ISSN NUMBER: 1938-7172
Issue 8.10 VOLUME 8 | NUMBER 10

Editor:
Michael A. Fiedler, PhD, CRNA

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

Guest Editor:
Kenneth J. Taylor, DNP, CRNA

Assistant Editor
Jessica Floyd, BS

A Publication of Lifelong Learning, LLC © Copyright 2014

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

OBSTETRIC ANESTHESIA
A retrospective assessment of the incidence of respiratory depression after neuraxial morphine administration for postcesarean delivery analgesia
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PAIN
Liposome bupivacaine (EXPAREL®) for extended pain relief in patients undergoing ileostomy reversal at a single institution with a fast-track discharge protocol: an IMPROVE Phase IV health economics trial
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PATIENT SAFETY
Risk factors associated with ischemic optic neuropathy after spinal fusion surgery
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PHARMACOLOGY
Therapeutic effect of inhaled budesonide (Pulmicort Turbuhaler) on the inflammatory response to one-lung ventilation
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Effect of preoperative gabapentin on postoperative analgesia in patients with inflammatory bowel disease following major bowel surgery: a randomized, placebo-controlled trial
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Perioperative Metoprolol and Risk of Stroke after Noncardiac Surgery
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None of the editors or contributors have any real or potential conflicts of interest to disclose.


Obstetric Anesthesia
A retrospective assessment of the incidence of respiratory depression after neuraxial morphine administration for postcesarean delivery analgesia

Anesth Analg 2013;117:1368-70

Crowgey TR, Dominguez JE, Peterson-Layne C, Allen TK, Muir HA, Habib AS


Abstract

Purpose The purpose of this study was to describe the incidence of clinically significant respiratory depression as defined by the need for naloxone administration or rapid response team intervention in parturients who underwent cesarean delivery and received neuraxial opioids.

 

Background Neuraxial morphine is commonly administered after cesarean delivery. However, neuraxial opioids have a risk of both early and delayed-onset respiratory depression, with a reported incidence ranging from 0% to 0.9%. Many anesthesia providers feel neuraxial opioids provide superior analgesia and with minimal risk of respiratory depression. However, there are some providers who withhold neuraxial morphine in parturients with a high body mass index (BMI) or obstructive sleep apnea (OSA) out of fear they may experience clinically significant respiratory depression.

 

Methodology This was a retrospective analysis of all parturients who underwent cesarean delivery and received neuraxial morphine at Duke University from December 1, 2006 to December 31, 2011. Adverse drug event surveillance databases were examined to identify parturients who received naloxone and/or required rapid response team (RRT) intervention for respiratory depression.

 

All parturients at Duke University who receive neuraxial morphine are monitored for signs of respiratory depression hourly for the first 2 hours, then every 2 hours for 24 hours. Monitoring consists of vital signs, oxygen saturation, respiratory rate, pain score, and sedation scores. Standing orders are in place to administer naloxone for respiratory rates <8/min, or Richmond Agitation Sedation Scale (RASS) ≤ 3, together with immediate notification of the medical staff. Medical staff were also notified for oxygen saturations <90% or RASS < 2.

 

Postoperative analgesia consisted of around-the-clock nonsteriodal anti-inflammatory medications and acetaminophen 325mg/oxycodone 5 mg 1 to 2 tablets as needed. Breakthrough pain was managed by the obstetricians in consultation with anesthesia.

 

Data collected included demographics, morphine dose, and nature of event requiring naloxone or rapid response team involvement.

 

Result There were 5,036 parturients who received neuraxial morphine for postoperative analgesia after cesarean delivery. Of those, 3,554 received spinal morphine (most common dose = 0.15 mg, range 0.05-0.25 mg) and 1,080 received epidural morphine (most common dose = 3 mg, range 1 to 5 mg). The mean BMI was 33.7 (range 17.1-79.4), with 28.4% being overweight (BMI 25-29.9), 28.3% obese class I (BMI 30-34.9), 17.1% obese class II (BMI 35-39.9), and 17.6% BMI class III (≥40). Seventy-eight percent (78%) of the parturients were ASA I-II, 21.6% ASA III, and 0.2% ASA IV.

 

There were no cases reported in the database of need to administer naloxone for respiratory depression and there were 2 cases of administration of naloxone for pruritus treatment. There was 1 rapid response team call 55 hours after cesarean delivery in a severe preeclamptic patient who developed hypotension and hypoxemia (91-93%) after receiving nifedipine. The upper confidence limit for the incidence of clinically significant respiratory depression (need for naloxone or rapid response team intervention) was 0.07% (1 in 1,429 cases).

 

Conclusion The investigators found no cases of clinically significant respiratory depression in their series of 5,036 parturients (obesity rate = 63%) who had received neuraxial morphine for postoperative analgesia after cesarean delivery. 

 

Comment

Obstetrical anesthesia providers are not going to find these results surprising; that neuraxial morphine administered for postoperative analgesia after cesarean delivery is generally safe. However, the study was retrospective and thus we do not know if there are other factors that may have influenced the results. For example, could patients who were suspected of having OSA or other comorbidities that increased their risk have received a higher level of monitoring or treatment (i.e., oxygen, CPAP) by nursing staff that was not captured in the databases? Did their order sets eliminate sedating medications (i.e., no Benadryl or Phenergan)? Did interventions occur (patient aroused by nurse) that mitigated the need for naloxone or rapid response team intervention?

 

The question I often struggle with is how to manage parturients with suspected or known moderate-severe OSA and/or other comorbidities that increase their postoperative risk, especially if they did not receive neuraxial opioids (i.e., crash cesarean delivery under GETA). Should parturients with suspected moderate-severe OSA receive a higher level of monitoring after cesarean delivery? What are valid tools to identify parturients with moderate-severe OSA? What type of monitoring (i.e., continuous end-tidal CO2)? Some facilities are starting to monitor for respiratory depression with continuous end-tidal COin surgical patients, and some have this capability on postpartum wards. The question is, which parturients, if any, need this level of monitoring?

 

Just because one study did not identify any cases of clinically significant respiratory depression does not mean we should not seek to find answers to these questions. I know from my personal experience and in talking to anesthesia providers around the country that cases of clinically significant respiratory depression have occurred in parturients who received neuraxial morphine. Further research is needed to develop evidence-based recommendations in parturients at risk for respiratory depression.

Dennis Spence, PhD, CRNA


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 2014 Anesthesia Abstracts · Volume 8 Number 10, October 15, 2014




Pain
Liposome bupivacaine (EXPAREL®) for extended pain relief in patients undergoing ileostomy reversal at a single institution with a fast-track discharge protocol: an IMPROVE Phase IV health economics trial

J Pain Res 2013;6:605–610

Vogel JD


Abstract

Purpose The purpose of this study was to evaluate the efficacy of an Exparel® (liposomal bupivacaine) opioid-sparing multimodal analgesic regimen on reducing opioid consumption, hospital length of stay, and hospitalization costs when compared with IV opioid patient-controlled analgesia (PCA) in patients undergoing ileostomy reversal.

 

Background Opioid consumption after ileostomy repair is associated with postoperative ileus and prolonged hospitalization and costs. Many centers utilize fast-track protocols for rapid recovery after ileostomy reversal. Exparel is a liposomal bupivacaine mixture that has been found to provide up to 72 hours of analgesia. A previous IMPROVE trial (designated IMPROVE, for Extended PaIn Relief Trial Utilizing the Infiltration of a Long-Acting Multivesicular LiPosome FoRmulation Of BupiVacaine, Exparel®) in patients undergoing open colectomy demonstrated reduced hospital length of stay, costs, and opioid use compared to IV opioid PCA. This current study is part of the IMPROVE series of studies to evaluate the efficacy and economic impact of a multimodal analgesic regimen with liposomal bupivacaine, acetaminophen, and NSAIDS when compared to IV opioid PCA in patients undergoing ileostomy reversal.

 

Methodology This was a Phase IV, prospective, single-center, open-label (no blinding), sequential cohort study. The investigators enrolled sequential cohorts of all patients undergoing ileostomy reversal (IV opioid PCA groups first, followed by Exparel group) who met inclusion criteria. Exclusion criteria included hepatic impairment; substance abuse; and intraoperative administration of long-acting opioids, NSAIDS, local anesthetics, or alvimopan. Patients in the PCA group had a PCA started with either morphine or hydromorphone immediately after surgery. Patients in the multimodal Exparel group had 266 mg in 30 mL of normal saline injected by the surgeon into the stoma site. They also received ketorolac 30 mg at the end of surgery, followed by acetaminophen 1,000 mg (IV or oral) and ibuprofen 600 mg every 6 hours for 72 hours, starting when oral fluids were tolerated. Rescue pain medications were administered as needed.

The primary outcomes included total postoperative opioid consumption in morphine equivalents, hospitalization costs, and length of stay. Secondary outcomes included median time to first opioid consumption and number of patients experiencing opioid-related adverse events. Outcomes were assessed until patient discharge or 30 days after surgery. Statistical analysis was appropriate. All patients who underwent the surgery and met inclusion criterial were enrolled.

 

Result There were 43 subjects enrolled (Exparel multimodal group n = 23 and IV opioid PCA n = 20). Patient demographics and baseline characteristics were similar. Total opioid consumption was 45% lower in the Exparel multimodal group compared to the IV opioid PCA group (P = 0.004; Figure 1). The median length of stay was similar between the two groups (Exparel multimodal group = 3 days vs. IV opioid PCA group = 3.8 days, P = NS). Mean total hospitalization costs were slightly lower in the Exparel multimodal group but not significantly different from the IV opioid PCA group ($6,611 vs. $6,790). The median time to first opioid consumption was significantly longer in the Exparel multimodal group compared to the IV opioid PCA group (0.7 hours vs. 1.1 hours; P = 0.04). Opioid-related side effects were experienced by one patient in the IV opioid PCA group (vomiting) and by two patients in the Exparel multimodal group (constipation and urinary retention).

 

Figure 1. Total Postoperative Opioid Consumption

Figure 1

 

Conclusion A multimodal analgesic regimen consisting of Exparel liposomal bupivacaine combined with non-opioid analgesics in patients undergoing ileostomy reversal resulted in reduced postoperative opioid consumption when compared to IV opioid PCA therapy. While not statistically significant, the one day faster time to discharge in the Exparel multimodal group may be a clinically significant finding in this population.

 

Comment

Randomized controlled trials are considered the gold standard for evaluating clinical, experimental research because they utilize powerful controls, which reduce bias and helps determine the true effect of an intervention on outcome measures. In this study the investigator used a quasi-experimental design (open-label design with sequential enrollment) to compare the two groups. The investigator argued that this design made the study more feasible at their institution by minimizing surgeon, patient, and site burden, thus reflecting “real-world” clinical practice, thus making the results more generalizable. While I agree this design may reflect a more “real-world” setting, I believe this was a weak design and lessens validity of the results. This design introduces bias, in part, because it does not control for subjects’, providers’, or nurses’ reactions or management.

 

The design would have been stronger if the investigator had randomized subjects, used a multimodal regimen, and included a placebo in both groups. Use of a multimodal analgesic plan in the Exparel group biases the results toward this group, and thus this could partially explain the differences in opioid consumption. Therefore, we do not know the true effect Exparel had on the outcomes measured in this study.

 

This is not to say I do not think Exparel does not have an important place in our armamentarium. However, I think investigators in the future should use randomized, controlled, double-blind studies to really measure the true effect Exparel has on outcomes. It is important to point out that this study was sponsored by the Pacira Pharmaceuticals, the manufacturer of Exparel. Whether or not this influenced the results is unknown. I believe you should decide for yourself.

Dennis Spence, PhD, CRNA


Exparel is FDA approved (since October 2011) for single-dose infiltration into the surgical site to produce postsurgical analgesia. Exparel is a multivesicular liposome-based local anesthetic that utilizes the DepoFoam delivery platform to deliver bupivacaine over an extended period of time. The DepoFoam delivery platform consists of a small amount of free bupivacaine (3%) and microscopic, spherical, lipid-based particles combined in a honeycomb matrix that encapsulates the remaining bupivacaine. Over time there are erosion and/or reorganization of the particle lipid membranes resulting in release of the drug. After injection into soft tissues there is an immediate local anesthetic effect from the free bupivacaine followed by a delayed release from the liposomes for approximately 96 hours. Systemic plasma levels of bupivacaine following administration of Exparel are not correlated with local efficacy.

 

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 2014 Anesthesia Abstracts · Volume 8 Number 10, October 15, 2014




Patient Safety
Risk factors associated with ischemic optic neuropathy after spinal fusion surgery

Anesthesiology 2012;116:15-24

The Postoperative Visual Loss Study Group


Abstract

Purpose  The purpose of this study was to identify risk factors for Ischemic Optic Neuropathy after spinal fusion surgery by examining the American Society of Anesthesiologists (ASA) Postoperative Visual Loss Registry.

 

Background  Spinal fusion surgery is associated with improved quality of life; however these types of surgeries are also associated with large blood loss, prolonged duration, and in rare cases, Postoperative Visual Loss. Postoperative Visual Loss is purported to be caused by Ischemic Optic Neuropathy. Visual deficits range from blurred vision to permanent blindness. The estimated incidence ranges from 0.017% to 0.1%. Numerous risk factors have been identified for Ischemic Optic Neuropathy including:

  • anemia
  • hypotension
  • large fluid shifts
  • venous congestion of the orbits
  • large blood loss
  • atherosclerotic vascular disease
  • obesity
  • diabetes
  • hypertension

Unfortunately, most reports of Postoperative Visual Loss are limited by small sample sizes and lack detailed information on perioperative events. The ASA Postoperative Visual Loss registry includes a large collection of detailed information on Ischemic Optic Neuropathy cases associated with prone spinal surgery. This study identified risk factors for Ischemic Optic Neuropathy after prone spinal fusion surgery using the ASA Postoperative Visual Loss registry.

 

Methodology  This was a multi-center case-control study comparing 80 cases of Ischemic Optic Neuropathy after prone spinal fusion surgery with a randomly selected control group of 315 subjects from 17 academic centers. The 80 cases of Ischemic Optic Neuropathy were taken from the ASA Postoperative Visual Loss registry; inclusion criteria included age ≥ 18 years, spine fusion as the first and only surgery associated with admission, surgery date between 1991 and 2006, prone position for portion of procedure, anesthetic duration ≥4 hours, and surgery between T-1 and S-5 spinal levels. Patients with a history of perioperative cardiopulmonary resuscitation, stroke, multiple staged spine surgery preceding Ischemic Optic Neuropathy, and incomplete or inadequate data were excluded. Current Procedural Terminology codes were used to identify prone spine surgical procedures from the 17 academic institutions. A total of 43,410 potential control cases were identified. Four cases to every one Ischemic Optic Neuropathy case were randomly selected from eligible cases. Cases selected were matched by year of surgery.

 

Data collection and analysis were performed in stages. Multivariate analysis was used to identify risk factors for Ischemic Optic Neuropathy. A P < 0.05 was considered significant.

 

Result Multivariate analysis identified male gender, obesity, use of a Wilson frame, anesthetic duration, increased blood loss, and less colloid administration as risk factors for postoperative Ischemic Optic Neuropathy (see Table 1). Some factors were associated with decreased risk of Ischemic Optic Neuropathy. For every 5% colloid administered (as a percent of total non-blood replacement) there was a 0.67 reduction in the odds of Ischemic Optic Neuropathy (P < 0.001). However, the difference in average percent of colloid administration between case and control subjects was only 4%. Anemia and prolonged hypotension (blood pressure > 40% below baseline for 30 minutes) were not independent predictors of Ischemic Optic Neuropathy. Table 2 presents the relative risk of patients developing Ischemic Optic Neuropathy based on multiple risk factors. This table can be used by clinicians to evaluate patients’ risk for developing Ischemic Optic Neuropathy.

 

Risk Factor

Risk Increase

Male Gender

2.35*

Obese BMI > 30

2.83

Wilson frame

4.30

Each hour duration

1.39

Each Liter blood loss

1.34

NOTE: *Male gender P = 0.005. All other P values = 0.001. 

 

Table 2. Risk of Ischemic Optic Neuropathy after Major Prone Spine Surgery

Gender

Obesity

Wilson Frame

Duration (h)

EBL  (L)

Colloid (%)

Relative Risk

Female

No

No

5

1

10

1.0

Female

Yes

No

5

1

10

2.83

Female

No

Yes

5

1

10

4.30

Female

No

No

7.5

1

10

2.26

Female

No

No

10

1

10

5.12

Female

No

No

5

2

10

1.34

Female

No

No

5

3

10

1.78

Female

No

No

5

1

0

2.24

Female

Yes

Yes

10

3

0

249

Male

No

No

5

1

10

2.53

Male

Yes

No

5

1

10

7.17

Male

No

Yes

5

1

10

10.91

Male

No

No

7.5

1

10

5.74

Male

No

No

10

1

10

12.98

Male

No

No

5

2

10

3.39

Male

No

No

5

3

10

4.52

Male

No

No

5

1

0

5.67

Male

Yes

Yes

10

3

0

632

Note. Results presented as relative risk of Ischemic Optic Neuropathy compared to the lowest risk set in row 1.

  

Conclusion  This study determined that obesity, male gender, use of the Wilson frame, longer duration of anesthesia, greater estimated blood loss, and decreased colloid administration were independent predictors of Ischemic Optic Neuropathy after prone spinal fusion surgery. Anesthesia providers should use these results and prediction models when planning for spinal fusion surgery.

 

Comment

Postoperative Visual Loss is a rare, but devastating, complication that can occur after spinal fusion. This is the first large case-control study to identify risk factors for development of Ischemic Optic Neuropathy after spinal fusion. I believe these results will help inform anesthesia management for spinal fusion surgery and now furnish anesthesia providers with some evidence upon which to base their decisions and informed consent process.

 

In this study obese men who had prolonged surgery on a Wilson frame with significant blood loss were at the greatest risk for developing Ischemic Optic Neuropathy. The authors speculated the reduced risk for females was secondary the protective effects of estrogen on specific optic nerve disease found in animal studies. Also preexisting diseases such as atherosclerosis were not predictors of Ischemic Optic Neuropathy, which the authors suggested may mean Ischemic Optic Neuropathy is more strongly influenced by perioperative factors than underlying disease.

 

Obese patients who have prolonged surgery on a Wilson frame have the greatest increase in intrabdominal pressure thereby causing increased venous engorgement and pressures in the head and orbits of the eye. This can be further exacerbated if the head of the bed is lower than the level of the heart, which is common with this type of surgery on the Wilson frame. Elevated venous pressure in the orbit leads to interstitial edema and reduced intraocular perfusion pressures, which may contribute to the development of Ischemic Optic Neuropathy. This can be further exacerbated with excessive crystalloid administration and increased blood loss; in this study higher amounts of colloid administration appeared to confer a small reduction in risk of Ischemic Optic Neuropathy.

 

I think these results have the potential to reduce Ischemic Optic Neuropathy by giving anesthesia providers and surgeons evidence of factors they may be able to modify to reduce risk. If I have an obese male presenting for spinal fusion I might point out some of these risk factors and ask the surgeon if he can use another frame besides the Wilson frame and possibly consider reducing his surgical duration or performing a staged procedure.

Dennis Spence, PhD, CRNA


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 2014 Anesthesia Abstracts · Volume 8 Number 10, October 15, 2014




Pharmacology
Therapeutic effect of inhaled budesonide (Pulmicort Turbuhaler) on the inflammatory response to one-lung ventilation

Anaesthesia 2014;69,14-23

Ju NY, Gao H, Huang, W, Niu FF, Lan X, Li F, Gao W.


Abstract

 

Purpose The purpose of this study was to determine the effect of inhaled budesonide on mechanical lung function and the pro-inflammatory response in response to one lung ventilation (OLV).

 

Background One lung ventilation optimizes operating conditions during thoracic surgical procedures. One lung ventilation has the potential to induce a severe inflammatory response. Factors known to induce pulmonary inflammation are: hypoxia, low perfusion secondary to hypoxic pulmonary vasoconstriction, and surgical manipulation. Inflammation is marked by high levels of inflammatory infiltrates, including alveolar macrophages, granulocytes, and pro-inflammatory cytokines. The inflammation ultimately produces postoperative lung trauma.

 

In clinical practice, glucocorticoids have successfully attenuated the edema induced by inflammation in patients who have suffered a lung injury. Furthermore, methylprednisone has effectively improved lung function and decreased the pro-inflammatory response in patients who underwent one lung ventilation.

 

Methodology This was a prospective, double-blind, randomized study performed between September 2012 and February 2013. Initially, 100 study participants were consented to be studied. They consisted of ASA physical status 1-2 patients, ages 20 years to 60 years scheduled for thoracic surgery (lung cancer lobectomy). To insure ASA 1-2 status, exclusion criteria were extensive. Ultimately, 84 participants completed the study. Furthermore, study participants whose pulse oximeter (SpO2) oxygen saturation fell below 90% during one lung ventilation were excluded from the study. Patients were randomly assigned to the budesonide or saline group using a random number table.

 

In the preoperative suite, patients received 1 mg nebulized budesonide or saline over 20 minutes. Upon entering the surgical suite, a radial arterial line was inserted as well as a thoracic epidural at the T5-T6 to T7-T8 interspace. Induction consisted of intravenous lidocaine, fentanyl, rocuronium, and propofol. As surgically indicated, a left or right double lumen endobronchial tube was inserted and proper position confirmed via fiberoptic bronchoscopy. Anesthesia maintenance consisted of sevoflurane with an epidural infusion of lidocaine 1% mixed with ropivacaine 0.5%, administered at 6 mL per hour.

 

During the operation, one lung ventilation was achieved with a volume-controlled setting of 6 mL/Kg at a rate of 12-15 breaths per minute with an additional 5 cm H2O PEEP. Prior to one lung ventilation, a bilateral functional capacity breath of 30 cm H2O was manually administered over 10 seconds. FiO2 ranged from 0.8 to 1.0, in order to maintain SpO2 > 95%. Brochoaveolar lavage was performed on either the ventilated or collapsed lung, but not both lungs due to ethical concerns. Brochoaveolar lavage specimens were obtained before one lung ventilation and then 30 minutes following re-expansion after ceasing one lung ventilation. Prior to extubation, the lungs were bilaterally ventilated four times with a pressure of 30 cm H2O over 10 second intervals. For postoperative pain control, morphine and ropivacaine were infused via the epidural catheter.

 

The 4 primary study components were:

  • peak airway pressure
  • plateau pressure
  • lung compliance
  • alveolar-arterial (A-a) oxygen index

The inflammatory response to one lung ventilation was a secondary study outcome.

Data and blood samples were collected at the following six time-points:

  • (T0) prior to administration of nebulized drug 
  • (T1) before one lung ventilation
  • (T2) 30 minutes following lung re-expansion
  • (T3) 24 hours following surgery
  • (T4) 48 hours following surgery
  • (T5) 72 hours following surgery

Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze and calculate the serum and brochoaveolar lavage concentration of pro-inflammatory cytokines. All data were analyzed in a correct manner. 

 

Results Following lung re-expansion, peak airway pressure (19 cm H2O vs 27 cm H2O, P<0.001) and plateau pressure (16 cm H2O vs 23 cm H2O, P<0.001) were lower in the budesonide group. Dynamic compliance improved to 57.5 in the budesonide group vs 40.1 ml/cm H2O in the saline group (P<0.001). Initially, the A-a oxygen index was comparable between groups; however, upon return to the ward, the oxygen index was higher in the budesonide group. There was no difference found of PaCO2 (47 cm H2O vs 48 cm H2O, P<0.001) or PaO2 (78 mm Hg vs 76 mm Hg, P<0.001) between groups.

 

Overall, pro-inflammatory cytokine levels were significantly decreased in the budesonide group 30 minutes following lung re-expansion. In addition, interleukin-10 was greatly increased in the budesonide group. Intraoperatively, serum cytokine levels were no different between groups.

 

Conclusion In patients requiring one lung ventilation for thoracic surgery, preoperative nebulized budesonide improved respiratory mechanics, increased the anti-inflammatory cytokine interleukin-10, and decreased pro-inflammatory cytokines captured in brochoaveolar lavage specimens. 

 

Comments

 

Anesthesia providers are known for our intraoperative management; however, our role in our patients’ postoperative course is often under appreciated. It’s not uncommon for our attention to be focused on intraoperative patient management as the majority of our time is spent delivering anesthesia. For that reason, I appreciate the information provided by the authors of this article. They assist us in “stepping back” and better understanding the potential postoperative benefits we can provide our thoracic surgery patients.

 

Immediately after reading this article, I had the classic “why didn’t I think of that?" moment. This thought is somewhat justified as providing an adequate surgical environment for intrathoracic surgery via one lung ventilation can be a difficult task. Anesthetic variables range from adequate single lung isolation to poor lung compliance to treatment of intraoperative bronchospasm. The point being: our energy and attention can often be focused on intraoperative management rather than preoperatively optimizing the patient.

 

This article sheds light upon a quick preoperative intervention that produces intraoperative and, more importantly, 72 hours of postoperative benefits. Lobectomy patients are prone to great postoperative discomfort which patients respond to with shallow breathing (there are many approaches to postoperative pain management but this is a topic for another abstract/day). Continual shallow tidal volumes often result in progressive atelactasis and then pneumonia. When these poor respiratory habits are adopted in a patient who has inflamed and edematous lungs, their respiratory status is significantly compromised.

 

Not only does this article suggest anesthetists can improve patients’ postoperative lung compliance, but the inflammatory process can be attenuated as well. Theoretically, the nebulized budesonide will decrease the incidence of intraoperative brochospam. By preventing the detrimental ventilatory compliance effects this complication causes, clinicians should be capable of ventilating one lung ventilation patients with lower peak pressures, further mitigating the risk of lung injury and inflammation.

 

Patients’ hospital length of stay and participation in postoperative rehabilitation was not recorded. This was not the aim of the study, but the data could have been of great benefit. If the length of stay was decreased, one could assume patient satisfaction was increased and costs were reduced. If patients with improved lung function were more able to participate in their postoperative rehabilitation, one could again assume their outcomes could be improved as well.

 

Kenneth J. Taylor, DNP, CRNA


© Copyright 2014 Anesthesia Abstracts · Volume 8 Number 10, October 15, 2014





Effect of preoperative gabapentin on postoperative analgesia in patients with inflammatory bowel disease following major bowel surgery: a randomized, placebo-controlled trial

Pain Pract 2014;14:132-9

Siddiqui N, Fischer H, Guerina L, Friedman Z


Abstract

Purpose The purpose of this study was to test the hypothesis that a single preoperative dose of gabapentin 600mg would reduce postoperative opioid requirements and minimize the side effects and adverse effects of opioids following surgery for inflammatory bowel disease.

 

Background Inflammatory bowel disease (IBD) is an umbrella term that includes a group of pathologies caused by autoimmune and immune-mediated reactions against the gastrointestinal tract. Successful pain management strategies for those suffering from IBD are marginally effective, and this is problematic for those diagnosed with inflammatory bowel disease. IBD is chronic in nature. Many of these patients have developed tolerance to opioids due to the length of time they have used them for pain relief. In addition, nonsteroidal anti-inflammatory agents are relatively contraindicated as many believe they increase the risk of disease flare-up. Also, the potential for bleeding with NSAID use may outweigh the benefits. And while the use of immunosuppressive therapy is ‘typical’ for long-term treatment, immunosuppressives have been implicated in epidural abscess formation for reasons not totally clear. This concern regarding epidural abscess formation restricts the use of epidural analgesia for postoperative pain management. Collectively, these facts minimize providers’ choices for pain management strategies, and the result is typically opioid IV patient-controlled analgesia and the frustrating cycle of the side effects and adverse effects associated with their use.

 

Methodology This study was carried out as a randomized, placebo-controlled, double-blind clinical trial. Patients between 18 years and 60 years of age diagnosed with inflammatory bowel disease and scheduled for elective open bowel surgery with a midline incision were consented to participate. Enrollees were randomized into one of two groups:

  • Group 1 received 600 mg of oral gabapentin one hour before surgery
  • Group 2 received placebo orally one hour prior to surgery

All patients were administered a standardized general anesthetic that included fentanyl 1-2 µg/kg, morphine 1-2 mg/kg or hydromorphone 0.01 – 0.05 mg/kg and ketorolac 15-30 mg as analgesics during the maintenance phase of anesthesia. Patients were extubated at case end and placed on a morphine PCA pump in the PACU when alert. If pain was not controlled with morphine PCA, patients were switched to hydromorphone with the same mode of delivery. Outcome criteria assessed and measured postoperatively for 48 hours included:

  • Opioid consumption
  • Supplemental analgesia
  • Changes to PCA orders as a result of insufficient analgesia
  • Time to return of bowel sounds, passage of flatus, & start of clear fluid diet
  • Time to hospital discharge
  • Side effects/adverse effects
  • Pain score both at rest and with movement using the visual analog scale

Result A total of 72 patients completed the experiment; 36 in each group. Statistical significance was not observed in any of the outcome criteria. Total consumption of morphine equivalents was reduced 12.1% (13.2 mg) in the gabapentin group compared to placebo. The gabapentin group had return of bowel function sooner than placebo, a shorter total hospital length of stay, and lower pain scores; however, none of these results were statistically significant. Side effects/adverse effects were equivalent in both groups.

 

Conclusion There was a 12.1% reduction in total opioid use in the gabapentin group. There were no statistically significant clinical benefits experienced by the patients following surgery for IBD.

 

Comment

I wholeheartedly agree with the authors that pain following surgery may not be all nociceptive in origin, and individualized assessments (knowing the history) can provide us with an understanding of which treatment modalities have potential to be optimal for specific patients in certain situations. Pain may be the result of inflammation, have neurogenic and visceral components, and is often multimodal. Understanding different types of pain is critical for us as providers of care. Selection of pharmacologic and non-pharmacologic approaches should be based on the most likely causes of pain. Those with autoimmune disorders will not respond to opioids as an opioid-naive person would undergoing an appendectomy procedure; therefore, they should not be treated as such. Utilizing multi-modal analgesia is an evidence-based approach that has become grounded in theory. Those with a diagnosis of IBD have not found pain management approaches to be satisfactory due to their disease process and have used opioids unsuccessfully for way too long, all the while suffering from the beyond-frustrating side effects. I continue to be impressed by the current research and clinical trials attempting to understand the different types of pain, different theories and causes of pain, and scientists who are assessing new approaches and uses for ‘older’ pharmacologic agents based on newer concepts of the physiology and pathophysiology of pain.

Mary A Golinski, PhD, CRNA


Nociceptive Pain is most commonly defined as a noxious response from pain receptors. Nociceptors are the neurons which sense and respond to cells that suffer from trauma. Nociceptors signal tissue irritation, impending injury, or actual injury. When activated, they transmit pain signals to the brain. Nociceptive pain is usually time-limited, meaning when the tissue damage heals, the pain typically resolves. (Arthritis is a notable exception in that it is not time-limited.) Another characteristic of nociceptive pain is that it tends to respond well to treatment with opioids.

 

Neuropathic Pain is associated with post herpetic or post shingles neuralgia, sympathetic dystrophy or nerve trauma, certain cancer pains, and peripheral neuropathies (not all inclusive). Diabetes is a common cause of neuropathic pain but other conditions predispose one to experiencing neuropathic pain. It is typically the result of an injury or ‘malfunction’ in the peripheral or central nervous system. The pain is often triggered by an injury, but this injury may or may not involve actual damage to the nervous system. Nerves can be infiltrated or compressed by tumors, strangulated by scar tissue, or inflamed by infection. Persistent allodynia, pain resulting from a non-painful stimulus such as a light touch, is also a common characteristic of neuropathic pain. The pain may persist for months or years beyond the apparent healing of any damaged tissue. Neuropathic pain is frequently chronic, and tends to have a less complete response to treatment with opioids, but may respond well to other drugs such as anti-seizure and antidepressant medications. 

 

Visceral Pain is a type of nociceptive pain; typically it originates from the internal abdominal organs and is hard for some to pinpoint. It’s often described as generalized aching and may radiate. 

 

Gabapentin- is an antiepileptic type drug most often used to treat chronic neuropathies and sometimes postoperative pain. The mechanism of action is theorized to include a decrease in neurotransmitter release through sensory neurons in a calcium channel dependent process (at the cellular level). Its analgesic effect is postulated to be related to modulations of NMDA and other receptors. 


© Copyright 2014 Anesthesia Abstracts · Volume 8 Number 10, October 15, 2014





Perioperative Metoprolol and Risk of Stroke after Noncardiac Surgery

Anesthesiology 2013;119:1340-6

Mashour G, Sharifpour M, Freundlich R, Tremper K, Shanks A, et al


Abstract

Purpose The purpose of this study was twofold: first, to identify risk factors of perioperative stroke in the noncardiac and non-neurosurgical population and second, to establish an understanding of the role of metoprolol (as a specific and widely prescribed beta blocker) in perioperative stroke following noncardiac surgery.

 

Background It is an accepted and unfortunate fact that perioperative stroke occurs in high-risk individuals having both cardiac and noncardiac surgery. Stroke in this setting is clearly associated with an increase in mortality. The POISE trial (Peri-Operative Ischemic Evaluation) conducted in the mid-2000s was stopped prematurely because preliminary results demonstrated an increased risk of stroke following noncardiac surgery in those given the ‘study dose’ of metoprolol versus placebo. Controversy surrounding the POISE trial reflects concern regarding routine dosing of metoprolol succinate which did not seem appropriately individualized and as a result contributed to a higher incidence of hemodynamic changes not typically observed in everyday clinical practice. Guidelines now state that perioperative beta blockers should be carefully titrated in terms of dosage, especially for those at a greater than usual risk.

 

Following the POISE trial, a retrospective case control study did not identify an increased risk of perioperative stroke with ‘typical doses’ of beta blockers; however, the study did not assess the adverse effects of different classes of beta blockers, but rather beta blockers in aggregate. It remains unclear whether perioperative metoprolol is associated with perioperative stroke compared to other beta blockers. 

 

Methodology This was a retrospective chart review. Electronic medical records were examined and data collected for those who had noncardiac and non-neurologic surgery from July 2003 to June 2009 at a University Health System. Exclusion criteria included intracranial neurosurgical cases, cardiopulmonary bypass, carotid endarterectomy, major vascular cases for vessels above the diaphragm, implantable cardiac defibrillator and ablation procedures, otolaryngology cases involving the base of the skull, trauma, oral maxillofacial cases, multiple organ trauma, and organ procurement procedures.

  1. Demographic information including extensive health history
  2. Preoperative medication 
    1. Preoperative beta blocker use:  metoprolol or atenolol
  3. Surgical procedure
    1. Emergent or not
    2. Type of surgical procedure
    3. Type of anesthesia administered
    4. Specific beta blocker used intraoperatively 
  4. Intraoperative invasive and non-invasive blood pressure values
    1. Calculation of median intraoperative MAP or SABP values < 20, 30, or 40% of baseline 

The primary outcome variable from the electronic record was the occurrence of perioperative stroke. This was confirmed by neuroimaging and medical record documentation within the first 30 days after surgery. Additionally, quantification and determinants of all-cause mortality at 30-days and 1-year postoperatively were recorded.

 

Sophisticated statistical processes were used to identify whether the outcome measures differed for those taking metoprolol versus other beta blockers such as atenolol in this population. Patients were ‘matched’ based on a number of comorbidities as well as age.

 

Result There were 57,218 patients who underwent noncardiac and non-neurosurgical procedures who were not excluded. The incidence of stroke was 0.09%; 55 patients had a perioperative stroke and 2 of the 55 had a diagnosis of subarachnoid hemorrhage.

Preoperative variables associated with stroke:

  • Age
  • BMI
  • Emergent surgery
  • Atrial fibrillation
  • Hypertension
  • History of MI or CAD
  • Heart valve disease
  • Renal insufficiency or failure
  • History of stroke or TIA
  • Preoperative metoprolol use

Preoperative metoprolol was associated with a 4 times increased risk of perioperative stroke. Preoperative atenolol, bisoprolol, carvedilol, nadolol, propranolol, or satalol were not associated with stroke; however, significantly fewer patients were prescribed these beta blockers.

intraoperative variables associated with stroke:

  • Relative MAP or SABP < 20%, 30%, or 40% of baseline
  • Intraoperative IV metoprolol use

Intraoperative IV metoprolol use was associated with a 3% increased risk of stroke, not seen with intravenous esmolol or labetalol.

  • Perioperative stroke was associated with an 18 times increase in 30-day mortality and an 11 times increase in 1-year mortality
  • 7 patients taking metoprolol had a postoperative stroke compared with none in the atenolol group (p = 0.016)
  • A history of atrial fibrillation and stroke or TIA, were independent predictors of stroke in those over 40 years of age.

Conclusion This retrospective chart review of over 57,000 cases showed that people who had noncardiac surgery and a history of preoperative metoprolol use had an increased risk of perioperative stroke compared with those who took atenolol in matched cohort analysis. Intraoperative IV metoprolol use was associated with an increased risk of perioperative stroke, whereas labetolol and esmolol were not.

 

Comment

I appreciated the utility of the researchers commenting on all the limitations of this study including the fact that the overall occurrence of stroke in this setting is rare, that much information about preoperative drug doses was not available nor was patient compliance with preoperative prescribed regimes, that patients experienced strokes intraoperatively also with the administration of metoprolol tartrate, and finally there may have been an underestimation of the total incidence of stroke due to loss of follow-up information. While acknowledging these limitations, robust data clearly was obtained from this large pool; a very real benefit of having large databases to draw from. This appears to be consistent with other studies. While many of the demographic variables associated with the risk of stroke are simply beyond our control, choosing which beta blocker to use as an adjunct is something we can control. There is a difference between the generations of beta blockers and the risk associated with each drug. Historically, it appears that not much scrutiny was given to whether the drugs were controlled release or immediate release, even when it was the same medication. New discoveries are being made each day and I imagine that we will continue to learn more - not only regarding generational differences, but differences that exist between different drugs within the same generation. I absolutely will think twice about using intravenous metoprolol for high-risk patients as a result of this information. I have several other options and the evidence to date supports something other than metoprolol may lend to more favorable outcomes.

Mary A Golinski, PhD, CRNA


Notes: The original POISE Trial was published in the Lancet in 2008; 371: 1839-47, and is titled: “Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomized controlled trial.”

Metoprolol tartrate- Immediate release, typically administered in daily divided doses.

Metoprolol succinate- Extended release, usually once daily oral administration, oral administration plasma half-life varies between 3-7 hours.


© Copyright 2014 Anesthesia Abstracts · Volume 8 Number 10, October 15, 2014