ISSN NUMBER: 1938-7172
Issue 5.4 VOLUME 5 | NUMBER 4

Editor:
Michael A. Fiedler, PhD, CRNA

Contributing Editors:
Penelope S Benedik, PhD, CRNA, RRT
Mary A Golinski, PhD, CRNA
Gerard Hogan Jr., DNSc, CRNA
Alfred E Lupien, PhD, CRNA
Lisa Osborne, PhD, CRNA
Dennis Spence, PhD, CRNA
Cassy Taylor, DNP, DMP, CRNA
Steven R Wooden, DNP, CRNA

Assistant Editor
Jessica Floyd, BS

A Publication of Lifelong Learning, LLC © Copyright 2011

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
The effect of time of day on outcome of unscheduled cesarean deliveries
Download Text File

PAIN
  Comparison of neosaxitoxin versus bupivacaine via port infiltration for postoperative analgesia following laparoscopic cholecystectomy
Download Text File

The effects of oral ibuprofen and celecoxib in preventing pain, improving recovery outcomes and patient satisfaction after ambulatory surgery
Download Text File

PHARMACOLOGY
A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy
Download Text File

The end-tidal desflurane concentration for smooth removal of the laryngeal mask airway in anaesthetised adults
Download Text File

The 50% and 95% effective doses of desflurane for removal of the classic laryngeal mask airway in spontaneously breathing anaesthetized adults
Download Text File

POLICY, PROCESS, & ECONOMICS
Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application to healthy patients undergoing elective procedures
Download Text File

Attention subscribers licensed in Alabama, Alaska, Idaho, Kentucky, Nevada, and New Mexico:

This issue contains 1 PHARMACOLOGY specific CE credit.


Obstetric Anesthesia
The effect of time of day on outcome of unscheduled cesarean deliveries

J Matern Fetal Neonatal Med 2011 (Epub ahead of print)

Peled Y, Melamed N, Chen R, Pardo J, Ben-Shitrit G, Yogev Y


Abstract

Purpose The purpose of this study was to determine if there was a difference in outcomes after unscheduled cesarean deliveries based on the time of day.

 

Background Sleep deprivation and fatigue in providers is associated with increased medical errors and decreased patient safety. On an obstetrical unit provider sleep deprivation and time of day may affect outcomes for unscheduled cesarean deliveries. However, there is limited data evaluating the association between time of day and short-term complications after unscheduled cesarean delivery.

 

Methodology This was a retrospective cohort study of 9,944 unscheduled cesarean deliveries between 1997 and 2007 at a tertiary care facility in Tel Aviv, Israel. Patients were categorized based on the work shift on which the patient entered the operating room: morning shift, 0700-1500, evening shift, 1501-2300, and night shift, 2301-0700. In this facility, staff obstetricians and anesthesia providers work 24 hour shifts. Data extracted from the medical record included demographic characteristics, past medical and obstetrical history, indication for cesarean delivery, type of anesthesia, and maternal and neonatal outcomes. Composite maternal morbidity was defined as: postpartum endometritis or wound infection, immediate hemorrhage (<6 h postpartum) or need for blood transfusion, bladder or bowel injury, or prolonged hospitalization (>7 days). Composite neonatal outcomes included: 5-min Apgar scores <7.0, umbilical artery pH <7.0, neonatal intensive care unit admission, neurological morbidity or trauma. Descriptive and inferential statistics were used to analyze the results. Multivariable logistic regression was used to determine predictors of neonatal or maternal complications. A P <0.05 was considered significant.

 

Result During the 10 year study period, there were 16,318 cesarean deliveries (CS); an average of 4.47 CS per day; with 61% of them being unscheduled (9,944; average 2.7 CS per day). Of the surgeries in this study, 30.1% (2,995) occurred during the morning shift, 46.4% (4,618) during the evening shift, and 23.5% (2,331) during the night shift. There were an average of 0.82, 1.26, and 0.63 unscheduled CS per day during the morning, evening and night shifts, respectively.

The average age of all patients was approximately 31 years; 21% were over the age of 35. Significantly more failed labor inductions required CS on the night shift (Table 1). The rate of general anesthesia was significantly higher on the night shift (23.4%) and day shift (21%) as compared to the evening shift (P < 0.001; see Table 1).

 

Table 1. Comparison of characteristics by time of day

 

Morning

n = 2995

Evening

n = 4618

Night

n = 2331

P Value

Age

30.9 ± 5.6

30.9 ± 5.5

30.5 ± 5.8

0.014

Nulliparous

39.2%

40.1%

39.5%

0.3

Gestational DM

1.6%

1.5%

1.1%

0.32

Gestation, wks

38.1 ± 3.3

38.4 ± 2.7

38.1 ± 3.8

 0.003

<37 weeks gestation

20.6%

18.2%

19.3%

0.03

Failed induction

9.1%

8.0%

11.5%

< 0.001

Previous CS

26%

26.3%

21.6%

< 0.001

Multiple gestation

8.7%

8.0%

8.7%

0.46

Placental abruption

3.2%

2.3%

3.3%

0.018

General anesthesia

21%

16.3%

23.4%

< 0.001

Anesthesia time

15 ± 9

15 ± 8

16 ± 10

< 0.001

Operation time

30 ± 16

31 ± 15

34 ± 20

< 0.001

Operation time >40 min

16%

17.1%

19.9%

< 0.001

 

There were no significant differences in bowel or bladder injury, or wound infection between groups (P > 0.05). Significantly more patients had a postpartum hemorrhage on the night shift (2.7%) as compared to the evening (1.9%) or day shift (1.7%; P = 0.02). Likewise significantly more patients required a blood transfusion on the night shift (1.5%) as compared to the evening (0.8%) or day shift (0.9%; P = 0.01). Prolonged hospitalization, defined as > 7 days, was more common in patients who had an unscheduled CS on the night shift (4.2%) compared to the evening (3.0%) or day shift (3.5%; P = 0.03). There were no significant differences in neonatal outcomes according to working shift with regards to 5 min Apgar <7, umbilical artery pH <7, NICU admission, neurological morbidity, or clavicular or other fractures (P > 0.05). There was a slightly higher, though not statistically significant, rate of NICU admission requirement on the night shift (13.8%) as compared to the evening (12.2%) or day shift (12.3%; P = 0.13).

 

Logistic regression was used to examine rates of maternal and neonatal morbidity by time of day while adjusting for the following risks factors: age, parity, diabetes, chronic hypertension or preeclampsia, previous cesarean delivery, fetal growth restriction, indication for cesarean delivery, and gestational age. The odds of maternal morbidity were 1.3 times more likely on the night shift as compared to the day shift (95% CI, 1.1-2.6, P < 0.05). However, the risk of maternal morbidity was not significantly increased on the evening shift when compared to the day shift (OR: 1.1, 95% CI, 0.9-1.3, P > 0.05). Neonatal morbidity did not differ by working shift (P > 0.05).

 

Conclusion Patients who required unscheduled cesarean deliveries on the night shift required longer operative times and had an increased risk for maternal, but not neonatal, morbidity.

 

Comment

This was an interesting study because it suggests there might be increased maternal morbidity associated with working 24 hour shifts on labor and delivery units. In this study the authors compared maternal and neonatal outcomes after unscheduled cesarean delivery based on the time of day. In their introduction they alluded to the fact that sleep deprivation and fatigue may be associated with adverse maternal and neonatal outcomes in sleep deprived or fatigued providers. They reported that all obstetric and anesthesia staff providers worked 24 hours shifts, but did not report whether or not obstetric or anesthesia residents were involved in the cases, or if the residents worked 24 hour shifts as well. This study would have been improved if this information was provided. Additionally, they provided no data on the level of sleep deprivation or fatigue experienced by the providers. A big question would be on average how much rest or sleep time are the providers able to get when working a 24 hours shift? Given this is a tertiary care center I suspect the providers may have gotten very little sleep, though they averaged less than 1 unscheduled cesarean delivery per night.

 

Despite being a busy tertiary care center, overall their maternal morbidity rates were fairly low. The most frequent adverse outcome on the night shift was maternal endometritis; almost 7% experienced this complication. This may reflect a lack of consistent antibiotic prophylaxis. Likewise, it is no surprise that the need for general anesthesia was more common on the night shift as was the frequency of postpartum hemorrhage and need for a blood transfusion. The need for general anesthesia have been associated with the increased anesthesia time on the night shift. These findings are most likely due to the relative urgency of unscheduled cesarean deliveries on the night shift.  At night, it is harder to get additional providers (surgeons, anesthesia providers, and ancillary staff) to support when an emergency or urgent cesarean delivery is required. Therefore I am not surprised with these results.

 

This study made me think of some important points that our readers who provide obstetric anesthesia should consider. Things to consider include: (1) knowing what resources you have available (i.e., airway equipment, blood, support staff, etc.); (2) call for help early when faced with an emergency; (3) consider calling for an ICU or ER nurse if an extra “pair of hands” is needed when working at a small facility; (4) ensure you maintain frequent communication with nursing and obstetric staff; and (5) sleep when you can; consider taking frequent naps especially when working a 24 hour shift. These are just a few tips I have learned over the years in working in both small and large facilities that you might find helpful.

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 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011




Pain
Comparison of neosaxitoxin versus bupivacaine via port infiltration for postoperative analgesia following laparoscopic cholecystectomy

Reg Anesth Pain Med 2011;36:103-109

Rodriguez-Navorro A, Berde C, Wiedmaier G, Mercado A, Garcia C, Iglesias V, Zurakowski D


Abstract

Purpose The purpose of this study was to compare the postoperative analgesia effect of neosaxitoxin to bupivacaine when used to anesthetize the port sites for laparoscopic cholecystectomy.

 

Background Infiltration of local anesthetic agents at the incision site has been shown to contribute to postoperative pain relief. However, current local anesthetic agents, when used for wound site infiltration, are limited to a maximum effective time of 6 to 8 hours. Site 1 toxins, including tetrodotoxin, saxitoxin, and neosaxitoxin (neoSTX) appear to have prolonged anesthetic action while having benign effect on peripheral nerves and muscles, as well as minimal direct cardiotoxicity.

 

Methodology This study was a randomized, parallel-group, double-blind trial comparing neoSTX 100 µg to bupivacaine 50 mg for wound infiltration. Each drug was selected randomly to be infiltrated at the port insertion sites for patients 18 to 80 years old undergoing laparoscopic cholecystectomy. A standard general anesthetic technique was used for the patient population which included fentanyl, propofol, rocuronium, sevoflurane, air, and oxygen. Each patient received ketorolac 30 mg IV in the recovery room. Patients converted to open cholecystectomy were excluded from the study. Patients were monitored for postoperative pain during the 30 days immediately following surgery. Daily phone calls were made to each patient and a physical examination was conducted on postoperative days 7 and 30. Pain was evaluated by the nursing staff using a standard pain visual analog scale (VAS). During the first 12 hours postoperatively, if a patient had a VAS score of 5 or greater, they were given 2 mg of morphine IV. Ondansetron 4 mg IV was used on demand for nausea. After the first postoperative day, patients were instructed to use sodium diclofenac 50mg three times a day PRN for pain.

 

The primary outcome of this study was incisional pain at 12 hours. The secondary outcome measured pain at numerous intervals after the 12 hour primary outcome period. Adverse outcome data, patient subjective ratings, and return to work time were also collected. Pain scores using the VAS were analyzed statistically and two tailed P values of less than 0.05 were considered significant.

 

Result Out of 166 patients evaluated for inclusion in the study, 150 were randomized. Because of patients lost during follow-up, and those converted to open cholecystectomy, the total number of final study patients was 69 in the neoSTX group and 68 in the bupivacaine group. The primary outcome of pain at 12 hours postoperatively resulted in less pain reported for the neoSTX group overall. In addition, the number of patients reporting VAS pain scores of less than 5 at 12 hours postoperative was greater in the neoSTX group. Both groups had similar time to discharge from the hospital. Patients returned to work 2 days earlier in the neoSTX group. The frequency of intraoperative and postoperative problems was similar in each group, and there were no reported problems that would have been suggestive of an adverse reaction to neoSTX.

 

Conclusion For patients undergoing laparoscopic cholecystectomy, infiltration of the port sites with neoSTX significantly reduced the amount of postoperative pain, and allowed patients to return to work more quickly than those who had port sites infiltrated with bupivacaine. The ultra-long acting neoSTX appears to be a safe alternative to other local anesthetic agents. NeoSTX appears to provide anesthesia for 1 to 3 days following wound infiltration, and does not appear to have any significant adverse effects at the doses used in these patients. Other studies with neoSTX suggest that combining neoSTX with bupivacaine or epinephrine produce more intense and prolonged analgesia than neoSTX alone. The maximum safe dose of neoSTX has not yet been determined.

 

Comment

This was an interesting and fairly straight forward study of an ultra-long acting anesthetic agent that is not yet available on the general market. However, I felt it was worth reporting because of the potential for an agent like neoSTX to make a dramatic change to the way we provide anesthesia today.

 

The use of shell fish toxins such as neoSTX for anesthesia and analgesia looks to be very promising. I am excited about the possibility of having a local anesthetic that can last for several days without significant adverse reactions. I am aware of other studies showing that adding neoSTX to bupivacaine can produce effective regional anesthesia for up to 7 days. It has been reported that good analgesia with minimal motor effect is possible with various combinations of neoSTX and other local anesthetic agents. If the studies continue to produce good results and we see a neoSTX agent on the market soon, it could cause a revolution in pain management and regional anesthesia. An ultra-long acting agent used effectively could eliminate postoperative pain for peripheral surgery and minimize incisional pain for extended periods of time. Brush up on your regional techniques and get ready for the revolution. Of course we have seen other promising agents shelved when clinical trials revealed nasty side effects. I hope this will not be the case with neoSTX.

Steven R Wooden, MS, CRNA


Editor’s Note: This is an experimental drug. The trial reported here represents a collaboration between a Chilean biotech company, Proteus SA (Santiago, Chile) and the Children's Hospital Boston.  From a USA perspective it is very early in clinical trials.


© Copyright 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011





The effects of oral ibuprofen and celecoxib in preventing pain, improving recovery outcomes and patient satisfaction after ambulatory surgery

Anesth Analg 2011;112:323-9

White PF, Tang J, Wender RH, Zhao M, Time M, Zaentz A et al


Abstract

Purpose The purpose of this study was to evaluate the efficacy of ibuprofen and celecoxib on preventing pain, decreasing opiate consumption, and improving patient satisfaction and recovery outcomes after ambulatory surgery.

 

Background Non-steroidal anti-inflammatory drugs (NSAIDS) are effective in decreasing postoperative pain, opioid consumption, and improving recovery after ambulatory surgery. However, concern over gastrointestinal and operative site bleeding due to blockade of prostaglandin synthesis at the cyclooxygenase (COX)-1 enzyme limit there widespread use. COX-2 selective inhibitors, such as celecoxib, reduce postoperative pain and opioid consumption, have a lower risk of bleeding, and thus may be safe alternatives to COX-1 NSAIDS. Unfortunately, some studies suggest that celecoxib is associated with cardiovascular complications with short-term postoperative use. Furthermore, subsequently retracted COX-2 publications have called into question previous positive findings on these classes of drugs. This study sought to compare outcomes after ambulatory surgery in patients administered either maximum daily doses of ibuprofen 1,200 mg/day or celecoxib 400 mg/day for four days.

 

Methodology This was a prospective, randomized, double-blind, placebo controlled study of 180 ASA I to III patients undergoing superficial surgery, such as knee arthroscopy, inguinal hernia repair, breast lumpectomy, or lipoma excision. Patients were randomly assigned to one of three groups; ibuprofen 1,200 mg/day (400 mg TID), celecoxib 400 mg (200 mg BID), or placebo. All drugs were started 20 minutes after arrival in the PACU and continued for 3 days after surgery.

 

In the operating room anesthesia was induced with propofol and an LMA was placed. Anesthesia was maintained with a propofol infusion, and fentanyl 50-200 µg was titrated as needed. Surgical incisions were injected with 1% lidocaine and 0.25% bupivacaine. Prior to emergence, all patients received 4 mg ondansetron, 4 mg dexamethasone, and 10 mg metoclopramide. After completion of the surgery, patients were taken to the PACU. Twenty minutes after arrival patients in the ibuprofen group received ibuprofen 400 mg, those in the celecoxib group received 400 mg, and those in the placebo group received placebo capsules and tablet matching the treatment drugs.  Patients were prescribed Vicodin (5 mg hydrocodone + acetaminophen 500 mg) for breakthrough pain in the PACU or at home.

 

Patients were contacted by telephone at 24, 48, and 72 hours after surgery by a trained interviewer who was unaware of group assignment. Outcome data included the following:

  • opioid consumption (number of pills)
  • maximum pain scores (0-10 scale)
  • satisfaction with postoperative pain management (0 = poor, 1 = fair, 2 = good, 3 = very good, 4 = excellent)
  • quality of recovery (QoR; 9-item questionnaire, 0-18) See Notes at end.
  • side effects
  • time to return of bowel function
  • incidence of constipation
  • time to resumption of normal activities of daily living

At their 7 and 30 day follow-up evaluations patients were asked about the number of days it took to tolerate normal fluids and solid food, for return of normal bowel function, and resume normal activities of daily living. At the time of the initial post-surgical visit, and at 30 days, the presence of wound  complications was recorded (i.e., bleeding, hematomas, and infections), as was the occurrence of any cardiovascular complications. The primary outcome for which the sample size was based was the time in days to return of normal activities of daily living. Descriptive and inferential statistics were used to analyze the results. A P value less than 0.05 was significant.

 

Result Sixty subjects were enrolled in each of the three groups. Patient demographic characteristics, duration of surgery and anesthesia, and anesthetic drug doses were similar between the three groups (P > 0.05). The majority of the patients were Caucasian, with a mean age of approximately 48 years. Most surgeries were hernia repairs. Time to return of bowel function was one day less in the ibuprofen and celecoxib groups (2 ± 2 days) compared to the placebo group (3 ± 2 days). However, this difference was not statistically significant. Likewise, the time to return of normal physical activities did not differ between groups (ibuprofen: 7 ± 5 d vs. celecoxib: 8 ± 6 d vs. placebo: 7 ± 4 d; P = ns).

 

Postoperative maximum pain scores at 24 and 48 hours were similar between the three groups (Figure 1). However, at 72 hours patients in the ibuprofen group had significantly less pain than those in the placebo group (P < 0.05; Figure 1). Overall, maximum pain scores for the 72 hour period were less in the ibuprofen and celecoxib groups (4 ± 3) compared to the placebo group (5 ± 3) (P < 0.05). Opioid requirements were significantly less in the ibuprofen and celecoxib groups when compared to the placebo group at 24, 48, and 72 hours (P < 0.05; Figure 2). Patient satisfaction with postoperative pain management was higher in the ibuprofen and celecoxib groups (3 ± 1) when compared to the placebo group (2 ± 2) (P = 0.02). Patients in the two treatment groups rated their pain management as very good compared to only good in the placebo group. Quality of recovery scores were significantly higher on all three postoperative days in the ibuprofen and celecoxib groups when compared to the placebo group (P < 0.01; Table 1). The incidence of postoperative emesis was similar in all groups. However, the incidence of constipation was significantly higher in the control group with 18.3% complaining of constipation compared to only 5% in the ibuprofen and 3.3% in the celecoxib groups (P < 0.05). None of the patients in the two treatment groups experienced postoperative bleeding, wound infection or cardiovascular complications during the follow-up evaluations at 7 or 30 days.

 

 

 

Figure 1. Comparison of Pain Scores

Figure 1

Note. VNRS = verbal numeric rating scale.


 

 

Figure 2. Comparison of Opioid Consumption

Figure 2

Note. Patients were given Vicodin (5 mg hydrocodone + acetaminophen 500 mg) for breakthrough pain.

 

  

 

Table 1. Comparison of Quality of Recovery scores

 

Ibuprofen

(n = 60)

Celecoxib

(n = 60)

Placebo

(n = 60)

24 hr

16 +/- 0.2

16 +/- 0.2

15 +/- 0.3

48 hr

17 +/- 0.2

17 +/- 0.2

16 +/- 0.2

72 hr

17 +/- 0.2

17 +/- 0.2

16 +/- 0.2 

Note. QoR scores were significantly higher in the two treatment groups when compared to the control group (P < 0.01).

 

Conclusion Ibuprofen 400 mg TID and celecoxib 400 mg BID were found to be equivalent in their ability to reduce pain, opioid consumption and the incidence of constipation, and improve patient satisfaction and quality of life. Given the lower cost of ibuprofen when compared to celecoxib, these data suggest that it may be a more cost effective alternative to celecoxib when administered as part of a multimodal post-surgical pain management regimen after ambulatory surgery.

 

Comment

The results of this study are not surprising. Multimodal therapy, which combines the use of local anesthetics injected into the wound along with opioids, acetaminophen, and NSAIDS or COX-2 inhibitors, is better than opioids alone. In this study, the investigators found lower pain scores and opioid consumption, and higher patient satisfaction and quality of recovery scores. However, these differences were not as dramatic when compared to the difference seen in the incidence of constipation. Patients in the placebo group had an absolute 15% higher incidence of constipation when compared to the two treatment groups. This was most likely due to the decreased opioid consumption in the two treatment groups. I suspect the lower incidence of constipation contributed to the higher patient satisfaction and quality of recovery scores.

 

The decreased pain and opioid consumption outcomes in the two treatment groups were modest at best and are probably a reflection of the types of surgeries (i.e., hernia repair, lipoma excision) and judicious use of local anesthetics. It is important to point out that volatile anesthetics where not used in these cases, and this may have influenced the results. I think this study demonstrates that these types of procedures can be performed under local anesthesia and TIVA with propofol and fentanyl.

 

The authors based their power analysis on the number of days until resuming normal activities. However, the investigators failed to provide a clear definition of what this outcome meant. I view this as a limitation. Additionally, by choosing this outcome for sample size calculation they were more likely to find statistically significant, though not clinically significant differences. For example, they found patient satisfaction was significantly higher in the treatment groups, however the groups only differed by one point.

 

Nonetheless, I think these findings support the use of multimodal therapy with NSAIDS or COX-2 inhibitors. The investigators recommended ibuprofen because it costs much less than celecoxib; however in terms of ease of use, celecoxib may be better because patients only have to take it twice a day rather than three times a day with ibuprofen. Celecoxib has a lower risk of bleeding. Anesthesia providers should consider the findings of this study and these issues when making recommendations to surgeons and patients on postoperative analgesic regimens. I think the key is around the clock administration of non-opioid analgesics for at least the first 72 hours after ambulatory surgery.

Dennis Spence, PhD, CRNA


1. Myles PS, Hunt JO, Nightingale CE, et al. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg. 1999;88:83-90.


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 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011




Pharmacology
A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy

Anesth Analg 2011;112:813-8

Habib AS, Keifer JC, Borel CO, White WD, Gan TJ


Abstract

Purpose The purpose of this study was to compare the cumulative incidence of vomiting in post-craniotomy patients who received the combination of aprepitant and dexamethasone versus ondansetron and dexamethasone.

 

Background Postoperative nausea and vomiting (PONV) can be a significant problem after craniotomy. The reported incidence of PONV after craniotomy can be as high as 70%, and even with prophylaxis, the incidence of emesis is approximately 40%. Besides being distressing to patients, emesis can result in increased intracranial pressure and may increase morbidity after craniotomy.

 

Aprepitant, a neurokinin-1 (NK-1) receptor antagonist has a half-life of 9 to 12 hours. In animal studies NK-1 antagonize the central effects of substance P in central emetic areas in the dorsal vagal complex and area postrema. NK-1 antagonists may act peripherally as well. Aprepitant has no sedative side effects; and has been found to be effective in preventing vomiting for up to 48 hours after surgery. However, it has not been studied after craniotomy.

 

Methodology This was a prospective, randomized, double-blind, placebo controlled trial of 115 ASA I-III adult patients undergoing elective craniotomy under general anesthesia. Patients were excluded if they had taken medications with antiemetic properties (except dexamethasone) in the 12 hours before surgery, had a baseline nausea verbal numeric rating scale (VNRS; 0-10) >3, or were expected to require postoperative nasogastric tube suctioning. Patients were randomized to receive aprepitant 40 mg or placebo 1 to 3 hours before induction of anesthesia or ondansetron 4 mg within 30 minutes of the end of surgery. All patients received 10 mg of dexamethasone after induction of anesthesia. Anesthetic technique was standardized with isoflurane and oxygen/air mixture, remifentanil, and fentanyl. Postoperative analgesia was standardized. PONV was treated initially with ondansetron 4 mg. All further events were treated at the discretion of the surgical team. All patients received postoperative dexamethasone per the surgical protocol starting the evening before surgery and throughout the hospitalization.

 

Data were collected on the incidence and severity of nausea and vomiting using a 0-10 VNRS. Additional data collected included frequency of need for rescue antiemetic, sedation scores, adverse events, and postoperative analgesic requirements. Significant nausea was defined as ≥4 out of 10 on a VNRS. An emetic episode was defined as a single vomit or retch or any number of continuous vomits or retches. A complete response was defined as no PONV or requirement for rescue medication. Data were collected at 0, 30, 60, 90 and 120 minutes postoperatively, and then again at 24 and 48 hours. At 24 and 48 hours a 5-point Likert scale was used to evaluate patients’ satisfaction with the control of nausea and vomiting in the previous 24 hours.

 

The primary outcome was the cumulative incidence of vomiting from 0 to 48 hours. Secondary outcomes included the incidence of vomiting at 2 and 24 hours, incidence of nausea and significant nausea (>3/10), use of rescue antiemetic; and complete response for 0 to 2 hours, 0 to 24 hours, and 0 to 48 hours. Statistical analysis was appropriate. A P < 0.05 was considered significant.

 

Result A total of 203 subjects were screened for eligibility, 115 were enrolled, and 104 completed the study (n = 53 in ondansetron group and n = 51 in aprepitant group). No significant differences were noted in demographics, risk factors for PONV, surgical duration, and intraoperative or postoperative opioid consumption. The total number of patients who vomited between 0 and 48 hours was significantly less in the aprepitant group compared to the ondansetron group (16% vs. 38%, P = 0.01). The cumulative incidence of nausea between 0 and 48 hours was similar between the groups (69% vs. 60%, P = 0.40). There was no significant difference  in the number of vomiting episodes, incidence or severity of nausea, need for rescue antiemetic, or complete response on postoperative day #2 (48 hours after surgery) (P = NS). The survival analysis revealed a significantly lower risk of vomiting when compared to ondansetron (hazard ratio = 0.292, 95% CI, 0.116-0.731, P = 0.009). The time to vomiting was significantly longer in the aprepitant group (P = 0.008).

 

The incidence of vomiting was significantly less at 2 and 24 hours (P < 0.05), but similar at 48 hours (P = NS; Figure 1). The number of vomiting episodes was significantly less between 0 and 2 hours, and 0 and 24 hours in the aprepitant group (P < 0.05). Groups were similar in the incidence of nausea (Figure 2), headache and sedation, nausea scores, need for rescue antiemetics, or complete response (no PONV or need for rescue therapy) (P = NS). The percent of patients who reported being completely satisfied with the degree of vomiting control was higher, in the aprepitant group at 24 hours (71% vs. 60%; P = 0.18) and 48 hours (73% vs. 60%; P = 0.27), however these differences were not statistically significant.

 

Figure 1. Incidence of vomiting post-craniotomy

Figure 1

 

Figure 2. Incidence of nausea post-craniotomy

Figure 2

 

Conclusion A single prophylactic dose of aprepitant and dexamethasone significantly reduced the incidence of vomiting after general anesthesia for craniotomy. However, the incidence of nausea was still high in both groups despite prophylaxis.

 

Comment

Vomiting after craniotomy can lead to significant morbidity due to increased ICP and possible intracranial bleeding. Interventions to minimize vomiting should be carried out to reduce these complications after craniotomy. Aprepitant has a long duration of action and is more effective in preventing vomiting. Unfortunately, nausea rates in this study were still significantly high in both groups despite prophylaxis. This is probably not surprising given that craniotomy is associated with a high rate of PONV. I wonder if we can expect much better anti-nausea rates than reported in this study. Maybe if a TIVA anesthetic was used.

 

At my institution, we have found similar results with aprepitant. That is, it reduces the incidence of emesis, but is not as effective in reducing nausea compared to other medications. I think if anesthesia providers wish to use aprepitant I would reserve it for cases were vomiting could lead to increased postoperative morbidity. Surgeries I think it would be most appropriate for would include craniotomy, inner ear surgery, and abdominoplasty. I am sure there are procedures for which it would be effective, but given the cost, providers may want to weigh the cost to benefit ratio when considering administering this medication. In addition, it needs to be given 1 to 3 hours before surgery. If I were to prescribe it, I would give the patient a prescription to take a dose on the morning of surgery.

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 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011





The end-tidal desflurane concentration for smooth removal of the laryngeal mask airway in anaesthetised adults

Eur J Anaesthesiol 2011;28:187-89

Sahiner Y, Özkan D, Akkaya T, Göral N, Alptekin A, Gümüs H


Abstract

Purpose The purpose of this study was to determine the end-tidal concentration for safe, smooth removal of the laryngeal mask airway (LMA) in anesthetized adults.

 

Background The manufacturer of the LMA recommends that it be removed after return of airway reflexes. However, many anesthesia providers remove the LMA when the patient is still deeply anesthetized. Desflurane has a rapid onset and offset; unfortunately it is not known what end-tidal desflurane concentration is needed to ensure a safe, smooth removal of the LMA in anesthetized adults.

 

Methodology This was a prospective, descriptive investigation of 23 ASA I patients presenting for urological surgery under general anesthesia with LMA. Patients were excluded if they had a recent URI, abnormal airway anatomy, BMI > 30 kg/m2, or a history of gastroesophageal reflux disease. No premedication was administered. Intravenous induction was completed with propofol 2.5 mg/kg and remifentanil 10 µg, and an LMA classic (size based on weight) was placed. Anesthesia was maintained with desflurane and nitrous oxide 50% and oxygen 50%. A semi-closed circuit was used with a fresh gas flow at 6 lpm.

 

End-tidal concentration for desflurane for subject #1 was maintained at 4% for 10 minutes prior to removal at the end of surgery. All LMAs were removed with the cuff inflated. Secretions on the LMA were checked for pH to determine the presence of gastric secretions. Using the Dixon up-and-down method, a 0.5% change up or down in desflurane concentration was made for each subsequent patient based on failure or success of removal. The minimum alveolar concentration (MAC) was calculated by analyzing the midpoint concentration between each failure-success for all independent pairs of patients. Unsuccessful LMA removal was defined as the occurrence of the following complications:

  • coughing
  • teeth clenching
  • gross purposeful movements
  • breath holding
  • laryngospasm
  • desaturation <90% within 1 minute of LMA removal

 

Probit logistic regression was used to calculate a dose-response curve to estimate the ED50 and ED95 end-tidal desflurane concentration for smooth LMA removal.

 

Result Twenty three (n = 23) subjects completed the study. The mean age was 54.8 ± 15, with the majority being men (n = 20) with a BMI = 27 kg/m2. All LMAs were placed on the first attempt. Median secretion pH was 6 (3-8). LMAs remained in place an average of 55.2 ± 17.1 minutes. Only one patient had secretions with a pH of 3; suggestive of gastric secretions.

 

The ED50 for smooth LMA removal was 2.1% (95% CI 1.1-2.9%) and the ED95 was 3.9% (95% CI 3.1-7.9%) (Figure 1). The ED50 and ED95 percent concentration corresponded to desflurane MAC values of 0.4 and 0.7 MAC, respectively.

 

Figure 1. Dixon up-down method to determine end-tidal desflurane concentration for smooth removal

Figure 1

Note. A total of 23 consecutive patients enrolled. Blue dots represent success and black dots failure (i.e., presence of coughing, teeth clenching, gross purposeful movement, breath holding, laryngospasm, or desaturation <90%). EC50 = effective concentration at which 50% of patients have smooth LMA removal. EC95 = effective concentration at which 95% of patients have smooth LMA removal. MAC for smooth LMA removal in 50% of patients was 2.7 ± 0.6%.

 

Ten patients experienced complications. Several patients experienced more than one complication. The most common complication was teeth clenching (n = 8), followed by cough (n =3), laryngospasm (n = 3), desaturation < 90% (n = 3), movement (n = 2) and breath holding (n = 1). Patients 12 through 14 experienced laryngospasm and desaturation that was easily treated with positive pressure. The secretions of patient #13 had a pH of 3. No serious complications occurred in any patient.

 

Conclusion The desflurane concentration at which 95% of patients had a smooth LMA removal was 3.9% (0.7 MAC).

 

Comment

This was an interesting study because it sought to answer a common clinical question. That is, how deep does the patient need to be to remove the LMA? When using desflurane I routinely remove the LMA after the patient has return of their airway reflexes and is following commands. Desflurane comes off so fast that I feel it is better to remove it at that point. However, many anesthesia providers remove the LMA deep. This study adds to our knowledge on what MAC of desflurane an LMA can safely be removed in a majority of the patients (i.e., ED95). For those providers who choose to remove the LMA deep, this study provides some evidence to support this practice.

 

There are a few limitations to this study. First, I think the authors should have reported the smoking history of patients as this may have potentially confounded their results. In addition, the investigators administered nitrous oxide which may have increased their LMA cuff pressures, which in turn may have influenced their results. A better study would have been limited to nonsmokers and adjust the LMA cuff pressure periodically during the case to keep it < 60 cm H2O. Nonetheless, this was still a good study that provides some evidence to support the practice of removing the LMA while the patient is deeply anesthetized. Patients with a history of violent wake-ups (i.e., combat veterans, history of post traumatic stress disorder) may benefit from this practice.

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 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011





The 50% and 95% effective doses of desflurane for removal of the classic laryngeal mask airway in spontaneously breathing anaesthetized adults

Anaesthesia 2011;66:274-277

Hui MT, Subash S, Wang CY


Abstract

Purpose The purpose of this study was to determine the 50% and 95% effective dose (ED) at which the classic LMA could safely be removed in anesthetized adults who were spontaneously breathing desflurane.

 

Background LMAs are used extensively for airway management in patients presenting for outpatient surgery requiring general anesthesia. Some recommend removing the LMA when the patient is still deeply anesthetized, while others only recommend removal after the patient is awake. The rationale for removing the LMA when the patient is still deeply anesthetized is that this minimizes the incidence of coughing, bucking, breath holding, biting on the tube, bronchospasm, and laryngospasm. Desflurane has a rapid recovery profile for return of upper airway reflexes, and some investigators recommend removing the LMA when the patient is still deeply anesthetized because airway reflexes return quickly.

 

Methodology This was a prospective, descriptive study of 38 adult (18-44 years) ASA I or II patients presenting for elective minor surgery under general anesthesia with an LMA.  Patients with a history of GERD, substance abuse, neck pathology, reactive airway disease, suspected difficult airway or BMI > 35 kg/m2 were excluded. After informed consent was obtained, unsedated patients were transported to the operating room for induction of anesthesia. Anesthesia was induced with propofol 3.5 mg/kg, then an LMA size 4 for males and size 3 for females was placed according to the manufactures recommendations. Anesthesia was maintained with 50% nitrous oxide and 50% oxygen at 2 LPM and desflurane. Paracoxib 40 mg was given after induction. Local anesthesia or regional blockade was performed on all patients. No opioids were administered.

 

At the end of the surgery the nitrous oxide was discontinued and oxygen increased to 6 LPM. The end-tidal desflurane concentration for patient number one was set to 6% for 10 minutes before removal of the LMA. All LMAs were removed after suctioning and lifting the jaw (authors did not state if cuff was deflated). The patient was then given oxygen via face mask at 10 LPM.

 

Using the Dixon up-down method, each subsequent patient had the desflurane concentration increased or decreased in increments of 0.1%, depending on the previous patient’s response. Successful removal of the LMA was defined as: absence of coughing, gagging, clenched teeth, biting on tube, airway obstruction, body movement within 1 minute of removal, breath holding, laryngospasm or desaturation to SPO2 <90%, and bronchospasm. If removal was successful the next patient had their end-tidal concentration decreased by 0.1%, if removal was unsuccessful the concentration was increased by 0.1%. This continued until at least 6 crossover pairs occurred. The ED50 and ED95 were determined using Probit analysis.

 

Result A total of n = 38 subjects completed the study. Three were excluded; 1 had a severe laryngospasm on induction and the other 2 required opioids to facilitate LMA placement. This left n = 35 for the analysis. Seventy-one percent of subjects were female with a mean age of 27 ± 6 years, weight of 56 ± 12 kg, and height of 161 ± 0.1 cm. Surgical duration was 49 ± 26 minutes. The most common surgical procedure was breast biopsy (66%), followed by minor orthopedic procedures (28%), inguinal hernia repair (13%), and lipoma excision (3%). None of the patients reported pain after completion of the surgeries. 

 

There were 13 subjects who had failed LMA removal. The reasons for failed LMA removal are listed in Table 1. The desflurane ED50 for smooth LMA removal was 5.29% (95% CI: 5.13-5.38%) and the desflurane ED95 for smooth LMA removal was 5.55% (95% CI: 5.43-6.39%) (Figure 1). The MAC ratio for the ED50 was 0.88 and for the ED95 was 0.93.

 

Table 1. Causes of failed LMA removal in n = 13 subjects

Gross purposeful movement

8     (62%)

Airway obstruction

6     (46%)

Clenching of teeth

6     (46%)

Coughing

4     (31%)

Biting on LMA

3     (23%)

Breath holding

2     (15%)

Gagging

1     (8%)

Laryngospasm

1     (8%)

Bronchospasm

0     (0%)

Desaturation < 90%

0     (0%)

Note. Data is n (%). Some subjects experienced more than one event.

 

Figure 1. ED50 and ED95 for safe LMA removal with desflurane

Figure 1

 

Conclusion In unpremedicated ASA I and II patients who received desflurane and no opioid for maintenance, the effective concentration for safe LMA removal in 50% and 95% of patients was 5.29% and 5.55%, respectively.

 

Comment

This is the second study this year published on the safe removal of the classic LMA when desflurane was used. This study was conducted in Malaysia and the previous study by Sahiner et al in Turkey.1 Both studies are reviewed in this edition of Anesthesia Abstracts.

 

In both investigations, the methodology and patient populations were similar, with the exception that this current study had a higher proportion of women when compared to the study by Sahiner et al.1 In both studies nitrous oxide was used but turned off 10 minutes before beginning to change the desflurane concentration. The major differences I see between the studies are that the desflurane concentration started at 6% in this current study and was titrated down in 0.1% increments. Whereas in the Sahiner et al1 study the desflurane concentration was set at 4% and titrated up or down in 0.5% increments. Additionally, in this current study more events were used to classify “LMA removal failure.” In the Sahiner et al1 study unsuccessful LMA removal was defined as the occurrence of the following complications: coughing, teeth clenching, gross purposeful movements, breath holding, laryngospasm, or desaturation <90% within 1 minute of LMA removal.

 

In the Sahiner et al1 study the ED50 and ED95 were 2.1% (95% CI: 1.1-2.9%) and 3.9% (95% CI: 3.1-7.9%), respectively. The ED50 and ED95 to the MAC ratio of desflurane were 0.4 and 0.7, respectively. However, in this current study the ED50 and ED95 were considerably higher at 5.29% and 5.55%, respectively. These results make me scratch my head as to why one would see such dramatic differences. I think the broader list of events defined as LMA failure is probably the most likely explanation for the higher ED50 and ED95 found in this current study. This would result in more events being defined as a failure unless anesthetic depth was increased. The higher desflurane concentration at which the first patient started may have influenced the results in some way as well.

 

Limitations to this study include that the investigators did not report the frequency of smoking in their sample. Additionally, the investigators did not state if the LMA was removed inflated or deflated. If the LMA was removed deflated, it is possible this could have contributed to the higher MAC ratios as compared to the Sahiner et al study. In the Sahiner et al1 study the LMA was removed inflated.

 

So at what desflurane concentration can one safely remove an LMA? Well, I think it is probably somewhere between 4%1 and 6%, which is the ED95 in both studies. It is important to point out that in both studies the patients did not receive any opioids. Given opioids blunt the airway response, I think if the patient has a good opioid load on board, one could safely remove the LMA when the patient is at a lower concentration. If minimal or no opioids are used then I would go at closer to 6%. Of course, one must consider the patient’s comorbidities and other surgical/anesthetic factors when deciding to remove the LMA deep. I tend to leave the LMA in until the patient is fully awake, however results of this study and the one by Sahiner et al1 at least provide me with some evidence to support removal of the LMA deep in a patient who received desflurane.

Dennis Spence, PhD, CRNA


1. Sahiner Y, Özkan D, Akkaya T, Göral N, Alptekin A, Gümüs H. The end-tidal desflurane concentration for smooth removal of the laryngeal mask airway in anaesthetised adults. Eur J Anaesthesiol 2011;28:187-89.


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 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011




Policy, Process, & Economics
Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application to healthy patients undergoing elective procedures

Anesthesiology 2011;114:495-511

American Society of Anesthesiologists Committee


Abstract

Purpose The purpose of this article was to describe the latest recommendations for practice regarding pulmonary aspiration risk reduction.

 

Background General anesthesia impairs upper airway protective reflexes, putting patients at risk for pulmonary aspiration. Preoperative assessment and preparation includes management of factors contributing to aspiration in order to reduce the risk of its occurrence. Management strategies aimed to reduce the risk of aspiration include requiring patients to fast prior to anesthesia, and the administration of medications that influence gastric volume and acidity.

 

Methodology Practice guidelines regarding pulmonary aspiration were originally developed by a Task Force of the American Society of Anesthesiologists (ASA) in 1999, and are periodically evaluated and revised. Synthesis and analysis of current literature, expert opinion, open forum commentary, and clinical feasibility data were used to formulate the guidelines.

 

Current recommendations are based upon an update of scientific evidence and expert opinion. Literature published since the previous guidelines were evaluated for robustness of article type (meta-analysis of multiple trials, single randomized controlled trial, etc.) and strength of support for the conclusions (supportive, suggestive, mixed results, or evidence insufficient to draw conclusion). New surveys were conducted to describe practitioner opinions.

 

Result While little literature evidence was found evaluating the effectiveness of preoperative assessment, there was strong expert opinion that identification of aspiration risk factors and verification of appropriate fasting were important steps to be taken with every patient.

 

Strong literature evidence and expert opinion were cited to support fasting from clear liquids for 2 hours before anesthesia in both adults and children. Meta-analysis results demonstrated that gastric volume was smaller and pH higher in patients who had been allowed clear liquids up to 2 hours before anesthesia, compared to those who were required to fast longer. Literature regarding breast milk, infant formula, nonhuman milk, or a light breakfast was mostly equivocal and/or insufficient. There were two exceptions. Studies in children given nonhuman milk less than 4 hours before anesthesia demonstrated higher gastric volumes. Also, hypoglycemia was associated with fasting times longer than 8 hours in children. No literature evidence was cited regarding the intake of fried or fatty food. Expert opinions for fasting times were:

  • breast milk 4 hours
  • infant formula 6 hours
  • nonhuman milk 6 hours
  • light breakfast 6 hours
  • fried or fatty food 8 hours

 

The effectiveness of metoclopramide to reduce gastric volume was supported by the literature, but no support was found regarding gastric acidity reduction. Literature supported reduced gastric volume and acidity with the use of cimetidine, ranitidine, famotidine, omeprazole, and lansoprazole. Studies of sodium citrate and magnesium trisilicate demonstrated increased gastric pH with equivocal results on gastric volume. The effect of droperidol and ondansetron to reduce nausea and vomiting was confirmed by the literature. Evidence for the effects of anticholinergics to reduce gastric volume or acidity was equivocal. Insufficient literature was found to make any conclusion regarding the effect of any of these drugs to influence the occurrence of pulmonary aspiration. There was no expert opinion support for the routine administration of any of these medications prior to anesthesia.

 

Conclusion Recommendations for fasting times are summarized in the following table.

 

Table 1: Recommended fasting times for adults and children

 

Adults

Infant and children

Clear liquids

2 hours

2 hours

Breast milk

--

4 hours

Infant formula

--

6 hours

Nonhuman milk

6 hours

6 hours

Light breakfast

6 hours

6 hours

Fried or fatty food

8 hours

8 hours

 

Comment

These practice guidelines provide us with tools to make evidence based decisions regarding prevention of pulmonary aspiration. These recommendations were issued as practice guidelines. Scientific review supports these management practices, but the evidence is not strong enough for them to be issued as professional standards. While standards are generally accepted principles that should be followed under most circumstances, guidelines may be modified or rejected as determined by individual clinical need.

 

It is important to remember that these guidelines are designed for the specific setting of a healthy patient undergoing an elective anesthetic. There is no recommendation that they be applied to patients who are not receiving anesthesia for their surgery or procedure. They are not meant to be applied to women in labor or emergent anesthetics. Many co-existing health conditions delay gastric emptying, making patients at increased risk for aspiration. Such patients will probably need additional management strategies in order to be anesthetized safely.

 

Those additional strategies we might choose for patients at increased risk include medication administration. All the medications reviewed for this update were found to be effective, but evidence was not sufficient to conclude any of them should be routinely given to healthy patients without elevated risk for aspiration. While these guidelines don’t tell us we have to choose any of them, the evidence is there that these medications do what they are supposed to do. When we decide that the situation is appropriate for inclusion of these medications, due to our assessment of an individual patient’s risk for aspiration, the evidence supports that medication decision.

 

While published research was reviewed for this update, expert opinion was also incorporated into these guidelines. It would seem that opinion had a significant influence on the end results. Despite equivocal literature evidence regarding milk and solids, these recommendations included limits supported by expert viewpoints. This decision reflected an appropriate application of the principles of evidence based practice. While research evidence is the foundation for practice decisions, there isn’t empiric evidence about everything and we should not disregard our clinical expertise in any given situation. Even though studies do not clearly demonstrate the increased risk of allowing milk or solids before anesthesia, our practitioner common sense helps us determine the risk is too great to allow it. The risk-benefit comparison is somewhat different with respect to clear liquids. The literature strongly supports the safety of clear liquid intake up to 2 hours before anesthesia. Additionally, there is clear evidence of the harm of a longer fast from clear liquids. Fast times longer than 2 hours were associated with increased gastric volume and acidity, which could paradoxically increase the risk of aspiration.

 

These guidelines remain essentially unchanged from the previous ones issued in 1999. And yet, many of us practice in departments that still maintain the traditional “NPO after midnight” standard. The reasons for maintaining traditional standards are many and varied. The consistency of a one-size-fits all standard facilitates patient compliance. “NPO after midnight” is ingrained in our health care culture, not only among providers but among consumers as well.

 

These guidelines are not standards to be adopted verbatim. Instead, they provide us important information that we can use in the evaluation and revision of our departmental policies and in our clinical practice decisions which incorporate both research findings and patient specific individualization.

Cassy Taylor, DNP, DMP, CRNA


© Copyright 2011 Anesthesia Abstracts · Volume 5 Number 4, April 29, 2011