ISSN NUMBER: 1938-7172
Issue 9.9 VOLUME 9 | NUMBER 9

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

AIRWAY
Changes in endotracheal tube cuff pressure during laparoscopic surgery in head-up or head-down position
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GENERAL
Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: a prospective randomized controlled study
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OBSTETRIC ANESTHESIA
Screening of obstructive sleep apnea during pregnancy: differences in predictive values of questionnaires across trimesters
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PHARMACOLOGY
The RECITE Study: a Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade
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Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial
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The effect of intravenous midazolam on postoperative nausea and vomiting: A meta-analysis
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None of the editors or contributors have any real or potential conflicts of interest to disclose.


Airway
Changes in endotracheal tube cuff pressure during laparoscopic surgery in head-up or head-down position

BMC Anesthesiology 2014;14:75-80

Wu C-Y, Yeh Y-C, Wang M-C, Lai C-H, Fan S-Z


Abstract

 

Purpose The purpose of this study was to observe for changes in endotracheal tube (ETT) cuff pressure associated with abdominal insufflation and position changes during laparoscopic surgery. A secondary goal was to correlate these changes with airway pressure, Body Mass Index (BMI), and intra-abdominal pressure.

 

Background High volume, low pressure ETT cuffs are commonly inflated to between 20 cmH2O and 30 cmH2O to achieve a proper seal. A number of factors can change ETT cuff pressure after the start of surgery. During laparoscopic surgery, elevated intrathoracic pressure from abdominal insufflation and changes in patient position, especially steep Trendelenburg position, might be expected to affect ETT cuff pressure. However, neither of these factors have been studied. Excessive ETT cuff pressure results in postoperative coughing, sore throat, and hoarseness. In particular, the incidence of postoperative sore throat increases sharply at ETT cuff pressures above 30 cmH2O.

 

Methodology This was a prospective, observational study of adult patients undergoing elective laparoscopic surgery with a position change to head-up or head-down tilt for the procedure. Patients undergoing open abdominal surgery in the supine position were used as controls. Patients with airway abnormalities or lung disease were excluded from participation.

 

All patients received general anesthesia with thiamylal [Surital, a thiobarbiturate induction drug] 3 mg/kg - 5 mg/kg, fentanyl 1.5 µg/kg - 2.5 µg/kg, cisatracurium 0.15 mg/kg - 0.2 mg/kg, and 1.3 MAC sevoflurane in air and oxygen. Nitrous oxide was not used. Male patients received a 7.5 mm ETT and female patients a 7 mm ETT. Mechanical ventilation used tidal volumes of 8 mL/kg - 10 mL/kg with a rate of 8 to 14 breaths per minute. No PEEP was used. ETT cuff pressure was checked with a manometer before incision. Cuff pressures were adjusted to eliminate any airway leak within the range of 20 cmH2O to 30 cmH2O. Leak checks were performed by auscultation with a stethoscope. Laparoscopic surgery patients were insufflated to abdominal pressures between 10 mmHg and 15 mmHg. Next, patient position was changed to either 30° head up or head down depending upon the type of surgery. In laparoscopic surgery patients, airway pressure and ETT cuff pressure data were collected at baseline - immediately after induction - and 2 minutes after positioning head up or head down. In open abdominal supine patients - control patients - airway pressure and ETT cuff pressure were measured every 5 minutes for the first 20 minutes after induction.

 

Result The study included 70 laparoscopic surgery patients; 38 in the head-down position and 32 in the head-up position. Head-down patients underwent colorectal tumor resection. Head-up patients underwent cholecystectomy. There were also15 open abdominal control patients in the supine position. There were no significant demographic differences between patients in the three groups.

 

Laparoscopic surgery patients underwent abdominal insufflation while in the supine position resulting in a mean increase in ETT cuff pressure of 6 cmH2O (P<0.001). In general, the absolute change in mean ETT cuff pressure was from about 27±3 cmH2O to 33±5 cmH2O. ETT cuff pressure increased following abdominal insufflation in all patients. The greatest increase in ETT cuff pressure was 20 cmH2O. Likewise, mean airway pressure increased 7 cmH2O following abdominal insufflation (P<0.001). The increase in mean ETT cuff pressure correlated well with abdominal insufflation (r=0.68, P<0.05) but not with airway pressure.

 

After abdominal insufflation, the position change to 30° head down resulted in only small changes in ETT cuff and airway pressure. Mean ETT cuff pressure increased by only 2 cmH2O from 33±5 cmH2O to 35±5 cmH2O (P<0.001). Not all head-down patients experienced these small increases in ETT cuff pressure, however. Six patients in the head-down group (19% of this group) had an increase in ETT cuff pressure > 10 cmH2O, and in one of these patients ETT cuff pressure increased by 20 cmH2O. Mean airway pressure increased by only 1 cmH2O in head-down patients.

 

In patients who were positioned 30° head up there were no mean changes in either ETT cuff pressure or airway pressure. Surprisingly, however, 8 patients in the head-up group (21% of this group) had an increase in ETT cuff pressure > 10 cmH2O and in one of these patients ETT cuff pressure increased by 18 cmH2O.

 

Conclusion Mean endotracheal tube cuff pressure increased to the greatest degree following abdominal insufflation. On average the 30° head-down position resulted in a slight additional increase in mean ETT cuff pressure. In general, the 30° head-up position did not change ETT cuff pressure or airway pressure. Nevertheless, about 20% of laparoscopic surgery patients positioned head up or head down experienced an increase in ETT cuff pressure > 10 cmH2O with some increases up to 20 cmH2O.

 

Comment

I love straightforward, simple studies like this one that have clear implications for clinical practice. I’m probably not the only one of us who was unaware that abdominal insufflation for laparoscopic cases caused an increase in ETT cuff pressure. My sense is that pediatric anesthetists who use cuffed tubes are starting to understand the wisdom of measuring ETT cuff pressure. But in adult OR patients most of us rarely, if ever, measure actual ETT cuff pressure. I’m not ready to say we need to measure cuff pressure routinely. I do think we should be aware that insufflating the abdomen, and several other things that patients experience during general anesthesia such as changes in position, can significantly alter ETT cuff pressure. In my mind, that means we need to check and adjust cuff pressure a second time once we get everything set for the surgeon to start. My habit has long been to just get the cuff inflated at induction and not worry about finding the lowest cuff pressure that prevents a leak at that time. Then, once I get the patient settled and ready for the surgeon I revisit the ETT cuff inflation, and at that time I find the minimum volume needed to prevent a leak around the ETT. My rationale has been that most of the things, like position changes, that will change cuff pressure have happened by then and the lowest “no leak” cuff pressure established at that time will probably work for the rest of the case.

 

Overall, most of the increases in cuff pressure in this study were not that large. The patients in this study were mostly near ideal body weight and, judging by their airway pressures, pretty easy to ventilate. It would be easy to file this study away and decide that the average increases in ETT cuff pressure were not big enough to worry about clinically. I suggest we do pay attention for several reasons. The increase in ETT cuff pressure correlated pretty well with abdominal insufflation pressure, and I suspect your surgeons sometimes use pressures above 15 mm Hg so the increase in ETT cuff pressure may be greater than reported here. Some of your patients are going to need higher airway pressures for adequate ventilation which means a higher ETT cuff pressure to prevent a leak. In those patients a small additional increase in cuff pressure may be clinically important. And, lastly, let’s not forget that in about 20% of patients the increase in ETT cuff pressure was between 10 cmH2O and 20 cmH2O. Clearly, these are clinically important increases.

 

So now we know one more thing that increases ETT cuff pressure of which to be mindful. I expect we will see a lower incidence of sore throat and hoarseness, and thus more satisfied patients, if we avoid unnecessary increases in ETT cuff pressure. And, of course, for some patients ETT cuff pressure can be an issue of tracheal perfusion, which is a much greater concern than postoperative sore throat. Let’s work toward having an ETT cuff pressure manometer available in all OR suites so we can start checking actual cuff pressures when we need to.

Michael A. Fiedler, PhD, CRNA


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 9, September 30, 2015




General
Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: a prospective randomized controlled study

Gynec Oncol 2015;138:609-13

Hutchins J, Delaney D, Vogel RI, Ghebre RG, Downs LS, Carson L, Mullany S, Teoh D, Geller MA


Abstract

 

Purpose The purpose of this study was to compare ultrasound-guided bilateral subcostal transversus abdominis plane infiltration using liposomal bupivacaine (Exparel) against 0.25% bupivacaine with 1:200,000 epinephrine on total opioid consumption, pain scores, rates of nausea, length of stay, and patient satisfaction during the first 72 hours after robotic-assisted hysterectomy.

 

Background Postoperative pain can impair recovery after robotic-assisted hysterectomy. Opioids are routinely administered postoperatively; however, they are associated with opioid-related side effects such as nausea, vomiting, constipation, and respiratory depression. Ultrasound-guided transversus abdominis plane (TAP) infiltration with standard bupivacaine has been reported to provide effective pain relief and to reduce opioid consumption after lower abdominal surgery. Liposomal bupivacaine (Exparel) is a multivesicular liposomal formulation of 1.3% bupivacaine that can provide up to 72 hours of pain relief after infiltration into the surgical wound or via TAP block. The investigators designed this study to test the hypothesis that use of liposomal bupivacaine administered via TAP block would provide effective pain control after robotic-assisted hysterectomy.

 

Methodology This was a prospective, randomized, controlled trial of 58 women who underwent robotic-assisted hysterectomy. Patients were randomized to receive a preoperative ultrasound-guided bilateral subcostal TAP block with either 10 mL of 1.3% liposomal bupivacaine diluted to 30 mL with normal saline or 30 mL 0.25% bupivacaine with 1:200,000 epinephrine. The same local anesthetic solution was used on both sides of the abdomen. All patients received a standardized general anesthetic and postoperative pain regimen. All surgical, nursing, and research personnel were blinded to each patient’s group assignment. TAP blocks were performed by one of four anesthesiologists.

 

Data was collected during the first 72 hours after surgery. The primary outcome was total morphine equivalents administered during the 72-hour period. Secondary outcomes included:

  • pain scores
  • frequency of pain medication use
  • nausea or vomiting
  • length of stay
  • patient satisfaction with pain control

Outcomes were assessed at 0-24, 24-48, and 48-72 hours postoperatively by a blinded data collector. Statistical analysis and power analysis were appropriate. The sample size calculation was based on a 30% difference in total morphine equivalents between the two groups.

 

Result No significant differences were found in patient demographics or surgery characteristics between the two groups. Patients in the liposomal bupivacaine group required 50% less total morphine equivalents during the first 72 hours after surgery (P = 0.002; Figure 1). Specifically, total morphine equivalents required were significantly lower while in the PACU and during the 0-24 and 24-48 hour time periods in the liposomal bupivacaine group (P < 0.05; Figure 2). Maximum pain scores were significantly lower at all time points in the liposomal bupivacaine group when compared to the standard bupivacaine group (P < 0.05; Figure 3). Minimum pain scores were significantly lower in the liposomal bupivacaine group in the PACU (1.5 vs. 3) and during the 0-24 hour (1.5 vs. 3) time periods (P < 0.05). Nausea rates were also significantly lower in the liposomal bupivacaine group (25% vs. 57%, P = 0.014). No statistically significant difference was found in length of stay, although the average stay was shorter in the liposomal bupivacaine group. A similar percentage of patients in both groups reported being highly satisfied with their pain control (92.9% vs. 82.8%, P = NS).

 

Figure 1. Postoperative Opioid Use

Figure 1

 

Figure 2. Total Opioid Use

Figure 2

 

Figure 3. Maximum Postoperative Pain Scores

Figure 3

 

Conclusion Liposomal bupivacaine infiltration via ultrasound-guided subcostal TAP blocks decreased total opioid consumption and pain scores during the first 72 hours after robotic-assisted hysterectomy compared to 0.25% bupivacaine with 1:200,000 epinephrine.

 

Comment

Liposomal bupivacaine (Exparel) is increasingly being used to provide extended postoperative pain relief. The advantage of this medication is that it does not require infusion pumps. The disadvantage is that there is a learning curve for infiltration techniques and a delay before the medication starts to be effective. This has led some groups to issue consensus recommendations on proper injection techniques.1 Some surgeons and anesthesia providers mix additional plain bupivacaine with the solution; however, this is an off-label use of the medication. If done, the milligram dose of bupivacaine added should not exceed 50% of the Exparel dose.2

 

Cost is also a concern. The average wholesale price of a 20-mL vial of Exparel is $285 compared to an average wholesale price of a vial of standard bupivacaine of $1 to $3. However, the high costs of Exparel may be offset by a decrease in opioid-related adverse events, decreased length of stay, and reduced supply and manpower costs. While this study did not address costs, I suspect the 50% reduction in opioid requirements and rate of nausea, and decreased length of stay was probably offset by the increased cost of Exparel. Additionally, many patients are willing to pay upwards of $100 to avoid experiencing postoperative nausea and vomiting.3

 

What I found surprising was that the liposomal bupivacaine group had significantly lower pain and opioid requirements in the PACU and during the first 24 hours after surgery. The difference in the PACU is interesting, as I would have suspected both groups would have had similar pain scores and opioid consumption immediately after surgery. This would make me think there could have been some bias towards the liposomal bupivacaine group. The difference in pain scores was only one point and 3 mg for total morphine equivalents, which may not be clinically significant. However, the TAP blocks were performed by one of four experienced anesthesiologists, so I doubt bias occurred. TAP blocks with bupivacaine are reported to last anywhere from 6 to 24 hours.4 It may be that the regular bupivacaine had a shorter duration of action than the liposomal bupivacaine. Liposomal bupivacaine works best if it stays where it is injected, which is possibly what happened in this study.

 

We desperately need more studies examining the costs of different interventions we perform. As surgeons and anesthesia providers get more proficient with the injection of liposomal bupivacaine, administrators are going to want to see data showing it reduces overall costs before allowing its widespread use.

 

Dennis Spence, PhD, CRNA


1. Joshi GP, et al. Techniques for periarticular infiltration with liposomal bupivacaine for the management of pain after hip and knee arthroplasty: a consensus recommendation. J Surg Orth Adv 2015;24:27-35.

2. Exparel [prescribing information]. Parsippany, NJ: Pacira Pharmaceuticals, Inc.; 2011.

3. Gan T, Sloan F, Dear Gde L, El-Moalem HE, Lubarsky DA. How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesth Analg 2001;92:393-400.

4. Niraj G, Kelkar A, Powell R. Ultrasound-guided subcostal transversus abdominis plane block. Int J Appl Technol Perioper Care 2010;1:9-12.


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 2015 Anesthesia Abstracts · Volume 9 Number 9, September 30, 2015




Obstetric Anesthesia
Screening of obstructive sleep apnea during pregnancy: differences in predictive values of questionnaires across trimesters

J Clin Sleep Med 2015;11:157-63

Tantrakul V, Sirijanchune P, Panburana P, Pengjam J, Suwansathit W, Boonsarngsuk V, Gulleminault C


Abstract

 

Purpose The purpose of this study was to determine if the Berlin and STOP-BANG Questionnaires were predictive of obstructive sleep apnea (OSA) across pregnancy as defined by an apnea hypopnea index ≥5.

 

Background Sleep disordered breathing ranges from snoring to severe OSA. It is suspected that the hormonal changes and weight gain/edema that occur as pregnancy progresses contribute to worsening OSA severity in later trimesters. Recent research has found that diagnosed OSA is associated with an increased risk of:

  • in-hospital mortality
  • cardiopulmonary complications
  • preeclampsia/eclampsia
  • gestational hypertension
  • gestational diabetes
  • cesarean delivery
  • early-onset delivery
  • increased hospital stay

Unfortunately, there are no validated questionnaires for screening pregnant women for OSA. The most common questionnaires used in non-pregnant individuals include the Berlin and STOP-BANG Questionnaires. The purpose of this study was to examine the predictive value of each of these instruments in the first, second, and third trimesters in a sample of high-risk pregnant women in Thailand.

 

Methodology  This was a prospective observational study that enrolled women with singleton pregnancies who had been referred to a high-risk antenatal clinic at a university hospital in Bangkok, Thailand. High-risk pregnancies were defined as women with chronic hypertension, preeclampsia, gestational diabetes, pre-pregnancy obesity (Asian cutoff BMI ≥ 27.5 kg/m2), or a history of previous pregnancy complications. Participants were enrolled during the first, second, or third trimester. The same women were not followed longitudinally throughout pregnancy.

 

Each of the women completed the Berlin Questionnaire and the STOP-BANG questionnaire and then were asked to complete an overnight sleep study using the Watch-PAT 200 device (Itamar, Cesarea, Israel).

 

The Berlin questionnaire collects information on:

  • snoring frequency (category 1)
  • daytime somnolence (category 2)
  • presence of obesity or hypertension (category 3)

OSA is considered positive if symptoms exist in two of the three categories.

 

The STOP-BANG questionnaire consists of eight yes/no questions on:

  • snoring
  • tiredness during the day
  • obstructions during sleep
  • high blood pressure
  • BMI ≥27.5 kg/m2
  • age over 50
  • neck circumference ≥40 cm
  • male gender

Male gender and age over 50 were not applicable in this setting. A score ≥3 is predictive of OSA. Both instruments have good sensitivity and specificity in non-obstetric populations. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were calculated for each questionnaire to predict an AHI ≥5 events/hour.

 

Results There were 72 women enrolled in the study (First Trimester n = 23; Second Trimester n = 24; Third Trimester n = 25; Table 1). About a third of women had OSA in each trimester. Patients with OSA were slightly older (35 years vs. 33 years, P = NS), had a significantly greater pre-pregnancy BMI (30 ± 8.5 vs. 23 ± 4.6, P < 0.001), higher rate of obesity (BMI ≥ 27.5 kg/m2) 87% vs. 29% (P < 0.001), higher BMI during pregnancy (33 ± 7.1 vs. 25 ± 4.8, P < 0.001), a larger neck circumference (36 inch vs. 33 inch, P = 0.002), and had higher rates of hypertension (35% vs. 10%, P = 0.01) and diabetes (74% vs. 37%, P = 0.003).

 

There was a significantly higher percentage of patients with OSA who had a positive Berlin questionnaire in the second and third trimesters, whereas in all three trimesters there was a significantly higher percentage of patients with OSA who had a positive STOP-BANG questionnaire (Figure 1). Throughout all trimesters both the Berlin and STOP-BANG questionaries had limited predictive value for identifying high-risk pregnant women with OSA in the first trimester (Table 1). However, both instruments performed better at predicting undiagnosed OSA during the second and third trimesters, with the Berlin questionnaire performing slightly better than the STOP-BANG later in pregnancy.

 

Figure 1. Comparison of OSA Screening in High-Risk Pregnancy

Figure 1

Note: Overall N = 72. OSA = Obstructive Sleep Apnea

 

Table 1. Comparison for OSA diagnosis (AHI ≥5)
(Overall Across all Three Trimesters)

 

Berlin

STOP-BANG

Sensitivity (%)

57%

61%

Specificity (%)

88%

90%

PPV (%)

68%

73%

NPV (%)

81%

90%

Note: OSA = Obstructive Sleep Apnea, PPV = Positive Predictive Value, NPV = Negative Predictive Value

 

In the third trimester, patients who snored loudly (OR = 17), had a higher BMI (OR = 1.4), and had greater weight gain during pregnancy (OR = 1.35) were more likely to have OSA.

 

Conclusion Obstructive Sleep Apnea is a dynamic process that tends to worsen in the latter stages of pregnancy. The Berlin questionnaire and the STOP-BANG questionnaire are most useful for screening high-risk pregnant women for undiagnosed OSA in the second or third trimester.

 

Comment

Obstructive Sleep Apnea (OSA) is way underdiagnosed in pregnancy. Previous research has found that the rate of OSA diagnosis in 2009 in delivery-related discharges was only 7.3 per 10,000 (or 0.0007%).1 However, in this small study of high-risk pregnancies the rate of undiagnosed OSA was approximately 30%. The problem is the lack of good screening tools for OSA during pregnancy. Fortunately, this study has helped address that problem by demonstrating that the Berlin Questionnaire and STOP-BANG have fair to good predictive capabilities (as measured by their Area Under the Curve {AUC} results) for undiagnosed OSA in the second and third trimesters.

 

The STOP-BANG is probably the most commonly used screening tool in non-obstetrical patients. This study now provides some evidence (albeit in a sample of Thai women) supporting its use as a screening tool for undiagnosed OSA during pregnancy. For example, the authors’ results for the STOP-BANG in the third trimester had a positive predictive value of 71.4% and a negative predictive value is 83.3%. This tells us that in a high-risk pregnant patient who has a score on the STOP-BANG ≥3 that they have a 71.4% chance of really having OSA (AHI ≥5) but that if their STOP-BANG score is <3 they have an 83.3% chance of really NOT having OSA. The AUC was 0.75, which is acceptable for a screening test, although it might misclassify some patients as not having OSA. While the authors did not test it, one could assume that if a pregnant woman has a higher STOP-BANG score (i.e., ≥4), then the probability that she has OSA will go up. In non-obstetrical patients, the higher the score, the higher the likelihood of moderate to severe undiagnosed OSA.

 

At our institution we have recently completed some research on the STOP-BANG in pregnancy and found 25% of our patients at the time of delivery had a STOP-BANG score of ≥3. If they had a positive STOP-BANG score they were three times more likely to experience a complication of pregnancy (i.e., preeclampsia, gestational hypertension, preterm delivery, need for cesarean delivery, etc.).

 

So while the STOP-BANG is not a perfect screening tool, it is the best thing we have right now, and using it is better than not using anything at all.

 

Dennis Spence, PhD, CRNA


1. Louis JM, Mogos MF, Salemi JL, Redline S, Salihu HM. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009. SLEEP 2014;37:843-849.


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 2015 Anesthesia Abstracts · Volume 9 Number 9, September 30, 2015




Pharmacology
The RECITE Study: a Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade

Anesth Analg 2015;121:36672

Fortier LP, McKeen D, Turner K, de Medicis E, Warriner B, Jones PM, Chaput A, Pouliot JF, Galarneau A


Abstract

 

Purpose The purpose of this study was to examine the incidence and severity of residual neuromuscular blockade after elective surgery at eight Canadian Hospitals.

 

Background Postoperative residual neuromuscular blockade is defined as a train-of-four ratio (TOFr) <0.90. The incidence ranges from 26% to 88%. When the TOFr was introduced in the 1970s, a TOFr <0.7 was defined as residual neuromuscular blockade; however, recent research has demonstrated that a TOFr between 0.70-0.90 is associated with increased risk of:

  • aspiration
  • airway obstruction
  • hypoxia
  • increased post-anesthesia recovery room stay

Numerous publications and the Anesthesia Patient Safety Foundation have recommended a TOFr of ≥0.90 as an adequate degree of neuromuscular activity for extubation. There have been no previous studies which have examined the incidence and severity of residual neuromuscular blockade in Canadian Hospitals. Therefore, the investigators sought to examine the incidence of residual NMB in hospitals across Canada.

 

Methodology This was a prospective, observational, multicenter study conducted at eight hospitals in Canada between June 2011 and May 2012. Inclusion criteria were adults undergoing open or laparoscopic abdominal surgery expected to last <4 hours, ASA physical status I–III, and scheduled for general anesthesia with at least one dose of a nondepolarizing neuromuscular blocking agent. Investigators used acceleromyography to record the TOFr with a TOF-Watch SX in all subjects at baseline, extubation, and upon arrival to the recovery room. Only the TOFr recorded at extubation and upon arrival to the recovery room were used in the analysis. Normalized TOFr, defined as the TOFr divided by the baseline TOFr, was reported. Anesthesia providers and nurses were blinded to TOF-Watch results. In this observational study, providers were allowed to use qualitative TOF monitors at their discretion or use no neuromuscular blockade monitoring at all. Statistical analysis was appropriate. Qualitative peripheral neuromuscular monitors include our traditional train-of-four “twitch” monitors which, unlike quantitative monitors such as the TOF-Watch, do not need to be calibrated prior to use.

 

Results Data from 241 patients were available for analysis at extubation and from 207 patients in the recovery room (Table 1). The incidence of residual neuromuscular blockade - TOFr <0.90 - at tracheal extubation was 56%. The incidence of residual neuromuscular blockade at recovery room arrival was 44%.

 

At extubation 34% of patients had a TOFr ≤0.70 (Editor’s Note: using a TOFr ≤0.70 as the definition of residual neuromuscular blockade is now the old criteria and considered too lax a standard given what we now know about PACU adverse events in these patients), and upon arrival to the recovery room 20% of patients had a TOFr ≤0.70. There were no significant differences between any of the TOFr and any demographic characteristics. The use of qualitative peripheral neuromuscular monitoring vs. no neuromuscular block monitoring, was associated with an absolute 16% lower incidence of residual NMB at recovery room arrival (51% vs 67%; P = 0.028). Larger doses of neuromuscular blocking agents and a shorter time between neostigmine administration and extubation or arrival to the recovery room were associated with a higher incidence of residual neuromuscular blockade (P < 0.05; Table 2). Interestingly, the total dose of neostigmine was not associated with the incidence of residual neuromuscular blockade.

 

For each 0.1 increase in the TOFr there was a significantly lower odds the patient required oxygen in the recovery room (OR = 0.894). Likewise, for every 0.1 increase in the TOFr there was a 4% decrease in the number of visits recovery room nurses made to the patients’ bed (P = 0.013).

 

Table 1. Reversal and Nerve Stimulator Use

 

Extubation

N = 241

Recovery Room

N = 207

Reversal agent use

74%

72%

Peripheral nerve stimulator use

67%

66%

 

Figure 1. Incidence of Residual Neuromuscular Blockade

Figure 1

Note: TOF = train-of-four

 

Table 2. Factors Influencing Residual Neuromuscular Block

 

TOF > 0.9

(n = 106)

TOF < 0.90

(n = 135)

P Value

Total dose of rocuronium per minute of surgery (µg/kg/min)

6.1 + 2.6

7.0 + 3.2

0.021

Total dose of neostigmine (mg/kg)

0.034 + 0.012

0.035 + 0.012

NS

Time between last dose of neostigmine and tracheal extubation (min)

15.4 + 7.0

12.5 + 5.8

0.002

Time between last dose of neostigmine and PACU arrival (min)

21.1 + 8.2

17.4 + 6.2

0.007

Note: TOF = train-of-four

 

Conclusion Residual neuromuscular blockade continues to be a problem despite the use of qualitative TOF monitors and reversal agents. Further education and better monitoring technology (i.e., quantitative TOF monitors) are needed to help reduce the incidence of residual NMB.

 

Comment

These results confirm that residual neuromuscular blockade continues to be a problem. Residual neuromuscular blockade is associated with postoperative complications. For example, Todd et al1 reported on a patient who required emergent reintubation in the recovery room due to profound residual neuromuscular blockade, despite administration of neostigmine shortly before extubation and the provider reporting the patient had four twitches (qualitative monitor used). This case highlights the limitations of qualitative twitch monitors and argues for the use of quantitative TOFr monitoring.

 

Quantitative monitoring is the most accurate way to monitor for residual NMB. However, the equipment is expensive, and there are multiple technical, cultural, and practical challenges to implementation of this technology in an anesthesia department. Anesthesia providers are encouraged to read an excellent article by Todd et al about their implementation of quantitative monitoring at an academic anesthesia department. I would encourage any anesthesia providers working on their doctorate of nursing practice to consider implementing a similar project at their institution.

 

Dennis Spence, PhD, CRNA


1. Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department. Anesth Analg 2014;119:323-31. Abstract and comment available in the April 2014 issue of AnesthesiaAbstracts.com.

 


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 2015 Anesthesia Abstracts · Volume 9 Number 9, September 30, 2015





Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial

Anesthesiology 2015; 123:ahead of print

Leslie K, Myles PS, Kasza J, Forbes A, Peyton PH, Chan MTV, Paech MJ, Sessler DI, Beattie WS, Devereaux PJ, Wallace S


Abstract

 

Purpose The purpose of this study was to look for any association between nitrous oxide use during general anesthesia in patients with cardiovascular disease and death, disability, myocardial infarction, or stroke up to one year postoperatively.

 

Background It is well established that nitrous oxide inhibits methionine synthase and results in an increase in plasma homocysteine. Hyperhomocysteinemia, in turn, results in vascular endothelial damage and is associated with cardiovascular disease and stroke. In 2011, an “Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia” (ENIGMA) was published that examined the link between nitrous oxide use and death, myocardial infarction, and stroke. In the original 2011 ENIGMA study, plasma homocysteine levels were significantly increased in patients who received nitrous oxide. Long-term follow-up of the original 2011 ENIGMA trial occurred a median of 3.5 years after patients had their anesthetics. However, the range of follow-up times was 0 to 6 years postoperatively and about 20% of patients had no follow-up at all. Follow-up from the original ENIGMA trial showed that nitrous oxide use increased the risk of later myocardial infarction in noncardiac surgery patients by 59% (Odds Ratio 1.59). Due to methodological problems in the original 2011 ENIGMA trial [see comment following] the ENIGMA-II trial was undertaken to reexamine the interaction of nitrous oxide and cardiovascular disease with a stronger methodology.

 

Methodology The ENIGMA-II study was an international, double-blind, prospective, randomized trial. It included 7,112 noncardiac surgery patients at risk for cardiovascular complications and over 45 years of age. The study was conducted at N hospitals in each of the following countries:

  • Australia 14
  • Canada 5
  • Hong Kong 3
  • Malaysia 1
  • New Zealand 3
  • Saudi Arabia 1
  • Singapore 1
  • United Kingdom 7
  • USA 3

Patients were randomly assigned to one of two groups:

  • 70% N2O & 30% O2
  • 70% Nitrogen & 30% O2

All other aspects of the general anesthetic were at the discretion of the anesthesia provider. All patients had a 12-lead ECG preoperatively and on postoperative days 1 and 3. All patients had troponin levels or creatine kinase-MB at two time points postoperatively. One year follow-up consisted of reviewing the patients’ medical records and interviews by phone. Phone interviews were conducted with the patients themselves when possible. Otherwise, phone interviews were conducted with relatives or the patient’s physician. Outcomes examined included:

  • death
  • myocardial infarction
  • cardiac arrest
  • pulmonary embolism
  • stroke
  • disability

Outcomes were defined by the patient, relative, patient’s physician, or findings in the medical record.

 

Result As with all large studies, not all patients completed the study. In this case, 5,844 patients, 88% of those enrolled, had completed follow-up one year later. Of these patients in both groups, 7.4% died within one year postoperatively, 1.7% died within 30 days, and 5.7% died from 30 days to one year postoperatively.

 

Nitrous oxide had no effect on the aggregate risk of death and cardiovascular events (P=0.27). The following factors were associated with an increased aggregate risk of death and cardiovascular events:

  • increased age
  • higher ASA class
  • lower exercise capacity
  • coronary artery disease
  • emergency surgery
  • longer duration of general anesthetic

Nitrous oxide had no effect on the risk of disability or death. Nitrous oxide had no effect on the risk of myocardial infarction (P=0.78). Nitrous oxide had no effect on the risk of stroke (P=0.7). Each of these one year follow-up findings were also true at 30 days post-op.

 

Conclusion Nitrous oxide 70% included as part of a general anesthetic in patients with known or suspected cardiovascular disease did not increase the risk of death or cardiovascular morbidity. It is safe to use nitrous oxide in patients with cardiovascular disease.

 

Comment

The original ENIGMA study had a number of important methodological problems including the following two:

  1. The presence of known or suspected cardiovascular disease was not an inclusion criteria. Neither was the information known about patients enrolled in the study. As a result, patients with cardiovascular disease were not randomized into the two groups. Thus, IF there were more patients with cardiovascular disease in the nitrous oxide group than in the no-nitrous group, this fact alone could have produced an increase in morbidity and mortality in the nitrous group completely unrelated to nitrous oxide.
  2. Nitrous oxide use was not the only difference between the groups. The nitrous group received only 30% oxygen while the no-nitrous group received 80% oxygen.

The original ENIGMA study, and its 2011 follow-up secondary analysis, showed that patients who received nitrous oxide were significantly more likely to have a myocardial infarction and/or die within a widely varying length of time postoperatively. Conversely, the ENIGMA-II study using a much-improved methodology, showed that nitrous oxide did not increase the risk of any of the outcomes of interest - death, myocardial infarction, stroke, or disability.

 

These two studies are themselves a case study in the importance of proper research methodology and critical analysis of published studies. We should never read the results of a study and believe that they are true simply because they were published.

 

Michael A. Fiedler, PhD, CRNA


Editor’s Note: An Abstract and Comment of the 2011 secondary analysis of the original “Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia” (ENIGMA) study is available for your review on page 18 of the April, 2012 issue of Anesthesia Abstracts.


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 9, September 30, 2015





The effect of intravenous midazolam on postoperative nausea and vomiting: A meta-analysis

Anesth Analg 2015 ahead of print

Grant MC, Kim J, Page AJ, Hobson D, Wick E, Wu CL


Abstract

 

Purpose The purpose of this study was to analyze previous randomized controlled trials to assess the association between IV midazolam and Postoperative Nausea and Vomiting (PONV) in adults within 24 hours after surgery.

 

Background Postoperative Nausea and Vomiting (PONV) is a common adverse event following general anesthesia with an incidence estimated to be up to 80% in at-risk patients. PONV is unpleasant and can contribute to morbidity, delayed discharge home, and increased cost of care. Midazolam is commonly used for preoperative sedation and for coinduction of general anesthesia in combination with one or more other drugs. It is known to possess both amnestic and anesthetic properties. Several previous studies have found that midazolam reduced the incidence of PONV. However, some of these previous studies have since been retracted and the idea that midazolam is an “antiemetic” is probably not widely embraced. A mechanism for antiemetic action for midazolam is not known.

 

Methodology This was a meta-analysis of previously published studies. The search for these studies was conducted according to the recommendations of the Cochran Handbook for Systematic Reviews of Interventions. MEDLINE, EMBASE, and CINAHL were searched. Studies between 1971 and October 2014 involving adult patients who received a general anesthetic were identified. Other inclusion criteria were administration of IV midazolam, measurement of PONV, nausea alone and/or vomiting alone, as well as administration of rescue antiemetics, and a randomized controlled study design. The midazolam may have been administered preoperatively, during induction of anesthesia, or during general anesthesia. All studies meeting the inclusion criteria were analyzed cumulatively. Additionally, the following study subgroups were analyzed separately:

  • midazolam as part of an antiemetic combination
  • gender
  • surgery type
  • midazolam timing & dose

 

Result Although initially over 700 studies were identified, only 12 met all inclusion criteria. These 12 studies included 841 subjects, 363 of whom received no midazolam (controls) and 478 of whom received IV midazolam.

  • 6 studies used normal saline control vs. midazolam
  • 4 studies used an antiemetic as control & added midazolam to the antiemetic in the experimental group
  • 2 studies had multiple groups including a saline control group

 

The meta-analysis showed a significant decrease in the combination of postoperative nausea and vomiting (P<0.0001), nausea alone (P=0.02), and vomiting alone (P=0.001) in patients who received midazolam. The need for a rescue antiemetic was also significantly less common in patients who received midazolam (P<0.0001). A number needed to treat analysis revealed that four patients needed to receive midazolam for a patient to benefit from midazolam in the prevention of PONV. The length of PACU stay and the incidence of “significant sedation” was no different in patients who received midazolam and those who didn’t.

 

In the subgroup analysis midazolam continued to be associated with decreased PONV, nausea alone, vomiting alone, and rescue antiemetic use during the first 24 hours postoperatively in the following subgroups:

  • female patients
  • high PONV risk surgery
    • middle ear
    • thyroid
    • laparoscopic
    • gynecologic

 

The dose of midazolam and the timing of administration didn’t seem to influence the beneficial effect of midazolam in lowering PONV. Administration preoperatively (P=0.001), during induction of general anesthesia (P=0.01), or at the end of surgery (P=0.004) were all associated with a reduction in PONV. Likewise, doses as small as 2 mg were similarly effective to doses greater than 5 mg.

 

Conclusion Midazolam appears to act as an antiemetic in adults at doses as small as 2 mg IV and for periods up to 24 hours postoperatively. Its antiemetic effect is in addition to that produced by primary antiemetic drugs. Midazolam should be considered for use not only as an anxiolytic but also as part of multimodal PONV prophylaxis and treatment.

 

Comment

This is a pretty convincing study. It was perhaps 10 years ago that I first ran into studies that purported to show midazolam to be an antiemetic under at least some fairly narrow circumstances. I took note of them but didn’t give them much credence because they weren’t generalizable and they were fairly small. But now we have a meta-analysis that does what a meta-analysis is supposed to do, reveal more about a question than the multiple smaller studies that make it up. And what it shows is that even 2 mg doses of midazolam given just about anytime in the perioperative period reduce the incidence of PONV, alone or in combination with other antiemetics, even in patients at high risk for PONV.

 

So how do we use this information? In some practices midazolam is given to almost every patient that receives a general anesthetic. If that is you, the antiemetic effect of midazolam is likely already figured in to your PONV rates. To the extent that you don’t give midazolam to every patient, this study may provide you with an additional way to view midazolam and another indication for administering it.

Michael A. Fiedler, PhD, CRNA


Lee Y., Wang J., Yang Y., Chen A., & Lai H. Midazolam vs ondansetron for preventing postoperative nausea and vomiting: a randomised controlled trial. Anaesthesia, 2007;62:18. Summary available in the March 2007 issue of Anesthesia Abstracts.

 


© Copyright 2015 Anesthesia Abstracts · Volume 9 Number 9, September 30, 2015