ISSN NUMBER: 1938-7172
Issue 9.12 VOLUME 9 | NUMBER 12

Editor:
Michael A. Fiedler, PhD, CRNA

Contributing Editors:
Mary A Golinski, PhD, CRNA
Dennis Spence, PhD, CRNA
Steven R Wooden, DNP, CRNA, NSPM-C

Assistant Editor
Jessica Floyd, BS

A Publication of Lifelong Learning, LLC © Copyright 2015

New health information becomes available constantly. While we strive to provide accurate information, factual and typographical errors may occur. The authors, editors, publisher, and Lifelong Learning, LLC is/are not responsible for any errors or omissions in the information presented. We endeavor to provide accurate information helpful in your clinical practice. Remember, though, that there is a lot of information out there and we are only presenting some of it here. Also, the comments of contributors represent their personal views, colored by their knowledge, understanding, experience, and judgment which may differ from yours. Their comments are written without knowing details of the clinical situation in which you may apply the information. In the end, your clinical decisions should be based upon your best judgment for each specific patient situation. We do not accept responsibility for clinical decisions or outcomes.

Table of Contents

PHARMACOLOGY
A prospective observational study of maternal oxygenation during remifentanil patient-controlled analgesia use in labour
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Does fentanyl lead to opioid-induced hyperalgesia in healthy volunteers?
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Perioperative dextromethorphan as an adjunct for postoperative pain
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A randomised controlled trial of perineural vs intravenous dexamethasone for foot surgery
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IV and perineural dexmedetomidine similarly prolong the duration of analgesia after interscalene brachial plexus block
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Appropriate dosing of sugammadex to reverse deep rocuronium-induced neuromuscular blockade in morbidly obese patients
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This issue includes 2 PHARMACOLOGY CE credits.

None of the editors or contributors have any real or potential conflicts of interest to disclose.


Pharmacology
A prospective observational study of maternal oxygenation during remifentanil patient-controlled analgesia use in labour

Anaesthesia 2016;71:17176

Messmer AA, Potts JM, Orlikowski CE


Abstract

 

Purpose The purpose of this study was to review maternal oxygen saturation during remifentanil IVPCA for labor analgesia. The primary objective was to observe the frequency, lowest value, and duration of oxygen saturation <90%.

 

Background No institutional ethics review of this study was required because the care delivered was a longtime standard at the institution and the data collected was only observational; it was not experimental. The study center had been using a remifentanil IVPCA protocol since 2007. Labor analgesia has been provided in a few locations with remifentanil IVPCA for over 15 years. It has not gained widespread use, probably in part due to safety concerns. One study reported that parturients receiving remifentanil IVPCA had an oxygen saturation <90% for 5% of the time they were in labor. A review of 10 additional studies reported that 32% of parturients experienced respiratory depression during remifentanil IVPCA. Case reports of cardiac and respiratory arrest during remifentanil IVPCA also exist.

 

Methodology This was a prospective, observational study of oxygen saturation in healthy, laboring women receiving remifentanil IVPCA for analgesia. Women with any type of fetal compromise or respiratory disease were excluded from the study. Remifentanil IVPCA was set up with an initial bolus dose of 20 µg, but the bolus was adjusted up or down according to patient response. Lockout was 1 minute. There was no background infusion. Maximum hourly bolus dose was set to 5,000 µg/hour. All women receiving remifentanil IVPCA received continuous care by a nurse midwife. Self-administered nitrous oxide could be used in addition to remifentanil IVPCA at concentrations between 30% and 70% (balance oxygen) under supervision of the midwife. All parturients were continuously monitored with pulse oximetry which continuously recorded saturation readings. Desaturation was defined as an oxygen saturation of <90%. Periods of poor oximeter signal quality were excluded from analysis. The pulse oximeter was set to alarm at 94%, which was the threshold value at which protocol prescribed supplemental oxygen administration, 2L by nasal cannula. Once oxygen was applied, it remained on the patient throughout labor.

 

While saturation data was recorded prospectively, information about nitrous oxide use and application of nasal cannula oxygen was gathered retrospectively from the patient chart. The investigator who analyzed the saturation data was blinded to parturient clinical details, such as nitrous oxide use.

 

Result During the study period, 61 women received remifentanil IVPCA for labor analgesia. A total of 148 hours of pulse oximeter data was analyzed; 10 hours were rejected due to poor signal quality. This represented 6% of all oximetry data. Average maternal age was 27 years. Average BMI was 28.5 Kg/m2. Average gestational age was 40 weeks. The remifentanil IVPCA bolus dose used after adjustment was 20 µg in 71% of women, but 1% of women were adjusted down as low as 15 µg and 3% adjusted up as high as 50 µg.

 

Most parturients, 70%, had an oxygen desaturation episode. Parturients who received remifentanil IVPCA desaturated “regularly,” though usually for short periods. The median length of desaturation was 16 seconds, and the median lowest saturation value was 87%. The median number of episodes was 3 each, but some women experienced up to 14. There were 10 occurrences of oxygen saturation below 80% in a total of six different women (about 15% of women). The worst episode involved a desaturation to 68% lasting 1 minute and 44 seconds. All recovered to a saturation of ≥ 90% spontaneously. No naloxone, airway maneuvers, or ventilation was needed for any women. Overall, 63% of women were placed on nasal cannula oxygen during labor. Some of the women were receiving nasal cannula oxygen when the desaturation began. Of the 61 women included in analysis, 12 (20%) received nitrous oxide intermittently during remifentanil IVPCA. [Editor’s Note: the percent nitrous oxide used was not reported.]

 

Women who were on 2 L nasal cannula oxygen were less likely to have oxygen desaturation than those breathing room air. But supplemental oxygen did not affect the severity of the desaturation episodes when they occurred. The remifentanil IVPCA bolus dose was not correlated with the incidence of desaturation. Likewise, nitrous oxide use was not associated with the frequency, severity, or duration of desaturation.

 

Most neonatal APGAR scores were 8 or 9, but the low was 2 at 1 minute and 5 at 5 minutes. Eight neonates required face mask ventilation upon delivery. However, 6 of the mothers received no remifentanil for at least 45 minutes before delivery. The other two women had used remifentanil IVPCA up until delivery.

 

Conclusion Supplemental oxygen should be administered to all parturients receiving remifentanil IVPCA.

 

Comment

Disclosure: Though I have done a lot of OB anesthesia over my career, I’ve not used remifentanil IVPCA for labor analgesia, nor have I ever worked anywhere it was used. I think there is a good reason for this, and it is outlined in both the study background and results. But, not having tried it, that may be my bias.

 

With my bias disclosed, I’ll say I believe this study does have things to teach us and they are probably all bad. And while I am usually loath to criticize care I wasn’t present to witness, I have some real problems with what is reported here.

 

The investigators were wise to fine-tune the remifentanil bolus dose early in labor. This action no doubt helped minimize the incidence of oxygen desaturations. But on top of an opioid that we know decreases MAC for anesthesia, in pregnant women who have a lower MAC already, they then allowed women to self-administer nitrous oxide up to 70%!!! I have no doubt that 70% nitrous and the remifentanil would produce general anesthesia in some. I consider that reckless in the absence of direct care by an anesthesia provider. But here, the only supervision was a midwife. I’m amazed.

 

My next concern is that 70% of women experienced desaturations, and 10 of them were to sats less than 80%. At the very least, this is a risky practice because during that time there was no longer any margin of safety for those women. Next we are told, “No naloxone, airway maneuvers, or ventilation was needed for any women.” But, we are told this right after we learn that the worst oxygen desaturation was 68% and lasted almost 2 minutes. I would argue that a pregnant woman under the care of anesthesia with an almost 2 minute deep desaturation demands intervention long before the 2 minute mark. So, really, it wasn’t that no treatment was “needed” but simply that none was provided, and it should have been.

 

The only part of the plan for data analysis described was that, “Standard descriptive statistics were used for analysis.” Since descriptive statistics by their nature tell us nothing about correlations, associations, or, in this case, any connection between treatment and outcome, I’m uncertain how the investigators decided that there was no connection between the remifentanil bolus dose or nitrous oxide use and the incidence and severity of oxygen desaturation as they reported. At best it was simply their opinion.

 

Now, to be fair, while this data looks bad (and personally I think it was), we don’t have much to compare it to. For example, we can see how frequently and deeply parturients in this study desaturated, but we don’t know if parturients with no anesthetic intervention do the same. I’d be shocked if there wasn’t a huge difference. But, since we don’t have that data to make a comparison, we don’t know for sure.

 

In my opinion, this study adds to the body of evidence that should inhibit us from using the described technique for labor analgesia. I’m not saying there can’t be a way to safely use remifentanil IVPCA for labor analgesia, simply that I don’t think this is it. In any case, the risk-benefit decision would have to include not only a comparison to doing nothing but also a comparison to tried and true labor analgesia techniques that already have a long track record of safe use.

 

 

Michael A. Fiedler, PhD, CRNA


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 12, December 31, 2015





Does fentanyl lead to opioid-induced hyperalgesia in healthy volunteers?

Anesthesiology 2016;124:453-63

Mauermann E, Filitz J, Dolder P, Rentsch KM, Bandschapp O, Ruppen W


Abstract

 

Purpose The purpose of this study was to define the association between different doses of fentanyl and postoperative:

  • acute pain
  • hyperalgesia*
  • allodynia**

 

Background Information in some previous studies suggests that opioids administered during a general anesthetic may induce hyperalgesia in the immediate postoperative period. This is termed “Opioid-iInduced Hyperalgesia.” Hyperalgesia frequently develops post surgery. Hyperalgesia and the intensity of the baseline pain experienced correlate poorly. The little information available about opioid-induced hyperalgesia in opioid-naïve patients reports higher pain scores after high-dose fentanyl. There is little to any clinically relevant information about this phenomenon postoperatively. However, animal studies have conclusively shown that fentanyl produces opioid-induced hyperalgesia. Central Sensitization***, and the resulting hyperalgesia and allodynia, can be prevented in some cases by the administration of an NMDA receptor blocker and the anti-seizure drugs gabapentin (Neurontin) and pregabalin (Lyrica).

 

Methodology This was a prospective, randomized, double-blind study of ASA class I or II male volunteers. The study was performed in a laboratory setting with no surgical procedure. Exclusion criteria included drug abuse, opioid use during past month, previous motion sickness, chronic pain, and obstructive sleep apnea. The phenomena of interest were assessed with well-accepted models used to study pain, intradermal electrical stimulation and the Cold Pressor Pain test. The Cold Pressor Pain test involves immersing the subject’s arm in an ice-water bath.

 

The study used two different doses of fentanyl, a 1 µg/Kg dose and a 10 µg/Kg dose. Both doses were administered as an IV infusion over a one-hour time period. For clinical context, the 10 µg/Kg group received fentanyl at a rate of 50 µg (1cc / 1mL) approximately every 4.3 minutes. All patients were monitored with ECG, pulse oximetry, and BP. While the fentanyl infusion lasted only 1 hour, the study period was 6.5 hours long. All pain dimensions were tested during the first 2 hours and again during the last 2 hours of the 6.5-hour data collection period. Data was collected on the following pain dimensions:

  • Intensity of Pain (numeric rating scale)
  • Area of Hyperalgesia
  • Area of Allodynia
  • Area of Secondary Hyperalgesia****

Hyperalgesia, secondary hyperalgesia, and allodynia are all the result of a continuous painful sensation. In this study, the baseline continuous painful stimulation was produced by an intradermal electrical current. During the 6.5-hour data collection period, the intradermal electrical current was on for the first 2 hours, followed by a 2.5-hour rest period, and ending with another 2 hours of electrical current. In order to accurately assess pain, a constant and repeatable source of pain that did not harm the subjects was needed. Pain was assessed by two methods. One method was to apply pressure on the skin with a Frey filament. The other method was to immerse the arm in an ice bath kept at 0° to 1° C. There are established pain research protocols for each method. A cotton swab was gently brushed over the skin to assess allodynia.

 

Result Not surprisingly, since volunteers were recruited specifically to be similar, demographic data was similar between the two fentanyl groups. One factor that may have differed within groups was the plasma level of fentanyl produced by each of the fentanyl infusions. It was not statistically significantly different within groups. Another factor that may have varied between volunteers was the baseline pain produced by the standard stimuli. This too was similar between groups.

 

Fentanyl infusion reduced pain scores in all subjects. The area of hyperalgesia surrounding the location of pain stimulus was smaller in the 10 µg/Kg fentanyl group during the first two hours of the 6.5-hour study period. However, during the last two hours, the area of hyperalgesia increased by 31% (P=0.001).

 

The area of allodynia was similar in size in the 1 µg/Kg fentanyl group and the 10 µg/Kg fentanyl group during both the first and last 2 hours of data collection. However, the size of the area of allodynia decreased significantly over time (P=0.01).

 

During the last 2 hours of data collection, the 10 µg/Kg fentanyl group had a larger area of secondary hyperalgesia than the 1 µg/Kg fentanyl group.

 

No major adverse events occurred in any subject. Nausea and vomiting occurred in less than half of the 10 µg/Kg fentanyl group. Oxygen desaturation to <90%, requiring a reminder to breathe and/or supplemental oxygen, occurred in almost all 10 µg/Kg fentanyl subjects. None needed assisted ventilation.

 

Conclusion Fentanyl 10 µg/Kg resulted in an increase in the area of hyperalgesia and secondary hyperalgesia four hours after infusion compared to only 1 µg/Kg fentanyl. Conversely, the area of allodynia decreased over time after 10 µg/Kg fentanyl.

 

Comment

Let me start out by putting this laboratory study into a clinical context. We know that surgical pain can become increased postoperatively through a physiologic process called central sensitization. This results in pain becoming more intense, the area which is painful getting larger around a surgical wound, and pain being experienced from stimuli that would not normally be painful, e.g. a breeze blowing across the skin. There is some evidence that using greater doses of fentanyl class opioids during general anesthesia may worsen central sensitization. If true, this would have significant implications for our anesthetic techniques.

 

So, think of this study like a two-hour anesthetic and the first 4.5 hours post-op; together they make up the 6.5-hour study period. During the first part of the study period, the anesthetic period, volunteers received either 1 µg/Kg fentanyl or 10 µg/Kg fentanyl, low dose and high dose. Various pain parameters were measured during that time. Then, during the last part of the study period, the post-op period, the pain parameters were measured again to see if there was a difference in central sensitization in the low-dose vs. high-dose fentanyl groups. What they learned was that 10 µg/Kg fentanyl increased the pain sensation subjects experienced at the surgical wound and the area surrounding it. But, high-dose fentanyl did not cause pain from stimuli that would normally not cause pain (allodynia). It is important to understand that this is a different phenomenon than acute tolerance to opioids. It is not that the opioids are not relieving pain as well. It is that the pain level increased due to a “windup” feedback process in the CNS.

 

What does this mean for us clinically? There is much more to learn about this topic, so my answer to that question is tentative. That said, it looks like sad news for people like me who have long favored high-dose opioids during general anesthesia for the stability they bring to an anesthetic and the ability to awaken patients who are pain free. While there are probably still times to use that technique, in general it looks like “less is best” for opioids during general anesthesia in terms of postoperative pain. But there is a flip side. NMDA receptor blockers have been shown to prevent central sensitization. Ketamine is a potent NMDA receptor blocker. Dextromethorphan and magnesium sulfate are weak NMDA receptor blockers. Two anti-seizure drugs have also been shown to prevent central sensitization, gabapentin (Neurontin) and pregabalin (Lyrica). NMDA receptor blockers have also been shown to help prevent chronic pain postoperatively. So, it is likely that using one of these drugs will allow the use of high-dose opioids during general anesthesia without the development of central sensitization.

 

Michael A. Fiedler, PhD, CRNA


*Hyperalgesia = a type of CNS sensitization in which there is increased pain sensation from a stimulus that would normally be expected to be painful.

**Allodynia = a type of CNS sensitization in which there is increased pain sensation from a stimulus that would normally not be expected to be painful, e.g. being touched with a cotton ball.

***Central Sensitization = a feedback mechanism in the CNS that results in increased pain sensation in response to constant acute pain stimuli. Central sensitization results in hyperalgesia and allodynia and is often referred to as “wind-up.”

****Secondary Hyperalgesia = increased pain sensation in undamaged tissue around tissue which has been physically damaged, e.g. by a surgical incision.


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 12, December 31, 2015





Perioperative dextromethorphan as an adjunct for postoperative pain

Anesthesiology 2016;124:696-705

King MR, Ladha KS, Gelineau AM, Anderson TA


Abstract

 

Purpose The purpose of this study was to examine the effects of preoperative dextromethorphan on postoperative opioid use and pain scores.

 

Background NMDA antagonists are useful adjuncts for prevention of postoperative pain. Ketamine is a potent and well-studied NMDA antagonist shown to result in “preemptive” analgesia when given preoperatively, intraoperatively, and postoperatively. Dextromethorphan is a weak NMDA receptor antagonist most commonly used as an over-the-counter cough medicine. Preemptive analgesia caused by NMDA receptor blockade is thought to change pain impulse transmission in the spinal cord and CNS. Doing so prevents a pain syndrome commonly referred to as “windup” which amplifies pain perception. In previous studies, dextromethorphan has been shown to decrease chronic pain from diabetic neuropathy, postherpetic neuralgia, and phantom limb pain. Nevertheless, dextromethorphan seems to be used infrequently to help reduce postoperative pain. Doses of dextromethorphan greater than 2 mg/Kg PO may produce dissociative effects.

 

Methodology This was a meta-analysis of previously published studies. The following search terms were used to locate subject studies in multiple databases:

  • dextromethorphan
  • acute pain
  • postoperative pain
  • pain

Studies were only included in the meta-analysis if they were randomized, double blind, placebo controlled, and the dextromethorphan was administered preoperatively. Studies on patients less than 12 years old were excluded. After discovering when each study had tracked opioid use and pain scores, the meta-analysis organized opioid consumption into 24-h and 48-h time periods. Pain scores were grouped by 1 h, 4 h, 6 h, and 24 h post-op. All opioids were converted into IV morphine equivalents for comparison.

 

Result The meta-analysis included 21 studies, but not all studies had the required data for each category. Each category, e.g. post-op pain scores, included 12 to 14 studies. Likewise, the number of patients represented by these different numbers of studies varied between 799 and 849. In some of the studies, dextromethorphan was administered more than once preoperatively. Some studies administered dextromethorphan PO while others used IM dosing. [Editor’s Note: dextromethorphan is only available orally in the USA.] The dose of dextromethorphan ranged from 30 mg to 200 mg. Most doses were between 40 mg and 60 mg.The time of dosing ranged from the night before surgery to 30 min preoperatively. The surgical procedures involved ranged widely including orthopedic, major abdominal, and ENT.

 

Preoperative dextromethorphan reduced average 24-h or 48-h IV morphine use by over 10 mg (P=0.0006). In three studies IV morphine use was decreased by over 20 mg, while in three other studies IV morphine use was slightly increased (14 total studies). Morphine use was reduced by between 5 mg and 17 mg in 95% of patients.

 

Mean pain scores at 1 h postoperatively (1 lowest to 10 highest) were1.6 lower in the dextromethorphan group (P=0.00001). Pain scores at 4 h, 6 h, and 24 h were statistically significantly lower but the actual difference was less than 1. None of the studies included in the meta-analysis showed a higher pain score in patients who had received dextromethorphan.

 

Side effects were tracked in 18 studies. Side effects were similar for both dextromethorphan and opioids:

  • nausea
  • vomiting
  • dizziness
  • lightheadedness

In 10 of the 18 studies, there were either no side effects reported or the incidence of side effects were similar between the dextromethorphan and control groups. Fewer side effects were reported in the dextromethorphan group in 5 studies.

 

Conclusion Preoperative dextromethorphan significantly decreased postoperative pain and opioid use. The optimum dose and preoperative timing of dextromethorphan is not yet known.

 

Comment

You can choose to look at this study one of two ways. I’ll try to present both of them.

 

Position 1: Preoperative dextromethorphan is cheap, easy, low risk, and may produce a significant reduction in postoperative pain. For clinical and scientific reasons, I believe investigators too often get over enthusiastic about differences in pain scores. In this study the differences in pain scores are small enough that they may not impress you either. But, an average reduction in IV morphine use in the early post-op period of over 10 mg is something I think we can agree is a good thing. So what dose of dextromethorphan do you use? This meta-analysis doesn’t tell us. My guess is that most CRNAs are going to want to use a single dose. That dose should probably be within two hours of induction. Lest you are worried about administering a PO medication, remember that we are talking about a cough medicine, a teaspoon or two. As to the dose, my personal guess for the dose to start at is 1 mg/Kg. This is similar to most of the studies in the meta-analysis and well below the point where dysphoric reactions have been reported.

 

There are different genotypes that determine the hepatic elimination half-life of dextromethorphan. In some the half-life will be only 4 hours. But ketamine produces preemptive analgesia for longer than its half-life so dextromethorphan may too. In other patients the elimination half-life is 24 hours. This fact probably accounts for some of the wide differences seen in the studies. It may also mean that it works great for some of your patients and just so-so in others. Personally, this first position is the one I now hold.

 

Position 2: Preoperative dextromethorphan is just another thing to do that at best produces only modest reductions in postoperative pain. It is not worth the bother. I agree that the improvement in postoperative analgesia wasn’t uniformly impressive. This may have been due to the wide range of doses that were used (some too small?), the difference in how quickly dextromethorphan was eliminated in different genotypes, or just not being a very effective intervention. But the reduction in opioid pain medication required was still fairly impressive. Nevertheless, if this is your position, you may want to learn more about a strong NMDA receptor blocker, ketamine, which is well documented to prevent windup type postoperative pain.

 

Postoperative pain highly influences patient satisfaction and is an area in which we still have lots of room for improvement. Let’s learn everything we can about preventing acute pain and keep after it.

 

Michael A. Fiedler, PhD, CRNA


NMDA = N Methyl-D-Aspartate


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 12, December 31, 2015





A randomised controlled trial of perineural vs intravenous dexamethasone for foot surgery

Anaesthesia 2016;71:28590

Dawson RL, McLeod DH, Koerber JP, Plummer JL, Dracopoulos GC


Abstract

 

Purpose The purpose of this study was to compare the duration of ankle block combined with dexamethasone in the local anesthetic solution, dexamethasone IV, or placebo IV. A secondary purpose was to assess postoperative pain.

 

Background Same day orthopedic surgery often results in moderate to severe postoperative pain. Regional anesthesia can prevent postoperative pain while avoiding opioid side effects and increasing patient satisfaction. With a long-acting local anesthetic, an ankle block may provide analgesia for as much as 14 hours. Unfortunately, 14 hours post-op is often the middle of the night and patients may be awakened by pain. Dexamethasone has been shown to prolong the duration of several regional blocks, both when added to the local anesthetic and when co-administered intravenously. The mechanism by which the blocks are prolonged is unknown. However, not all studies have shown prolongation of regional block following dexamethasone by either route.

 

Methodology This was a prospective, double-blind study of 90 adult ASA I-III patients scheduled for metatarsal osteotomy. Patients with an infection at the site of the block and those regularly taking opioids or glucocorticoids were excluded. All blocks were done by the same anesthesiologist, all surgeries by the same surgeon. Patients were randomized into one of three groups. All patients in each group received an ankle block with 0.75% ropivacaine. About 22 mL of ropivacaine was used for each ankle block. The differences in the three study groups were as follows:

  • Regional Dex
    8 mg Decadron added to local anesthetic
    + 2 mL IV saline placebo
  • IV Dex
    8 mg Decadron IV
  • Placebo
    2 mL saline IV

Patients were discharged home with both NSAIDs and oxycodone 5 mg. They recorded the time when sensation began to return in their foot, pain scores, and analgesic use in a diary. Statistical analysis was appropriate.

 

Result Over 80% of subjects were women. Patients in all three study groups were otherwise demographically similar. Dexamethasone in the local anesthetic or administered IV prolonged the duration of the ankle block. Ankle block prolongation in the Regional Dex group and the IV Dex group was similar. There were also no significant differences in postoperative pain scores or total PO pain medicine use among any of the three groups.

 

Conclusion Dexamethasone 8 mg, either mixed with the local anesthetic or administered IV, significantly prolonged the duration of the ankle block.

 

Comment

This was an interesting little study. I’m not sure how I missed it, but I was unaware that IV dexamethasone would prolong the duration of many regional blocks. The study itself was short and sweet but in this case a little too short. There was more information in the study than was included in the text.

 

Figure 1 that follows is called a box and whisker plot. The “box” shows the limits of where 50% of the patients fell in terms of when their block began to wear off. The line through the box is the “median” (most common) value for that group. The “whiskers” are the lines that extend from the top and bottom of the box. They show the range of time in hours before the block started wearing off for the other 50% of patients in that group. As the investigators said in the text, you can see that most patients, the 50% represented by the boxes in the Regional Dex and IV Dex groups, had the block start to wear off about the same time. But what they didn’t tell you is that the range of time over which the block started wearing off in the other 50% of patients was much narrower in the IV Dex group. The “whiskers” are shorter in the IV Dex group. This means that there is much more uniformity in when the block started to wear off in the IV Dex group. As a result, I would use IV dexamethasone to prolong my block. The prolongation is more reliable.

 

Figure 1: Time Until Sensation Began to Return

Figure 1

Note: X axis shows the 3 study groups. Y axis show hours until ankle block began to wear off. Adapted from Anaesthesia 2016, 71, 285–290 Figure 2.

 

Another thing that went unsaid was how much longer the blocks lasted when patients received dexamethasone. It looks like dexamethasone prolonged the ankle blocks by about 8 hours, from about 15 hours in the placebo group to about 23 hours in the dexamethasone groups. This is great news. It means that patients are likely to be awake when their block starts to wear off and they can take pain medicine early, before severe pain begins. In the placebo group, patients would most likely have their blocks wear off while they were sleeping, as the investigators predicted.

 

Early in my anesthesia career we almost never gave dexamethasone for anesthetic purposes. Now we know that it makes patients feel better post-op, which can lead to earlier outpatient surgery discharge, it reduces postoperative pain, it helps prevent PONV, and now, even IV it prolongs the analgesia from some regional blocks. At this point I think the question is, “can I think of any reason not to give dexamethasone to this patient?”

 

Michael A. Fiedler, PhD, CRNA


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 12, December 31, 2015





IV and perineural dexmedetomidine similarly prolong the duration of analgesia after interscalene brachial plexus block

Anesthesiology 2016;124:683-95

Abdallah FW, Dwyer T, Chan VWS, Niazi AU, Ogilvie-Harris DJ, Oldfield S, Patel R, Oh J, Brull R


Abstract

 

Purpose The purpose of this study was to compare the duration of an interscalene brachial plexus block when dexmedetomidine (Precedex) was added to the local anesthetic vs. administered as an IV infusion. Secondary goals were to compare 24-hour postoperative opioid consumption.

 

Background Dexmedetomidine (Precedex) is an alpha2 agonist. It has been associated with the prolongation of analgesia following regional blocks. Many previous studies of dexmedetomidine added to local anesthetics for regional blocks are small studies with variable dosing or poor block assessment methods. They produced inconsistent results. In this study the investigators used a Precedex dose of 0.5 µg/Kg based on their prior clinical experience. Another alpha2 agonist, clonidine, is known to prolong regional blocks when added to the local anesthetic or, in some cases, when administered systemically. Clonidine has not gained much acceptance for prolonging regional blocks, probably because of its propensity to cause hypotension.

 

Methodology This was a prospective, randomized, triple-blind study of ASA I-III adult patients scheduled for elective arthroscopic shoulder surgery with general anesthesia. Patients with a BMI > 38 Kg/m2, preexisting neurologic deficits, or daily use of > 30 mg oxycodone equivalents were excluded. All patients were premedicated with 1 Gm oral acetaminophen and 400 mg celecoxib. Up to 4 mg midazolam and/or 25µg fentanyl were given IV during placement of the interscalene block.

 

Patients were randomized into one of three groups. All patients in each group received an ultrasound-guided interscalene block with 15 mL of 0.5% ropivacaine with 5 µg/mL epinephrine. The C5-6 nerve roots were targeted. The differences in the three study groups were as follows:

  • Regional Dexmed
    0.5 µg/Kg Precedex added to local anesthetic
    + 50 mL IV saline infusion
  • IV Dexmed
    0.5 µg/Kg Precedex in 50 mL IV infusion
  • Placebo
    50 mL saline infusion

The IV Precedex or saline placebo was infused over 30 minutes starting immediately after induction of general anesthesia. General anesthesia included 1 - 3 µg/Kg fentanyl, 2 - 4 mg/Kg propofol, and 0.6 mg/Kg rocuronium. Anesthesia was maintained with 5% to 7% desflurane in 40:60 oxygen:air. Additional fentanyl or morphine was allowed during general anesthesia. Decadron was discouraged for PONV prevention because it too can prolong the duration of regional blocks. Muscle relaxation was antagonized with neostigmine. Patients were discharged home with a diary. They recorded the time when they first experienced pain, pain scores, return of arm strength, and analgesic use in the diary, which they returned to investigators by mail. Statistical analysis was appropriate.

 

Result Over 76% of subjects were male. Patients in all three study groups were otherwise demographically similar. Data from 99 patients were analyzed; Regional Dexmed = 33, IV Dexmed = 34, placebo = 32. Time from block completion to the start of the Precedex or placebo IV infusion averaged 42 minutes.

 

Both Precedex mixed with local anesthetic or IV Precedex prolonged the duration of the interscalene block. Average block durations were as follows :

  • Regional Dexmed 11 hours
  • IV Dexmed 10 hours
  • Placebo   7 hours

 

Block duration was statistically significantly longer in either of the Dexmed groups compared to placebo (P=0.001). However, while Precedex prolonged analgesia from the interscalene block, motor block was not prolonged. Interscalene block prolongation in the Regional Dexmed group and the IV Dexmed group was similar. Visual Analogue Pain Scores at 8 hours post-op were lower in both Dexmed groups (9 mm Regional Dexmed, 13 mm IV Dexmed) compared to the placebo group (26 mm [P = 0.006]). Cumulative 24-hour oral pain medication use was about 25% greater in the placebo group compared to either of the Dexmed groups (P=0.001).

 

Bradycardia and hypotension were “very low” on the day of surgery for all three study groups.

 

Conclusion Dexmedetomidine (Precedex) 0.5 µg/Kg, either mixed with local anesthetic or administered after induction of general anesthesia as a 30-minute infusion, resulted in a significantly longer duration of interscalene block than 0.5% ropivacaine with 5 µg/mL epinephrine alone. The need for PO pain medication was also reduced during the first 24 hours post-op when Precedex was administered with the block. Since Precedex also produces sedation, opioid-sparing, and perhaps antiemesis, it may have advantages for prolonging regional blocks. Bradycardia and hypotension may have been avoided due to the slow infusion of Precedex.

 

Comment

When we were investigating the use of clonidine to prolong regional blocks, I read some studies that reported longer block duration following PO clonidine. It didn’t end up being helpful because there were differences in effective prolongation of the block depending upon when the PO clonidine was taken and whether or not the patient took clonidine as a daily antihpyertensive medication. Clonidine added to the local anesthetic lost favor due largely to its hemodynamic effects.

 

This study is helpful because a newer alpha2 agonist, dexmedetomidine (Precedex), has also been shown to prolong the duration of a regional block but without hemodynamic complications. Like the Decadron study in this same issue, Precedex works when added to the local anesthetic or when administered as an IV infusion. The data presented in this study doesn’t show me any advantages to adding Precedex to the local anesthetic or administering it IV, so the decision of how to use it is probably one of convenience. One note, however. The investigators chose their 0.5 µg/Kg dose of Precedex based upon their experience alone. After completing their study, they found scientific evidence that a 1 µg/Kg dose of Precedex added to the local anesthetic produced even longer block durations. So you may want to try several doses of Precedex before settling on one.

 

The investigators stated that Precedex did not prolong the motor block compared to ropivacaine with epinephrine alone. Figure 3 in their research report gives a little more detail. According to that graph, the rate at which motor block wore off was similar in the Precedex and placebo groups for about the first 10 hours. From about 10 to 15 hours, motor block clearly wore off more quickly in the placebo group. After that it was similar again, though only about 15% of patients had any motor block remaining by that time.

 

Lastly, I don’t want to miss the idea of combining the information from this study and the Decadron ankle block study elsewhere in this issue. Both Decadron and Precedex prolong regional block, whether added to the local anesthetic or administered IV. This raises the obvious question, do I want to use both to make the block last even longer? Well, first, for several reasons I wouldn’t add both Decadron and Precedex to the local anesthetic solution. Second, it would be nice to see a study using both before we all jump in. But, if you have a clinical need for postoperative analgesia that lasts even longer (shoulder surgery comes to my mind), using a combination of Decadron and Precedex may produce the results you are looking for.

 

Michael A. Fiedler, PhD, CRNA


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 12, December 31, 2015





Appropriate dosing of sugammadex to reverse deep rocuronium-induced neuromuscular blockade in morbidly obese patients

Anaesthesia 2016;71:265-72

Loupec T, Frasca D, Rousseau N, Faure J-P, Mimoz O, Debaene B


Abstract

 

Purpose The purpose of this study was to attempt reversal of sugammadex neuromuscular block with a range of doses based upon Ideal Body Weight to identify the most appropriate dosing scheme for morbidly obese patients.

 

Background Deep neuromuscular block may improve operative conditions during some surgical procedures. Sugammadex reverses rocuronium neuromuscular block with less variability than neostigmine. The effective dose of sugammadex was determined only in patients with a body mass index (BMI) <25 Kg/m2. Sugammadex is hydrophilic and, thus, should distribute to fat poorly. Sugammadex studies in morbidly obese patients have shown that reversals based upon Ideal Body Weight are inadequate. A sugammadex dose based upon something less than Actual Body Weight nevertheless seems logical in obese patients.

 

Methodology This was a prospective, randomized, double-blind study of adults, ASA class I-IV, with a BMI > 40 Kg/m2. All were scheduled for elective surgery which required deep neuromuscular block. Exclusion criteria were, in part, renal failure, treatment with an aminoglycoside or magnesium, preexisting neuromuscular disease, and hypothermia. Anesthesia induction was standardized with remifentanil and either 4-5 mg/Kg thiopental or 2-3 mg/Kg propofol. Rocuronium 1-1.2 mg/Kg was used for paralysis. Neuromuscular monitoring was with the TOFWatch SX at the adductor pollicis. The TOFWatch was calibrated to each patient just before the rocuronium dose. Anesthesia was maintained with a remifentanil infusion and desflurane. Rocuronium was redosed if there were more than 5 post-tetanic twitches. The Train-of-4 ratio (TOFr) was determined at the end of wound closure before sugammadex administration. To proceed in the study, the TOFr must have been between one and five post-tetanic twitches, indicating deep neuromuscular block. Subjects were randomized to receive one of three doses of sugammadex based upon Ideal Body Weight:

  • 4 mg/Kg
  • 2 mg/Kg
  • 1 mg/Kg

After administration of the study dose of sugammadex, the TOFr was measured every 15 seconds until it was ≥ 0.9. Reversal was defined as a failure if the TOFr was less than 0.9 by 10 minutes after sugammadex administration.

 

Result The study was completed by 50 patients. Subjects were mostly female, 86% of the 50 who finished the study. BMI ranged from 42 to 46 across the three sugammadex dosing groups. Total Body Weight (TBW) averaged about 120 Kg while Ideal Body Weight (used for sugammadex dosing) was less than half of TBW. No patient had any Train-of-4 twitches when they were reversed with sugammadex. The average number of post-tetanic twitches (“post-tetanic count” or PTC) at the time of reversal was greater in the medium and low dose sugammadex groups:

  • 1 PTC in 4 mg/Kg group
  • 3 PTC in 2 mg/Kg group
  • 3 PTC in 1 mg/Kg group

Here is the average time between the last rocuronium dose and sugammadex administration:

  • 11 min in 4 mg/Kg group
  • 16 min in 2 mg/Kg group
  • 22 min in 1 mg/Kg group

 

Recovery from deep neuromuscular block was significantly faster in the 4 mg/Kg group (P<0.0001) as follows:

  • 2 min 15 s ± 1 min 3 s    4 mg/Kg
  • 7 min 9 s ± 1 min 42 s    2 mg/Kg
  • 9 min 41 s ± 2 min 24 s  1 mg/Kg

The rate of successful reversal of neuromuscular block within 10 minutes of sugammadex administration was as follows:

  • 93% @ 4 mg/Kg
  • 77% @ 2 mg/Kg
  • 22% @ 1 mg/Kg

In the “high dose” 4 mg/Kg by Ideal Body Weight group, one patient still had residual neuromuscular block 10 minutes after sugammadex administration. Additionally, one patient in the 2 mg/Kg group was initially reversed by sugammadex but became reparalyzed 6 minutes later.

 

Conclusion The investigators recommended that morbidly obese patients receive 4 mg/Kg sugammadex based upon Ideal Body Weight. They further observed that sugammadex should not be “used sparingly because of cost.” After reversal, patients should be assessed for complete reversal.

 

Comment

This is an important study. The investigators had a good idea but chose to study it with methods I found confusing. However, the data produced was not at all confusing. Nevertheless, the investigators’ conclusions were not entirely supported by their data. Let’s make some sense of it all.

 

The sugammadex (Bridion) package insert recommends a dose of 4 mg/Kg for deep neuromuscular block. These investigators rightly noted that sugammadex is not very lipophilic and wondered if the dose of sugammadex could be based upon something less than Actual Body Weight. This is a reasonable question. But they noted in their background section that “studies in morbidly obese patients have shown that reversal based upon Ideal Body Weight is inadequate.” Then they not only based their dosing upon Ideal Body Weight but they used the recommended dose and two smaller doses. Not surprisingly, the smaller doses failed to reverse many subjects, even after waiting 10 minutes. And this despite the fact that they were less paralyzed than the 4 mg/Kg sugammadex group and it had been longer since their last dose of rocuronium when they were reversed.

 

I’m not willing to accept the investigators’ recommendation that deeply paralyzed morbidly obese patients receive 4 mg/Kg sugammadex based upon Ideal Body Weight. Why? Because studies are carried out under the most controlled and ideal circumstances possible. And yet 1 of 15 patients who received the 4 mg/Kg dose was not reversed. Maybe we don’t need to give morbidly obese patients a dose based on Actual Body Weight, but I want to give them enough that everyone is likely to be reversed in real world circumstances. I’m also not willing to start out using a dose based upon Ideal Body Weight when one study showed that it worked for almost everyone and other studies said it didn’t work (cited in their background section).

 

Any of us who remember the introduction of sufentanil or midazolam remember that drug company recommended doses are not always right when a new drug is first released. I expect that sugammadex is going to contribute significantly to reducing the number of patients with residual neuromuscular block and subsequent critical respiratory events. But sugammadex isn’t a miracle drug. We may not yet know the best doses to use in morbidly obese patients or lean patients. All patients who are given a reversal drug should be assessed for residual neuromuscular block after the reversal has had time to work.

 

Michael A. Fiedler, PhD, CRNA


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 12, December 31, 2015