others received 100 μg. In patients reporting insufficient analgesia, the initial dose could be repeated once or twice after 10 and 25 minutes, respectively.[1]

 


 

The smaller decrease in level of pain suggests that they were more cautious in administering fentanyl to the comorbid patients.

The time between doses did lead to some extended scene times (first dose at 0 minutes, second dose at least 10 minutes later, and the third dose at least 35 minutes after the first dose), but that is usually preferable to causing extreme pain by moving the patient with inadequate pain management, regardless of the proximity of the hospital.
 


 

What many people fail to realize, doctors included, is that the hospital may only be five minutes away after we are in the ambulance, but we need to manage the pain before we move toward the ambulance. When I call for orders to give more pain medicine than I can give on standing orders, medical command doctors sometimes ask how far away from the hospital we are. I respond that it depends on when the pain is managed. Unless there is some medical condition that requires us to move the patient more quickly, we should move the patient only when the patient feels the pain is managed.
 

How effective was the intranasal fentanyl at managing pain?
 

I would prefer to lower the level of pain by more than they did, but I am accustomed to giving IV (IntraVenous) fentanyl, so I am able to titrate it more accurately.
 


 

Patients received 1 (n=526), 2 (n=333), or 3 (n=44) doses of fentanyl, with a mean cumulative dose of 114 μg.[1]

 

Fewer than 5% of patients required more than two doses.

They did give a variety of total doses of fentanyl. The result seemed to be similar regardless of the total dose. This could indicate that fentanyl is just a placebo (unlikely) or that the EMTs did a good job of titrating the medicine to the response.
 


 
 

This was a safety study, so how safe was intranasal fentanyl?
 

The criterion for hypotension is a bit different from what I am accustomed to. Even using MAP (Mean Arterial Pressure), I have not considered patients to be hypotensive above a MAP of 60.
 

We calculated the mean arterial pressure (MAP) and defined hypotension as a MAP reduction greater than or equal to 10 mm Hg and an end MAP less than or equal to 70 mm Hg.14 [1]

 

How much respiratory depression and hypotension did they have?
 

We did not observe respiratory depression (respiratory rate less than 11 breaths/min), GCS score reduction to 14 in 5 patients was transient, and there was no use of naloxone or mask ventilation. Ten patients (1%) had measurable hypotension; however, none experienced syncope and only 1 experienced dizziness, suggesting that these events were of low clinical importance. Indeed, pain relief may be partially responsible for the decrease in MAP.[1]

 

Studies repeatedly show that fentanyl can be given safely to hypotensive patients and half of the hypotensive patients were no longer hypotensive after fentanyl was given in one prehospital trauma study.[2] This suggests that a fluid bolus may be less effective than fentanyl at getting rid of hypotension.
 

As pointed out by O’Donnell et al,20 out-of-hospital undertreatment of pain in pediatric patients may be due to safety concerns. Our study supports the safety of intranasal fentanyl in children.[1]

 

Fentanyl is even safe in children and safe in adults with comorbidities even when given by basic EMTs.

It seems that fentanyl is safe and much more effective than not treating the pain. Is IN fentanyl more effective than other pain medicines? We still do not know.

Footnotes:

[1] Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study.
Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS.
Ann Emerg Med. 2014 Jun;63(6):699-703. doi: 10.1016/j.annemergmed.2013.10.025. Epub 2013 Nov 22.
PMID: 24268523 [PubMed – in process]

[2] Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia.
Krauss WC, Shah S, Shah S, Thomas SH.
J Emerg Med. 2011 Feb;40(2):182-7. Epub 2009 Mar 27.
PMID: 19327928 [PubMed – in process]

Full Text PDF Download at medicalscg.

My review of this paper –

Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia
Fri, 27 May 2011
Rogue Medic
Article

Krauss, W., Shah, S., Shah, S., & Thomas, S. (2011). Fentanyl in the Out-of-Hospital Setting: Variables Associated with Hypotension and Hypoxemia The Journal of Emergency Medicine, 40 (2), 182-187 DOI: 10.1016/j.jemermed.2009.02.009

Karlsen AP, Pedersen DM, Trautner S, Dahl JB, & Hansen MS (2014). Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study. Annals of emergency medicine, 63 (6), 699-703 PMID: 24268523

.

Is It Wrong To Medicate To The Point Of Needing Ventilation – Question from mpatk


Image credit.
 

In the comments to Where is the Line Between Good Pain Management and Bad, mpatk write the following –
 

To clarify, would you consider it acceptable to sedate to the point of requiring assisted ventilation for a sufficiently painful injury (e.g. multiple long bone fx’s)?

 

I have not needed to ventilate any of these patients, but I have added oxygen to keep some patients’ oxygen saturation above 93%.

Would it be wrong to medicate to the point of needing to ventilate?

There was a time when I would have taken the position that this is an indication of bad pain management/bad sedation, but I no longer agree with that.

We are there to provide appropriate care for the patient, not appropriate care for the patient up to the point of needing to assist with ventilation.

Most medical directors will probably disagree with me, but medical directors are getting better at encouraging appropriate pain management and sedation.

You, and I, do not have access to ketamine, but ketamine would be the ideal drug for many painful injuries. Ketamine provides sedation, analgesia, and dissociation, but generally does not cause any respiratory depression. Ketamine can occasionally cause laryngospasm, but that is easy to manage. I need to follow up on some earlier posts on ketamine and laryngospasm.[1],[2],[3]

But we do not have ketamine. should our patients suffer because we do not have the best drug for these patients?

No.

What is going to happen in the hospital?

The patient is going to need surgery, which generally involves ventilation through an endotracheal tube, or an LMA (Laryngeal Mask Airway). We could anticipate that and place an airway for ventilation.

We could give tiny titrated doses of naloxone (for suspected opioid-induced hypoventilation) and/or tiny titrated doses of flumazenil (for suspected benzodiazepine-induced hypoventilation).

This problem is not a lack of oxygenation, because we could treat that with a higher concentration of oxygen. This is a problem of inadequate removal of CO2 (Carbon DiOxide), or it is a combined problem of hypoxia and hypercarbia.

There is a discussion of procedural sedation by Dr. Al Sacchetti that is essential listening for anyone who provides sedation and/or pain management.[4]

Why should paramedics listen to this? Because this is important material to understand to be good at sedation and pain management.

Pay attention to the whole presentation, because Dr. Sacchetti makes some excellent points.

Most relevant to what I am writing is what he says from 27:00 to 28:15.

Would an LMA have been more appropriate? Maybe. Maybe not.

At 29:30 Dr. Sacchetti says –
 

The medication with the lowest complication rate is . . .
 
Propofol (Diprivan)?

Midazolam (Versed)?

Ketamine (Ketalar)?

Morphine?

Hydromorphone (Dilaudid)?

Fentanyl (Sublimaze)?

What do you think was the safest drug (lowest complication rate)?
 

 

 

 

 

 

 

 

 

 

ketamine.
 

Zero major complications.
 

At 30:00 he puts the safety of fentanyl and etomidate (EMS medications) in perspective, when compared with ketamine and propofol, which are often considered too dangerous for EMS.
 

Fentanyl has the highest complication rate followed by etomidate.
 


This list is in alphabetical order, not in order of complications, or number of patients, or . . . .
 

Perspective is important.

Airway management skill is essential.

Limiting EMS to the least safe medications does not protect patients.

Footnotes:

[1] Laryngospasm, hypoxia, excited delirium, and ketamine – Part I
Thu, 21 Jun 2012
Rogue Medic
Article

[2] Laryngospasm, hypoxia, excited delirium, and ketamine – Part I
Mon, 25 Jun 2012
Rogue Medic
Article

[3] Serious adverse events during procedural sedation with ketamine – Part I
Thu, 27 Sep 2012
Rogue Medic
Article

[4] Al Sacchetti: Procedural Sedation in the Community ED
April 28, 2010
Free Emergency Medicine Talks
Al Sacchetti
Page with free download of presentation in mp3 format.

The reference is to the ProSCED registry, which is described in the papers below – both are free.

Procedural sedation in the community emergency department: initial results of the ProSCED registry.
Sacchetti A, Senula G, Strickland J, Dubin R.
Acad Emerg Med. 2007 Jan;14(1):41-6. Epub 2006 Aug 31.
PMID: 16946280 [PubMed – indexed for MEDLINE]

Page With Free Full Text in PDF Download format from Academic Emergency Medicine. Click on Get PDF (97K).
 

The safety of single-physician procedural sedation in the emergency department.
Hogan K, Sacchetti A, Aman L, Opiela D.
Emerg Med J. 2006 Dec;23(12):922-3.
PMID: 17130600 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

.

Where is the Line Between Good Pain Management and Bad

 

Almost everything exists on a continuum. Pain management is no different.

The idea of completely good, or completely bad, pain management may not even be appropriate in describing the extremes, because clear distinctions are imaginary.
 

Anesthesia exists along a continuum. For some medications there is no bright line that distinguishes when their pharmacological properties bring about the physiologic transition from the analgesic to the anesthetic effects. Furthermore, each individual patient may respond differently to different types of medications.[1]

 


Image credit.
 

The definitions of sedation/analgesia as Moderate or Deep provide excellent examples.
 

Moderate
 

Moderate sedation/analgesia: (“Conscious Sedation”): a drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Cardiovascular function is usually maintained. CMS, consistent with ASA guidelines, does not define moderate or conscious sedation as anesthesia (71 FR 68690-1).[1]

 

Deep
 

Deep sedation/analgesia: a drug-induced depression of consciousness during which patients cannot be easily aroused but respond purposefully following repeated or painful stimulation. The ability to independently maintain ventilatory function may be impaired. Patients may require assistance in maintaining a patent airway, and spontaneous ventilation may be inadequate. Cardiovascular function is usually maintained. Because of the potential for the inadvertent progression to general anesthesia in certain procedures, it is necessary that the administration of deep sedation/analgesia be delivered or supervised by a practitioner as specified in 42 CFR 482.52(a).[1]

 

Respond purposefully is in the description of both. Respond purposefully should also be in the description of minimal sedation/analgesia and the description of no sedation/analgesia. The difference is the amount of stimulus required – following repeated or painful stimulus vs. to verbal commands, either alone or accompanied by light tactile stimulation. This is the primary difference.
 

Patients may require assistance in maintaining a patent airway,

Does that mean that a patient who does not require assistance in maintaining a patent airway is not receiving Deep sedation/analgesia?

No.

and spontaneous ventilation may be inadequate.

Does that mean that a patient with adequate spontaneous ventilation is not receiving Deep sedation/analgesia?

No.
 

What if supplemental oxygen is provided in anticipation of the potential for hypoxia, but the patient never becomes hypoxic?

What if supplemental oxygen is provided in response to hypoxia, the hypoxia resolves and does not return, but no ventilatory assistance is provided?
 

Should the following be added to the moderate sedation/analgesia definition?

Because of the potential for the inadvertent progression to deep sedation/analgesia in certain procedures, . . . .

If that is true, then what about adding the following to the definition of minimal sedation?

Because of the potential for the inadvertent progression to moderate sedation/analgesia in certain procedures, . . . .

Only no sedation/analgesia does not qualify for this kind of warning, but my point is not to provide a slippery slope justification for unethically withholding sedation/analgesia.

I am pointing out what a continuum means.

All of this raises the question, What is too much?

We cannot really consider that question without also raising the question, What is not enough?
 


Download YouTube Video | YouTube to MP3: Vixy | Replay Media Catcher
 

How do we differentiate among the various possibilities of sedation/analgesia?

We differentiate according to the response of the patient, not so much according to whether the patient responds to verbal, painful, or repeated stimuli, but by the response to the question, Do you want more pain/sedation medicine?

One determines how we respond to potential ventilation needs of the patient, while the other determines how we respond to the sedation/analgesia needs of the patient.

What is too much?

That seems to depend on where the patient is on the sedation/analgesia continuum as determined by someone other than the patient.

What is not enough?

That seems to depend on where the patient is on the sedation/analgesia continuum as determined by the patient.

We cannot ask one question without implying the other question, so why do we address them in isolation so often?

Footnotes:

[1] Revised appendix A, interpretive guidelines for hospitals— state operations manual, anesthesia services.
Centers for Medicare & Medicaid Services (CMS).
Effective December 2, 2011.
Free Full Text Download in PDF Format from CMS.

.

Dilaudid – Start With 2 mg or Start With 1 mg?

ResearchBlogging.org
 
What is the proper interval before we should give another dose of opioid to patients who still have significant pain?

The authors of this study suggest that 3 to 5 minutes would be ideal, but that the ED (Emergency Department) is not a setting where that is practical.
 

Administration of small doses of intravenous opioids every 3 to 5 minutes until pain relief is achieved, as typically practiced in postoperative care settings, is highly appealing. However, this is simply not feasible in most EDs because of ubiquitous and progressive crowding.18,19

Taking into consideration the heightened risk of adverse effects associated with administration of too large or too rapid a dose of intravenous opioid, we wished to develop a modified titration strategy appropriate to the constraints of the ED.[1]

 

This would seem to make EMS the right people to administer opioids at theat ideal frequent rate of every 3 to 5 minutes. The main problem with having EMS do this seems to be the continuing refusal of many medical directors to do what is best for the patient.

Because of the staffing limitations of the ED, something that does not apply to EMS, the authors chose 15 minutes as the Do you want more pain medication? interval for their ED study.
 

The primary efficacy outcome was the difference in the proportion of patients in each arm who, when asked, declined additional pain medication at 60 minutes after receiving their first dose of intravenous hydromorphone. The primary safety outcome was use of naloxone as a reversal agent.[1]

 

One group received 2 mg hydromorphone intially and appears to have been asked an hour later if they wanted more pain medicine. The other group received 21 mg hydromorphone intially, was asked at 15 minutes if they want any more pain medicine and only appears to have been asked again an hour later if they wanted more pain medicine.

The outcome showed no statistically significant difference between the groups.

There was never any need for naloxone for any patient, but that should not be a surprise to anyone who has treated severe pain more aggressively than was treated in this study.

Only one patient had an oxygen saturation that dropped below 95%, but that was in the 1+1 group. It is not documented whether this was after the initial 1 mg, after a repeat dose of 1 mg, or after doses beyond the protocol (it is not clear if any doses were administered beyond the protocol).
 


Click on images to make them larger.
 

All patients received supplemental 2 L nasal cannula oxygen in response to a greater-than-expected incidence of oxygen desaturation in a previous study of the safety and efficacy of the 2 mg intravenous hydromorphone protocol.26 [1]

 

This is not unreasonable in an ED that is busy, but EMS should be able to more closely assess the oxygenation and avoid this medical intervention. In EMS, since we are usually with the patient at all times, it is easy to just get the patient to talk if the oxygen saturation drops below 94%, or the heart rate drops to something undesirable, or if hypotension develops (usually just a reaction to histamine when using morphine). When the patient talks, the patient ventilates and oxygenates. Problem solved. If the patient takes a nap, that is not a problem.
 

Do you want more pain medication? as the primary efficacy endpoint. This measure has a number of advantages and limitations. It is a simple, patient-centered index, with an immediate and unambiguous treatment strategy embedded within it. It invites the patient to take into account not only severity of pain but also other clinically relevant considerations, such as common opioid adverse effects that patients may find more unpleasant than partially attenuated pain.[1]

 

As much as we may think we know the patient’s pain level better than the patient, or the authenticity of the patient’s pain better than the patient, it is unlikely that we are right. Feel free to provide some research to contradict me, if you disagree.
 

Even after receiving the approximate equivalent of 14 mg morphine either all at once or in 2 equally divided doses, one third of patients still wanted additional analgesia. This is consistent with the work of other investigators, demonstrating similar and substantial interindividual variation in opioid requirement.10-12,35 [1]

 

We are sometimes discouraged from providing good patient care because of numbers that we might think are too much.

The problem is when not some numbers are too much.

The problem is when the patient’s pain is too much.
 


 

The mean level of pain was clearly lower at all times in the study.

With more attention to the patient’s pain and to the possible side effects, we can prove more aggressive pain management that is just as safe, if not more safe, than less aggressive dosing with opioids.
 

The difference between the conclusions we would have drawn according to a retrospective analysis indirectly comparing studies that appeared to constitute a valid comparison versus what we have concluded according to the current randomized clinical trial is a useful reminder of the hazards of using historical comparison groups, even if they are samples from the same population. Had we not performed a randomized trial to confirm our previous findings, we would have concluded that the 2 mg hydromorphone bolus protocol was superior to the 1+1 titration protocol.[1]

 

An initial 2 mg bolus does not appears to increase the benefits to the patients in this ED study.

In EMS our goal is usually to manage the pain before we move the patient.

In EMS an initial 1 mg hydromorphone, with 5 minute repeat doses would not appear to delay benefits, but the study’s end point was the need for more medicine at 1 hour, not the ability to adequately control the patient’s pain before moving the patient.

Footnotes:

[1] Randomized Clinical Trial of the 2 mg Hydromorphone Bolus Protocol Versus the “1+1″ Hydromorphone Titration Protocol in Treatment of Acute, Severe Pain in the First Hour of Emergency Department Presentation.
Chang AK, Bijur PE, Lupow JB, Gallagher EJ.
Ann Emerg Med. 2013 May 16. doi:pii: S0196-0644(13)00201-1. 10.1016/j.annemergmed.2013.02.023. [Epub ahead of print]
PMID: 23694801 [PubMed – as supplied by publisher]

http://www.clinicaltrials.gov/ct2/show/NCT01311895 (NCT01311895

Chang AK, Bijur PE, Lupow JB, & Gallagher EJ (2013). Randomized Clinical Trial of the 2 mg Hydromorphone Bolus Protocol Versus the “1+1″ Hydromorphone Titration Protocol in Treatment of Acute, Severe Pain in the First Hour of Emergency Department Presentation. Annals of emergency medicine PMID: 23694801

.

If the patient is asleep, does that mean that the pain is gone?

ResearchBlogging.org
 

Is it appropriate to stop giving pain medicine just because the patient is asleep?

My little burned patient was probably not expressing relief from pain with her periods of unresponsiveness – especially since she had not received anything for her severe pain. Each time that she woke up screaming, that was also a clue. the medical command doctor’s orders were to give no pain medicine.[1]

Is propofol effective at putting patients to sleep without relieving their pain?

Sleep does not mean pain relief, but many of us assume that is exactly what it means.

What does this study show?
 

The main goals of the study were to assess prospectively the temporal relationship between morphine titration, analgesia and sedation and to determine whether patients who sleep during i.v. morphine titration are simply sedated or are actually relieved from their pain.[2]

 

This study was done in a PACU (Post-Anesthesia Care Unit). This study looks at whether sleep after a painful surgery indicates that the pain is well controlled.
 

Among morphine‐induced side‐effects, sedation occurs in up to 60% of cases during morphine titration, and represents a common cause of discontinuation of titration for reasons of safety.3 The assumption is usually made that patients sleep when their pain has been relieved. Nevertheless, some patients complain of persistent pain when they awake and morphine titration is frequently resumed.[2]

 

If the patient wakes up with pain, was the pain always there, or has the pain returned?

In this study, they woke patients from sleep to find out.

Did you fall asleep because your pain is well managed or do you still have significant pain?
 

Although the optimal dose of morphine is still a matter of debate, the usual recommendations for morphine titration include a short interval between two boluses (5–7 min) and no upper limit for the total administered dose.2 3 [2]

 

They did not place an upper limit on the total dose, but it did seem to take a long time to manage the pain at just 2 mg to 3 mg at a time.
 

Boluses of i.v. morphine were 3 or 2 mg when patient’s weight was above or below 60 kg, respectively. The interval between boluses was 5 min, without an upper dose limit. Morphine titration was discontinued when VAS was inferior to 30 mm, in case of side‐effects such as nausea and/or vomiting, respiratory depression (SpO2 <92%, ventilatory frequency rate 3 min, RS >2). An RS on a 6‐point scale was used (1=anxious and agitated patient; 2=cooperative patient; 3=asleep patient, brisk response to loud voice; 4=asleep patient, sluggish response to loud voice; 5=no response to loud voice; score of 6=no response to pain).[2]

 

A common measure of sedation is the RS (Ramsay Score), but like the GCS (Glasgow Coma Score) this relies heavily on the eye opening of the patient.
 

When a patient slept while receiving morphine, its administration was discontinued.[2]

 

They were giving boluses of morphine every 5 minutes. If the patient was not awake, they did not awaken the patient to evaluate the level of pain. For this study, sleeping patients were awoken every 10 minutes to evaluate pain level.

Most of the patients who remained awake had good pain management, although it took a while for about a quarter of them to get relief from pain.

 

 

The numbers in the two graphs may not be comparable.

The three measurements in the Awake group are 10 minutes and 20 minutes after initiation of morphine titration and at the end of morphine titration.

The three measurements in the Sleep group are 10 minutes, 20 minutes, and 30 minutes after the onset of sleep.
 

There were significantly more men and the surgical duration was shorter in the Awake group compared with the Sleep group. In the Sleep group, the mean time to the sleep onset of initiation of morphine titration was 22 (10) min.[2]

 

The Awake group graph looks at 10 minutes and 20 minutes after initiation of morphine titration, and at the end of titration.

The Sleep group graph looks at about 32 minutes, 42 minutes, and 52 minutes after initiation of morphine titration.

And why did they stop titration with 5% of the Awake patients still experiencing significant pain?

5% is just one of the 21 Awake patients, but they state that they had no upper limit on the morphine administered, so why did they not even get this one patient down to a pain level of 5/10? The comparison with the Awake patients appears to have been well intended, but it does not appear to have contributed anything useful to the results.
 

 

The current study suggests that sedation during morphine titration occurs before patients have been completely relieved from their pain (as mean VAS at sleep onset was ∼50 mm), and that sleep encountered during morphine titration is mainly related to the sedative properties of morphine.[2]

 

That appears to have been well demonstrated.
 

The second important finding of this study is that among patients in whom morphine titration is discontinued because of sedation, 25% still bear a high level of pain (VAS >50 mm) whereas only 50% have satisfactory pain relief (VAS <30 mm).[2]

 

We do not expect people to be able to sleep with more than 5/10 pain, but some do.

Sedation is not pain relief, even if the sedation is causing the patient to sleep.
 

Finally, this study suggests that morphine‐induced sedation should not be considered as an indirect indicator of a correct level of analgesia during i.v. morphine titration.[2]

 

What I think matters most is that this study provides documentation that about a quarter of the sleeping patients had significant pain (greater than 5/10) when awoken and asked about pain level.

Just because we can sedate a patient to the point of sleep does not mean that the we have relieved the patient’s pain.

Just because we have prevented the patient from moving, by giving a paralytic, does not mean that we have relieved the patient’s pain.

We need to assess the patient’s pain to find out if the patient is experiencing significant pain.

Footnotes:

[1] Burns and Pain and Little Kids
Rogue Medic
Sun, 18 May 2008
Article

[2] Is morphine-induced sedation synonymous with analgesia during intravenous morphine titration?
Paqueron X, Lumbroso A, Mergoni P, Aubrun F, Langeron O, Coriat P, Riou B.
Br J Anaesth. 2002 Nov;89(5):697-701.
PMID: 12393765 [PubMed – indexed for MEDLINE]

Free Full Text from British journal of Anaesthesia

Paqueron X, Lumbroso A, Mergoni P, Aubrun F, Langeron O, Coriat P, & Riou B (2002). Is morphine-induced sedation synonymous with analgesia during intravenous morphine titration? British journal of anaesthesia, 89 (5), 697-701 PMID: 12393765

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Geriatric patients may not experience increased risk of oligoanalgesia in the emergency department

ResearchBlogging.org

The current Annals of Emergency Medicine has an editorial and two studies of pain management in older adults.

One study is a 10-year prospective, observational study of a convenience sample of patients who had pain on presentation to the ED. Over 10 years any Hawthorne effect can be expected to wear off. Over a decade a lot can change, especially with the ways that pain management has progressed.

Exclusion criteria included patients younger than 18 years, patients with a critical illness, or patients meeting criteria for trauma designation.[1]

It would be nice to know how many patients were affected by the trauma exclusion.

Advanced age significantly affects trauma triage decisions. If trauma patients had been included, would this be likely to show a significant difference in either direction?


Click on images to make them larger.

There is a big difference in chest pain, but that does not appear to alter the results.

Patient information was collected 7 days a week, between 8AM and midnight, during the 10-year period.[1]

Hence, a convenience sample.

Opiate analgesia was defined as any oral, intramuscular, or intravenous opioid medication, including morphine, hydromorphone, acetaminophen with oxycodone, and acetaminophen with codeine, administered in the ED. Morphine dose was calculated only for intravenous administration of morphine.[1]

Acetaminophen with codeine for moderate to severe pain? I have not seen that used much, but I have never seen it improve the patient’s pain rating. It would be nicer if they had fewer drug variables.

After multivariable adjustment for sex, race, chief complaint, and the degree of pain at presentation, the geriatric patients on average received lower doses of morphine (3.3 versus 4.2 mg) and had longer waiting times for their initial dose of analgesic medication (65 versus 75 minutes).[1]

The lower dosing of morphine is to be expected in older patients. We are advised to decrease dosing in older patients.

I start at about half of what I would for a young, otherwise healthy patient, but that is an important difference – otherwise healthy. The increased age is not always the most important factor limiting doses. Many of these patients will have illnesses that affect the metabolism of opioids, illnesses that may produce exaggerated side effects when opioids are given (such as COPD), illnesses that are treated with medications that interact with opioids, and other co-morbid complications.

This does not mean that we should not use opioids, but that we should start with lower doses and/or consider using other medications.
 

The range of morphine doses is much narrower in older patients. Is this due to a difference in comfort level with repeat dosing?

The doses of morphine are smaller in older patients, too.

Are these differences due to more appropriate caution, more inappropriate caution, more successful pain management, or something else?

We excluded patients with comprehension barriers, including dementia or delirium. So our results are limited to a nondemented, nondelirious patient group, which means that oligoanalgesia in demented, delirious patients is still a possibility.[1]

This is a group of patients that my protocols prohibit me from treating on standing orders.


Protocol limitation source.[2]

Are disoriented patients going to receive more aggressive care in the ED?

Is there any good reason to not treat the pain of disoriented patients?

Maybe, but that depends on what is going on.

Is the patient not fully oriented because the patient is truly having 10 out of 10 pain?[3]

Footnotes:

[1] Geriatric patients may not experience increased risk of oligoanalgesia in the emergency department.
Cinar O, Ernst R, Fosnocht D, Carey J, Rogers L, Carey A, Horne B, Madsen T.
Ann Emerg Med. 2012 Aug;60(2):207-11.
PMID: 22818367 [PubMed – in process]

[2] Musculoskeletal Trauma 6003 and Burns 6071
Pennsylvania Statewide Advanced Life Support Protocols
7007 – ALS – Adult/Peds
Page 73/128 and Page 80/128
Free Full Text PDF of All ALS Protocols

[3] Is It Possible To Be Alert And Oriented With 10/10 Pain – Part I
Rogue Medic
Thu, 01 Mar 2012
Article

Cinar O, Ernst R, Fosnocht D, Carey J, Rogers L, Carey A, Horne B, & Madsen T (2012). Geriatric patients may not experience increased risk of oligoanalgesia in the emergency department. Annals of emergency medicine, 60 (2), 207-11 PMID: 22818367

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These authors read far too much into their limited study – Part II

ResearchBlogging.org

Continuing from Part I.

The authors do not find dramatic differences between fentanyl and morphine in their ability to relieve pain in patients who are not hypotensive. In the discussion, they begin to give their reasons for not wanting to use fentanyl.

Why?

I don’t know why they are not fond of fentanyl, but this is what they write in their discussion.

Our study opens the door for debate regarding the value of including fentanyl in limited formularies such as medical helicopters and ambulances given its higher cost and lack of any detectable advantages when compared to morphine. Whereas at our institution fentanyl costs approximately the same as morphine, costs may vary widely in other institutions.[1]

The authors state that their cost is about the same for morphine and for fentanyl, but they think that the possibility that someone somewhere might be paying a lot more for fentanyl is reason enough to limit their choices to morphine.

Both drugs are available as generics, so there does not appear to be any reason to bring a hypothetical difference in price into the discussion. Both generic drugs are affected by the current drug shortages.

If we are much more concerned about giving morphine to hypotensive patients, than we are about giving fentanyl to hypotensive patients, is that worth a bit of a premium in the price of fentanyl?

I think so. More on fentanyl and hypotensive patients in a little bit.

There is also the question of whether including fentanyl in prehospital formularies is worth the risk given its abuse potential among medical staff. Although surveillance data suggest that nationally, fentanyl is one of the least abused drugs in the non-physician population, fentanyl abuse by physicians is a well-recognized concern (24,25).[1]

The first reference does not even mention fentanyl abuse. the second reference appears to be there as a reference for the lack of abuse by non-physicians.

There is no reference for the statement that fentanyl abuse by physicians is a well-recognized concern.

Is fentanyl more of a concern than morphine?

Is fentanyl less of a concern than morphine?

There is nothing in this paper to answer that question. Are the authors using a traditional doctors’ tale an old wives’ tale?

It looks that way.

There was no detectable difference with the limited number of patients, the limited dosing of medication, and the refusal to include patients with a blood pressure that was not at least 10 points above where hypotension begins.

Patients were excluded if they reported an allergy to morphine or fentanyl, or if they were hypotensive before receiving the first dose of the study drug (systolic blood pressure < 100 mm Hg).[1]

It isn’t as if they would have been giving large doses.

It isn’t as if there is a significant concern that fentanyl will cause hypotension.

Fentanyl appears to be one of our most effective treatments for getting rid of hypotension.

There was a 47% chance that a hypotensive patient would no longer be hypotensive after a dose of fentanyl.

the safety of fentanyl as demonstrated in the current study may be related to more conservative dosing in unstable patients, but the parallel message is that experienced EMS crews are able to exercise judgment in determining which patients should receive cautious drug dosing.[2]

Should we assume that there is no judgment going into the dosing of patients?
 

experienced EMS crews are able to exercise judgment in determining which patients should receive cautious drug dosing.
 

When should we expect hypotension after giving a dose of fentanyl?

When the patient is already hypotensive.

I have written more about this study.[3]
 

The study is not a bad idea, since the information on the lack of hypotensive effect of fentanyl[2] was not yet published. However, the conclusions are not justified by the results of this study.

The conclusions may best be described as imaginative.

The authors seem to be experiencing a case of the vapors and might want to consider taking some anti-anxiety medication.

According to the available research, which is much more extensive than this study, fentanyl is very safe, even when the patient is hypotensive.

There is less evidence to demonstrate that the morphine is safe for treating hypotensive patients with pain, but that does not appear to be a concern of the authors, even though the pain of hypotensive patients should be the concern of all of us who treat hypotensive patients.

Is fentanyl expensive?

No.

Is fentanyl effective?

Yes.

Is fentanyl dangerous?

Fentanyl is one of the safest drugs we use.

The ignorance of those on the pushing end of the fentanyl syringe is what is dangerous.

The problem is not the fentanyl, but the ignorance.

Footnotes:

[1] The Effectiveness and Adverse Events of Morphine versus Fentanyl on a Physician-staffed Helicopter.
Smith MD, Wang Y, Cudnik M, Smith DA, Pakiela J, Emerman CL.
J Emerg Med. 2012 Jul;43(1):69-75.
PMID: 21689900 [PubMed – in process]

There is one unusual aspect to the study that does not appear to affect the outcome, but raises questions about how many obstacles to research we create, when the obstacles may not be valid.

The study was fully reviewed by our Institutional Review Board, and given that both treatment arms are considered acceptable practice with equal risk, informed consent was not deemed necessary for this study. Upon completion of participation, each patient was given a verbal and written debriefing of his or her study involvement.[1]

[2] Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia.
Krauss WC, Shah S, Shah S, Thomas SH.
J Emerg Med. 2011 Feb;40(2):182-7. Epub 2009 Mar 27.
PMID: 19327928 [PubMed – in process]

Full Text PDF Download at medicalscg.

[3] Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia
Rogue Medic
Fri, 27 May 2011
Article

Chart Version – Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia
Rogue Medic
Sun, 05 Jun 2011
Article

Safety of prehospital intravenous fentanyl for adult trauma patients
Rogue Medic
Thu, 03 May 2012
Article

Smith MD, Wang Y, Cudnik M, Smith DA, Pakiela J, & Emerman CL (2012). The Effectiveness and Adverse Events of Morphine versus Fentanyl on a Physician-staffed Helicopter. The Journal of emergency medicine, 43 (1), 69-75 PMID: 21689900

Krauss WC, Shah S, Shah S, & Thomas SH (2011). Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia. The Journal of emergency medicine, 40 (2), 182-7 PMID: 19327928

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These authors read far too much into their limited study – Part I

ResearchBlogging.org

There is a new study that looks at prehospital fentanyl. It starts out well, it is even randomized, blinded, and prospective, but it loses focus and draws conclusions that are not remotely justified by the study. Starting out well –

In one study looking at patients transported to EDs by ambulance with painful extremity injuries, patients who did not receive analgesics during transport waited approximately 75 min after arrival to the hospital before receiving any analgesic medication (2).[1]

This is a real problem.

Does prehospital fentanyl decrease that delay, or in other ways improve outcomes?

The authors cite several possible benefits – takes effect more quickly, is metabolized more quickly, causes less nausea, and causes less hypotension. However, they seem to ignore the last one – less likely to produce hypotension. In prehospital treatment, this is important.

They do not have many scene transports (only 16%) and they have doctors on the helicopters, so the authors’ flight service appears to take a conservative approach to treatment. On the other hand, their study protocol makes me look like Scrooge.

Each milliliter of study drug contained either 4 mg of morphine or 50 mg of fentanyl. The dosing was kept below the recommended loading doses of each narcotic to aid in blinding and allow for repeat dosing in small aliquots in the concentrations available in our pharmacy.[1]

However, that non sequitur plan appears to have worked even worse than we would expect.

Why not start out with a double dose?

The dose of morphine used in many studies is 1.0 mg/kg followed by doses of 0.05 mg/kg.

The repetition of the dose every 5 minutes should have made this not a problem, but the study protocol had a ridiculous limitation.

Each patient was allowed a maximum of five doses of the study drug.[1]

That is a maximum of 20 mg morphine or 250 µg fentanyl.

Depending on the weight of the patient, I can give more morphine or fentanyl on standing orders than these doctors can. If I reach my standing orders maximum, I can call medical command for orders to give more.

The authors even acknowledge this in their discussion.

Our initial doses correspond to 0.05 mg/kg of morphine and 0.71 mg/kg of fentanyl for a 70-kg adult, whereas others have found that sufficient pain relief required doses of 1.0 mg/kg and 1.6 mg/kg, respectively (7,20).[1]

What is the point of arbitrarily limiting the total dose?

The point certainly does not have anything to do with good patient care, since there is no evidence that any such arbitrary limit in any way improves outcomes.

If anyone knows of any research to suggest that this limitation improves outcomes, please provide it, but I do not know of any justification for this limit.
 


 

An average (mean) of 3 doses of morphine and 3.3 doses of fentanyl. That is 12 mg morphine and 165 µg fentanyl. These are not large doses, but the results show that they only had very limited success in managing pain.

Although they could start treating at a pain level of 1 out of 10, they still stopped at 5 out of ten – a pain level that would be appropriate for me to start treating with morphine or fentanyl, or to continue treating with morphine or fentanyl. I treat moderate to severe pain.

But it gets worse.

Of patients in the study, 57.5% received analgesics before being enrolled, without a significant difference between either arm. Although the medication name was recorded, the dose was not always recorded by the flight crew. Average doses of morphine, Dilaudid, and fentanyl were 4 mg, 1 mg, and 100 mg, respectively, and were similar in both arms, based on available data.[1]

Most of these patients had already received an average of one dose of study drug (or the equivalent amount of hydromorphone [Dilaudid]) prior to being entered in the study, so the pain management should have just been a continuation of treatment, even though the dose they already received had been inappropriately low for a starting dose.

Patients who reported any pain score other than zero were then given the study drug in a 1-mL intravenous bolus. Patients were then reassessed every 5 min (normal flight protocol, with automated monitor and clinical evaluation) during transport with a complete set of vital signs (including pulse oximetry) and another numeric pain score. During each reassessment, a 1-mL bolus of the study drug was given for any pain score > zero.[1]

Except that does not appear to be even close to what happened.

Although the study protocol called for administration of medication every 5 min, a mean of only three doses was given despite a mean patient care time of 40 min.[1]

A change of 13 mm on the visual analog scale and a corresponding change of 1.3 on the NPS have been generally accepted as a clinically significant change in pain relief (8,12,13). We found that both morphine and fentanyl at repeated study doses provided clinically significant pain relief by decreases in mean pain scores of 2.2 and 2.5, respectively.[1]

Yes, the difference was clinically significant, but we can do much better. Here are the details of the pain levels –

The mean pain score at the beginning of enrollment was 8.0 ± 2.0 in the morphine arm and 8.0 ± 1.8 in the fentanyl arm. The mean final pain score was 5.8 ± 2.7 in the morphine arm and 5.5 ± 2.4 in the fentanyl arm. The median initial pain score was 8, with an IQR of 3. There was no difference between the two groups. The median final pain score was 5, with an IQR of 3.5, with no significant difference between the two groups (Table 2).[1]

Starting morphine pain level from 6 to 10 out of 10.   Starting fentanyl pain level from 6.2 to 9.8 out of 10.

Ending morphine pain level from 3.1 to 8.5 out of 10.   Ending fentanyl pain level from 3.1 to 7.9 out of 10.
 


 

This is not even cutting the pain in half – this is only cutting the pain a little.

that is still important, but it could be much better.

61.5% of morphine patients and 69% of fentanyl patients had a significant improvement in pain level (≥2 according to their predefined criteria).

There were no incidences of pruritis or vomiting in either group. There were no episodes of hypotension in either group.[1]

To be continued in Part II.

Footnotes:

[1] The Effectiveness and Adverse Events of Morphine versus Fentanyl on a Physician-staffed Helicopter.
Smith MD, Wang Y, Cudnik M, Smith DA, Pakiela J, Emerman CL.
J Emerg Med. 2012 Jul;43(1):69-75.
PMID: 21689900 [PubMed – in process]

There is one unusual aspect to the study that does not appear to affect the outcome, but raises questions about how many obstacles to research we create, when the obstacles may not be valid.

The study was fully reviewed by our Institutional Review Board, and given that both treatment arms are considered acceptable practice with equal risk, informed consent was not deemed necessary for this study. Upon completion of participation, each patient was given a verbal and written debriefing of his or her study involvement.[1]

Smith MD, Wang Y, Cudnik M, Smith DA, Pakiela J, & Emerman CL (2012). The Effectiveness and Adverse Events of Morphine versus Fentanyl on a Physician-staffed Helicopter. The Journal of emergency medicine, 43 (1), 69-75 PMID: 21689900

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