ISSN NUMBER: 1938-7172
Issue 13.3

Editor:
Michael A. Fiedler, PhD, CRNA

Contributing Editors:
Mary A Golinski, PhD, CRNA
Dennis Spence, PhD, CRNA

Assistant Editor
Heather Whitten, MEd.


A Publication of Lifelong Learning, LLC © Copyright 2019

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
Randomised double-blind comparison of bolus phenylephrine or ephedrine for treatment of hypotension in women with preeclampsia undergoing caesarean section

Intravenous vs oral acetaminophen as a component of multimodal analgesia after total hip arthroplasty: a randomized, blinded trial

Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised, triple-blinded crossover study in volunteers

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

 

This program has been prior approved by the American Association of Nurse Anesthetists for 20 Class A CE credits; Code Number 1037484; Expiration Date 03/31/2022.

Pharmacology
Randomised double-blind comparison of bolus phenylephrine or ephedrine for treatment of hypotension in women with preeclampsia undergoing caesarean section

Anaesthesia 2018;73:839–846

DOI: 10.1111/anae.14268

Mohta M, Duggal S, Chilkoti GT


Abstract

 

Purpose   The purpose of this study was to compare the effect of phenylephrine and ephedrine on umbilical artery pH in preeclamptic women undergoing cesarean section with spinal anesthesia.

 

Background   Preeclampsia is a pathology of pregnancy characterized by excessive vasomotor response and placental hypoperfusion. One of the diagnostic criteria for preeclampsia is a maternal BP ≥ 140/90 (severe preeclampsia ≥160/110). Neuraxial anesthesia frequently results in hypotension in pregnant women which increases the risk of uteroplacental hypoperfusion. Historically, ephedrine was the preferred vasopressor in pregnancy while phenylephrine was thought to have harmful effects on placental perfusion due to vasoconstriction. More recently ephedrine has been questioned on the basis of fetal pH (acidosis) while phenylephrine has been shown to be safe, at least in healthy term pregnant women. The effects of these vasopressors in preeclamptic women are not well defined, especially in terms of neonatal outcomes.

 

Methodology   This was a randomized, controlled, double-blind study of preeclamptic women with singleton pregnancies. All women were scheduled for cesarean section with a subarachnoid block. Exclusion criteria were chronic hypertension, cardiovascular disease, cerebrovascular disease, and fetal distress. Groups were randomized to receive either phenylephrine 50 µg (Group P) or ephedrine 4 mg (Group E) for hypotension. [Editors Note: these doses are roughly equivalent.]

 

Baseline blood pressure was established by taking the average of three readings. The spinal block was performed with a 25 g needle in the midline of L3-4 or L2-3 with 11 mg hyperbaric bupivacaine. Immediately following, 10 mL/Kg of lactated Ringer’s was infused IV. A minimum T-6 level was achieved. Blood pressure and heart rate were measured every minute until delivery of the neonate. Hypotension was defined as a decrease in systolic pressure below 80% of baseline or an absolute decrease to less than 100 mm Hg.

 

At delivery, umbilical artery and umbilical vein blood gasses were analyzed. The primary outcome was the umbilical artery pH. Secondary outcomes included:

  • APGAR scores at 1 & 5 min
  • Umbilical artery pH <7.2
  • Number of vasopressor boluses given
  • Number of hypotensive episodes
  • HR > 130
  • Hypertension >120% of baseline

Result   The study randomized 150 subjects. Patient demographics were similar, and, specifically, baseline blood pressures were similar. Baseline HR was higher in Group E (89 vs. 84) before treatment with the study vasopressor. Over a third in both groups were hypertensive enough to be given labetalol. Severe preeclampsia was present in 17 women in Group P and 15 women in Group E (P=0.082). Of those 10 and 9 respectively were also receiving MgSO4 to prevent seizures.

 

The median number of hypotensive episodes and vasopressor administrations were similar between groups. Heart Rate was significantly higher in Group E throughout data collection (P<0.0001) though no patients met the criteria for tachycardia (HR > 130). Fetal acid-base status and APGAR scores were similar between groups.The mean umbilical artery pH was 7.26 in Group P and 7.25 in Group E (P=0.86).

 

Neonatal acidosis (umbilical artery pH <7.2) occurred in 23% of Group P and 28% of Group E (P=0.08). Two neonates in Group P had an APGAR score below 7 with an umbilical artery pH of 7.08 and 6.75 (severe preeclamptic mothers). All other neonates in both groups had 1 min and 5 min APGARs of 7 or higher.

 

There were no statistically significant differences in any of the secondary outcomes. A subgroup analysis of only women with severe preeclampsia also showed no difference in neonatal outcomes between those who received phenylephrine and those who received ephedrine.

 

Conclusion   There was no difference in umbilical artery pH when either phenylephrine or ephedrine was used to treat hypotension in preeclamptic women undergoing cesarean section with spinal anesthesia. Both drugs effectively treated hypotension.

 

Comment

 

About 10 years ago now, a study was published comparing phenylephrine and ephedrine use in pregnant women and subsequent neonatal pH. In what I thought was amazingly poor judgment, the investigators stated that neonates born after maternal ephedrine administration were “more acidotic” than after phenylephrine. In reality, while the umbilical artery pH was lower in the ephedrine group than the phenylephrine group, it was still firmly within the normal range. While there was a difference between groups, there were no abnormal values, and there were no adverse effects on the neonates. Nevertheless, some in the anesthesia community latched on to the investigators “more acidotic” statement and decided that ephedrine was harmful in pregnant woman. Since that time a number of studies, including this one, in both healthy pregnant women and pregnant women with comorbidities affecting uteroplacental perfusion have shown that both ephedrine and phenylephrine are safe.

 

There are a number of reasons to choose to use either phenylephrine or ephedrine to treat maternal hypotension during neuraxial analgesia or anesthesia. I’ve used both. All I ask is please don’t make your choice based upon a sound bite from one study, critically review what you read. Bottom line: the best scientific evidence we have available right now supports the use of either drug to treat maternal hypotension.

 

Michael A. Fiedler, PhD, CRNA


Notes: this article is available free full text at the following url: https://onlinelibrary.wiley.com/doi/full/10.1111/anae.14268

 

More on this topic at AnesthesiaAbstracts.com

Maternal and neonatal effects of bolus administration of ephedrine and phenylephrine during spinal anaesthesia for caesarean delivery: a randomised study

https://anesthesiaabstracts.com/abstracts.php?issueID=48#465

 

A randomized double-blinded comparison of phenylephrine and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for cesarean delivery: the effects on fetal acid-base status and hemodynamic control

https://anesthesiaabstracts.com/abstracts.php?issueID=36#324

 

Up-down determination of the 90% effective dose of phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients undergoing cesarean delivery

https://anesthesiaabstracts.com/abstracts.php?issueID=47#449


© Copyright 2019 Anesthesia Abstracts · Volume 13 Number 3, April 27, 2019





Intravenous vs oral acetaminophen as a component of multimodal analgesia after total hip arthroplasty: a randomized, blinded trial

J Arthroplasty 2019; ahead of print

DOI: 10.1016/j.arth.2019.02.030

Westrich GH, Birch GA, Muskat AR, Padgett DE, Goytizolo EA, Bostrom MP, Mayman DJ, Lin Y, YaDeau JT


Abstract

 

Purpose   The purpose of this study was to compare the analgesic effectiveness of IV acetaminophen vs. PO acetaminophen as part of multimodal analgesia following total hip replacement.

 

Background   Hundreds of thousands of total hip replacements are performed in the USA every year. In previous studies, patients who received an articular local anesthetic injection rather than neuraxial analgesia received over 50% more opioid and had higher pain scores. Some studies have shown that acetaminophen reduces the need for opioid analgesia. Specifically, IV acetaminophen has reduced morphine use by a third following some orthopedic procedures. IV acetaminophen passes the blood brain barrier faster than PO acetaminophen resulting in CSF concentrations that are twice as high as PO. Thus, the study investigators hypothesize that IV acetaminophen would reduce — pain with activity, opiate use, and opioid related side effects after total hip replacement.

 

Methodology   This was a double-blind, randomized controlled trial. It included patients undergoing primary total hip replacement between the ages of 18 and 90 years old. Following is a partial list of exclusion criteria: abnormal liver or kidney function, planned general anesthesia, rheumatoid arthritis, planned periarticular local anesthetic injection, daily opioid use during the month before surgery, chronic pain, and opioid abuse.

 

Subjects received either IV acetaminophen and PO placebo (IV group), or PO acetaminophen and IV placebo (PO group). The first dose of acetaminophen, by either route, was administered 30 minutes after arrival in the PACU.

 

For their anesthetic, all patients received up to 5 mg of IV midazolam, propofol sedation, and a combined spinal epidural anesthetic. No subjects received any ketamine or opioids preoperatively or interoperatively. Additionally, all subjects received dexamethasone, ondansetron, famotidine, and ketorolac. Postoperatively, all subjects received patient controlled epidural analgesia with bupivacaine and clonidine. They also received IV ketorolac every eight hours for two days followed by PO meloxicam. Subjects had PO tramadol 50 to 100 mg or oxycodone 5 mg available by request for pain. Rescue analgesia was 2 mg IV hydromorphone.

 

Result   Data from 154 subjects were analyzed. There were no differences between the IV group and PO group for pain at rest or during physical therapy, cumulative opioid dose used, or opioid side effects. The average dose of oral morphine equivalents over a three day period was 199 mg. This is approximately equivalent to patients taking two 100 mg tramadol per day. Likewise, there was no difference between groups for any of the secondary outcomes; time to discharge, pain scores, satisfaction, and cognitive effects.

 

Conclusion   IV acetaminophen provided no benefit compared to PO acetaminophen as part of multimodal analgesia following total hip replacement.

 

Comment

 

This study gives us a couple things to talk about, which is good since it doesn’t have a lot to teach us.

 

When IV acetaminophen came out, I wasn’t impressed. I’d never found Tylenol (a brand name from a different manufacturer) to do much for any pain I had. But then I learned that IV acetaminophen worked differently than PO, producing more potent analgesia. It certainly does provide meaningful analgesia under some conditions. Still, it is expensive so the question of just how much better IV is than PO is a legitimate one. This study tried to answer that question for total hip patients who received multimodal analgesia. The problem is that all patients got:

  • a combined spinal / epidural
  • epidural PCA
  • dexamethasone
  • ketorolac
  • meloxicam

What more can you expect acetaminophen to do after all that? A basic concept in research methodology is “effect size.” Simply put, the bigger the effect, the more likely you are to be able to see it in research results. Here this tenet worked against us. The effect of everything else patients received for pain was very big, and the difference, if any, between IV and PO acetaminophen was small by comparison. Thus, if there was any difference between IV and PO acetaminophen at all, we simply couldn’t see it in the research.

 

There would seem to be little downside to giving PO acetaminophen, and it is cheap. So adding it for even a small benefit may contribute some opioid sparing; a good thing. But IV acetaminophen is expensive. If we are going to use it we’ll want to think about what more it will add beyond the other things we plan to give.

 

Lastly, a quick thought on exactly why we need to critically review everything we read. This study included the following statement: “… the study supports routine use of oral acetaminophen for these [total hip] patients.” The fact is, however, that their data does not support this statement. First, there was no difference between the IV and PO groups so the study didn’t “support” one over the other. Second, the study did not compare any acetaminophen group with a group that did not receive acetaminophen. As such, this study doesn’t provide any evidence that acetaminophen did anything in this combination of patients and anesthetic technique. Please don’t believe everything you read.

 

Michael A. Fiedler, PhD, CRNA


© Copyright 2019 Anesthesia Abstracts · Volume 13 Number 3, April 27, 2019





Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised, triple-blinded crossover study in volunteers

Br J Anaesth 2019;122:525-531

DOI: 10.1016/j.bja.2019.01.004

Marhofer P, Columb M, Hopkins PM, Greher M, Marhofer D, Bienzle MRL, Zeitlinger M


Abstract

 

Purpose   The purpose of this study was to determine the efficacy of dexamethasone, administered either intravenously or perineurally, on extending the duration of ropivacaine sensory blockade.

 

Background   The efficacy of perineural or systemically administered dexamethasone in combination with local anesthetics has been evaluated in multiple systematic reviews. Some reports suggest that dexamethasone may have a small effect on increasing the duration of sensory blockade but may only occur when the local anesthetic solution contains epinephrine. A problem identified by many of the systematic reviews was that the studies were of low quality and the heterogeneity between the studys’ methodology made it difficult to draw definitive conclusions about the efficacy of perineural dexamethasone. Another weakness was that most studies evaluated the efficacy of dexamethasone in a clinical environment. Volunteer studies may allow for a more accurate assessment of whether or not dexamethasone prolongs peripheral nerve local anesthetic block.

 

Methodology   This was a prospective, randomized, triple-blind, cross-over study. Twenty-four ASA I male volunteers, aged 18-55 Kg, BMI 18-35 Kg, were enrolled. Each subject received an ultrasound-guided ulnar nerve block on three different days with 4 mL 0.56% ropivacaine plus one of the following:

  1. perineural dexamethasone 4 mg + IV saline 1 mL
  2. perineural saline 1 mL+ IV dexamethasone 4 mg
  3. perineural saline placebo 1 mL + IV saline placebo 1 mL

Blocks were performed by two investigators. The ulnar nerve was chosen because it has a constant sensory distribution pattern with low intra- and inter-individual variability.

 

The sequence of block administration was randomized with a minimum of seven days between each block. Sensory block was evaluated with pinprick testing with a short bevel needle in five different sensory areas supplied by the ulnar nerve: dorsal, ulnar, and palmar aspects of the side of the medial aspect of the hand; the little finger; and the medial side of the ring finger. Testing was performed before the block and then 2, 4, 6, 8, 10, 15, 20, 30, and 60 minutes after the block, and thereafter every 60 minutes. Sensory block onset was defined as a Visual Analogue Pain Score (VAS) <10 mm in four of the five areas tested. Sensory block duration was defined as the time to a VAS >20 mm in at least one of the five areas.

 

Statistical analysis and sample size calculation were appropriate. Bonferroni correction was used to correct for multiple comparisons; therefore, a P < 0.017 was considered statistically significant.

 

Result   There were 24 subjects who completed the study. Their median age and age range was 30 (22-55) years and their mean BMI was 24. No significant difference was found in sensory block onset or duration between the three different groups (Figures 1 and 2). Median sensory block onset time was between six and eight minutes and block duration between 6.9 and 7.4 hours. All subjects had full sensory and motor recovery after each block. No complications were reported.

 

Figure 1. Onset of Sensory Block

 

Figure 2. Comparison of Block Duration

 

Conclusion   Perineural or intravenous dexamethasone 4 mg added to ropivacaine for ulnar nerve block did not hasten sensory block onset time or prolong block duration in volunteers.

 

Comment

 

I thought this was a very well-designed study that demonstrates that the addition of 4 mg dexamethasone, either perineural or intravenous, combined with ropivacaine for ulnar nerve block in volunteers does not hasten onset or prolong the duration of sensory block when compared to a saline control group. The study was well-designed because it used volunteers, randomized the sequence of block administration solution, and each subject served as their own control. I agree with the authors argument that this study design provides for a more accurate assessment of sensory block onset and duration when compared to clinical studies because in clinical studies it is often difficult to measure each of these outcomes accurately, especially because of dressings and patient discharge before being able to evaluate block recovery. However, I am not sure if a pinprick test is a good surrogate marker of postoperative pain.

 

A weakness of this study is that they only checked the sensory block every 60 minutes, so the results are only accurate to the nearest hour. I would have liked to have seen the investigators measure sensory block duration at least every 15 minutes. Nonetheless, the data reported indicate that sensory blockade with ropivacaine 0.56% will last approximately six to eight hours. These results are consistent with my clinical experience. I think this useful information that we can use to care for our patients; although, it may not apply to blocks at different types of blocks.

Dennis Spence, PhD, CRNA


More on this topic at AnesthesiaAbstracts.com

A randomized comparison between intravenous and perineural dexamethasone for ultrasound-guided axillary block

https://anesthesiaabstracts.com/abstracts.php?issueID=149#1023

 

Notes: this article is available free full text at the following url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435911/

 

The views expressed in this article are those of the author and do not reflect official policy or position of the Department of the Navy, the Department of Defense, the Uniformed Services University of the Health Sciences, or the United States Government.


© Copyright 2019 Anesthesia Abstracts · Volume 13 Number 3, April 27, 2019